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introducing

Liver REGENERATOR

MASTER Hepatoprotective FORMULA


200:1 Concentration

Featuring: (−)-4′-O-Methylepigallocatechin • 3,5-Di-O-Caffeoyl Quinic Acid • 5,7,4′-Trihydroxy-3′- Methoxyisoflavone • Aburs Cantoniensis Extract • Acacia Confusa Merr. (Leguminosae), • Actinoscirpus Grossus Tubers • Adenosine Triphosphate • Agathisflavone • Amaranthus Spinosus L • Amorphophallus Campanulatus Roxb. Tubers • Anastatin A • Anastatin B • Andrographolide • Angelica Sinensis (Oliv.)Diels Root Extract • Arjunolic Acid • Aronia Melanocarpa • Artemisia Capillaris • Artemisia Iwayomogi • Artemisia Scoparza Waldst.Et Kit Extract • Asparagus Racemosus Willd. Root Extract • Astragalus Membranaceus Extract • Astragalus Mongholicus Bunge Extract • Berberine • Beta Vulgaris Linn.(Bv, Chenopodiaceae) Leaves • Betalain • Bupleurum Chinense Root Extract • Cassia Seed Extract • Catechin • Chestnut (Castanea Crenata) Inner Shell Extract • Chrysanthemum Indicum L. Extract • Cichorium Inthybus L. • Cichorium Intybus Root Extract • Cimicifuga Foetida L.Root Extract • Cinnamomum Cassia Presl Extract • Coptis Chinensis Franch Root Extract • Cordyceps Sinensis( Berk.)Sacc. Extract • Cortex Dictamni Aqueous Extract • Crataegus Pinnatifi Da Bge. Var. Major Leaves Extract • Curcuma Longa L. Extract • Curcuma Phaeocaulis Radix • Curcumin • Curdrania Tricuspidata Leaves • Dendropanax Morbifera Leveille Leaves • Desmodium Triquetrum Leaf • Dl-Methionine • Dropwort (Oenanthe Javanica) • Eclipta Alba • Epicatechin • Forsythia Suspensa Extract • Fructus Schisandrae (Wuweizi In Chinese) • Galangin • Ganoderma Lucidum • Garlic (Aged Black) • Genistein • Gentiana Scabra Bunge Extract • Glycyrrhiza Glabra • Glycyrrhiza Uralensis Fisch. Extract • Glycyrrihizin • Gossypin • Halichrysin A And B • Hedyotis Diffusa Extract • Hibiscus Vitifolius Root Extract • Houttuynia Cordata Thunb Extract • Hovenia Dulcis Extract • Hypophyllanthin • Imperata Cylindrica Beauv.Var. Major( Nees)C.E.Hubb. Root Extract • Isatis Indigotica Fort.Root Extract • Isoquercitrin • Kaempferol • Kolaviron • Kutkoside • Ligularia Fischeri • Ligusticum Chuanxiong Hort Extract • Limonium Tetragonum • Lithospermum Erythrorhizon Sieb. Et Zucc Extract • Lonicera Japonica Thunb. Extract • Luteolin • Lycium Barbarum L. Extract • Lysimachia Christinae Hance Extract • Mangiferin • Murraya Koenigii • Naringenin • Nelumbo Nucifera Gaertn. • Neoandrographolide • Nepenthes Khasiana Hook. F • Onitin • Ornithine Aspartate • Oxymatrine • Paeonia Lactiflora Pall Root Extract • Panax Ginseng C. A. Meyer Extract • Panaxnotoginseng(Burk.)F.H.Chen Root Extract • Patrinia Scabiosaefolia Extract • Penthorum Chinense Pursh Extract • Phellodendri Cortex (Pc; Bark Of Phellodendron Amurense Rupr.) • Phloridzin • Phyllanthin • Phyllanthus Emblica L. (Amla) • Phyllanthus Niruri • Picrorhiza Kurroa • Picroside • Plumbagin • Polydatin • Polyene Phosphatidyl Choline • Polygonum Cuspidatum Sieb.Et Zucc Extract • Polyporus Umbellatus Extract • Poria Cocos • Psoralea Corylifolia L. (Pc) Seeds Extract (Pce) • Puerarin (Pr), An Active Component Extracted From The Kudzu Root • Quercetin • Radix Puerariae • Rehm,Annia Glutinosa Libosch. Extract • Rheum Palmatum L Extract • Rubiadin • Rutin • Salidroside • Salvia Miltiorrhiza Bge Root Extract • Sanguisorba Officinalis L Extract • Schisandra Chinensis(Turcz.)Baill. Extract • Scopoletin • Scutellaria Barbata D. Don Extract • Sedum Sarmentosum Bunge Extract • Semen Hoveniae • Sida Cordifolia Linn. (Malvaceae) • Silybin, Isosilybin, Silychristin, Silydianin • Silybum Marianum (L.) Gaertn. Extract • Spatholobus Suberectus Dunn Extract • Stephania Tetrandra S.Moore Root Extract • Superoxide Dismutase [Cu-Zn] • Tarax Acum Mongolicum Extract • Taraxacum Officinale (Dandelion) Extract • Troxerutin • Vitexin 7-O-Β-L-Glucopyranoside & Vitexin 2″-O-Β-Glucopyranoside • Vitis Amurensis Seeds (Procyanidins From Wild Grape) • Wedelolactone • Wighteone • Withaferin A • Wu-Zi-Yan-Zong-Wan • Β-Sitosterol •


Introduction to Liver

In the human body, the Liver plays a crucial role in regulating many biological processes, such as detoxification, metabolism of fat, carbohydrate, and protein, secretion of bile, removal of components from the blood circulation, and storage of vitamins. Through these physiological actions, the Liver supports the maintenance, performance, and regulation of the human body’s homeostasis. It also involves multiple biochemical pathways related to energy provision, fighting against disorders/diseases, nutrient supply, growth, and reproduction. The Liver is also an abundant source of essential (histidine and threonine) and nonessential (aspartate, alanine, glycine, glutamate, and serine) amino acids.

From the 1970s, several researchers analyzed the ability of the Liver to synthesize useful agents to detoxify drugs, waste substances, xenobiotics, and toxic metabolites from portal circulation by using various models in humans and animals. This detoxification of the Liver makes it liable to preserve attacks on offending endogenous and/or exogenous substances, causing Liver dysfunction. Generally, Liver disease is defined as an injury to hepatic cells and tissues. The hepatic diseases are mainly categorized into two subtypes, namely acute and chronic hepatitis, associated with inflammatory complications like hepatosis. It is estimated that about two million hepatic disease–related deaths are recording annually across the world. Of these, 50% of the cases are caused by cirrhosis (Liver fibrosis), and the rest are the result of hepatitis and hepatocellular carcinoma. Overall, hepatic-related deaths accounted for ∼3% of all the deaths annually worldwide, highest in Latin America and Africa, followed by Asia.

Mostly, hepatic diseases are caused by viral infections (Hepatitis A–E), autoimmune diseases, high doses of drug consumptions (i.e., paracetamol, acetaminophen, and antibiotics), hazardous compound exposure (aflatoxin, CCl4, GalN, dimethylnitrosamine, chlorinated hydrocarbons, peroxidized oil, and thioacetamide), and excessive intake of Alcohol. Etiological studies identified that Liver dysfunction is chiefly induced by lipid peroxidation in the Liver, followed by cirrhosis and hepatitis. Despite broad advances in current medicine, there are no effective treatments of choice for stimulating hepatic function or aid in rejuvenating hepatic cells. Moreover, hepatic disease treatments are controversial because most of the current synthetic drugs for managing these diseases cause severe side effects. Therefore, it is in great demand to search for alternative medicine to treat hepatic diseases with less toxicity and adverse effects. This current review aimed to provide sufficient information about hepatic diseases and their current diagnostic methods. Additionally, the use of bioflavonoids in the treatment of hepatic diseases was discussed.

Hepatic diseases: The Liver is the largest internal organ of the human body, with an average weight of 1.36–1.59 Kg, connected to almost all essential processes in the human body. Also, it controls the internal environment of the body via various physiological and metabolic processes, either independently or with other organs. Unfortunately, Liver dysfunction affects the quality of life, as well as life expectancy. 1 out of every 2500 live births affect neonatal hepatic disease.

As the Liver is close to the gastrointestinal system, it is susceptible to viral infections and toxic substances due to its unique metabolism. Usually, the Liver gets drained with the concentrated forms of drugs and xenobiotic substances from the gastrointestinal organs’ blood. The accumulated xenobiotics and toxic substances get activated in the Liver and produce reactive metabolic species as byproducts.

These unstable species induce hepatic damage or worsen the injury by several mechanisms. Also, hepatotoxic chemicals such as amiodarone, ethanol, GalN, halothane, isoniazid, CCl4, phenytoin, methyldopa, paracetamol, and inorganic compounds (arsenic, copper, phosphorus, and iron) harm the hepatic cells mostly by inducing lipid peroxidation in the Liver. The various types of hepatotoxicity conditions are mentioned below.

Alcoholic Liver Disease : It is evidenced that excessive Alcohol consumption causes the chronic hepatic disease that damages the Liver and buildups of inflammation, fats, and scars. Usually, Alcoholic Liver disease has four phases—Alcoholic fatty Liver disease, Alcoholic hepatitis, fibrosis, and cirrhosis. In early stage, Alcoholic Liver disease can be diagnosed by abdominal pain, diarrhea, and vomiting. Later stages include edema of the lower limbs, jaundice, ascites, fever, itchy skin, clubbing, blood in stools and vomit, and significant bodyweight reduction. Avoiding excessive Alcohol consumption has been noted as the best and only way to avoid Alcoholic Liver disease.

Various types of hepatic diseases.

Cirrhosis: Long-term inflammation of the Liver creates a life-threatening condition called cirrhosis. During cirrhosis, fibrosis is formed in the Liver leading to scarring and loss of organ function. It is well known that all chronic forms of hepatic disease finally end with cirrhosis, characterized by the reduced capability to rejuvenate hepatic cells, decreased blood flow, and loss of hepatic cells. In the beginning, cirrhosis shows no abnormalities on imaging or in blood tests. There is a loss of hepatic function due to internal bleeding and fluid accumulation in the abdominal cavity in the long run. To date, Liver transplantation is the only treatment for last-stage cirrhosis.

Hepatocellular carcinoma: Hepatocellular carcinoma is the most common kind of hepatic cancer in humans with chronic hepatic diseases. It is categorized into two major subtypes, namely hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Hepatic cancer is diagnosed by blood tests, imaging, and Liver biopsy. Current treatments include chemotherapy, surgery, immunotherapy, radiation therapy, and Liver transplantation.

Hepatitis: Hepatitis is an inflammatory disorder of the hepatic system mostly caused by viruses (Hepatitis A, B, C, D, or E) and rarely by an autoimmune reaction (autoimmune hepatitis). Hepatitis A and E are acute (short term), while others are chronic forms (on-going). Hepatitis A is transmitted via food and/or water or contaminated feces from the infected person. Hepatitis B and C are transmitted via infectious body fluids or sex with an infected person. Hepatitis D (Δ-hepatitis) is the rarest form of hepatitis and is transmitted mainly by direct contact with infected blood. Hepatitis E, on the other hand, is waterborne and very dangerous to pregnant women. The main symptoms of hepatitis are flu-like symptoms, dark urine, yellow skin and eyes, signs of jaundice, pale stool, and abdominal pain. The treatment of hepatitis varies depending on the means of viral transmission. However, hepatitis is prevented by lifestyle precautions and immunizations.

NonAlcoholic fatty Liver disease:  NonAlcoholic fatty Liver is the most common disorder that refers to a higher accumulation of fat in the hepatic cells due to obesity and diabetes in people who do not abuse Alcohol. Although the presence of fat in the Liver is abnormal, it does not harm the Liver. The majority of the patients with fatty Liver show no signs and symptoms, except abdominal pain in some cases. Epidemiological studies suggest that for only a few people, fatty Liver may lead to non-Alcoholic steatohepatitis, a severe condition involving inflammation in fatty Liver cells. The clinicopathological studies show that fatty Liver is a significant cause of cryptogenic hepatocellular carcinoma, cryptogenic cirrhosis, and hepatic transaminases. However, clinical studies on fatty Liver suggest that it could be treated by controlled weight loss and physical activities.

Plants and their phytochemicals used in hepatic diseases: From prehistoric times, plants have been the primary source for managing several ailments due to the presence of high bioactive compounds with low toxicity. Nearly 80% of the world’s population has employed plant materials (also known as traditional medicine) for healthcare. The etiology of hepatic diseases is diverse, and a variety of medicinal plants has been reported to have Hepatoprotective activity through various mechanisms, such as reducing peroxidation, improvement of antioxidant defense (CAT, GPx, and SOD activity), antioxidant properties, reversed hepatic fibrosis, activation of hepatic stellate cells, anti-inflammatory activity, and antifibrotic properties.

Moreover, basic clinical research has exposed the mechanism of actions by which a few plants produce their beneficial properties in regards to cirrhosis, Liver regenerating effects, fatty Liver, radiation toxicity, ischemic injury, viral hepatitis, and toxic hepatitis. Several medicinal plants were subjected to chemical examination to identify potential bioactive metabolites having Hepatoprotective properties, which led to the identification of phytochemicals of phenolics, terpenoids, flavonoids, lignans, carotenoid, steroids, amino acids, proteins, carotenoid, tannins, glycosides and alkaloids classes.

Bioflavonoids with Hepatoprotective activity: Bioflavonoids or flavonoids are low-molecular-weight phenolics that possess a basic C6–C3–C6structure of an aromatic ring (A) attached to a benzene ring (B) fused to a heterocyclic ring (C) with a single C–C bond. Flavonoids can be divided into a number of groups that differ from each other according to the degree of oxidation on ring C, the degree of unsaturation, and the number and position of –OH groups on flavones, flavanones, flavonols, flavanonols, isoflavones, isoflavanones, flavans, and anthocyanidins.. Flavonoids are often bound to glycosides, such as arabinose, d-glucose, galactose, l-rhamnose, glucorhamnose, etc., and are termed as flavonoid-glycosides. Similarly, glycoside forms of anthocyanidins are called as anthocyanins. On the other hand, flavonoids bound to lignans are termed as flavonolignans.

Biologically, flavonoids are found in various plant parts and are mostly used for plant growth and defensive mechanisms. These molecules also act as a UV filter to plants and protect them from different abiotic and biotic stresses. They have mostly been identified in fruits, flowers, vegetables, leaves, cocoa, tea, onions, and dietary products, and they have been reported to have multiple bioactivities such as antioxidant, anticancer, and antidiabetic anti-inflammation, antimicrobial, immunomodulatory, and Hepatoprotective properties. They are also well acknowledged to have potent inhibitory properties for different enzymes such as cyclooxygenase, α-amylase, phosphoinositide, lipoxygenase, xanthine oxidase, α-glucosidase, and aldose reductase. Flavonoids have been long credited for their beneficial effects on human health and recently tested for their chemoprevention and disease therapy. To date, nearly 6000 flavonoids have been identified from fruits, seeds, flowers, stems, roots, buds, and vegetables of various medicinal plants. Of these, approximately 100 bioflavonoids have been reported for their Hepatoprotective activites.


INGREDIENTS & SCIENCE:



(−)-4′-O-Methylepigallocatechin


Hepatoprotective and antioxidative properties of Salacia reticulata: preventive effects of phenolic constituents on CCl4-induced Liver injury in mice.


These results suggest that the antioxidative activity of the principal phenolic compounds is involved in the Hepatoprotective activity of S. reticulata.



3,5-Di-O-caffeoyl quinic acid


In Vitro Hepatoprotective compounds from Suaeda glauca


Bioassay-guided fractionation of the MeOH extract of Suaeda glauca yielded four phenolic compounds, methyl 3,5-di-O-caffeoyl quinate (1) and 3,5-di-O-caffeoyl quinic acid (2), isorhamnetin 3-O-β-D-galactoside (3), and quercetin 3-O-β-D-galactoside (4). Compounds 1 and 2 were Hepatoprotective against tacrine-induced cytotoxicity in human Liver-derived Hep G2 cells with the EC50 values of 72.7±6.2 and 117.2±10.5 μM, respectively. Silybin as a positive control showed an EC50 value of 82.4±4.1 μM.


Four Di-O-caffeoyl Quinic Acid Derivatives from Propolis. Potent Hepatoprotective Activity in Experimental Liver Injury Models


The water extract of propolis (PWE) showed a strong Hepatoprotective activity against CCl4-toxicity in rats and D-galactosamine (GalN)/lipopolysaccharide (LPS)-induced Liver injury in mice.



5,7,4′-Trihydroxy-3′- methoxyisoflavone


New Isoflavones and Pterocarpane with Hepatoprotective Activity from the Stems of Erycibe expansa


The methanolic extract from the stems of Erycibe expansa was found to show a Hepatoprotective effect on D-galactosamine-induced cytotoxicity in primary cultured mouse hepatocytes. By bioassay-guided separation, two new prenylisoflavones and a pterocarpane, erycibenins A (1), B (2), and C (3), were isolated from the active fraction (the EtOAc-soluble fraction) together with ten isoflavones (4 – 13) and seven pterocarpanes (14 – 20).

The stereostructures of the new compounds were determined on the basis of chemical and physicochemical evidence including modified Mosher’s method. In addition, the isolated constituents, erycibenin A (1, IC50 = 79 μM), genistein (6, 29 μM), orobol (7, 36 μM), and 5,7,4′-trihydroxy-3′-methoxyisoflavone (8, 55 μM) exhibited inhibitory activity on D-galactosamine-induced cytotoxicity in primary cultured mouse hepatocytes.


Hepatoprotective potential of bioflavonoids


The Liver controls the body’s internal environment via various physiological and metabolic processes, either independently or together with otfher organs. Liver disease is defined as an injury to the hepatic cells and tissues, mainly caused by viral infections, toxic compounds, high doses of drugs, and excessive Alcohol intake. There are an estimated two million hepatic disease–associated deaths recorded annually worldwide with a diverse etiology.

Numerous medicinal plants and their phytochemicals have been reported to display Hepatoprotective activity. Among those, bioflavonoids, low-molecular-weight phenolics possessing a basic C6–C3–C6 structure, have been reported to have the ability to treat hepatic diseases. In the current study, we aimed to summarize hepatic diseases and strategies to treat them and added a brief note on the bioflavonoids that have been tested against hepatic diseases.



Aburs cantoniensis extract


Protective Effect of Ethanol Extraction of Abrus cantoniensis on Non-Alcoholic Fatty Liver in Rats


CONCLUSION: Ethanol extraction of A.cantoniensis can reduce the content of ALT and AST in serum and Liver index,and relieve the pathologic damage and the degree of fatty degeneration of hepatic tissue.Ethanol extraction of A.cantoniensis can improve fatty Liver induced by CCl4 and high-fat feeding in rats.


Abrusamide A and B, two Hepatoprotective isomeric compounds from Abrus mollis Hance


Two isomeric compounds, abrusamide A (1) and abrusamide B (2), were isolated from the leaves of Abrus mollis Hance. Their structures were well defined by means of UV, HR–ESI–MS, 1H NMR, 13C NMR and 2D NMR techniques. From a biogenetic point of view, these two compounds including a cyclobutane basic core should be considered as a [2+2] dimerization product of (E)-N-(4-hydroxycinnamoyl) tyrosine (3), which was also isolated from the plant for the first time. They were also tested for their Hepatoprotective effects on human L-02 cells and displayed significant promote effects on the proliferation of L-02 cells and significant Hepatoprotective effects on CCl4-induced injury of L-02 cells.


Kaikasaponin III and Soyasaponin I, Major Triterpene Saponins of Abrus cantoniensis, act on GOT and GPT: Influence on Transaminase Elevation of Rat Liver Cells Concomitantly Exposed to CCl4 for One Hour


The antihepatotoxic activities of soyasaponin I and kaikasaponin III, triterpenoidal saponins isolated from Abri Herba, the whole plant of Abrus cantoniensis, were studied on Liver injury induced by CCl4 in primary cultured rat hepatocytes. The antihepatotoxic activities of these saponins and glycyrrhizin (positive control) were demonstrated by measuring the levels of glutamic pyruvic transaminase (GPT) and glutamic oxaloacetic transaminase (GOT). Soyasaponin I inhibited the elevation of GOT and GPT activities. The activities were comparable to those of glycyrrhizin.

On the other hand, kaikasaponin III was more effective than soyasaponin I and glycyrrhizin. Kaikasaponin III showed the antihepatotoxic activity at less than 100 µg/ml. Furthermore, the highest activity was observed even in the lower doses (50, 100 µg/ml). However, soyasaponin I and kaikasaponin III showed some toxicity at the highest dose (500 µg/ml), though glycyrrhizin did not show toxicity at any dose.


Phytochemical profiles, antioxidant activities of functional herb Abrus cantoniensis and Abrus mollis


It has been claimed that consumptions of Abrus cantoniensis (AC) and Abrus mollis (AM) as folk beverages and soups are good to cleanse Liver toxicants and prevent Liver diseases. There is scant information on the phytochemical profiles and antioxidant activities of these two varieties. Five major phytochemicals in these two cultivars were qualitatively and quantitatively compared using UPLC-PDA. A high level of total phenolic content (TPC) and total flavonoid content (TFC) was found in AC and AM. AC, in general, showed some antioxidant activities comparable to that of BHT, and stronger radical scavenging activities and higher reducing power than that of AM (p < 0.05). When principal component analysis (PCA) was applied, high correlation between TPC, TFC and their antioxidant activities was found. Hence, this study proved that, both AC and AM could serve as antioxidant-rich component in foods or beverages to promote health function.



Acacia confusa Merr. (Leguminosae)


Protective effect of Acacia confusa bark extract and its active compound gallic acid against carbon tetrachloride-induced chronic Liver injury in rats


These results suggested that the ACBE and gallic acid exhibit potent hepatoprotection against CCl4-induced Liver damages in rats, and the Hepatoprotective effects of ACBE and gallic acid may be due to the modulation of antioxidant enzymes activities and inhibition of lipid peroxidation and CYP2E1 activation.


A review of antioxidant and pharmacological properties of phenolic compounds in Acacia confusa


In the present review article, the phytochemical, antioxidant and pharmacological studies are congregated and summarized concerning the current knowledge of the phenolic compounds of a traditional medical plant Acacia confusa in Taiwan.

This plant is native to Taiwan and South-East Asia. It possesses major pharmacological activities, including antioxidant and radical scavenging activity, Hepatoprotective effect, xanthine oxidase inhibition, semicarbazide-sensitive amine oxidase inhibition, angiotensin I converting enzyme inhibition, antihyperuricemic effect and anti-inflammatory activity.


Anti-hepatitis C virus activity of Acacia confusa extract via suppressing cyclooxygenase-2


Chronic hepatitis C virus (HCV) infection continues to be an important cause of morbidity and mortality by chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC) throughout the world. It is of tremendous importance to discover more effective and safer agents to improve the clinical treatment on HCV carriers. Here we report that the n-butanol–methanol extract obtained from Acacia confusa plant, referred as ACSB-M4, exhibited the inhibition of HCV RNA replication in the HCV replicon assay system, with an EC50 value and CC50/EC50 selective index (SI) of 5 ± 0.3 μg/ml and >100, respectively. Besides, ACSB-M4 showed antiviral synergy in combination with IFN-α and as HCV protease inhibitor (Telaprevir; VX-950) and polymerase inhibitor (2′-C-methylcytidine; NM-107) by a multiple linear logistic model and isobologram analysis.

A complementary approach involving the overexpression of COX-2 protein in ACSB-M4-treated HCV replicon cells was used to evaluate the antiviral action at the molecular level. ACSB-M4 significantly suppressed COX-2 expression in HCV replicon cells. Viral replication was gradually restored if COX-2 was added simultaneously with ACSB-M4, suggesting that the anti-HCV activity of ACSB-M4 was associated with down-regulation of COX-2, which was correlated with the suppression of nuclear factor-kappaB (NF-κB) activation. ACSB-M4 may serve as a potential protective agent for use in the management of patients with chronic HCV infection.



Actinoscirpus grossus tubers


Protective effect of ethanolic extract of Actinoscirpus grossus tubers against ethanol induced Liver toxicity in albino rats


Thus, tubers of A. grossus plant may serve as reservoir of natural products having diverse functions and could be utilised as a potent Hepatoprotective agent.



Agathisflavone


Agathisflavone: Botanical sources, therapeutic promises, and molecular docking study


CONCLUSION: Agathisflavone may be one of the promising plant-derived lead compounds in the treatment of oxidative stress, inflammatory diseases, microbial infection, hepatic and neurological diseases and disorders, and cancer.


Structure and Hepatoprotective Activity of a Biflavonoid from Canarium manii


Canarium manii (Burseraceae) was chemically investigated and the presence of the biflavonoid agathisflavone is reported for the first time from this plant. Pharmacologically, this biflavonoid in doses 50.0 mg and 100.0 mg given orally exhibited dose-dependent Hepatoprotective activity against experimentally-induced carbon tetrachloride-hepatotoxicity in rats and mice.


Hepatoprotective potential of bioflavonoids


The Liver controls the body’s internal environment via various physiological and metabolic processes, either independently or together with other organs. Liver disease is defined as an injury to the hepatic cells and tissues, mainly caused by viral infections, toxic compounds, high doses of drugs, and excessive Alcohol intake. There are an estimated two million hepatic disease–associated deaths recorded annually worldwide with a diverse etiology.

Numerous medicinal plants and their phytochemicals have been reported to display Hepatoprotective activity. Among those, bioflavonoids, low-molecular-weight phenolics possessing a basic C6–C3–C6 structure, have been reported to have the ability to treat hepatic diseases. In the current study, we aimed to summarize hepatic diseases and strategies to treat them and added a brief note on the bioflavonoids that have been tested against hepatic diseases.


Research on the Scientific Evolution of the Flavonoid Agathisflavone


CONCLUSION: Although agathisflavone has been known in the literature since at least 1969, only 23 of the eligible articles found evaluated its possible therapeutic effects. The demonstrated biological activities of agathisflavone range from antiprotozoal to neurogenesis and neuroprotection, however, the molecule needs to be better studied at the in vivo and human level.


A review of natural products with Hepatoprotective activity


Liver diseases are a major worldwide health problem, with high endemicity in developing countries. They are mainly caused by chemicals and some drugs when taken in very high doses. Despite advances in modern medicine, there is no effective drug available that stimulates Liver function, offer protection to the Liver from damage or help to regenerate hepatic cells. There is urgent need, therefore, for effective drugs to replace/supplement those in current use. The plant kingdom is undoubtedly valuable as a source of new medicinal agents. The present work constitutes a review of the literature on plant extracts and chemically defined molecules of natural origin with Hepatoprotective activity. The review shows 107 plants, their families, geographical distribution, plant parts utilized, type of assay and inducer of Liver damage. It also includes 58 compounds isolated from higher plants, classified into appropriate chemical groups. This work intends to aid researchers in the study of natural products useful in the treatment of Liver diseases.


A quest for staunch effects of flavonoids: Utopian protection against hepatic ailments


The role of flavonoids as the major red, blue and purple pigments in plants has gained these secondary products a great deal of attention over the years. Flavonoids are polyphenols and occur as aglycones, glycosides and methylated derivatives. Flavonoids are the main components of a healthy diet containing fruits and vegetables and are concentrated especially in tea, apples and onions. Till date, more than 6000 flavonoids have been discovered, out of which 500 are found in free state.

They are abundant in polygonaceae, rutaceae, leguminosae, umbelliferae and compositae. Flavonoids are powerful antioxidants. In addition to their role in nutrition, flavonoids possess many types of pharmacological activities, including anti-inflammatory, antioxidative, Hepatoprotective, vasorelaxant, antiviral and anticarcinogenic effects. The present review is focused on flavonoids derived from natural products that have shown a wise way to get a true and potentially rich source of drug candidates against Liver ailments.

The present review initially highlights the current status of flavonoids and their pharmaceutical significance, role of flavonoids in hepatoprotection, therapeutic options available in herbal medicines and in later section, summarizes flavonoids as lead molecules, which have shown significant Hepatoprotective activities.



Amaranthus spinosus L


A review for discovering Hepatoprotective herbal
drugs with least side effects on kidney


The Liver is a vital organ which plays a major role in the metabolism and excretion of xenobiotics from the body, and Liver disease is a worldwide health problem. The currently available synthetic drugs to treat Liver disorders cause further damage to the Liver and kidney so it is imperative to find new drugs with least side effects. There are a number of treatment combinations which are derived from medicinal plants and commonly administered as tonic for the Liver.

In this review, we have introduced most important medicinal plants that are used in Liver disorders and have least side effects on kidney. In this regards, we have focused on their active constituents, effects and trial studies, mechanisms of action, pharmacokinetic characteristics, dosages, and toxicity.Amaranthus spinosusL.,Glycyrrhiza glabra,Cichorium inthybusL. Phyllanthus species (amarus,niruri,emblica),Picrorhiza kurroa, andSilybum marianumhave been extensively administered for the treatment of Liver disorders. The introduced medicinal plants can be used for production of new drugs via antioxidant-related properties, Hepatoprotective activities and least side effects on kidney for the prevention and treatment of Liver disorders


A Novel Tetraenoic Fatty Acid Isolated from Amaranthus spinosus Inhibits Proliferation and Induces Apoptosis of Human Liver Cancer Cells


Our results provide the first experimental evidence that a novel fatty acid isolated from A. spinosus exhibits significant antiproliferative activity mediated through the induction of apoptosis in HepG2 cells. These encouraging results may facilitate the development of A. spinosus fatty acid for the prevention and intervention of hepatocellular carcinoma.


Oxidative damage and hepatotoxicity associated with deltamethrin in rats: The protective effects of Amaranthus spinosus seed extract


CONCLUSION: The Hepatoprotective potential of ASS could be explained by its high phenolic content, antioxidant properties and phytochemical contents.


Chemoprotective and Antioxidant Activities of Methanolic Extract of Amaranthus Spinosus Leaves on Paracetamol Induced Liver Damage in Rats


CONCLUSION: This presence of amino acids, flavonoids and phenolic compounds in the MEAS might be responsible for its marked chemoprotective and antioxidant activities in paracetamol induced-Liver damage in Wistar rats.


Hepatoprotective activity of Amaranthus spinosus in experimental animals


The results of this study strongly indicate that whole plants of A. spinosus have potent Hepatoprotective activity against carbon tetrachloride induced hepatic damage in experimental animals. This study suggests that possible mechanism of this activity may be due to the presence of flavonoids and phenolics compound in the ASE which may be responsible to Hepatoprotective activity.


Protective effect of Amaranthus spinosus against d-galactosamine/lipopolysaccharide-induced hepatic failure


Results of this study revealed that A. spinosus extract could afford a significant protection against d-GalN/LPS-induced hepatocellular injury.



Amorphophallus campanulatus Roxb. tubers


PROTECTIVE ACTIVITY OF ETHANOLIC EXTRACT OF AMORPHOPHALLUS CAMPANULATUS AGAINST ETHANOL INDUCED HEPATOTOXICITY IN RATS


CONCLUSION: The results of this study strongly indicate that ethanolic extract of Amorphophallus campanulatus has potent Hepatoprotective action against ethanol induced hepatic damage particularly by scavenging free radicals and combating oxidative stress. Further investigation can lead to the development of phytomedicines of therapeutic significance against oxidative stress. Keywords: Amorphophallus campanulatus, Ethanol, Hepatoprotection, Oxidative stress, Phytomedicine


Hepatoprotective activity of Amorphophallus paeoniifolius tubers against paracetamol-induced Liver damage in rats


CONCLUSION: From the results it can be concluded that Amorphophallus paeoniifolius possesses Hepatoprotective effect against paracetamol-induced Liver damage in rats.


ANTIOXIDANT AND Hepatoprotective ACTIVITY OF ETHANOLIC AND AQUEOUS EXTRACTS OF AMORPHOPHALLUS CAMPANULATUS ROXB. TUBERS


The results of this study strongly indicate that Amorphophallus campanulatus (Roxb.) tubers have potent Hepatoprotective action against carbon tetrachloride induced hepatic damage in rats. The ethanolic extract was found Hepatoprotective more potent than the aqueous extract. The antioxidant activity was also screened and found positive for both ethanolic and aqueous extracts.

This study suggests that possible mechanism of this activity may be due to free radical scavenging potential caused by the presence
of flavonoids in the extracts.



Anastatin A


Anastatins A and B, new skeletal flavonoids with Hepatoprotective activities from the desert plant Anastatica hierochuntica


New skeletal flavonoids, anastatins A and B, were isolated from the methanolic extract of an Egyptian medicinal herb, the whole plants of Anastatica hierochuntica. Their flavanone structures having a benzofuran moiety were determined on the basis of chemical and physicochemical evidence. Anastatins A and B were found to show Hepatoprotective effects on d-galactosamine-induced cytotoxicity in primary cultured mouse hepatocytes and their activities were stronger than those of related flavonoids and commercial silybin.

New skeletal flavonoids, anastatins A and B, were isolated from the methanolic extract of an Egyptian medicinal herb, the whole plants of Anastatica hierochuntica. Their flavanone structures having a benzofuran moiety were determined on the basis of chemical and physicochemical evidence. Anastatins A and B were found to show Hepatoprotective effects on d-galactosamine-induced cytotoxicity in primary cultured mouse hepatocytes and their activities were stronger than those of related flavonoids and commercial silybin.


Antioxidant activities of anastatin A & B derivatives and compound 38c’s protective effect in a mouse model of CCl4-induced acute Liver injury


The results show that most of these flavonoid compounds have good antioxidant activity and low cytotoxicity in vitro. Among them, the most potent compound was 38c, which exhibited a protective effect on CCl4-induced hepatic injury by suppressing the amount of CYP2E1. These findings indicate that anastatin flavonoid derivatives have potential therapeutic utility against oxidative hepatic injury.


Phenolic compounds and Hepatoprotective potential of Anastatica hierochuntica ethanolic and aqueous extracts against CCl4-induced hepatotoxicity in rats


CONCLUSION: Biochemical observations, supplemented by histopathological examination revealed that AH affords extract-depending protection against CCl_4-hepatotoxicity.


Anti-Hepatotoxic Effect of the Methanolic Anstatica
Hierochuntica Extract In Ccl 4- Treated Rats


From the above results, it is concluded for the first time that methanolic Anastatica hierochuntica extract offers protective effect against CCl4-induced hepatotoxicity in experimental rats.


Anastatins A and B, new skeletal flavonoids with Hepatoprotective activities from the desert plant Anastatica hierochuntica


New skeletal flavonoids, anastatins A and B, were isolated from the methanolic extract of an Egyptian medicinal herb, the whole plants of Anastatica hierochuntica. Their flavanone structures having a benzofuran moiety were determined on the basis of chemical and physicochemical evidence. Anastatins A and B were found to show Hepatoprotective effects on d-galactosamine-induced cytotoxicity in primary cultured mouse hepatocytes and their activities were stronger than those of related flavonoids and commercial silybin.



Anastatin B


Anastatins A and B, new skeletal flavonoids with Hepatoprotective activities from the desert plant Anastatica hierochuntica


New skeletal flavonoids, anastatins A and B, were isolated from the methanolic extract of an Egyptian medicinal herb, the whole plants of Anastatica hierochuntica. Their flavanone structures having a benzofuran moiety were determined on the basis of chemical and physicochemical evidence. Anastatins A and B were found to show Hepatoprotective effects on d-galactosamine-induced cytotoxicity in primary cultured mouse hepatocytes and their activities were stronger than those of related flavonoids and commercial silybin.

New skeletal flavonoids, anastatins A and B, were isolated from the methanolic extract of an Egyptian medicinal herb, the whole plants of Anastatica hierochuntica. Their flavanone structures having a benzofuran moiety were determined on the basis of chemical and physicochemical evidence. Anastatins A and B were found to show Hepatoprotective effects on d-galactosamine-induced cytotoxicity in primary cultured mouse hepatocytes and their activities were stronger than those of related flavonoids and commercial silybin.



Andrographolide


Hepatoprotective activity of andrographolide from Andrographis paniculata against carbontetrachloride.


The results suggest that andrographolide is the major active antihepatotoxic principle present in A. paniculata.


Andrographolide induces autophagic cell death in human Liver cancer cells through cyclophilin D-mediated mitochondrial permeability transition pore


Taken together, our findings unveil a novel mechanism of drug action by andrographolide in Liver cancer cells and suggest that andrographolide may represent a promising novel agent in the treatment of Liver cancer.


Enhanced protective activity of nano formulated andrographolide against arsenic induced Liver damage


CONCLUSION: The results of this study suggest that NA could be beneficial against arsenic-induced Liver toxicity.


Natural product andrographolide alleviated APAP-induced Liver fibrosis by activating Nrf2 antioxidant pathway


In Summary, Nrf2 is critically involved in preventing Liver fibrosis induced by long-term administration of APAP in mice, and Andro alleviates APAP-induced Liver fibrosis by attenuating Liver oxidative stress injury via inducing Nrf2 activation. This study points out the potential application of Andro in the treatment of Liver fibrosis in clinic.


Andrographolide impairs alpha-naphthylisothiocyanate-induced cholestatic Liver injury in vivo


These data suggest that andrographolide may impair cholestatic Liver injury via anti-inflammatory and anti-oxidative stress.


Protective effect of andrographolide against concanavalin A-induced Liver injury


Thus, our results indicate that Ag prevents Con-A-induced Liver injury and reduced the hepatic oxidative stress response. The hepatic protective effect of Ag indicates that Ag supplementation may be beneficial in the treatment of immune-mediated Liver injury.


Effect of two andrographolide derivatives on cellular and rodent models of non-Alcoholic fatty Liver disease


Our results showed that IAN could be a promising lead to treat NAFLD with comparatively low toxicity and improved efficacy.


Protective Mechanism of Andrographolide against Carbon Tetrachloride-Induced Acute Liver Injury in Mice


AP can effectively prevent Liver injury induced by CCl4, which may be due to inhibition of oxidative stress and inflammatory responses.


Andrographolide protects Liver cells from H2O2 induced cell death by upregulation of Nrf-2/HO-1 mediated via adenosine A2a receptor signalling


CONCLUSION: Thus, andrographolide probably by binding to adenosine A2a receptor activates Nrf-2 transcription and also inhibits its exclusion from the nucleus by inactivating GSK-3β, together resulting in activation of HO-1.

We speculate that andrographolide can be used as a therapeutic drug to combat oxidative stress implicated in pathogenesis of various diseases such as diabetes, osteoporosis, neurodegenerative diseases etc.


Andrographolide Ameliorates Liver Fibrosis in Mice: Involvement of TLR4/NF-κB and TGF-β1/Smad2 Signaling Pathways


These results demonstrate that Andro prevents Liver inflammation and fibrosis, which is in correlation with the inhibition of the TGF-β1/Smad2 and TLR4/NF-κB p50 pathways, highlighting Andro as a potential therapeutic strategy for Liver fibrosis.


Andrographolide enhances redox status of Liver cells by regulating microRNA expression


Andrographolide thus, can play a beneficial role in modulating antioxidant defense in oxidative stress induced diseases such as diabetes, ageing etc.


CONCLUSION: ADH protected against LPS/D-GalN-induced Liver injury by inhibiting NF-κB and activating Nrf2 signaling pathway.


Andrographolide ameliorates d-galactosamine/lipopolysaccharide-induced acute Liver injury by activating Nrf2 signaling pathway


CONCLUSION: ADH protected against LPS/D-GalN-induced Liver injury by inhibiting NF-κB and activating Nrf2 signaling pathway.


Oral andrographolide nanocrystals protect Liver from paracetamol induced injury in mice


Pharmacodynamic studies on mice showed that AGNC exerted Hepatoprotective activity at a lower dose against paracetamol induced Liver injury, in comparison to crude AG. The work highlighted that nanocrystal technology can be considered as one platform for circumventing the biopharmaceutical limitations of AG. This also ensures significant successes in biological applications.



Angelica sinensis (Oliv.)Diels root extract


Protective effect of polysaccharides-enriched fraction from Angelica sinensis on hepatic injury


These findings suggest that the pathogenic mechanisms of both acetaminophen and CCl4 are different. AP is more effective in the protection against Liver damage induced by acetaminophen, which is associated with the glutathione depletion and nitric oxide synthase activation in the Liver.


Chronic administration of Angelica sinensis polysaccharide effectively improves fatty Liver and glucose homeostasis in high-fat diet-fed mice


Histological examination clearly showed that ASP reduced lipid accumulation in the Liver and attenuated hepatic steatosis in HFD-fed mice. In addition, ASP markedly alleviated serum and Liver lipid disorders and fatty Liver via the upregulation of PPARγ expression and the activation of adiponectin-SIRT1-AMPK signaling. Furthermore, ASP also significantly relieved severe oxidative stress, demonstrating that ASP might attenuate nonAlcoholic fatty Liver disease via a “two-hit” mechanism.

In addition, ASP reduced blood glucose levels and ameliorated insulin resistance via the regulation of related metabolic enzymes and by activating the PI3K/Akt pathway in HFD-fed mice. Our findings revealed that ASP might be used as an alternative dietary supplement or health care product to ameliorate metabolic syndrome in populations that consistently consume HFDs.


Angelica sinensis polysaccharide protects against acetaminophen-induced acute Liver injury and cell death by suppressing oxidative stress and hepatic apoptosis in vivo and in vitro


Taken together, our findings reveal that ASP has potential to be used as a Hepatoprotective agent for the management of APAP-induced Liver injury.


Angelica sinensis polysaccharide attenuates CCl4-induced Liver fibrosis via the IL-22/STAT3 pathway

CONCLUSION: ASP effectively alleviates chronic Liver fibrosis by inhibiting HSC activation through the IL-22/STAT3 pathway.


Self-assembled Angelica sinensis polysaccharide nanoparticles with an instinctive Liver-targeting ability as a drug carrier for acute Alcoholic Liver damage protection


According to the results, ACNPs may serve as a promising Liver-targeting drug deLivery carrier for Liver disease prevention.


Protective effects of Angelica sinensis polysaccharide against hyperglycemia and Liver injury in multiple low-dose streptozotocin-induced type 2 diabetic BALB/c mice


Our results showed that ASP had beneficial effects in preventing hyperglycemia, stimulating insulin secretion, promoting hepatic glycogen synthesis, regulating adipokine release, reducing Liver fat accumulation, and attenuating Liver injury.

Moreover, mechanistic studies illustrated that ASP could upregulate the expression of PPARγ and Liver insulin signaling proteins, including IRS-2, PI3K, Akt, p-Akt and GLUT2, increase anti-apoptotic protein Bcl-2, decrease pro-apoptotic protein Bax expressions, and protect the mice against hepatic damage. These findings revealed the potential mechanisms of ASP-mediated therapeutic effects in diabetic mice. It suggested that ASP might be used in prescriptions or functional foods for the prevention or treatment of diabetes and Liver diseases.


Extraction and structural analysis of Angelica sinensis polysaccharide with low molecular weight and its lipid-lowering effect on nonAlcoholic fatty Liver disease


Results revealed that low MW ASP dose-dependently decreased TG, TC in vitro and TG, TC, ALT, HDL-C, and LDL-C in vivo. Oil Red O-positive area and Nile red fluorescence intensity decreased in ASP treatment groups both in vitro and in vivo which suggested ASP could reduce lipid accumulation and fatty regeneration.

Hematoxylin–eosin staining results shown a decrease in hepatocytes ballooning indicating that ASP could ameliorate Liver lipid degeneration. Briefly, a novel polysaccharide with low MW was successfully obtained which can prospectively act as NAFLD therapy.


Protective effect of polysaccharides-enriched fraction from Angelica sinensis on hepatic injury


AP is more effective in the protection against Liver damage induced by acetaminophen, which is associated with the glutathione depletion and nitric oxide synthase activation in the Liver.


Angelica sinensis Supercritical Fluid CO2 Extract Attenuates D-Galactose-Induced Liver and Kidney Impairment in Mice by Suppressing Oxidative Stress and Inflammation


Results revealed that AS significantly improved Liver and kidney function as assessed by organ index and functional parameters. In addition, AS pretreatment effectively ameliorated the histological deterioration. AS attenuated the MDA level and markedly enhanced the activities and gene expressions of antioxidative enzymes, namely Cu, Zn-SOD, CAT, and GPx.

Furthermore, AS markedly inhibited the D-gal-mediated increment of expressions of inflammatory cytokines iNOS, COX-2, IκBα, p-IκBα, and p65 and promoted the IκBα expression level in both hepatic and renal tissues. In sum, AS pretreatment could effectively guard the Liver and kidney of mice from D-gal-induced injury, and the underlying mechanism was deemed to be intimately related to attenuating oxidative response and inflammatory stress.


New understanding of Angelica sinensis polysaccharide improving fatty Liver: The dual inhibition of lipid synthesis and CD36-mediated lipid uptake and the regulation of Alcohol metabolism


Our results showed that the lipid-lowering effect of ASP might result from the dual inhibition of lipid synthesis and CD36-mediated lipid uptake. The antioxidation of ASP might be attributed to the reversal of Alcohol metabolic pathways from CYP2E1 catalysis to ADH catalysis. Taken together, the study demonstrated the direct role of ASP in lipid metabolism for the first time and revealed the underlying mechanism of reducing ROS, providing an available strategy for ASP as a potential agent to treat AFLD.


Metabolomics research on the Hepatoprotective effect of Angelica sinensis polysaccharides through gas chromatography–mass spectrometry


The results of the pathological changes observed in the Liver, the biochemical parameters in plasma, and the metabolomics of the plasma and Liver homogenate all showed that Liver injury was successfully reproduced, ASP exhibited Hepatoprotective effect, and the medium dose of ASP exhibited the best. Nine endogenous metabolites in the Liver homogenate and ten endogenous metabolites in the plasma were all considered as potential biomarkers.

They were considered to be in response to Hepatoprotective effects of ASP involved in the amino acids metabolism, energy metabolism, and lipids metabolism. Therefore metabolomics is a valuable tool in measuring the efficacy and mechanisms of action of traditional Chinese medicines.


[Modulation of angelica sinensis polysaccharides on the expression of nitric oxide synthase and Bax, Bcl-2 in Liver of immunological Liver-injured mice].


CONCLUSION: NO production may play a role in the LPS-induced hepatotoxicity. Angelica Sinensis Polysaccharides can alleviate the immune Liver injury by modulating the expression of cNOS, iNOS, Bax, Bcl-2.


Modulation of GdCl3 and Angelica Sinensis polysaccharides on differentially expressed genes in Liver of hepatic immunological injury mice by cDNA microarray


CONCLUSION: cDNA microarray technique is effective in screening the differentially expressed genes between two different kinds of tissue. Further analysis of those obtained genes will be helpful to understand the molecular mechanism of hepatic immunological injury and to study the intervention of drug. Both ASP and GdCl3 can decrease the number of the differentially expressed genes in Liver tissue of mice with hepatic immunological injury.


Study on intervenient effect of angelica sinensis polysaccharide on immunological Liver injury and its mechanism in mice


CONCLUSION: Changes of NO production and TNF-α mRNA may play an important role in ILI. The mechanism of ASP in intervening ILI may be through modulation on cNOS, iNOS, bax, bcl-2 expression to block the damage of BCG vaccine and LPS on hepatocytes.


[Protective effect of Angelica sinensis polysaccharide against Liver injury induced by D-galactose in aging mice and its mechanisms].


CONCLUSION: ASP can antagonize the Liver injury induced by D-galactose in aging mice, and its mechanism may be related to the inhibition of oxidative stress.



Arjunolic acid


Involvement of both intrinsic and extrinsic pathways in hepatoprotection of arjunolic acid against cadmium induced acute damage in vitro


Results showed that Cd could trigger both intrinsic and extrinsic apoptotic pathways. In addition, Cd markedly increased NF-κB nuclear translocation in association with IKKα/β phosphorylation and IκBα degradation. Simultaneous treatment with AA (200 μM), however, reduced Cd-induced oxidative stress, attenuated the nuclear translocation of NF-κB and protects the hepatocytes from Cd-induced apoptotic death.

Combining, data suggest that Cd-induced hepatic dysfunction and apoptosis might be supported by the ROS formation and mediated via the activation of NF-κB. AA treatment, on the other hand, reduced Cd-induced oxidative stress, attenuated the activation of NF-κB and mitochondrion-dependent and independent apoptotic signaling pathways.


Protection of Arsenic-Induced Hepatic Disorder by Arjunolic Acid


CONCLUSION: The results suggest that arjunolic acid possesses the ability to attenuate arsenic-induced oxidative stress in murine Liver probably via its antioxidant activity.


Arjunolic acid: A new multifunctional therapeutic promise of alternative medicine


In recent years, a number of studies describing the effective therapeutic strategies of medicinal plants and their active constituents in traditional medicine have been reported. Indeed, tremendous demand for the development and implementation of these plant derived biomolecules in complementary and alternative medicine is increasing and appear to be promising candidates for pharmaceutical industrial research.

These new molecules, especially those from natural resources, are considered as potential therapeutic targets, because they are derived from commonly consumed foodstuff and are considered to be safe for humans.


Arjunolic acid, a triterpenoid saponin, prevents acetaminophen (APAP)-induced Liver and hepatocyte injury via the inhibition of APAP bioactivation and JNK-mediated mitochondrial protection


CONCLUSION: The data suggest that arjunolic acid affords protection against acetaminophen-induced hepatotoxicity through inhibition of P450-mediated APAP bioactivation and inhibition of JNK-mediated activation of mitochondrial permeabilization


Curative effect of arjunolic acid from Terminalia arjuna in non-Alcoholic fatty Liver disease models


The prevalence of Non Alcoholic Fatty Liver Disease (NAFLD) is increasing globally. Terminalia arjuna W. & Arn. (Combretaceae) is an endemic tree found in India and Sri Lanka and used traditionally for its cardioprotective and Hepatoprotective effects. Arjunolic acid (AA) is an oleanane triterpenoid found mainly in the heartwood of T. arjuna. This study was aimed to evaluate the Hepatoprotective effect of AA using cellular and rodent models of NAFLD. AA was isolated from the ethyl acetate extract of the heartwood of T. arjuna. The structure of AA was confirmed by physical and spectroscopic data. Steatosis was induced in HepG2 cells using palmitate-oleate mixture and the effects of AA on triglyceride accumulation and lipotoxicity were assessed. In vivo effect of AA on NAFLD was assessed using HFD fed rats. The treatment with AA did not affect the cell viability upto 100 μM and showed GI25 value of 379.9 μM in HepG2 cells. The treatment with AA significantly lowered the ORO concentration by 35.98% and triglyceride accumulation by 66.36% at 50 μM concentration (P < 0.005) compared to the vehicle treated group.

The treatment with AA also reduced the leakage of ALT and AST by 61.11 and 48.29% in a significant manner (P < 0.005). The in vivo findings clearly demonstrated that the animals treated with AA at 25 and 50 mg/kg concentrations showed a significant decrease in the levels of transaminases, phosphatase and GGT (P < 0.005). In the Liver, the expression of PPARα and FXRα expressions were upregulated, while PPARγ expression was downregulated by the treatment with AA. The Liver histology of the animals showed reduction in steatosis and MNC infiltration.

These preliminary evidences suggested that AA might be a promising lead to treat NAFLD. Future robust scientific studies on AA will lead to tailoring it for the treatment of NAFLD.


Contribution of type 1 diabetes to rat Liver dysfunction and cellular damage via activation of NOS, PARP, IκBα/NF-κB, MAPKs, and mitochondria-dependent pathways: Prophylactic role of arjunolic acid


Results of immunofluorescence (using anti-caspase-3 and anti-Apaf-1 antibodies), DAPI/PI staining, and DNA ladder formation and information obtained from FACS analysis confirmed the apoptotic cell death in diabetic Liver tissue. Histological studies also support the experimental findings. AA treatment prevented or ameliorated the diabetic Liver complications and apoptotic cell death. The effectiveness of AA in preventing the formation of ROS, RNS, HbA1C, AGEs, and oxidative stress signaling cascades and protecting against PARP-mediated DNA fragmentation can speak about its potential uses for diabetic patients.


Arjunolic acid from Cyclocarya paliurus ameliorates nonAlcoholic fatty Liver disease in mice via activating Sirt1/AMPK, triggering autophagy and improving gut barrier function


Collectively, our results convey that AA can substantially mitigate NAFLD via indirectly activating Sirt1/AMPK signaling, inducing autophagy and restoring gut barrier, and will be considered as a promising candidate for NAFLD therapy.


Involvement of both intrinsic and extrinsic pathways in hepatoprotection of arjunolic acid against cadmium induced acute damage in vitro


Results showed that Cd could trigger both intrinsic and extrinsic apoptotic pathways. In addition, Cd markedly increased NF-κB nuclear translocation in association with IKKα/β phosphorylation and IκBα degradation. Simultaneous treatment with AA (200 μM), however, reduced Cd-induced oxidative stress, attenuated the nuclear translocation of NF-κB and protects the hepatocytes from Cd-induced apoptotic death.

Combining, data suggest that Cd-induced hepatic dysfunction and apoptosis might be supported by the ROS formation and mediated via the activation of NF-κB. AA treatment, on the other hand, reduced Cd-induced oxidative stress, attenuated the activation of NF-κB and mitochondrion-dependent and independent apoptotic signaling pathways.


Hepatoprotective effect of arjunolic acid against cisplatin-induced hepatotoxicity: Targeting oxidative stress, inflammation, and apoptosis


This study explored for the first time the Arj Hepatoprotective effect against CP-induced hepatotoxicity through its antioxidant, anti-inflammatory, and antiapoptotic activities.


Protective effect of arjunolic acid against atorvastatin induced hepatic and renal pathophysiology via MAPK, mitochondria and ER dependent pathways


Results suggest that AA could effectively and extensively counteract these adverse effects and might protect Liver and kidney from ATO-induced severe tissue toxicity.



Aronia melanocarpa


Aronia melanocarpa Prevents Alcohol-Induced Chronic Liver Injury via Regulation of Nrf2 Signaling in C57BL/6 Mice


Altogether, AM prevented Alcohol-induced Liver injury, potentially by suppressing oxidative stress via the Nrf2 signaling pathway.


Protective Effects of Ligularia fischeri and Aronia melanocarpa Extracts on Alcoholic Liver Disease (In Vitro and In Vivo Study)


These results suggest that oral ingestion of LF and AM mixed composite is able to protect Liver against Alcohol-induced injury by increasing Alcohol metabolism activity and antioxidant system along with decreasing inflammatory responses.


Gut Microbiota Modulation by Polyphenols from Aronia melanocarpa of LPS-Induced Liver Diseases in Rats


These results showed that AMPs, as a bioactive substance, could enhance the intestinal barrier function and modulate the gut microbiota of LPS-induced Liver diseases.


Extract from Aronia melanocarpa L. Berries Protects Against Cadmium-induced Lipid Peroxidation and Oxidative Damage to Proteins and DNA in the Liver: A Study using a Rat Model of Environmental Human Exposure to this Xenobiotic


The results allow us to conclude that the consumption of aronia products under exposure to Cd may offer protection against oxidative injury of the main cellular macromolecules in the Liver, including especially lipid peroxidation, and in this way prevent damage to this organ.



Artemisia capillaris


Aqueous extract of Artemisia capillaris exerts Hepatoprotective action in Alcohol–pyrazole-fed rat model


CONCLUSION: These results support the relevance in clinical use of Artemisia capillaris for Alcohol-associated hepatic disorders. The underlying mechanisms may involve both enhancement of antioxidant activities and modulation of proinflammatory cytokines.


A Survey of Therapeutic Effects of Artemisia capillaris in Liver Diseases


Artemisia capillaris has been recognized as an herb with therapeutic efficacy in Liver diseases and widely used as an alternative therapy in Asia. Numerous studies have reported the antisteatotic, antioxidant, anti-inflammatory, choleretic, antiviral, antifibrotic, and antitumor activities of A. capillaris. These reports support its therapeutic potential in various Liver diseases such as chronic hepatitis B virus (HBV) infection, cirrhosis, and hepatocellular carcinoma. In addition, several properties of its various constituents, which provide clues to the underlying mechanisms of its therapeutic effects, have been studied.

This review describes the scientific evidence supporting the therapeutic potential of A. capillaris and its constituents in various Liver diseases.


Artemisia capillaris extract protects against bile duct ligation-induced Liver fibrosis in rats


Artemisia capillaris has been widely used as a traditional herbal medicine in the treatment of Liver diseases. However, no previous study has investigated whether A. capillaries alone is effective in treating pathological conditions associated with cholestatic Liver injury. In the present study, we evaluated the anti-hepatofibrotic effects of A. capillaris (aqueous extract, WAC) in a bile duct ligation (BDL)-induced cholestatic fibrosis model. After BDL, rats were given WAC (25 or 50 mg/kg) or urosodeoxycholic acid (UDCA, 25 mg/kg) orally for 2 weeks (once per day). The serum cholestatic markers, malondialdehyde, and Liver hydroxyproline levels were drastically increased in the BDL group, while administering WAC significantly reduced these alterations.

Administering WAC also restored the BDL-induced depletion of glutathione content and glutathione peroxidase activity. Cholestatic Liver injury and collagen deposition were markedly attenuated by WAC treatment, and these changes were paralleled by the significantly suppressed expression of fibrogenic factors, including hepatic alpha-smooth muscle actin (α-SMA), platelet-derived growth factor (PDGF), and transforming growth factor beta (TGF-β). The beneficial effects of WAC administration are associated with antifibrotic properties via both upregulation of antioxidant activities and downregulation of ECM protein production in the rat BDL model.


The aqueous extract from Artemisia capillaris Thunb. inhibits lipopolysaccharide-induced inflammatory response through preventing NF-κB activation in human hepatoma cell line and rat Liver


These results suggest that the inhibitory effect of AEAC on the expression of inflammatory proteins involves suppression of NF-κB activation.


A Water Extract of Artemisia capillaris Prevents 2,2′-Azobis(2-Amidinopropane) Dihydrochloride-Induced Liver Damage in Rats


These observations clearly indicate that ACWE contains antioxidant catechins capable of ameliorating the AAPH-induced hepatic injury by virtue of its antioxidant activity.


The essential oil of Artemisia capillaris protects against CCl4-induced Liver injury in vivo


To study the Hepatoprotective effect of the essential oil of Artemisia capillaris Thunb., Asteraceae, on CCl4-induced Liver injury in mice, the levels of serum aspartate aminotransferase and alanine aminotransferase, hepatic levels of reduced glutathione, activity of glutathione peroxidase, and the activities of superoxide dismutase and malondialdehyde were assayed.

Administration of the essential oil of A. capillaris at 100 and 50 mg/kg to mice prior to CCl4 injection was shown to confer stronger in vivo protective effects and could observably antagonize the CCl4-induced increase in the serum alanine aminotransferase and aspartate aminotransferase activities and malondialdehyde levels as well as prevent CCl4-induced decrease in the antioxidant superoxide dismutase activity, glutathione level and glutathione peroxidase activity (p < 0.01). The oil mainly contained β-citronellol, 1,8-cineole, camphor, linalool, α-pinene, β-pinene, thymol and myrcene.

This finding demonstrates that the essential oil of A. capillaris can protect hepatic function against CCl4-induced Liver injury in mice.


Effects of β-sitosterol derived from Artemisia capillaris on the activated human hepatic stellate cells and dimethylnitrosamine-induced mouse Liver fibrosis


CONCLUSION: This study shows the effect of β-sitosterol on the TGF-β -or DMN-induced hepatofibrosis. Hence, we demonstrate the β-sitosterol as a potential therapeutic agent for the hepatofibrosis.


Antifibrotic effects of Artemisia capillaris and Artemisia iwayomogi in a carbon tetrachloride-induced chronic hepatic fibrosis animal model


CONCLUSION: Our results show that AI exerts greater Hepatoprotective and anti-fibrotic effects as compared with AC via enhancing antioxidant capacity and downregulating fibrogentic cytokines.


Scoparone as a therapeutic drug in Liver diseases: Pharmacology, pharmacokinetics and molecular mechanisms of action


The results implicated that scoparone possesses a wide spectrum of pharmacological activities, including anti-inflammatory, antioxidant, anti-apoptotic, anti-fibrotic and hypolipidemic properties. Pharmacokinetic studies have addressed that isoscopoletin and scopoletin are major primary metabolites of scoparone. Moreover, hepatic dysfunction might promote bioavailability of scoparone due to limited intrinsic clearance. On the other hand, the bioavailability of multi-component including scoparone in certain TCM formula can also be enhanced by applying this formula at a high dose on account of their interacted effects.

In view of good pharmacological actions, scoparone is anticipated to be a potential drug candidate for various Liver diseases, such as acute Liver injury, fulminant hepatitis, Alcohol-induced hepatotoxicity, non-Alcoholic fatty Liver disease and fibrosis. However, further studies are warranted to clarify its molecular mechanisms and targets, elucidate its toxicity, and identify its interplay with other active ingredients of classical TCM formula in clinical settings.


Curative effects of extracts of Hericium erinaceum hypha cultivated with Artemisia capillaris (HEAC) and their primary active compounds on rat Liver disease


Taken together, HEAC and scoparone exerted protective effect against CCl4-induced Liver injury by attenuating hepatic lipid depots and reducing oxidative stress.


Protective effect of Artemisiae Capillaris Herba water extract on Liver injury induced by thioacetamide


CONCLUSION: Taken together, these data indicate that exposure to AC reduces the oxidative stress by inhibiting the expression of NADPH oxidase (NOX2 and p22phox) through the Nrf2 signaling pathway. We therefore propose the potential of AC for the prevention and treatment of TAA-induced Liver injury.


Hepatoprotective effects of Artemisiae Capillaris Herba and Picrorrhiza Rhizoma combinations on carbon tetrachloride–induced subacute Liver damage in rats


The Hepatoprotective properties of Artemisiae Capillaris Herba (AC) and Picrorrhiza Rhizoma (PR) are well known. The aim of this study was to determine the optimal composition of AC and PR mixtures for better complimentary or alternative regimens in reducing the level of hepatic fibrosis. Ten weeks of carbon tetrachloride injections caused subacute hepatic damage, manifested as significantly less body weight gain and hepatic protein content, and a higher Liver weight, serum aspartate aminotransferase and alanine aminotransferase levels, hepatic malondialdehyde (an index for lipid peroxidation), and hydroxyproline (an index for collagen synthesis) concentrations. The carbon tetrachloride–induced toxic effects were inhibited by 11 different AC/PR mixtures as well as the single AC or PR treatment.

More favorable effects were detected in all mixed-formulation groups compared with the AC or PR single formulations. Moreover, the AC/PR 2:1 formulation showed the most favorable Hepatoprotective activity. The AC and PR mixtures showed good synergic Hepatoprotective activity that was attributed to increasing free-radical scavenging ability. Among the 11 types of mixed formula tested in this study, the AC/PR 2:1 formulation had the most impressive synergic effects on inhibiting the subacute hepatic damage induced by carbon tetrachloride in rats and showed more favorable effects than with an equal dose of silymarin.


Hepatoprotective Effect of Artemisia capillaris Thunb Water Extract in an Animal Model of Liver Fibrosis

CONCLUSION: these results suggest that AE treatment alleviates hepatic fibrosis by reducing oxidative stress through the activation of the NF-E2-related factor 2 (Nrf2) pathway.


Ameliorative potential of Artemisia Capillaris Formula on nonAlcoholic fatty Liver disease in rats through regulation of fat metabolism


CONCLUSION: ACF ameliorates high-fat diet-induced hepatosteatosis and dyslipidemia in rats by altering lipid metabolism-related gene expression, specifically of FAS, ACC, and CPT.



Artemisia iwayomogi


Comparative Study of the Hepatoprotective Efficacy of Artemisia iwayomogi and Artemisia capillaris on Ethanol-Administered Mice


These results indicate that AIE and ACE exhibit Hepatoprotective and hypolipidemic properties by enhancing hepatic Alcohol, antioxidant, and lipid metabolism. AIE seemed to have more potent Hepatoprotective effects than ACE.


Antifibrotic effects of Artemisia capillaris and Artemisia iwayomogi in a carbon tetrachloride-induced chronic hepatic fibrosis animal model


CONCLUSION: Our results show that AI exerts greater Hepatoprotective and anti-fibrotic effects as compared with AC via enhancing antioxidant capacity and downregulating fibrogentic cytokines.


Aqueous extract of Artemisia iwayomogi Kitamura attenuates cholestatic Liver fibrosis in a rat model of bile duct ligation


Our data suggest that WAI may have antifibrotic properties via both improvement of antioxidant activities and inhibition of ECM protein production in the rat model of BDL.


The Ethanol-soluble Part of a Hot-water Extract from Artemisia iwayomogi Inhibits Liver Fibrosis Induced by Carbon Tetrachloride in Rats


The ethanol-soluble part of the hot-water extract from A. iwayomogi inhibited fibrosis and lipid peroxidation in rats with Liver fibrosis induced by carbon tetrachloride. Both hot-water extract (either ethanol-soluble or -insoluble) and methanol extract of A. iwayomogi also lowered serum cholesterol levels in fibrotic rats.


Comparative Study of the Hepatoprotective Efficacy of Artemisia iwayomogi and Artemisia capillaris on Ethanol‐Administered Mice


These results indicate that AIE and ACE exhibit Hepatoprotective and hypolipidemic properties by enhancing hepatic Alcohol, antioxidant, and lipid metabolism. AIE seemed to have more potent Hepatoprotective effects than ACE.


Study on the biological activity of Artemisia iwayomogi KITAMURA -Korean Journal of Medicinal Crop Science


In these results, AIWE seems to enhance hepato-protective and recoverable effect on induced hepatotoxicity in rats.


Artemisia iwayomogi plus Curcuma longa Synergistically Ameliorates NonAlcoholic Steatohepatitis in HepG2 Cells


CONCLUSION: we found synergic effects of A. iwayomogi and C. longa on NASH, supporting the clinical potential for fatty Liver disorders. In addition, modulation of ER stress-relative molecules would be involved in its underlying mechanism.


Extract of Hericium erinacium Cultivated with Artemisia iwayomogi


The improvement efficacy of Erinacol∨®, water extract of Hericium erinacium cultivated with Artemisia iwayoomogi, in comparison with that of Artemisia iwayomogi extract (AIE), on Alcoholic fatty Liver was investigated using Alcohol and high-fat diet combination model in rats. Male Sprague-Dawley rats were orally administered with 8 ml/kg (20 ml/kg as 40% in water) of ethanol for 1 week, and then with 6 ml/kg (15 ml/kg as 40%) for additional 3 weeks, under simultaneous feeding of a high-fat diet containing 5% corn oil, 1% cholesterol and 0.1% cholic acid for all 4 weeks. Erinacol∨® (33, 100 or 300 mg/kg) or their vehicle (water, 1 ml/kg) were orally treated 30 min prior to ethanol administration everyday.


Effect of Artemisia Iwayomogi water extract on hepatic injury by carbon tetrachloride in rats I


CONCLUSION: AIWE did not affect normal Liver function and had property of antioxidant, due to reduced lipid peroxidation by $CCl_4$. AIWE seems to have Hepatoprotective effects rather than direct preventive effects to $CCl_4$-induced necrotic degeneration of Liver cell, cholestasis and damages in metabolism of lipid.


Antihepatotoxic effect of Artemisia Iwayomogi methanol extract on acute hepatic injury by carbon tetrachloride in rat


CONCLUSION: AIME enhanced the amelioration process from -induced lipid peroxidation, degeneration of Liver cell, and impairment of protein and bilirubin metabolisms.


Effect of Artemisia Iwayomogi water extract on hepatic injury by carbon tetrachloride in rats II. Effect on serum ALP, LAP activities, total protein, bilirubin content and Liver glycogen content

CONCLUSION: AIWE did not affect normal Liver function and had Hepatoprotective effects rather than direct preventive effects to -induced cholestasis, damages in metabolisms of glucose, protein and bilirubin.


In vitro and in vivo anti-aging effects of compounds isolated from Artemisia iwayomogi


In Korean folk medicine, Artemisia iwayomogi has largely been employed for the improvement of diabetic complications and hepatic function as well as in the treatment of female diseases and skin whitening. Accordingly, the present study sought to assess cosmeceutical activity of Artemisia iwayomogi.



Artemisia scoparza Waldst.et Kit extract


Preliminary Screening of Active Part of Artemisia Scoparia Waldst.et Kit.in the Liver Protection


CONCLUSION: The chloroform extract is the effective part of Artemisia scoparia Waldst.et Kit.for Liver protection.


Artemisia scoparia extract attenuates non-Alcoholic fatty Liver disease in diet-induced obesity mice by enhancing hepatic insulin and AMPK signaling independently of FGF21 pathway


CONCLUSION: This study suggests that SCO may attenuate Liver lipid accumulation in DIO mice. Contributing mechanisms were postulated to include promotion of adiponectin expression, inhibition of hepatic lipogenesis, and/or enhanced insulin and AMPK signaling independent of FGF21 pathway.


Protective effect of Artemisia scoparia extract against acetaminophen-induced hepatotoxicity


These results indicate that Artemisia scoparia contains Hepatoprotective constituents and this study rationalizes the traditional use of this plant in hepatobiliary disorders.


Artemisia scoparia: Traditional uses, active constituents and pharmacological effects


CONCLUSION: As an important Chinese medicinal plant, modern pharmacological studies have demonstrated that A. scoparia has diverse bioactivities, especially on Liver protection and anti-inflammatory activities. These prominent bioactivities highlight prospects on new drug development. Nevertheless, the comprehensive evaluation, long-term in vivo toxicity, and clinical efficacy of A. scoparia require further in-depth research.


Hepatoprotective effects of artemisia scoparia against carbon tetrachloride: An environmental contaminant


The Hepatoprotective activity of crude extract of artemisia scoparia (aerial parts) was investigated against experimentally produced hepatic damage using carbon tetrachloride (CCl4) as a model hepatotoxin. CCl4 at the dose of 1.5 ml/kg, produced Liver damage in rats as manifested by the rise in serum levels of AST and ALT to 395 +/- 110 and 258 +/- 61 IU/l (mean +/- SEM; n = 10) respectively, compared to control values of 106 +/- 15 and 26 +/- 04. Pretreatment of rats with plant extract (150 mg/kg) significantly lowered (P < 0.01), the respective serum GOT and GPT levels to 93 +/- 05 and 27 +/- 03 IU/l, indicating Hepatoprotective action.

Pentobarbital sodium (75 mg/kg)-induced sleeping time in mice was found to be 140.8 +/- 1.5 min (n = 10) which was similar (P > 0.05) to that obtained in the group of animals pretreated with the plant extract (139.9 +/- 1.8 min). CCl4 treatment extended the pentobarbital sleeping time to 212.2 +/- 19.1 min and pretreatment of animals with plant extract reversed the CCl4-induced prolongation in pentobarbital sleeping time to 143.9 +/- 5.5 min (P < 0.001) which further confirms the protective action of the plant extract against CCl4-induced Liver damage.

These data indicate that the plant artemisia scoparia is Hepatoprotective and validate the folkloric use of this plant in Liver damage.


Anti-cancer effects of biosynthesized zinc oxide nanoparticles using Artemisia scoparia in Huh-7 Liver cancer cells


This study is aimed to synthesize zinc oxide nanoparticles (ZnO NPs) by Artemisia scoparia extract and explore their cytotoxic behavior against Huh-7 Liver cancer cells. The green-synthesized ZnO NPs were investigated using UV–Vis, FT-IR, XRD, TEM, FESEM, EDX, DLS, and Zeta potential. The anti-cancer activity of ZnO NPs and plant extract against cancer cells was evaluated by MTT assay and flow cytometry. The expression of apoptotic genes was assessed by qPCR.

The average size of the ZnO NPs was 9.00 ± 4.00 nm. The A. scoparia extract and spherical ZnO NPs both inhibited cell growth and induced apoptosis in Huh-7 cancer cells in a time- and dose-dependent manner. The IC50 values of ZnO NPs and extract were 10.26 and 310.24 µg/mL, respectively. The ZnO NPs also upregulated pro-apoptotic genes while downregulating anti-apoptotic genes. Considering the anti-cancer features of the ZnO NPs, it seems that the green-synthesized ZnO NPs have strong anti-cancer potential.


Heptoprotective-Role-of-Artemisia-scoparia-Waldst-and-Kit-Against-CCl4-induced-Toxicity-in-Rats


The findings of this study demonstrate that Artemisia scoparia plant extract plays a significant role in preventing the hepatic damages instigated with CCl4 and can be used as a protective agent against oxidative stress-associated disorders.


Hepatoprotective effects of artemisia scoparia against carbon tetrachloride: an environmental contaminant


The Hepatoprotective activity of crude extract of artemisia scoparia (aerial parts) was investigated against experimentally produced hepatic damage using carbon tetrachloride (CCl4) as a model hepatotoxin. CCl4 at the dose of 1.5 ml/kg, produced Liver damage in rats as manifested by the rise in serum levels of AST and ALT to 395 +/- 110 and 258 +/- 61 IU/l (mean +/- SEM; n = 10) respectively, compared to control values of 106 +/- 15 and 26 +/- 04.

Pretreatment of rats with plant extract (150 mg/kg) significantly lowered (P < 0.01), the respective serum GOT and GPT levels to 93 +/- 05 and 27 +/- 03 IU/l, indicating Hepatoprotective action. Pentobarbital sodium (75 mg/kg)-induced sleeping time in mice was found to be 140.8 +/- 1.5 min (n = 10) which was similar (P > 0.05) to that obtained in the group of animals pretreated with the plant extract (139.9 +/- 1.8 min). CCl4 treatment extended the pentobarbital sleeping time to 212.2 +/- 19.1 min and pretreatment of animals with plant extract reversed the CCl4-induced prolongation in pentobarbital sleeping time to 143.9 +/- 5.5 min (P < 0.001) which further confirms the protective action of the plant extract against CCl4-induced Liver damage.

These data indicate that the plant artemisia scoparia is Hepatoprotective and validate the folkloric use of this plant in Liver damage.



Asparagus racemosus Willd. root extract


Antioxidant properties of Asparagus racemosus against damage induced by γ-radiation in rat Liver mitochondria


Hence our results indicate that extracts from A. racemosus have potent antioxidant properties in vitro in mitochondrial membranes of rat Liver.


Hypolipidemic and antioxidant activities of Asparagus racemosus in hypercholesteremic rats


CONCLUSION: The present study demonstrates that addition of Asparagus racemosus root powder at 5 g% and 10 g% level as feed supplement reduces the plasma and hepatic lipid (cholesterol) levels and also decreases lipid peroxidation.


Protective effects of Asparagusracemosus on oxidative damage in isoniazid-induced hepatotoxic rats: an in vivo study


These results suggest that A. racemosus extract exerts its Hepatoprotective activity by inhibiting the production of free radicals and acts as a scavenger, reducing the free radical generation via inhibition of hepatic CYP2E1 activity, increasing the removal of free radicals through the induction of antioxidant enzymes and improving non-enzymatic thiol antioxidant GSH.


The effect of the aqueous extract of the roots of Asparagus racemosus on hepatocarcinogenesis initiated by diethylnitrosamine


The results of the biochemical determinations also show that pretreatment of Wistar rats with the aqueous extract of Asparagus racemosus leads to the amelioration of oxidative stress and hepatotoxicity brought about by treatment with DEN.

These results prove that the aqueous extract of the roots of Asparagus racemosus has the potential to act as an effective formulation to prevent hepatocarcinogenesis induced by treatment with DEN.


Asparagus Racemosus Roots Ameliorates Acetaminophen Induced Hepatotoxicity in Rats: An Experimental, Biochemical and Histological Study


These results indicate that the compounds present in the ethanol fraction of AR possesses Hepatoprotective activity against acetaminophen induced hepatotoxicity in rats.


Plant profile, phytochemistry and pharmacology of Asparagus racemosus (Shatavari): A review


Recently few reports are available demonstrating beneficial effects of Alcoholic and water extract of the roots of A. racemosus in some clinical conditions and experimentally indused disease e.g. galactogougue affects, antihepatotoxic, immunomodulatory effects, immunoadjuvant effect, antilithiatic effect and teratogenicity of A. racemosus. The present artical includes the detailed exploration of pharmacological properties of the root extract of A. racemosus reported so far.


Hepatoprotective effect of asparagus racemosus in paracetamol induced hepatotoxicity in rats


The results indicate that the Hepatoprotective properties of Asparagus racemosus against paracetamol-induced hepatotoxicity in rats


A Review on Pharmacological and Phytochemical Profile of Asparagus raecemosus


Ayurveda, an orthodox as well as main stream system of medicine has been with a source of new concepts and products for healthcare. Asparagus racemosus Willd. is an advantageously authenticated medicinal plant as observable from the literature. A. racemosus has also been used successfully by some Ayurvedic practitioners for inflammation, hepatic disorders, neurological disorder and certain infectious diseases. This study is a collective information concerning the ethnobotany, pharmacology, phytochemistry and biological activities of the Asparagus racemosus Willd.


A Comprehensive Review of the Pharmacological Actions of Asparagus Racemosus


Plants have been an important source for developing drugs since time immemorial. Various medicinal herbs are indigenous to the Indian subcontinent and Asparagus is one such plant. Asparagus racemosus Willd., more commonly known as Shatavari, has been traditionally used in  many systems of medicine such as Ayurveda, Unani and Siddha. It has been used for decades as a galactogogue, uterine tonic, adaptogen, and rejuvenator.
Also it has been used to mitigate symptoms of peptic ulcer, as an immunostimulant,nHepatoprotective, and aphrodisiac. In addition, several other health benefits of this wonder plant, such as antidepressant, antiamnesic, antianxiety, hypolipidemic, antidiabetic, and anticonvulsant effects have been discovered in the recent years. In this article, an effort has been made to comprehensively enumerate all the health benefits of A. racemosus, known so far


Astragalus membranaceus extract


Inhibition of Astragalus membranaceus polysaccharides against Liver cancer cell HepG2


Consequently, the results of the in vitro assays suggest that the A. membranaceus polysaccharides possesses strong antitumour activities, which is benefical to treatment of Liver cancer.


Research Progress in Astragalus Membranaceus and Its Active Components on Immune Responses in Liver Fibrosis


The interaction between immune cells and hepatic stellate cells (HSCs) can modulate the development of hepatic fibrosis. It can also regulate hepatic fibrosis and Liver cirrhosis caused by excessive deposition of extracellular matrix (ECM). This article reviews the action mechanism of immune cells on Liver fibrosis and the effect of Astragalus membranaeus and its active components on immune cells.

In-depth study of interaction between immune cells and HSCs on the pathogenesis of Liver fibrosis, and the regulatory effect of Astragalus membranaeus and its active components on immune mechanism will provide new insights in the treatment of Liver fibrosis.


Effects and mechanisms of extract from Paeonia lactiflora and Astragalus membranaceus on Liver fibrosis induced by carbon tetrachloride in rats


These results suggested that PAE significantly inhibited the progression of hepatic fibrosis induced by CCl4, and the inhibitory effect of PAE on hepatic fibrosis might be associated with its ability to scavenge free radicals, decrease the level of TGF-β1 and inhibit collagen synthesis and proliferation in HSCs.


Amelioration of age-related alterations in rat Liver: Effects of curcumin C3 complex, Astragalus membranaceus and blueberry


Ageing is an unavoidable, universal, biological phenomenon affecting all organisms, which involves variable declines of individuals motor and memory capabilities. This study aimed to investigate the potential ameliorating effects of curcumin C3 complex, Astragalus membranaceus and blueberry on certain age-related biochemical alterations in rat Liver. Four groups of rats, aged 12 months-old, were used. The first group; aged control group in which rats were left without any treatment until the age of 17 months. The other three groups received daily by oral gavage for 5 months the following supplements; curcumin C3 complex (110 mg/kg), Astragalus membranaceus (100 mg/kg) and blueberry (100 mg/kg) respectively.

Additionally, a fifth group of rats, aged 5 months-old, was used as an adult control group. Our supplements alleviated ageing-induced redox state imbalance and inflammation as evidenced by reduction of hepatic thiobarbituric acid reactive substances and 8-hydroxydeoxyguanosine levels, restoration of total antioxidant capacity and nitric oxide contents, and lessening of lipofuscin deposition.

All supplements decreased hepatic interlukin-6 gene expression and serum levels. Notably, Astragalus membranaceus and blueberry upregulated hepatic telomerase reverse transcriptase gene expression and increased telomere length. Our findings recommend the use of these natural Hepatoprotective supplements for the elderly to promote healthy ageing and minimize the risk of age-related Liver diseases.


Protective Effect of Extract from Paeonia lactiflora and Astragalus membranaceus against Liver Injury Induced by Bacillus Calmette‐Guérin and Lipopolysaccharide in Mice


These results suggest that P. lactiflora and A. membranaceus have a protective effect on BCG/LPS-induced Liver injury mice, which might be associated with the antioxidant properties, ability to reduce nitric oxide production and suppression of Kupffer cell activity and pro-inflammatory mediator and cytokines production.


The Antioxidant Effects of Radix Astragali (Astragalus membranaceus and Related Species) in Protecting Tissues from Injury and Disease


Specifically, constituents of the dried roots of Astragalus spp. (Radix Astragali) provide significant protection against heart, brain, kidney, intestine, Liver and lung injury in various models of oxidative stress-related disease. Different isolated constituents of Astragalus spp., such as astragalosides, flavonoids and polysaccharides also displayed significant prevention of tissue injury via antioxidant mechanisms. In this article, the antioxidant benefits of Astragalus spp. and its isolated components in protecting tissues from injury are reviewed, along with identification of the various constituents that possess antioxidant activity.


Inhibition of Astragalus membranaceus polysaccharides against Liver cancer cell HepG2


Consequently, the results of the in vitro assays suggest that the A. membranaceus polysaccharides possesses strong antitumour activities, which is benefical to treatment of Liver cancer


Astragalus membranaceus-Polysaccharides Ameliorates Obesity, Hepatic Steatosis, Neuroinflammation and Cognition Impairment without Affecting Amyloid Deposition in Metabolically Stressed APPswe/PS1dE9 Mice


hese findings suggest that Astragalus membranaceus-polysaccharides may be used to ameliorate metabolic stress-induced diabesity and the subsequent neuroinflammation, which improved the behavior performance in metabolically stressed transgenic mice.


A standardized extract from Paeonia lactiflora and Astragalus membranaceus attenuates Liver fibrosis induced by porcine serum in rats


The results showed that PAE displays antifibrotic effects in rats induced by PS, the mechanism by which might be associated with its ability to scavenge free radicals, decreasing the expression of PDGFR-β, inhibition of HSC proliferation and MAPK activation. These findings indicate that PAE is a potential agent for the prevention of Liver fibrosis.


Early nutrition programming with Astragalus membranaceus polysaccharide: its effect on growth, carcasses, immunity, antioxidants, lipid profile and Liver and kidney functions in broiler chickens


In CONCLUSION, our results indicate that in ovo injection of Astragalus membranaceus polysaccharides 1.5-4.5 mg in broiler eggs significantly improved serum ALT, AST, AP, creatinine enzymes, antioxidant activity, and immune function.


Protective effects of a mixed plant extracts derived from Astragalus membranaceus and Laminaria japonica on PTU‐induced hypothyroidism and Liver damages


Moreover, the results of AL mix are well-matched with the effects of standard drug levothyroxine in the present study. Therefore, appropriate dosage of AL mix will be promising as new medicinal food for preventing thyroid dysfunctions and its related Liver damages.


[Influence of Salvia miltiorrhizae and Astragalus membranaceus on hemodynamics and Liver fibrosis indexes in Liver cirrhotic patients with portal hypertension]


CONCLUSION: SM and AM could improve portal hypertension effectively in Liver cirrhosis patients, one of the mechanism may be related with the improvement of Liver fibrosis.


[Inhibiting effects of three components of Astragalus membranaceus on oxidative stress in Chang Liver cells].


Results showed that H2O2 decreased antioxidant activity, and increased ROS level and expression of CYP2E1. The above oxidative stress status had been changed with protections of the three components of Astragalus membranaceus (compared with oxidative stress group, P < 0.05, P < 0.01), which taken as a whole had equivalent effects as the drug of positive control group( bifendate). Taken together, three Astragalus membranaceus ingredients all had significant or extremely significant inhibiting effects on oxidative damaged Chang Liver cells which were induced by H2O2, and the oxidative damage of Chang Liver cells had been relieved.


Suppressive effect of Astragalus membranaceus Bunge on chemical hepatocarcinogenesis in rats


Astragalus membranaceus (AM) has been widely used for treating Liver diseases in traditional Chinese medicine. Experimental evidence indicates that it has antitumor potential. In this study, the effect of AM on hepatocarcinogenesis induced by diethylnitrosamine (DEN), two-thirds partial hepatectomy, and 2-acetylaminofluorene (2-AAF) (DEN-PH-AAF) was evaluated using glutathione S-transferase placenta form (GST-P) as marker. First, rats were injected intraperitoneally (i.p.) with DEN (200 mg/kg in saline), a two-thirds partial hepatectomy was carried out 2 weeks later, and the rats were then placed on a basal diet containing 0.02% AAF from week 3 to week 8 to induce hepatocarcinogenesis. The rats were given AM (90 mg/kg or 180 mg/kg body weight) by gavage from week 3 to week 8 (treatment groups). The formation of GST-P-positive foci and the expression of GST-P protein and mRNA caused by DEN-PH-AAF were reduced in the treatment groups, which clearly suggests that AM is effective in delaying DEN-PH-AAF-induced hepatocarcinogenesis.


A Standardized Composition from Extracts of Myristica Fragrans, Astragalus Membranaceus, and Poria Cocos Protects Liver from Acute Ethanol Insult


MAP showed statistically significant reduction in ballooning degeneration, vascular steatosis, cytoplasmic or nuclear condensation, and shrinkage, as well as inflammations when compared to vehicle-treated Alcohol-induced Liver toxicity model. Mice treated with MAP showed statistically significant reduction in ASH scoring when compared to vehicle control. Therefore, the composition MAP could be potentially utilized as an effective hepatic-detoxifying agent for the protection of Liver damage caused by Alcohol consumptions.


Hepatoprotective Activity of an Herbal Composition, MAP, a Standardized Blend Comprising Myristica fragrans, Astragalus membranaceus, and Poria cocos


Historically, botanicals have been reported to possess good antioxidative activities as demonstrated by their free radical scavenging property rendering their usage in Liver protection. In this study, we describe the potential use of MAP, a standardized blend comprising three extracts from Myristica fragrans, Astragalus membranaceus, and Poria cocos, in ameliorating chemically induced acute Liver toxicities. Acetaminophen (APAP) and carbon tetrachloride (CCl4)-induced acute Liver toxicity models in mice were utilized. Hepatic functional tests from serum collected at T24, histopathology analysis, and merit of blending three standardized extracts were evaluated. MAP administered at doses of 150-400 mg/kg showed statistically significant and dose-correlated inhibitions of serum alanine aminotransferase (ALT) ranging from 30.8% (P ≤ .05) to 88.1% (P = .0001) in the APAP and 66.9% (P = .002) to 83.7% (P = .0002) in the CCl4 models, respectively. Moreover, MAP resulted in up to 75.7%, 60.9%, and 33.3% reductions in serum aspartate aminotransferase (AST), bile acid, and total bilirubin, respectively. Mice treated with oral doses of composition of MAP at 300 mg/kg showed statistically significant reduction in hepatocyte necrosis when compared with vehicle control. Unexpected synergistic protection of Liver damage was also observed. Therefore, the composition, MAP, could be potentially utilized as an effective hepatic detoxifying agent for the protection of Liver damage.


A standardized extract from Paeonia lactiflora and Astragalus membranaceus induces apoptosis and inhibits the proliferation, migration and invasion of human hepatoma cell lines


These results clearly demonstrated that PAE induced hepatoma cell apoptosis through increasing the Bax-to-Bcl-2 ratio and upregulating the activation of caspase-3. In addition, the results of wound healing assay and Matrigel invasion assay showed that PAE displayed inhibitory activity on the migration and invasion of HCC cells. Taken together, the present data provides evidence that PAE is a potent antineoplastic drug candidate for the treatment of HCC.


Biological analysis of herbal medicines used for the treatment of Liver diseases


Herbal medicines have been used to treat Liver disorders for thousands of years in the East and have now become a promising therapy internationally for pathological Liver conditions. Biological analysis of Hepatoprotective herbs is an important issue from the pharmacokinetic perspective in developing new therapeutic managements for Liver disease. The biological analysis focuses on the pretreatment methods, separation and quantification of herbal medicines in biological samples. We have compiled and discuss the biological analytical method of six herbal medicines for Liver protection containing Silybum marianum(silymarin), Glycyrrhiza glabra, Scutellaria baicalensis, Schisandra chinensis, Salvia miltiorrhiza and Astragalus membranaceus. This review provides a convenient reference for researchers to reduce time-consuming method optimization.


Anti-Aging Implications of Astragalus Membranaceus (Huangqi): A Well-Known Chinese Tonic


Pharmacological research indicates that the extract component of Astragalus membranaceus can increase telomerase activity, and has antioxidant, anti-inflammatory, immunoregulatory, anticancer, hypolipidemic, antihyperglycemic, Hepatoprotective, expectorant, and diuretic effects. A proprietary extract of the dried root of Astragalus membranaceus, called TA-65, was associated with a significant age-reversal effect in the immune system.

Our review focuses on the function and the underlying mechanisms of Astragalus membranaceus in lifespan extension, anti-vascular aging, anti-brain aging, and anti-cancer effects, based on experimental and clinical studies.



Astragalus mongholicus Bunge extract


Suppressive effect of Astragalus membranaceus Bunge on chemical hepatocarcinogenesis in rats


Astragalus membranaceus (AM) has been widely used for treating Liver diseases in traditional Chinese medicine. The formation of GST-P-positive foci and the expression of GST-P protein and mRNA caused by DEN-PH-AAF were reduced in the treatment groups, which clearly suggests that AM is effective in delaying DEN-PH-AAF-induced hepatocarcinogenesis.


Chemical analysis of Astragalus mongholicus polysaccharides and antioxidant activity of the polysaccharides


CONCLUSION: A. mongholicus polysaccharides may offer good protection against oxidative stress.


Explore the Mechanism of Astragalus mongholicus Bunge against NonAlcoholic Fatty Liver Disease Based on Network Pharmacology and Experimental Verification


CONCLUSION: Our results indicated that quercetin, as the main active component in AMB, exerts an anti-NAFLD effect by regulating the AMPK/MAPK/TNF-α and AMPK/ACC/CPT1α signaling pathways to inhibit inflammation and alleviate lipid accumulation.


Astragalus mongholicus polysaccharides ameliorate hepatic lipid accumulation and inflammation as well as modulate gut microbiota in NAFLD rats


Therefore, mAPS supplementation ameliorates hepatic inflammation and lipid accumulation in NAFLD by modulating the gut microbiota and SCFA-GPR signaling pathways. The present study provides new evidence for mAPS as a natural active substance in the treatment of NAFLD.


Astragalus mongholicus Bunge and Curcuma aromatica Salisb. inhibits Liver metastasis of colon cancer by regulating EMT via the CXCL8/CXCR2 axis and PI3K/AKT/mTOR signaling pathway


CONCLUSION: In Summary, our research predicted the potential targets and pathways of LMCC, and experimentally demonstrated that AC might inhibit the growth and Liver metastasis in colon cancer by regulating EMT via the CXCL8/CXCR2 axis and PI3K/AKT/mTOR signaling pathway, which may facilitate the discovery of mechanisms and new therapeutic strategies for LMCC.


The Polysaccharide Extracts from Astragalus Mongholicus Bunge Protects Mice from Acetaminophen-Induced Hepatotoxicity by Modulating the Nrf-2/ARE, JNK and Autophagy Pathways


CONCLUSION: Our results demonstrate that APS plays a critical role in APAP-induced Liver injury and autophagy, providing a novel mechanism for the protective effects of APS on APAP-induced Liver injury.


Astragalus on the anti-fatigue effect in hypoxic mice


CONCLUSION: Astragalus can alleviate physical fatigue in mice under simulated plateau environment. It has an obvious anti-fatigue effect and it’s worthy of further study.



Berberine


Berberine attenuates nonAlcoholic hepatic steatosis through the AMPK-SREBP-1c-SCD1 pathway.


CONCLUSION: BBR reduces Liver TG synthesis and attenuates hepatic steatosis through the activation of AMPK-SREBP-1c-SCD1 pathway.


The pharmacological activity of berberine, a review for Liver protection


Liver plays an important role in bile synthesis, metabolic function, degradation of toxins, new substances synthesis in body. However, hepatopathy morbidity and mortality are increasing year by year around the world, which become a major public health problem. Traditional Chinese medicine (TCM) has a prominent role in the treatment of Liver diseases due to its definite curative effect and small side effects.

The Hepatoprotective effect of berberine has been extensively studied, so we comprehensively summarize the pharmacological activities of lipid metabolism regulation, bile acid adjustment, anti-inflammation, oxidation resistance, anti-fibrosis and anti-cancer and so on. Besides, the metabolism and toxicity of berberine and its new formulations to improve its effectiveness are expounded, providing a reference for the safe and effective clinical use of berberine.


Update on Berberine in NonAlcoholic Fatty Liver Disease


Berberine (BBR), an active ingredient from nature plants, has demonstrated multiple biological activities and pharmacological effects in a series of metabolic diseases including nonAlcoholic fatty Liver disease (NAFLD). The recent literature points out that BBR may be a potential drug for NAFLD in both experimental models and clinical trials.

This review highlights important discoveries of BBR in this increasing disease and addresses the relevant targets of BBR on NAFLD which links to insulin pathway, adenosine monophosphate-activated protein kinase (AMPK) signaling, gut environment, hepatic lipid transportation, among others. Developing nuanced understanding of the mechanisms will help to optimize more targeted and effective clinical application of BBR for NAFLD.


Molecular updates on berberine in Liver diseases: Bench to bedside


Liver diseases are life-threatening illnesses and are the major cause of mortality and morbidity worldwide. These may include Liver fibrosis, Liver cirrhosis, and drug-induced Liver toxicity. Liver diseases have a wide prevalence globally and the fifth most common cause of death among all gastrointestinal disorders. Several novel therapeutic approaches have emerged for the therapy of Liver diseases that may provide better clinical outcomes with improved safety. The use of phytochemicals for the amelioration of Liver diseases has gained considerable popularity. Berberine (BBR), an isoquinoline alkaloid of the protoberberine type, has emerged as a promising molecule for the treatment of gastrointestinal disorders. Accumulating studies have proved the Hepatoprotective effects of BBR. BBR has been shown to modulate multiple signaling pathways implicated in the pathogenesis of Liver diseases including Akt/FoxO2, PPAR-γ, Nrf2, insulin, AMPK, mTOR, and epigenetic pathways. In the present review, we have emphasized the important pharmacological activities and mechanisms of BBR in Liver diseases.

Further, we have reviewed various pharmacokinetic and toxicological barriers of this promising phytoconstituent. Finally, formulation-based novel approaches are also summarized to overcome the clinical hurdles for BBR.


Efficacy of Berberine in Patients with Non-Alcoholic Fatty Liver Disease


CONCLUSION: BBR ameliorates NAFLD and related metabolic disorders. The therapeutic effect of BBR on NAFLD may involve a direct regulation of hepatic lipid metabolism.


Berberine induces autophagic cell death and mitochondrial apoptosis in Liver cancer cells: The cellular mechanism


These results further demonstrate the potential of berberine as a therapeutic agent in the emerging list of cancer therapies with novel mechanisms.


Inhibitory effect of berberine on tert-butyl hydroperoxide-induced oxidative damage in rat Liver


These results lead us to speculate that berberine may play a chemopreventive role via reducing oxidative stress in living systems.


Berberine improves glucogenesis and lipid metabolism in nonAlcoholic fatty Liver disease


CONCLUSION: BBR improved NAFLD by inhibiting glucogenesis and comprehensively regulating lipid metabolism, and its effect on inhibiting hepatic lipogenesis was much stronger. The improvement may be partly mediated by weight loss. Berberine might be a good choice for patients with NAFLD and glucose metabolic disorder. Future clinical trials need to be conducted to confirm these effects.


PROTECTION BY AND ANTI‐OXIDANT MECHANISM OF BERBERINE AGAINST RAT Liver FIBROSIS INDUCED BY MULTIPLE HEPATOTOXIC FACTORS


These results suggest that berberine could be used to prevent experimental Liver fibrosis through regulation of the anti-oxidant system and lipid peroxidation.


Berberine reduces methylation of the MTTP promoter and alleviates fatty Liver induced by a high-fat diet in rats


These data indicate that DNA methylation of the MTTP promoter likely contributes to its downregulation during HFD-induced NAFLD and, further, that berberine can partially counteract the HFD-elicited dysregulation of MTTP by reversing the methylation state of its promoter, leading to reduced hepatic fat content.


Lipid profiling of the therapeutic effects of berberine in patients with nonAlcoholic fatty Liver disease


CONCLUSION: Berberine altered circulating ceramides, which may underlie the improvement in fatty Liver disease.


Berberine induces apoptosis via the mitochondrial pathway in Liver cancer cells


Results showed that berberine induced the apoptosis of Liver cancer cells through procaspase-9, and its effector caspases, procaspase-3 and procaspase-7. Flow cytometry revealed that berberine caused cell cycle arrest at the M/G1 phase. The results of reverse transcription-polymerase chain reaction showed that berberine increased the expression of Bax, which resulted in the activation of the caspase cascade. The present findings demonstrated that berberine induces the apoptosis of Huh7 cells via the mitochondrial pathway.


The Therapeutic Effect of Berberine in the Treatment of NonAlcoholic Fatty Liver Disease: A Meta-Analysis


CONCLUSION: According to analysis result, berberine has positive efficacy on blood lipids, blood glucose, Liver function, insulin resistance, and fatty Liver condition of NAFLD patients. However, due to the limitation of number and quality of trials included, more clinical randomized controlled trials with high quality are needed for further verification of the efficacy of berberine on NAFLD patients.


Hepatoprotective effect of berberine against methotrexate induced Liver toxicity in rats


Our results indicated that BBR might be useful for prevention of the hepatotoxicity induced by MTX via ameliorative effects on biochemical and oxidative stress indices.


Liver-target nanotechnology facilitates berberine to ameliorate cardio-metabolic diseases


Our results provide proof-of-concept for a Liver-targeting strategy to ameliorate CMD using natural medicines facilitated by Nano-technology.


Protective effect of berberine on antioxidant enzymes and positive transcription elongation factor b expression in diabetic rat Liver


These results suggest that the effects of berberine on up-regulation of P-TEFb expression, antioxidant and antilipid peroxidation may be related to its protective potential on diabetes.


The Potential Mechanisms of Berberine in the Treatment of NonAlcoholic Fatty Liver Disease


NonAlcoholic fatty Liver disease (NAFLD) is a globally observed metabolic disease with high prevalence both in adults and children. The immunologic mechanism of BBR in the treatment of NAFLD, development of berberine derivative, drug combinations, deLivery routes, and drug dose can be considered in the future research.


Hepatoprotective effects of berberine on Liver fibrosis via activation of AMP-activated protein kinase


Our studies firstly demonstrated that BBR exerted Hepatoprotective effects possibly via activation of AMPK, blocking Nox4 and Akt expression. Our findings may benefit the development of new strategies in the prevention of chronic Liver disease.


Berberine ameliorates nonAlcoholic fatty Liver disease by a global modulation of hepatic mRNA and lncRNA expression profiles


CONCLUSION: The findings for the first time provide a new genetic insight into the pharmaceutical mechanism of BBR in protecting against NAFLD.

Berberine Ameliorates Hepatic Steatosis and Suppresses Liver and Adipose Tissue Inflammation in Mice with Diet-induced Obesity


Taken together, these results suggest that BBR actions on improving aspects of NAFLD are largely attributable to BBR suppression of inflammation, which is independent of AMPK.


Berberine Inhibits Growth of Liver Cancer Cells by Suppressing Glutamine Uptake


CONCLUSION: Berberine can suppress the proliferation of Liver cancer cells by reducing SLC1A5 expression.

Berberine-loaded solid lipid nanoparticles are concentrated in the Liver and ameliorate hepatosteatosis in db/db mice


In Summary, we have uncovered an unexpected effect of BBR-SLNs on hepatosteatosis treatment through the inhibition of lipogenesis and the induction of lipolysis in the Liver of db/db mice.


Berberine reducing insulin resistance by up-regulating IRS-2 mRNA expression in nonAlcoholic fatty Liver disease (NAFLD) rat Liver


Our results indicate that berberine may improve insulin resistance of NAFLD by up-regulating mRNA and protein levels of IRS-2, a key molecule in the insulin signaling pathway, suggesting that berberine may be used to treat NAFLD.


Hepatoprotective effects of berberine on carbon tetrachloride-induced acute hepatotoxicity in rats


CONCLUSION: The present study demonstrates that berberine possesses Hepatoprotective effects against CCl4-induced hepatotoxicity and that the effects are both preventive and curative. Berberine should have potential for developing a new drug to treat Liver toxicity.


Berberine Inhibits Hepatic Stellate Cell Proliferation and Prevents Experimental Liver Fibrosis


Thus, berberine was able to prevent Liver fibrosis by inhibition of hepatic stellate cell proliferation.


Metabolic effects of berberine on Liver phosphatidate phosphohydrolase in rats fed on high lipogenic diet: an additional mechanism for the hypolipidemic effects of berberine


CONCLUSION: These results clearly suggested that BBR could be effective in reducing Liver PAP, lipid abnormality, Liver triglyceride and lateral side effects of hyperlipidemia.


Modulation of gut microbiota mediates berberine‐induced expansion of immuno‐suppressive cells to against Alcoholic Liver disease


CONCLUSION: Collectively, this study deLivered insight into the role of immunosuppressive response in ALD, and facilitated the understanding of the pharmacological effects and action mechanisms of berberine.

Anti-inflammatory activity of berberine in non-Alcoholic fatty Liver disease via the Angptl2 pathway


CONCLUSION: Our findings demonstrate that BBR might attenuate the Liver inflammatory response in the Livers of rats with high-fat diet-induced NAFLD through the regulation of the Angptl2 pathway.


Hepatoprotective role of berberine against paraquat-induced Liver toxicity in rat


BR treatment caused significant decrease in PQ-induced cell death, ROS formation, and LDH release. On the other hand, it was found that BBR inhibits cellular glutathione depletion in PQ-treated hepatocytes. Also, BBR treatment significantly diminished PQ-induced the Liver function enzyme elevation. These data mention the potential Hepatoprotective effect of BBR with therapeutic capability against PQ-induced Liver damage.


Berberine ameliorates methotrexate-induced Liver injury by activating Nrf2/HO-1 pathway and PPARγ, and suppressing oxidative stress and apoptosis in rats


CONCLUSION: BBR attenuated MTX-induced oxidative stress and apoptosis, possibly through up-regulating Nrf2/HO-1 pathway and PPARγ. Therefore, BBR can protect against MTX-induced Liver injury.


Berberine attenuates hepatic oxidative stress in rats with non‑Alcoholic fatty Liver disease via the Nrf2/ARE signalling pathway


In CONCLUSION, BBR may alleviate hepatic oxidative stress in rats with NAFLD, which may be partly attributed to the activation of the Nrf2/ARE signalling pathway.


Berberine protects acute Liver failure in mice through inhibiting inflammation and mitochondria-dependent apoptosis


In CONCLUSION, our findings suggest that BBR serves as a potential agent for preventing or treating human ALF by inhibiting inflammation and mitochondria-dependent apoptosis.



Beta vulgaris Linn.(BV, Chenopodiaceae) leaves


PROTECTIVE ROLE OF BETA VULGARIS L. LEAVES EXTRACT
AND FRACTIONS ON ETHANOL-MEDIATED HEPATIC TOXICITY


The present study concluded that BVBF possess potent Hepatoprotective effect against ethanol-induced hepatic toxicity and it may have a great potential role in the
management of Alcoholic Liver disease


Liver-protecting effects of table beet (Beta vulgaris var. rubra) during ischemia-reperfusion


CONCLUSION; It may be stated that a natural antioxidant-rich diet has a positive effect on redox homeostasis during hepatic ischemia-reperfusion.

Effects of Chard (Beta vulgaris L. var cicla) on the Liver of the Diabetic Rats: A Morphological and Biochemical Study


As a result of all the morphological and biochemical findings obtained, it was concluded that the extract of this plant has a protective effect on the Liver in diabetes mellitus.


Ameliorative Effect of Beta vulgaris Root Extract on Chlorpyrifos-Induced Oxidative Stress, Inflammation and Liver Injury in Rats


In CONCLUSION, RBR prevented CPF-induced Liver injury via attenuation of oxidative stress, inflammation and apoptosis. RBR enhanced antioxidant defenses, suggesting that it could be used as a potential therapeutic intervention to minimize CPF hepatotoxicity.


Beet Stalks and Leaves (Beta vulgaris L.) Protect Against High-Fat Diet-Induced Oxidative Damage in the Liver in Mice


The presence of flavonoids, such as Vitexin derivatives in beet stalks and leaves can help the Liver damage induced by HF diet.


Hepatoprotective activity of Beta vulgaris against CCl4-induced hepatic injury in rats


Ethanolic extract of Beta vulgaris roots given orally at doses of 1000, 2000 and 4000 mg/kg exhibited significant dose-dependent Hepatoprotective activity against carbontetrachloride (CCl4)-induced hepatotoxicity in rats. Hepatotoxicity and its prevention were assessed by serum markers viz. cholesterol, triglyceride, alanine amino transferase and alkaline phosphatase.


Chard (Beta vulgaris L. var. cicla) extract ameliorates hyperglycemia by increasing GLUT2 through Akt2 and antioxidant defense in the Liver of rats


Chard is a plant used as an alternative hypoglycemic agent by diabetic people in Turkey. The aim of this study was to examine the molecular mechanism of hypoglycemic effects of chard extract. Male Sprague-Dawley rats (6–7 months old) were divided into five groups for this investigation: (1) control, (2) hyperglycemic, (3) hyperglycemic + chard, (4) hyperglycemic + insulin, (5) hyperglycemic + chard + insulin. Fourteen days after animals were rendered hyperglycemic by intraperitoneal injection of 60 mg/kg streptozotocin, the chard water extract (2 g/kg/day) or/and insulin (6 U/kg/day) was administered for 45 days. Hypoglycemic effect of chard extract was demonstrated by a significant reduction in the fasting blood glucose and increased glycogen levels in Liver of chard extract-treated hyperglycemic rats. Moreover, activity of adenosine deaminase, which is suggested as an important enzyme for modulating the bioactivity of insulin, was decreased by chard treatment. Immunostaining analysis showed increased nuclear translocation of Akt2 and synthesis of GLUT2 in the hepatocytes of chard or/and insulin-treated hyperglycemic rats. The oxidative stress was decreased and antioxidant defense was increased by chard extract or/and insulin treatment to hyperglycemic rats according to the decreased malondialdehyde formation, the activities of catalase, superoxide dismutase, myeloperoxidase and increased glutathione levels. These findings suggest that chard extract might improve glucose response by increasing GLUT2 through Akt2 and antioxidant defense in the Liver.


Beta vulgaris L. (Beetroot) Methanolic Extract Prevents Hepatic Steatosis and Liver Damage in T2DM Rats by Hypoglycemic, Insulin-Sensitizing, Antioxidant Effects, and Upregulation of PPARα


In CONCLUSION, chronic feeding of BE to STZ/HFD-induced T2DM in rats prevents hepatic steatosis and Liver damage by its hypoglycemic and insulin-sensitizing effects and its ability to upregulate antioxidants and PPARα.


Beet root (Beta vulgaris) protects lipopolysaccharide and Alcohol-induced Liver damage in rat


These results indicated that BVEE would have protective effects in hepatotoxicity by altering various indicators related to the Liver damage induced by LPS or Alcohol.


Effect of Beta vulgaris Extract on Liver Enzymes in Patients with Non-Alcoholic Fatty Liver Disease: A Randomized Clinical Trial


CONCLUSION: Integration of Beta vulgaris extract in the standard treatment of NAFLD could significantly improve AST, ALP, FBS, LDL, and HDL. This study also revealed that the effect of Beta vulgaris on ALT increased over time.

Beet (Beta vulgaris L.) stalk and leaf supplementation changes the glucose homeostasis and inflammatory markers in the Liver of mice exposed to a high-fat diet


Although beet stalks and leaves are not consumed and are usually discarded, they are an important source of bioactive flavonoids possessing antioxidant and anti-inflammatory activity. The aim of this study was to assess the effect of supplementation with beet stalks and leaves on metabolic parameters and glucose homeostasis in mice exposed to a high-fat diet. Six-week-old male Swiss mice were randomly divided into five experimental groups submitted to either standard diet (CT) or high-fat diet (HF), and HF-fed mice were subdivided into three treatment groups supplemented with oven-dehydrated beet stalks and leaves (SL), lyophilized beet stalks and leaves (Ly) or beet stalk and leaf extract (EX). Supplementation with SL promoted a mild improvement in the glucose homeostasis and decreased the protein levels of TNFα with no alterations in hepatic triglyceride content. It remains to be clarified if the enhancement in the glucose homeostasis observed in HFSL could be a consequence of improvement in pancreatic insulin secretion and/or glucose uptake from skeletal muscle and white adipose tissues.


Red Beet (Beta vulgaris) Impact on Human Health


The last decade is characterized by an explosive growth of interest in the impact of red beet root on human health. In the review information on the chemical composition and nutritional value of red beet as well as pigments biological effects are presented. Analyzed reports abound on antioxidant, anti-inflammatory and chemo-preventive Beta vulgaris phytochemical activity, its impact on gastrointestinal and cardiovascular system as well as endurance exercise performance. I

n details the red beet nitrates bioconversion and its role in blood pressure regulation have been described. The first information on red beetroot juice impact on iron metabolism is summarized. Beet processing methods, which led to the appearance of a lot of conventional red beet products, functional food, and dietary supplements, are described. Fractionated red beetroot juice on the molecular mass basis is prospective for senile sarcopenia as well as senile cognitive decline and Alzheimer’s disease prevention.

The aim of this review is to discuss red beetroot biological effects and new trends in the studies, targeted on development of new functional food products as well as medicines.


Beta vulgaris subspecies cicla var. flavescens (Swiss chard)


The novel flavonoids, 2″,2″‘-di-O-α-rhamnopyranosyl-vicenin II, a di-C-glycosyl flavone, and herbacetin 3-O-β-xylopyranosyl- (1″‘ –> 2″)-O-β-glucopyranoside, were isolated from the leaves of Beta vulgaris subspecies cicla L. var. flavescens, an edible plant which is consumed in the Mediterranean areas, additional to the known flavonoids, 6-C-glucosyl isoscutellarein, vitexin-(1″‘ –> 2″)-O-β-xylopyranosyl, vitexin-(1′” –> 2″)-O-α-rhamnopyranosyI and vitexin.

All metabolites were established by conventional methods of analysis and their structures were confirmed by spectroscopic analysis, including 1 D and 2D-NMR and by HR-ESIMS, as well. The extract of the plant leaves shows Hepatoprotective effects in rats intoxicated by administration of acetaminophen and exhibits hypolipidemic activity in rats with high-fat-diet induced hypercholesterolemia. The evaluation was done through measuring the Liver function enzymes (aspartate and alanine aminotransferases and alkaline phosphatase, the lipid profile (total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol and triglycerides) and histopathological analysis of Liver slides.



betalain


Medicinal plants with Hepatoprotective activity in Iranian folk medicine


There are a number of medicinal combinations in the Iranian traditional medicine which are commonly used as tonic for Liver. In this review, we have introduced some medicinal plants that are used mainly for the treatment of Liver disorders in Iranian folk medicine, with focus on their Hepatoprotective effects particularly against CC14 agent. In this study, online databases including Web of Science, PubMed, Scopus, and Science Direct were searched for papers published from January 1970 to December 2013. Search terms consisted of medicinal plants, traditional medicine, folk medicine, Hepatoprotective, Iran, Liver, therapeutic uses, compounds, antioxidant, CC14, anti-inflammatory, and antihepatotoxic, hepatitis, alone or in combination. Allium hirtifolium Boiss., Apium graveolens L., Cynara scolymus, Berberis vulgaris L., Calendula officinalis, Nigella sativa L., Taraxacum officinale, Tragopogon porrifolius, Prangos ferulacea L., Allium sativum, Marrubium vulgare, Ammi majus L., Citrullus lanatus Thunb, Agrimonia eupatoria L. and Prunus armeniaca L. are some of the medicinal plants that have been used for the treatment of Liver disorders in Iranian folk medicine.

Out of several leads obtained from plants containing potential Hepatoprotective agents, silymarin, β-sitosterol, betalain, neoandrographolide, phyllanthin, andrographolide, curcumin, picroside, hypophyllanthin, kutkoside, and glycyrrhizin have been demonstrated to have potent Hepatoprotective properties. Despite encouraging data on possibility of new discoveries in the near future, the evidence on treating viral hepatitis or other chronic Liver diseases by herbal medications is not adequate.


Therapeutic Application of Betalains: A Review


Anthocyanins, betalains, riboflavin, carotenoids, chlorophylls and caramel are the basic natural food colorants used in modern food manufacture. Betalains, which are composed of red–violet betacyanin and yellow betaxanthins, are water-soluble pigments that color flowers and fruits. Betalains are pigments primarily produced by plants of the order Caryophyllales. Because of their anti-inflammatory, cognitive impairment, anticancer and anti-hepatitis properties, betalains are useful as pharmaceutical agents and dietary supplements. Betalains also exhibit antimicrobial and antimalarial effects, and as an example, betalain-rich Amaranthus spinosus displays prominent antimalarial activity.

Studies also confirmed the antidiabetic effect of betalains, which reduced glycemia by 40% without causing weight loss or Liver impairment. These findings show that betalain colorants may be a promising alternative to the synthetic dyes currently used as food additives.


Norisoprenoids and Hepatoprotective flavone glycosides from the aerial parts ofBeta vulgaris var.cicla


(+)-Dehydrovomifoliol (1), 3-hydroxy-5α,6α-epoxy-β-ionone (2), vitexin 7-O-β-D-glucopyrano-side (3), and vitexin 2″-O-β-D-glucopyranoside (4) were isolated as new constituents from the aerial parts ofBeta vulgaris var.cicla. Compounds3 and4 demonstrated Hepatoprotective activity with values of 65.8 and 56.1%, respectively, in primary cultured rat hepatocytes with CCI4-induced cell toxicity, compared to controls. This was comparable to that of silibinin (69.8 %) which was used as a positive control.


Improved Hepatoprotective activity of Beta vulgaris L. leaf extract loaded self-nanoemulsifying drug deLivery system (SNEDDS): in vitro and in vivo evaluation


CONCLUSION: The results indicate that SNEDDS, as a nanocarrier system, has potential to improve the Hepatoprotective activity of the BL extract.

Therapeutic effect of fractionated by ultrafiltration red beetroot (Beta vulgaris L.) juice in rats with food-induced fatty Liver


The prevalence of non-Alcoholic fatty Liver disease (NAFLD), being a component of metabolic syndrome, has increased (15-27%) in the industrialized world. The deep mechanism of this pathology is not clear, but it is multifactorial. There is a huge amount of food supplements and medicines with Hepatoprotective effect on the market, but the NAFLD problem is far from being resolved. Hepatoprotective products have to provide wide spectra of biological effects, including antioxidant, hypolipidemic, anti-inflammatory action. It is peculiar to natural compounds, including red beetroot juice, which is well known to most of the population. This is important in view of the high prevalence of NAFLD. The aim of this study is to evaluate the curative effect of fractionated by ultrafiltration red beetroot juice in rats with food-induced Liver steatosis.



Bupleurum chinense root extract


Evaluation of root quality of Bupleurum species by TLC scanner and the Liver protective effects of “Xiao-chai-hu-tang” prepared using three different Bupleurum species


Results with Bupleurum kaoi, the species native to Taiwan, showed that the roots, rhizomes and aerial parts (leaves and stem) have greater quantities of saikosaponins than cultivated B. falcatum var. komarowi and imported B. chinense. The Liver protective effects of water extracts of “Xiao-Chai-Hu-Tang” (XCHT), a mixture of seven crude drugs, prepared using roots of the three different Bupleurum species and aerial parts of B. kaoi and B. falcatum var. komarowi, were evaluated using CCl4-induced toxicity in rats. The acute increase of serum transaminase (SGOT and SGPT) levels caused by CCl4 administration (3.0 , s.c.) was dramatically reduced when treated with XCHT prepared with the roots of B. kaoi. The histological metamorphoses such as fatty changes, ballooning degeneration, cell necrosis and lymphocyte and Kupffer cell increases around the central vein, were clearly decreased by XCHT prepared with B. kaoi. Furthermore, water extracts of aerial parts of both B. kaoi and cultivated B. falcatum var. komarowi decreased SGOT and SGPT levels and moderately reduced the pathological changes.


Antioxidant activity and Hepatoprotective effect of a polysaccharide from Bei Chaihu (Bupleurum chinense DC)


These results clearly demonstrated that WBCP possess promising Hepatoprotective effects against GalN-induced Liver damage, which may be mediated through augmentation of antioxidant defenses.


[Comparative research of different Bupleurum chinense composition to influence of hepatotoxicity of rats and oxidative damage mechanism].


CONCLUSION: The different B. chinense composition all can induce hepatotoxicity damage, and the channel of hepatic damage is related with the peroxidative damage mechanism. The degree of hepatotoxicity damage caused by the Alcohol extracted composition is more serious than that by the water extracted composition.


Saikosaponin A of Bupleurum chinense (Chaihu) elevates bone morphogenetic protein 4 (BMP-4) during hepatic stellate cell activation


CONCLUSION: SSa could down-regulate BMP-4 expression and inhibit hepatic stellate cell activation. Therefore, SSa could be used for treatment of Liver disease with elevated BMP-4 expression.


The Medicinal Plant Pair Bupleurum chinense-Scutellaria baicalensis – Metabolomics and Metallomics Analysis in a Model for Alcoholic Liver Injury


Traditional Chinese Medicine (TCM), a complex natural herbal medicine system, has increasingly attracted attention from all over the world. Most research has illustrated the mechanism of TCM based on the active components or single herbs. It was fruitful and effective but far from satisfactory as it failed to gain insights into the interactivity and combined effects of TCM. In this work, we used Bupleurum chinense (B. chinense DC, a species in the genus Bupleurum, family Apiaceae) and Scutellaria baicalensis (S. baicalensis Georgi, a species in the genus Scutellaria, family Lamiaceae), an herbal pair in TCM, to illustrate the combined effect. We compared the diverse effects between the B. chinense-S. baicalensis herbal pair and its compositions in an animal model of Alcoholic Liver Injury to highlight the advantages of the formula. Biochemical and histological indicators revealed that the effect of B. chinense-S. baicalensis was better than its individual parts. Furthermore, metabolite profiling of the serum, Liver tissue, and feces were conducted to reveal that the herbal pair largely presented its effects through enhanced tissue penetration to maintain Liver-located intervention with less global and symbiotic disturbance.

Furthermore, we analyzed the distribution of the metal elements in extracts of the serum and Liver tissue and found that the herbal pair significantly regulated the distribution of endogenous selenium in Liver tissue. As selenium plays an important role in the anti-oxidative and Hepatoprotective effects, it may be the reason for combined effects in BS formula. This research could open new perspectives for exploring the material basis of combined effects in natural herbal medicine.


Comparison of Anti-inflammatory and Hepatoprotective Activities of Bupleurum marginatum Wall. ex DC. and Bupleurum chinense DC


CONCLUSION: Bupleurum marginatum Wall.ex DC.and Bupleurum chinense DC.have similar antiinflammatory and Hepatoprotective effects.


Spectrum-effect relationship of Bupleurum chinense for Hepatoprotective effect based on cluster analysis and typical correlation analysis


Component fingerprints are a recognized method used worldwide to evaluate the quality of traditional Chinese medicines (TCMs). To foster the strengths and circumvent the weaknesses of the fingerprint technique in TCM, spectrum-effect relationships would complementarily clarify the nature of pharmacodynamic effects in the practice of TCM. The application of the spectrum-effect relationship method is crucial for understanding and interpreting TCM development, especially in the view of the trends towards TCM modernization and standardization. The basic requirement for using this method is in-depth knowledge of the active material basis and mechanisms of action. It is a novel and effective approach to study TCMs and great progress has been made, but to make it more accurate for TCM research purposes, more efforts are needed. In this review, the authors summarize the current knowledge about the spectrum-effect relationship method, including the fingerprint methods, pharmacodynamics studies and the methods of establishing relationships between the fingerprints and pharmacodynamics. Some speculation regarding future perspectives for spectrum-effect relationship approaches in TCM modernization and standardization are also proposed.



Cassia seed extract


Cassia tora (Leguminosae) seed extract alleviates high-fat diet-induced nonAlcoholic fatty Liver


The aim of this study was to examine the effects of Cassia tora seeds on high-fat diet (HFD)-induced hepatic steatosis, and elucidate the molecular mechanisms behind its effects. After being fed a HFD for two weeks, rats were orally dosed with Cassia seed ethanol extract (CSEE) (100, 200, or 300 mg/kg) once daily for 8 weeks. CSEE induced dose-dependent reductions in plasma lipid levels, as well as decreased the over hepatic lipid accumulation. Furthermore, CSEE treatment improved HFD-induced hepatic histological lesions. CSEE enhanced the phosphorylation of AMP-activated protein kinase (AMPK) and its primary downstream targeting enzyme, acetyl-CoA carboxylase, up-regulated the gene expression of carnitine palmitoyl transferase 1, and down-regulated sterol regulatory element binding protein 1 and fatty acid synthase protein levels in the Livers of HFD-fed rats. AMPK inhibition by compound C retarded CSEE-induced reduction in triglyceride accumulation in HepG2 cells stimulated by insulin. Our findings suggest that CSEE may regulate hepatic lipid homeostasis related with an AMPK-dependent signaling pathway. Targeting AMPK activation with CSEE may represent a promising approach for the prevention and treatment of obesity-related non-Alcoholic fatty Liver disease.


Protective effects of cassia seed ethanol extract against carbon tetrachloride-induced Liver injury in mice.


These results suggested that CSE could protect mice against CCl(4)-induced Liver injury via enhancement of the antioxidant capacity.


Cassia tora (Leguminosae) seed extract alleviates high-fat diet-induced nonAlcoholic fatty Liver


The aim of this study was to examine the effects of Cassia tora seeds on high-fat diet (HFD)-induced hepatic steatosis, and elucidate the molecular mechanisms behind its effects. After being fed a HFD for two weeks, rats were orally dosed with Cassia seed ethanol extract (CSEE) (100, 200, or 300 mg/kg) once daily for 8 weeks. CSEE induced dose-dependent reductions in plasma lipid levels, as well as decreased the over hepatic lipid accumulation.

Furthermore, CSEE treatment improved HFD-induced hepatic histological lesions. CSEE enhanced the phosphorylation of AMP-activated protein kinase (AMPK) and its primary downstream targeting enzyme, acetyl-CoA carboxylase, up-regulated the gene expression of carnitine palmitoyl transferase 1, and down-regulated sterol regulatory element binding protein 1 and fatty acid synthase protein levels in the Livers of HFD-fed rats. AMPK inhibition by compound C retarded CSEE-induced reduction in triglyceride accumulation in HepG2 cells stimulated by insulin. Our findings suggest that CSEE may regulate hepatic lipid homeostasis related with an AMPK-dependent signaling pathway. Targeting AMPK activation with CSEE may represent a promising approach for the prevention and treatment of obesity-related non-Alcoholic fatty Liver disease.


Hepatoprotective effect of Cassia obtusifolia seed extract and constituents against oxidative damage induced by tert‐butyl hydroperoxide in human hepatic HepG2 cells


The aim of the present study was to investigate the Hepatoprotective effects of different soluble fractions of methanolic derived Cassia obtusifolia seeds extract (COE) and its active components in tert-butyl hydroperoxide (t-BHP)-induced oxidative stress in HepG2 cells. Among the tested fractions, the ethyl acetate (EtOAc) fraction was the most active Hepatoprotective fraction. From the active EtOAc fraction, six anthraquinones (alaternin, emodin, aloe emodin, 2-hydroxyemodin 1-methyl ether, chryso-obtusin-2-O-β-d-glucoside, and questin) and one naphthopyrone glycoside (cassiaside) were isolated. The cytotoxic effect in 200 µM t-BHP-induced HepG2 cells was inhibited by COE and their bioactive compounds.

The protective effect of COE in 200 µM t-BHP-induced HepG2 cells may be associated with positive regulation of glutathione (GSH) and decreased in reactive oxygen species (ROS) formation of their bioactive compounds. The increased ROS and decreased GSH levels observed in t-BHP-treated HepG2 cells were ameliorated by pretreatment with cassiaside, alaternin, and aloe emodin, indicating that the Hepatoprotective effects of these major constituents are mediated by induction of cellular defense against oxidative stress. Overall, COE displayed a significant cytoprotective effect against oxidative stress, which may most likely be because of active compounds like cassiaside, alaternin, and aloe emodin in COE, which leads to maintenance of the normal redox status of cells.


Extraction of the main functional components of Cassia seed


Results indicate that the MAE method could be an efficient technique for the extraction of CSPs with high antioxidant activity, and CSPs could be further explored as functional food ingredients.



Catechin


Hepatoprotective Effect of Green Tea (Camellia sinensis) Extract against Tamoxifen-induced Liver Injury in Rats


Supplementation of GTE could be useful in alleviating tamoxifen-induced Liver injury in rats.


Effects of green tea or green tea catechin on Liver enzymes in healthy individuals and people with nonAlcoholic fatty Liver disease: A systematic review and meta‐analysis of randomized clinical trials


In CONCLUSION, the results of this study suggest that the effect of green tea on Liver enzymes is dependent on the health status of individuals. While a moderate reducing effect was observed in patients with NAFLD, in healthy subjects, a small increasing effect was found.


Catechin Suppresses an Array of Signalling Molecules and Modulates Alcohol-Induced Endotoxin Mediated Liver Injury in a Rat Model


These findings suggest that catechin may alleviate experimental Alcoholic Liver disease by suppressing induction of NF-κB, a key component of signalling pathway, thus forming a pharmacological basis for designing novel therapeutic agents against Alcohol induced endotoxin-mediated Liver injury.


The antioxidant effect of green tea catechin ameliorates experimental Liver injury


CONCLUSION: Green tea catechin may reduce hepatic fibrosis by suppressing oxidative stress and controlling the transcription factor expression involved in stellate cell activation.

Effects of green tea catechin on enzyme activities and gene expression of antioxidative system in rat Liver exposed to microwaves


It is suggested that the damage of Liver tissues was alleviated and function rapidly recovered to the normal level due to probable to the correction of imbalances in the antioxidative system with the administration of green tea catechin.


Green tea with a high catechin content suppresses inflammatory cytokine expression in the galactosamine-injured rat Liver


These results suggest that the drinking of green tea with a high catechin content may help to prevent and/or attenuate the development of a certain type of hepatitis.


Effect of Green Tea and Green Tea Rich with Catechin on Blood Glucose Levels , Serum Lipid Profile and Liver and Kidney Functions in Diabetic Rats


Green tea plus high dose of catechin tended to improve Liver functions manifested by the reduction of the serum levels of (AST and ALT), as well as kidney functions manifested by the reduction in the serum levels of (uric acid, urea nitrogen and Creatinine). The tea supported with catechin, drunk for many weeks, may be beneficial for people suffering from moderate diabetes or hyperlipidemia, reducing its complications such as Liver and kidney disorders.


The anti-fibrotic effect of green tea with a high catechin content in the galactosamine-injured rat Liver


These results suggest that the drinking of green tea with a high catechin content may help to prevent and/or attenuate the development of fibrosis in hepatitis.


Pharmacological Actions and Underlying Mechanisms of Catechin


CONCLUSION: Catechin and its stereo-isomers have shown their effectiveness as anti-inflammatory, anti-diabetic, anti-cancer, anti-neuroprotective, bactericidal, memory enhancer, anti-arthritis, and hepato-protective mainly through its activity to alter the pathway by NF-ΚB, Nrf-2, TLR4/NF-ΚB, COMT, and MAPKs.


Antioxidant Role of Catechin in Health and Disease


A positive correlation between green tea consumption and cardiovascular health due to several actions such as antioxidative, antihypertensive, anti-inflammatory, antiproliferative, antithrombogenic, and anti-hyperlipidemic etc., is well established based upon epidemiological and experimental studies. Clinical studies have shown the beneficial effects of catechin due its antioxidant action.


Biochemical mode of action of a Hepatoprotective drug: Observations on (+)-catechin


Thus, (+)-catechin appears to mediate its effect on fat accumulation partly by correcting the ethanol-induced alterations in hepatic redox state as there is no evidence of the drug inhibiting ethanol metabolism.


COMPARATIVE STUDY OF THE EFFECTS OF ( + )-CATECHIN AND 3-PALMITOYL-( + )-CATECHIN ON AlcoholIC FATTY Liver IN THE RAT


Pharmacokinetic studies in which [U- 14 C] labelled 3-palmitoyl-( +)-catechin and (+ )-catechin were given orally (150mg/kg each) to male rats showed that 3-palmitoyl-( + )-catechin achieved a higher peak tissue concentration and remained in the Liver for a longer period than (+ )-catechin. These properties of 3-palmitoyl-( + )-catechin are thought to be due to its greater lipid solubility, thereby explaining its greater potency in the chronic fatty Liver studies.



chestnut (Castanea crenata) inner shell extract


Hepatoprotective effects of chestnut (Castanea crenata) inner shell extract against chronic ethanol-induced oxidative stress in C57BL/6 mice


These results suggest that CISE has protective effects against ethanol-induced oxidative damage, possibly by inhibition of lipid accumulation, peroxidation and increase of antioxidant defense system in the Liver.


Hepatoprotective effects of chestnut (Castanea crenata) inner shell extract against chronic ethanol-induced oxidative stress in C57BL/6 mice


These results suggest that CISE has protective effects against ethanol-induced oxidative damage, possibly by inhibition of lipid accumulation, peroxidation and increase of antioxidant defense system in the Liver.


Chestnut (Castanea crenata) inner shell extract inhibits development of hepatic steatosis in C57BL/6 mice fed a high-fat diet


Based on these results, we speculate that the inhibitory effect on hepatic steatosis of CISE containing scoparone and scopoletin may be the result of suppression of lipid synthesis and the acceleration of fatty acid oxidation in mice fed HFD, suggesting that CISE may be beneficial in preventing hepatic steatosis.


The aqueous fraction of Castanea crenata inner shell extract reduces obesity and intramuscular lipid accumulation via induction of mitochondrial respiration and fatty acid oxidation in muscle


CONCLUSION: ACCE increases mitochondrial respiration and FAO in skeletal muscle and protects muscle from IMCL and lipotoxicity, reducing plasma FFA and adiposity.



Chrysanthemum indicum L. extract


Hepatoprotective effect of water extract from Chrysanthemum indicum L. flower


CONCLUSION: HCIF inhibited bioactivation of CCl4-induced hepatotoxicity and downregulates CYP2E1 expression in vitro and in vivo.


Ameliorative effect of supercritical fluid extract of Chrysanthemum indicum Linnén against D-galactose induced brain and Liver injury in senescent mice via suppression of oxidative stress, inflammation and apoptosis


CONCLUSION: Taken together, our present results suggested that CISCFE treatment could effectively mitigate the D-gal-induced hepatic and cerebral injury, and the underlying mechanism might be tightly related to the decreased oxidative stress, inflammation and apoptosis, indicating CISCFE might be an alternative and promising agent for the treatment of aging and age-associated brain and Liver diseases.


Hepatoprotective effect of water extract from Chrysanthemum indicum L. flower


CONCLUSION: HCIF inhibited bioactivation of CCl4-induced hepatotoxicity and downregulates CYP2E1 expression in vitro and in vivo.


Chrysanthemum morifolium extract attenuates high-fat milk-induced fatty Liver through peroxisome proliferator-activated receptor α–mediated mechanism in mice


These findings demonstrate that polyphenol-rich CME may prevent hyperlipidemic fatty Liver in mice, and its mechanisms may be related to the modulation of sterol regulatory element binding protein–1c, FAS, lipoprotein lipase, and cholesterol 7α-hydroxylase 1 expression through the PPARα-mediated pathway.


Chrysanthemum indicum Inhibits Adipogenesis and Activates the AMPK Pathway in High-Fat-Diet-Induced Obese Mice


Some polyphenols derived from plants may ameliorate hyperlipidemic fatty Livers; therefore, we hypothesized that polyphenol-rich Chrysanthemum morifolium extract (CME) may exert an inhibitory effect on the formation of hyperlipidemic fatty Livers in mice. This study aimed to examine the effects of CME on lipids in blood and Liver and on peroxisome proliferator–activated receptor (PPAR)α–mediated gene expression. Mice with hyperlipidemic fatty Livers induced by orally administering high-fat milk via gavage and being simultaneously treated with 75 to 300 mg/kg CME for 6 weeks. After CME addition, the serum total cholesterol levels and hepatic weight coefficients decreased, but no significant reduction in the serum triacylglycerol levels were observed. It is important to note that CME might decrease hepatic lipid accumulation, sterol regulatory element binding protein–1c, and fatty acid synthase expression and increase hepatic PPARα, lipoprotein lipase, and cholesterol 7α-hydroxylase expression.

However, the expected reduction in hepatic diacylglycerol acyltransferase mRNA expression was not observed. These findings demonstrate that polyphenol-rich CME may prevent hyperlipidemic fatty Liver in mice, and its mechanisms may be related to the modulation of sterol regulatory element binding protein–1c, FAS, lipoprotein lipase, and cholesterol 7α-hydroxylase 1 expression through the PPARα-mediated pathway.


Chrysanthemum indicum L. ethanol extract reduces high‑fat diet‑induced obesity in mice


These results suggested that Chrysanthemum indicum L. flowers may be a potentially effective therapeutic agent for obesity and its associated complications.


Hepatoprotective effect of fermented Chrysanthemum indicum L. water extract on ethanol-induced Liver injury in HepG2 cells


These results suggest that FCI can be useful for the development of an effective Hepatoprotective agent.


Therapeutic effects and mechanisms of total flavonoids of Chrysanthemum indicum on Liver fibrosis in rats


CONCLUSION: TFC Has a significant curative effect on the Liver fibrosis rats, its mechanism probably be related to decrease the expression of TGF-beta;1.


Effects of an Ethylacetate Fraction of Chrysanthemi Flos on the Antioxidative System and Lipid Profile in Rats with Ethanol-Induced Liver Damage


To investigate the antioxidative effects of an etbylacetate fraction extracted from the flowers of Chrysanthemum indicum L. (Chrysanthemi Flos) on the antioxidative system and lipid profiles of rats with ethanol induced hepatotoxicity. Sprague-Dawley rats weighing 100~150 g were divided into 5 groups: normal group (NOR), Chrysanthemi Flos EtOAC fraction (200 mg/kg) treated group (S1), 35% etbanol (10 mL/kg) treated group (S2), Chrysanthemi Flos EtOAC fraction (200 mg/kg) and ethanol concomitantly treated group (S3) and Chrysanthemi Flos EtOAC fraction (400 mg/kg) and ethanol concomitantly treated group (S4), respectively.


Anti-obesity effects of Chrysanthemum indicum L. in C57BL/6 mice induced by high fat diet


These results suggested that Chrysanthemum indicum L. flowers may be a potentially effective therapeutic agent for obesity and its associated complications.



Cichorium inthybus L.


A review for discovering Hepatoprotective herbal
drugs with least side effects on kidney


Theintroduced medicinal plants can be used for production of new drugs via antioxidant-relatedproperties, Hepatoprotective activities and least side effects on kidney for the prevention and treatment of Liver disorders.


Hepatoprotective effect of Cichorium intybus on CCl4-
induced Liver damage in rats


The results of this study confirmed the Hepatoprotective activity effect of the hydroalcholic extract of C. intybus.


Medical importance of Cichorium intybus A review


It possessed Hepatoprotective, gastroprotective, cardiovascular, antioxidant, hypolipidemic, anticancer, reproductive, antidiabetic, anti-inflammatory, analgesic, sedative, immunological, antimicrobial, anthelmintic, anti-protozoal, wound healing and many other pharmacological effects. This review was designed to highlight the chemical constituents and medical importance of Cichorium intybus.


Ameliorating effect of chicory (Cichorium intybus L.)-supplemented diet against nitrosamine precursors-induced Liver injury and oxidative stress in male rats


So, it could be concluded that chicory has a promising role and it worth to be considered as a natural substance for ameliorating the oxidative stress and hepatic injury induced by nitrosamine compounds.


Hepatoprotective Efficacy of Cichorium intybus L. Extract Against Carbon Tetrachloride-induced Liver Damage in Rats


In CONCLUSION, of this investigation, the results ascertain that the herb extracts of C. intybus possess significant Hepatoprotective activity.


Anti-hepatotoxic effects of root and root callus extracts of Cichorium intybus L.


Results of this study revealed that Cichorium intybus root callus extract could afford a better protection against carbon tetrachloride induced heptocellular damage as compared to the natural root extract.


Effects of chicory (Cichorium intybus L.) on nonAlcoholic fatty Liver disease


Existing studies have shown that chicory supplementation has beneficial effects on nonAlcoholic fatty Liver disease, but the existence of only one human study and possible side effects of chicory necessitate further studies.


Hepatoprotective effect of Cichorium intybus L., a traditional Uighur medicine, against carbon tetrachloride-induced hepatic fibrosis in rats


CONCLUSION: CIE may effectively protect against CCl4-induced hepatic fibrosis in rats; thus, it is a promising anti-fibrotic therapeutic agent.


Hepatoprotective Activity of Silybum marianum and
Cichorium intybus Against Thioacetamide in Rat


This results prove the protective effect of extracts on Liver cells. The protective effects of this extracts can be due to the presence of flavonoids compounds and their antioxidant effects.


Hepatoprotective Effects of the Cichorium intybus Root Extract against Alcohol-Induced Liver Injury in Experimental Rats


These results indicated that ingestion of Cii inhibited Alcohol-induced Liver damage, indicating Cii as a useful treatment for Alcohol-induced Liver injury.


Hepatoprotective Activity Of Cichorium Intybus L. Leaves Extract Against Carbon Tetrachloride Induced Toxicity


The results of the present study therefore supported the traditional believes on Hepatoprotective effect of the Cichorium intybus extract, however, high concentrations were hepatotoxic.


Effects of the Mixture of ‎Cichorium intybus L. and Cinnamomum zeylanicum on Hepatic Enzymes Activity and Biochemical Parameters in Patients with NonAlcoholic Fatty Liver Disease


It is concluded that the mixture of Cichorium intybus L. and Cinnamon extracts has some benefits in NAFLD patients making them valuable for future investigations.



Cichorium intybus root extract


Hepatoprotective Effects of the Cichorium intybus Root Extract against Alcohol-Induced Liver Injury in Experimental Rats


These results indicated that ingestion of Cii inhibited Alcohol-induced Liver damage, indicating Cii as a useful treatment for Alcohol-induced Liver injury.



Cimicifuga foetida L.root extract


Cimicifuga foetida extract inhibits proliferation of hepatocellular cells via induction of cell cycle arrest and apoptosis


In CONCLUSION, EAF may potentially find use as a new therapy for the treatment of hepatoma.



Cinnamomum cassia Presl extract


The effect of Cinnamomum cassia extract on oxidative stress in the Liver and kidney of STZ-induced diabetic rats


CONCLUSION: Cinnamon extract due to its potent antioxidant property could be effective in decrease of diabetes-induced oxidative stress that plays a major role in renal and hepatic complications.

A review on pharmacological activities of Cinnamomum cassia Blume


The plant Cinnamon cassia Blume is commonly known as Chinese cinnamon. Mostly its bark and leaves are used in medicine. C. cassia is safe when used in small amounts as in foods and medicinal doses. The whole plant is medicinally important in Indian traditional system of medicine, particularly in Ayurveda. In this review, the reported pharmacological activities of C. cassia Blume to cure or prevent several diseases are summarised. Different pharmacological activities like anti‑inflammatory, antioxidant, Hepatoprotective activities of C. cassia Blume are discussed in this review.


The Hepatoprotective Effect of Cassia Cinnamon (Cinnamomum cassia) Ethanolic Extract Against Paracetamol Toxicity in Rats


It is concluded that Cassia cinnamon ethanolic extract at 320 mg/kg dose provides protection against Liver structural damage due to toxic doses of paracetamol.


The therapeutic effect of Cinnamomum cassia essential oil against hepatotoxicity induced by co-exposure to lead and manganese in developing Wistar rats


In this study, we can conclude that the Cinnamomum cassia essential oil showed a Hepatoprotective effect.


Cinnamomum cassia ameliorates Ni-NPs-induced Liver and kidney damage in male Sprague Dawley rats


The study provided preliminary information about the protective effect of C. cassia against Ni-NPs indicated Liver and kidney damages.


Antioxidant activity of Cinnamomum cassia


The present study concludes that EECC could be used as a good source of antioxidant in the dietary supplement.


Cinnamomum cassia Prevents High-Fat Diet-Induced Obesity in Mice through the Increase of Muscle Energy


Our results suggest CC extract controls weight gain in obese mice by inhibiting lipid accumulation and increasing energy expenditure, and that its action mechanism involves the up-regulation of mitochondrial biogenesis in skeletal muscle cells.



Coptis chinensis Franch root extract


Antioxidant activity and Hepatoprotective effect of 10 medicinal herbs on CCl4-induced Liver injury in mice


CONCLUSION: This study is of value to assist the selection of more effective natural products for direct consumption and the development of nutraceuticals or therapeutics to manage oxidative stress-related diseases.

Coptis chinensis Franch root extract


Thus, the results suggest that Coptis inflorescence would be effective in the prevention and management of coronary artery disease by lowering serum cholesterol and blood sugar.


The Hepatoprotective Effects Of Coptisine On Carbon Tetrachloride Induced Acute Liver Damage In Mice


CONCLUSION: The results of this study indicate that coptisine could be effective in protecting the Liver from acute CCl4-induced injury. The Hepatoprotective mechanisms of coptisine may through regulate the IL-6 pathway.


Antioxidant activity and Hepatoprotective effect of 10 medicinal herbs on CCl4-induced Liver injury in mice


CONCLUSION: This study is of value to assist the selection of more effective natural products for direct consumption and the development of nutraceuticals or therapeutics to manage oxidative stress-related diseases.

Hepatoprotective effects of Coptidis rhizoma aqueous extract on carbon tetrachloride-induced acute Liver hepatotoxicity in rats


CONCLUSION: The study is the first time to demonstrate that CRAE has Hepatoprotective effect on acute Liver injuries induced by CCl4, and the results suggest that the effect of CRAE against CCl4-induced Liver damage is related to antioxidant property.


Palmatine attenuates d-galactosamine/lipopolysaccharide-induced fulminant hepatic failure in mice


Palmatine attenuated the apoptosis of hepatocytes, as evidenced by the TUNEL method and capase-3 analysis. Our data suggest that palmatine alleviates GalN/LPS-induced Liver injury by modulating the cytokine response and inhibiting apoptosis.



Cordyceps sinensis( BerK.)Sacc. extract


Comparison of the Hepatoprotective activity between cultured Cordyceps militaris and natural Cordyceps sinensis


Taken together, our results suggest that CME could be a potentially useful source in substitution for CSE for preventing and treating hepatotoxicity.


Hepatoprotective and Antioxidant Capacities of Paecilomyces japonica and Cordyceps sinensis in Rats with CCl₄-Induced Hepatic Injury


This paper is a study on the Hepatoprotective and antioxidant effects of the fruiting bodies of Paecilomyces japonica and wild Cordyceps sinensis grown on silkworms. All of the 70% ethanol extracts of Cordyceps Cordyceps exhibited DPPH free radical scavenging activity, and Cordyceps sinensis (IC??=163.0㎛·㎖?¹) was 4.5 times higher in efficacy than Cordyceps Cordyceps (IC??=731.0㎛·㎖?¹). was shown.

In the case of carbon tetrachloride-induced Liver injury in rats, each Cordyceps cordyceps weakly decreased serum transaminase, and significantly increased the activities of superoxide dismutase (SOD) and catalase in the 300㎛ㆍkg?¹ administration group, as well as thiobarbituric acid ( The amount of malondialdehyde (MDA) measured by the TBA) reaction method was significantly reduced. Although it also increased the activity of another antioxidant enzyme, glutathione peroxidase (GSH-px), it did not show any significance.


Compound Cordyceps TCM-700C exhibits potent Hepatoprotective capability in animal model


Conclusively, the herbal preparation “Compound Cordyceps TCM-700C” is a potent Hepatoprotective preparation. For therapeutic use, a dosage of 286.2 mg/kg-bw would be sufficiently effective.


Combinatorial usage of fungal polysaccharides from Cordyceps sinensis and Ganoderma atrum ameliorate drug-induced Liver injury in mice


Taking together, the combinatorial approach based on CSP and PSG presented a practical option for the management of drug-induced Liver injury.


Cordyceps sinensis Prevents Apoptosis in Mouse Liver with D-Galactosamine/Lipopolysaccharide-Induced Fulminant Hepatic Failure


In Summary, C. sinensis alleviates GalN/LPS-induced Liver injury by modulating the cytokine response and inhibiting apoptosis.


Hepatoprotective effect of plant polysaccharides from natural resources: A review of the mechanisms and structure-activity relationship


Liver injury is a common pathological process, which can result in fatty Liver, cirrhosis, fibrosis and even cancer. Polysaccharides isolated from plants have been regarded as an important resource of anti-hepatic lesion due to widely distributed in nature and low toxicity. In order to have a better understand of the protective mechanism on Liver function, a comprehensive review of research into plant polysaccharides during recent five years was performed. In total, 66 types of polysaccharides from 58 kinds of plant have shown Hepatoprotective effect through the pathological process of inflammation, apoptosis and oxidative stress by regulating NF-κB, JAK/STAT, TGF-β, PI3K/AKT, MAPK, caspase cascade, p53 and Nrf2-Keap1 pathways, lipid metabolism as well as cytochrome P450 enzymes.

Moreover, correlations between structure and Hepatoprotective activities of plant polysaccharides including primary structure, conformation properties, structural modification and content of uronic acid were also preliminarily explored. This review will provide a comprehensive perspective for better understanding the mechanism and development of polysaccharides against Liver injury.


Bioactive principles from Cordyceps sinensis: A potent food supplement – A review


Cordyceps sinensis (CS) is a well-known entamophagus fungus, naturally distributed in the Tibetan Plateau of Asia and Himalayas. Recently this synonym is transferred to Ophiocordyceps by both scientific and non-scientific communities. It is widely used as a tonic and medicinal food in traditional Chinese medicine (TCM), as it possess wonderful health benefits.

To support its functional attributes, various investigations have been carried out to find out its adaptogenic, aphrodisiac, anti-oxidant, anti-aging, neuroprotective, nootropic, immunomodulatory, anti-cancer and Hepatoprotective role.


Cordyceps sinensis protects against Liver and heart injuries in a rat model of chronic kidney disease: a metabolomic analysis


CONCLUSION: Oral administration of Cordyceps sinensis significantly attenuates the Liver and heart injuries in CKD rats. The (1)H NMR-based metabolomic approach has provided a systematic view for understanding of CKD and the drug treatment, which can also be used to elucidate the mechanisms of action of other traditional Chinese medicines.



Cortex Dictamni aqueous extract


In vitro and in vivo antioxidative and Hepatoprotective activity of aqueous extract of Cortex Dictamni


CONCLUSION: CDAE exhibits good antioxidant performance in vitro, with marked radical-scavenging and anti-lipid peroxidation activities. CDAE is effective in preventing CCl4-induced hepatic damage in rats of both sexes. The Hepatoprotective activity of CDAE may be attributable to its antioxidant activity, which may involve Keap1-Nrf2-mediated antioxidant regulation.



Crataegus pinnatifi da Bge. var. major leaves extract


Study on effects of hawthorn leaves extract on fatty Liver in rats


CONCLUSION: The results demonstrated that HLE was beneficial to the treatment of fatty Liver through reducing blood lipid and improving the Liver functions in rats.


Crataegus pinnatifi da Bge. var. major leaves extract


The results indicate that the HPLC method developed can easily be applied to the determination of eight polyphenols in the leaves of Crataegus pinnatifida Bge. var. major.


Amelioration effects of traditional Chinese medicine on Alcohol-induced fatty Liver


CONCLUSION: TCM treatment causes significant reduction in Alcohol-induced lipid hepatic accumulation, reversing fatty Liver and Liver damage, and can be used as a remedy for Alcoholic fatty Liver.


Corosolic acid ameliorates non‐Alcoholic steatohepatitis induced by high‐fat diet and carbon tetrachloride by regulating TGF‐β1/Smad2, NF‐κB, and AMPK signaling pathways


Our results suggested that CA ameliorated NASH through regulating TGF-β1/Smad2, NF-κB, and AMPK signaling pathways, and CA could be developed as a potential health functional food or therapeutic agent for NASH patients.


Effect of the Fermentation Broth of the Mixture of Pueraria lobata, Lonicera japonica, and Crataegus pinnatifida by Lactobacillus rhamnosus 217-1 on Liver Health and Intestinal Flora in Mice With Alcoholic Liver Disease Induced by Liquor


In CONCLUSION, we may have discovered a new functional food raw material with great application potential. The above findings indicate that the fermentation broth can actively regulate the intestinal flora and improve Liver inflammation. The underlying mechanism might be that the fermentation broth could enhance intestinal permeability and reduce the inflammatory signals and LPS transmitted through the gut-Liver axis, thereby reducing the oxidative stress and inflammation of the Liver caused by Alcohol.


Hawthorn ethanolic extracts with triterpenoids and flavonoids exert Hepatoprotective effects and suppress the hypercholesterolemia-induced oxidative stress in rats


CONCLUSION: Data suggested that hawthorn’s extracts are able to protect from hypercholesterolemia-induced oxidative stress and hepatic injuries. Moreover, the hypocholesterolemic effect of extracts was found comparable to orlistat.

Polyphenolic Profile and Biological Activity of Chinese Hawthorn (Crataegus pinnatifida BUNGE) Fruit


Chinese hawthorn (Crataegus pinnatifida Bge.) fruits are rich in polyphenols (e.g., epicatechin, procyanidin B2, procyanidin B5, procyanidin C1, hyperoside, isoquercitrin and chlorogenic acid)—active compounds that exert beneficial effects. This review summarizes all information available on polyphenolic content and methods for their quantification in Chinese hawthorn berries and the relationships between individual polyphenolic compounds as well. The influence of species or cultivars, the locality of cultivation, the stage of maturity, and extract preparation conditions on the polyphenolic content were discussed as well. Currently, only fruits of C. pinnatifida and C. pinnatifida var. major are included in the Chinese Pharmacopoeia.

Recent trials have demonstrated the efficacy of Chinese hawthorn fruit in lowering blood cholesterol and the risk of cardiovascular diseases. The fruit has also demonstrated anti-inflammatory and anti-tumour activities. This review deals mainly with the biological activity of the fruit related to its antioxidant properties.


Liver Protective Activities of Korean Medicinal Plants -Pharmacology of Plantago Semen


Exceptionally high incidence rate of Liver diseases among Korean people has brought about one of social problem in public health area. Our current study aimed at investigating plausible Liver protecting agents originated from natural products through literature survey and evalu-ating potential hepatotonic plants against animal model of hepatitis. Among 76 medicinal plants described as hepatotonics-therapeutices in various literatures, 44 plants being available in Korea were collected and were expected with methanol-water solvent system. Potential hepatotonic activities of these plants extracts were evaluated against animal model of hepatitis produced by carbon tetrachloride (CC14) intoxication. Six species, Atractylodes japonica (Compositae), Gentiana scrabra (Gentianaceae), Plantago asiatica (Plantaginaceae), Citrus aurantium (Ruta-ceae), Polygonatum japonicum (Liliaceae) and Cyperus rotundus (Cyperaceae) exhibited potent hepatotonic activities.

Among these six species, Plantago semen was selected for further studies and the Plantago semen extract was fractionated with water, chloroform, petroleum ether, and n-butanol. Potential hepatotonic activities of the fractions were evaluated by means of pharmacological, biochemical and histological methods. The water fraction appeared to possess most profound hepatotonic activities, whereas, petroleum ether and n-butanol fractions exhibited rather toxicity. Measurement of serum GOT, GPT and histological findings.


Herbal medicines for fatty Liver diseases


CONCLUSION: Some herbal medicines seemed to have positive effects on aspartate aminotransferase, alanine aminotransferase, ultrasound, and computed tomography. We found no significant difference on adverse effects between herbal medicine and control groups. The findings are not conclusive due to the high risk of bias of the included trials and the limited number of trials testing individual herbal medicines. Accordingly, there is also high risk of random errors.


The Liver protective role of hawthorn (Crataegus sp.) in hypertriglycerdimic induced rats


The results recorded elevated fasting serum triglyceride and cholesterol levels in HTD, while consumption of hawthorn markedly and significantly suppressed these elevations in triglyceride and cholesterol. On the other hand, the Liver enzymes such as ALP, SGOT and SGPT were slightly lower after consumption of hawthorn. The histological sections of hypertriglyceridemia rat’s Liver revealed accumulation of lipid deposition, loss of hepatocytes integrity, hepatocytes enlargement and infiltration of the mononuclear cells and congestion of the blood vessels, while hawthorn administration resulted in recovery of theses alteration that were comparable with the control group.

Our findings suggest that hawthorn leaf powder is capable of significant reduction in triglyceride and might have a protective role in Liver due to the lowering of the Liver transaminase levels and retrieval of the hepatic cell morphology in Sprague-Dawley rats.



Curcuma longa L. extract


Hepatoprotective effect of ethanolic extract of Curcuma longa on thioacetamide induced Liver cirrhosis in rats


CONCLUSION: The progression of Liver cirrhosis could be inhibited by the antioxidant and anti-inflammatory activities of CLRE and the normal status of the Liver could be preserved.


Fermented Curcuma longa L. Prevents Alcoholic Fatty Liver Disease in Mice by Regulating CYP2E1, SREBP-1c, and PPAR-α


We examined the efficacy of fermented Curcuma longa L. (FT) on the development of Alcoholic fatty Liver in mice and investigated the underlying mechanism. The protective potential of FT against ethanol-induced fatty Liver was determined using C57BL/6 male mice allocated into four groups (8 mice/group). Control groups received either distilled water or 5 g/kg body weight (b.w.) per day ethanol for 8 days. Treatment groups were administered either 300 mg/kg b.w. per day of milk thistle or FT before receiving ethanol. FT contained a higher amount of caffeic acid and tetrahydrocurcumin than C. longa. FT pretreatment significantly suppressed the elevated hepatic lipid droplets associated with ethanol ingestion.

In comparison with ethanol-treated control, FT pretreated mice showed inhibited cytochrome P4502E1 (CYP2E1), sterol regulatory element-binding protein-1 (SREBP-1c), and acetyl-CoA carboxylase production but elevated AMP-activated protein kinase, peroxisome proliferator-activated receptor-alpha (PPAR-α), and carnitine palmitoyltransferase 1 (CPT-1) levels. Taken together, FT is a promising hepatoprotectant for preventing of Alcoholic fatty Liver through modulating fatty acid synthesis and oxidation.


Hepatoprotective effects of fermented Curcuma longa L. on carbon tetrachloride-induced oxidative stress in rats


These results suggest that FC could be a candidate used for the prevention against various Liver diseases induced by oxidative stress via elevating antioxidative potentials and decreasing lipid peroxidation.


Hepatoprotective and immunomodulatory properties of aqueous extract of Curcuma longa in carbon tetra chloride intoxicated Swiss albino mice


In CONCLUSION, the present study suggests that C. longa has immunotherapeutic properties along with its ability to ameliorate hepatotoxicity.

Antioxidant and Hepatoprotective potentials of curcuminoid isolates from turmeric (Curcuma longa) rhizome on CCl4-induced hepatic damage in Wistar rats


The present study examined the protective effects of curcuminoid isolates from Curcuma longa against carbon tetrachloride (CCL4)-induced hepatic injury in rats. The Hepatoprotective effect of the crude extract (150, 300 and 600 mg/kg bw) and curcuminoids (75, 150 and 300 mg bw) was evident by significant increases in the serum antioxidative defence capacities (super oxide dismutase, reduced glutathione, catalase) and reduction in biomarker enzymes of Liver integrity (aspartate transaminase, alanine transaminase and alkaline phosphatase) in comparison to the results obtained in the CCL4-untreated animals.

Some of these parameters were completely restored by pre-treatments with curcuminoids. Similarly, the curcuminoids increases the concentrations of total proteins, albumins and ameliorated histological changes observed in CCL4 injured rats. Therefore, curcuminoid could be considered a novel candidate for the development of new drug against Liver diseases.


Hepatoprotective effect of Curcuma longa against lead induced toxicity in Wistar rats


CONCLUSION: The study concludes that supplementation of Curcuma longa @ 500 mg/kg daily oral for 28 days has shown protection against lead inducedhepatotoxicity


Hepatoprotective properties of Curcuma longa L. extract in bleomycin-induced chronic hepatotoxicity


Curcuma longa L. (CLL) extract has previously been reported to alleviate Liver damage. The current study examined the antioxidant activity of CLL by which the extract protects the Liver against bleomycin (BLM)-induced hepatotoxicity in mice. The hypothesis was that CLL extract would protect the Liver by reducing oxidative stress (induced superoxide dismutase (SOD) and catalase (CAT) activity), inhibiting lipid peroxidation, lowering biochemical parameters, and decreasing ROS production. Hepatic toxicity was induced by intraperitoneal injection of mice once daily with BLM (0.069 U/mL; 0.29 U/kg bw.) for a period of 4 weeks. The CLL was administered once a day for 4 weeks, 2 h prior at dose (40 mg/mL; 0.187 mg/kg/day). CLL extract significantly protected the Liver, it decreased plasma bilirubin (BL) and gamma glutamyl transpeptidase (GGT), and it reduced lipid peroxidation levels. BLM intoxication produced oxidative stress, in which the antioxidant system functioned incorrectly and ROS production significantly increased.

The CLL extract provided significant hepatic protection against BLM toxicity by improving SOD, CAT (p < 0.05), and MDA levels and decreasing ROS in the group receiving BLM (p < 0.05), leading to reduced membrane lipid peroxidation. Throughout this study, the CLL extract facilitated recovery from BLM-induced hepatic injury by suppressing oxidative stress. Therefore, the CLL extract has the potential to serve as an antioxidant compound to treat chronic hepatotoxicity.


Diarylheptanoids with Free Radical Scavenging and Hepatoprotective Activity in vitro from Curcuma longa


Assay-guided fractionation of the EtOAc soluble fraction of the rhizomes of Curcuma longa furnished three DPPH free radical scavenging diarylheptanoids, curcumin (1), demethoxycurcumin (2), and bisdemethoxycurcumin (3). Compounds 1 – 3 showed the DPPH radical scavenging effects with IC50 values of 2.8, 39.2, 308.7 μM, respectively. L-Ascorbic acid and resveratrol as positive controls exhibited IC50 values of 22.5 and 25.0 μM, respectively. Compounds 1 – 3 showed significant Hepatoprotective effects on tacrine-induced cytotoxicity in human Liver-derived Hep G2 cells. The EC50 values of 1 – 3 are 86.9, 70.7, and 50.2 μM, respectively.


Hepatoprotective Activity of Fermented Curcuma longa L. on Galactosamine-Intoxicated Rats


These results suggest that FC displays Hepatoprotective activity and FC was able to lower the TG levels in serum; thus, FC may serve as a useful material for health food and clinical conditions associated with Liver disease.


Hepatoprotective activity of aqueous extract of Curcuma longa in ethanol induced hepatotoxicity in albino wistar rats


Present study suggests that aqueous extract of Curcuma longa has significant Hepatoprotective activity against ethanol intoxicated rats

In Vitro Hepatoprotective Effects of Fermented Curcuma longa L. by Aspergillus oryzae against Alcohol-Induced Oxidative Stress


Our findings suggest that FCC might be considered as a useful agent in the prevention of Liver damage induced by oxidative stress by increasing the antioxidant defense mechanism.


Hepatoprotective effect of sesquiterpenes in turmeric


Hepatoprotective effect of turmeric together with its sesquiterpenes and curcuminoids fractions were examined on D-galactosamine induced Liver injury in rats. All the diets individually contained the turmeric extract, the curcuminoids fraction, and the sesquiterpenes fraction suppressed the increase of LDH, ALT, and AST levels caused by D-GalN treatment. Since few anti-oxidative activities are expected in the sesquiterpenes fraction, it is presumed that Hepatoprotective mechanism of sesquiterpenes in turmeric is different from that of curuminoids.



Curcuma phaeocaulis Radix


Study on Quality Standards and Hepatoprotective Effect of Curcuma phaeocaulis Radix


We established an animal model of Qi stagnation and blood stasis in a clinical context. Pathological changes in Liver function indexes were evaluated to investigate the Hepatoprotective effect of Lüsiyujin.  The study demonstrated that Lüsiyujin inhibits hepatocyte damage and regulates the excretion and secretion of hepatic bile. Our findings provide a theoretical basis for the formulation of quality standards, clinical application, and resource development for the utilisation of Lüsiyujin.


Protein network module-based identification of key pharmacological pathways of Curcuma phaeocaulis Val. acting on hepatitis


CONCLUSION: The protein network module-based approach is an efficient way to investigate the pharmacological mechanisms of CP.



Curcumin


Antioxidant and Hepatoprotective potentials of curcuminoid isolates from turmeric (Curcuma longa) rhizome on CCl4-induced hepatic damage in Wistar rats


The Hepatoprotective effect of the crude extract (150, 300 and 600 mg/kg bw) and curcuminoids (75, 150 and 300 mg bw) was evident by significant increases in the serum antioxidative defence capacities (super oxide dismutase, reduced glutathione, catalase) and reduction in biomarker enzymes of Liver integrity (aspartate transaminase, alanine transaminase and alkaline phosphatase) in comparison to the results obtained in the CCL4-untreated animals.

Some of these parameters were completely restored by pre-treatments with curcuminoids. Similarly, the curcuminoids increases the concentrations of total proteins, albumins and ameliorated histological changes observed in CCL4 injured rats. Therefore, curcuminoid could be considered a novel candidate for the development of new drug against Liver diseases.


Hepatoprotective Effect of Curcumin on Lindane-induced Oxidative Stress in Male Wistar Rats


In CONCLUSION, curcumin has protective effect over lindane-induced oxidative damage in rat Liver.



Curdrania tricuspidata leaves


Hepatoprotective effect of 10% ethanolic extract from Curdrania tricuspidata leaves against ethanol-induced oxidative stress through suppression of CYP2E1


These results suggest that CTE could be a useful agent for the prevention of ethanol-induced oxidative damage in the Liver, elevating antioxidative potentials and alleviating oxidative stress by suppressing CYP2El.


In Vitro Hepatoprotective Effects of Fermented Curcuma longa L. by Aspergillus oryzae against Alcohol-Induced Oxidative Stress


Our findings suggest that FCC might be considered as a useful agent in the prevention of Liver damage induced by oxidative stress by increasing the antioxidant defense mechanism.


Hepatoprotective effect of 10% ethanolic extract from Curdrania tricuspidata leaves against ethanol-induced oxidative stress through suppression of CYP2E1


These results suggest that CTE could be a useful agent for the prevention of ethanol-induced oxidative damage in the Liver, elevating antioxidative potentials and alleviating oxidative stress by suppressing CYP2El.


Hepatoprotective Effect of Curdrania tricuspidata Extracts against Oxidative Damage


We investigated the antioxidant and Hepatoprotective effects of extracts from the leaves, stems, and fruit of Cudrania tricuspidata (CT) against or ethanol-induced oxidative damage. The total polyphenol and flavonoid content was the highest in the 80% ethanol extracts from the leaves of the plant (CTL80). Also, the radical scavenging activity of DPPH and ABTS in the CTL80 was significantly higher than that of the non-treated control.

To determine the Hepatoprotective effects of CT in and ethanol-induced oxidative damage, cell viability was measured using an XTT assay. Pre-treatment of CTL80 significantly increased cell viability compared with the non-treated control cells by 71.21% and 80.40%, respectively. The data suggests that CTL80 exhibits Hepatoprotective antioxidant effects. Therefore, CTL80 may be considered a potential agent to control or ethanol-induced Liver damage.


A synbiotic combination of Lactobacillus gasseri 505 and Cudrania tricuspidata leaf extract prevents hepatic toxicity induced by colorectal cancer in mice


Therefore, this study demonstrated that fermented milk containing novel synbiotics has the potential to prevent hepatic toxicity induced because of CRC owing to its enhanced anti-oxidative and anti-inflammatory activities.


Hepatoprotective effect of 10% ethanolic extract from Curdrania tricuspidata leaves against ethanol-induced oxidative stress through suppression of CYP2E1


These results suggest that CTE could be a useful agent for the prevention of ethanol-induced oxidative damage in the Liver, elevating antioxidative potentials and alleviating oxidative stress by suppressing CYP2El.



Dendropanax morbifera leveille leaves


Hepatoprotective effects of aqueous extracts from leaves of Dendropanax morbifera leveille against Alcohol-induced hepatotoxicity in rats and in vitro anti-oxidant effects


Protective effects of Dendropanax morbifera Lev. leaves (DM) against Alcohol-induced Liver injury in rat hepatocytes, and rats were investigated. Cell viability increased, and normally elevated intracellular reactive oxygen species (ROS) levels were reduced in cells treated with water extracts of DM (DMW) before ethanol treatment, compared with cells treated with 200 mM ethanol. DMW administration with ethanol resulted in prevention of ethanol-induced hepatotoxicity due to reductions of serum aspartate aminotransferase and alanine aminotransferase levels.

DMW supplementation reduced formation of malondialdehyde, and inhibited reductions of hepatic glutathione, catalase, glutathione-S-transferase, glutathione reductase, and glutathione peroxidase levels, compared with rats administered ethanol, and suppressed expression of cytochrome P-450 2E1 that was elevated by ethanol administration. DMW reduced blood ethanol concentrations, and enhanced Alcohol dehydrogenase and Alcohol dehydrogenase activities that are typically decreased by ethanol administration, compared with ethanol-administered rats. DM exerted Hepatoprotective effects against Alcoholinduced hepatocyte injury.


Hepatoprotective effects of aqueous extracts from leaves of Dendropanax morbifera leveille against Alcohol-induced hepatotoxicity in rats and in vitro anti-oxidant effects


Protective effects of Dendropanax morbifera Lev. leaves (DM) against Alcohol-induced Liver injury in rat hepatocytes, and rats were investigated. Cell viability increased, and normally elevated intracellular reactive oxygen species (ROS) levels were reduced in cells treated with water extracts of DM (DMW) before ethanol treatment, compared with cells treated with 200 mM ethanol. DMW administration with ethanol resulted in prevention of ethanol-induced hepatotoxicity due to reductions of serum aspartate aminotransferase and alanine aminotransferase levels. DMW supplementation reduced formation of malondialdehyde, and inhibited reductions of hepatic glutathione, catalase, glutathione-S-transferase, glutathione reductase, and glutathione peroxidase levels, compared with rats administered ethanol, and suppressed expression of cytochrome P-450 2E1 that was elevated by ethanol administration.

DMW reduced blood ethanol concentrations, and enhanced Alcohol dehydrogenase and Alcohol dehydrogenase activities that are typically decreased by ethanol administration, compared with ethanol-administered rats. DM exerted Hepatoprotective effects against Alcoholinduced hepatocyte injury.


Dendropanax morbifera Leaf Extracts Improved AlcoholLiver Injury in Association with Changes in the Gut Microbiota of Rats


Our results suggest that these Hepatoprotective effects are likely due to the increased activities of antioxidant enzymes and partially promoted by intestinal microbiota shifts.


Antioxidant, Alcohol Metabolizing Enzyme, and Hepatoprotective Activities of Dendropanax morbifera Water Extract


Based on our results, we concluded that D. morbifera leaf and stem water extracts may be used as major pharmacological agents, such as antioxidants, Alcohol metabolism, and anti-hepatitis remedies.


Dendropanax morbifera Leaf Polyphenolic Compounds: Optimal Extraction Using the Response Surface Method and Their Protective Effects against Alcohol-Induced Liver Damage


The findings of this study suggest that DMLE could prove useful as a functional food product supplement to prevent Liver injury caused by excessive Alcohol consumption.


The Antioxidant, Alcohol Metabolizing Enzyme, and Hepatoprotective Activities of Dendropanax morbifera Vinegar with Traditional Fermentation Methods


These results suggest that D. morbifera vinegar has great potential as a resource for high quality functional health beverages.



Desmodium triquetrum leaf


Hepatoprotective and Antioxidant Activities of Desmodium Triquetrum DC


The results indicated that D. triquetrum has potent Hepatoprotective and antioxidant activity that may be due to the presence of flavonoids in the plant.


Medicinal Plants Used in Liver Protection – A Review


Herbal medicines have been applied for the treatment of Liver disorder for a lengthy period. Many herbal preparations are available in the market and therefore present review is aimed to compile the data on promising phytochemicals from medicinal plants that have been tested in hepatotoxicity models using modern scientific system.


Hepatoprotective MEDICINAL HERBS AND ANIMAL MODELS FOR THEIR SCREENING -A REVIEW


The Liver is a vital solid organ in the upper abdomen that helps in digestion, detoxification and has other synthetic, metabolic and storage functions. Liver diseases are a major problem worldwide; viral hepatitis, Alcohol, malnutrition, autoimmune and drugs being most important causes. Currently there is no way to compensate for the absence of Liver function in the long term and Liver transplant is the only option for those with irreversible loss of hepatic function.

The scientific basis for the statement that plants and their active constituents play an important role in the prevention of diseases is continuously advancing. In this review some of the plants with their phyto-constituents studied for protective effect in Liver diseases are reviewed.


Natural Hepatoprotectives: Alternative medicines for hepatitis


Liver is the most important organ of the body and involves in the metabolism of various toxic substance of such type that if are not metabolized that can cause severe damage to the body. Some of drugs also damage the Liver cells such as paracetamol, carbon tetrachloride, excessive Alcohol consumption, microbes and antibiotics as well. There are many drugs available in the market which prepared synthetically to treat the Liver disorder but actually instead of cure, they may cause further damage to the Liver cells.

So plants have many useful effects to cure Liver disorder without any further side effects. Plants are more popular nowadays. In this review we discussed various plants that have significant impact on Liver injured cells, their efficacy & toxicity has been checked on different animals.



Dropwort (Oenanthe javanica)


Hepatoprotective effects of fermented field water-dropwort (Oenanthe javanica) extract and its major constituents


These results demonstrate the protective effects of FDE against hepatocytotoxicity induced by CCl4 and t-BHP in rats and HepG2 cells, thus indicating the potential of FDE as a therapeutic for acute Liver diseases.


Antioxidant Activity of Dropwort (Oenanthe javanica DC) Fermented Extract and its Hepatoprotective Effect against Alcohol in Rats


These results suggest that DFE has a protective effect against Alcohol-induced hepatotoxicity in SD rats.


Protective Effect of Oenanthe javanica Extract on Acetaminophen-induced Hepatotoxicity in Rats


In CONCLUSION, OJME administration maintains the Liver glutathione pool and hepatic glutathione S-transferase activity, in addition with its high anti-oxidative capability, to show Hepatoprotective effect from acetaminophen intoxication.


The effects of Oenanthe javanica extracts on hepatic fat accumulation and plasma biochemical profiles in a nonAlcoholic fatty Liver disease model


In CONCLUSION, the water- and n-butanol extracts of OJ and metadoxine improved hepatic fat accumulation, hyperglycemia, and dyslipidemia induced by high-fat highcholesterol diet although the effect of metadoxine on fatty Liver was not significant, suggesting their potential use for the prevention and treatment of NAFLD.


Bioactive Materials : Article ; The Effects of Oenanthe javanica Extracts on Hepatic Fat Accumulation and Plasma Biochemical Profiles in a NonAlcoholic Fatty Liver Disease Model


In CONCLUSION, the water- and n-butanol extracts of OJ and metadoxine improved hepatic fat accumulation, hyperglycemia, and dyslipidemia induced by high-fat high-cholesterol diet although the effect of metadoxine on fatty Liver was not significant, suggesting their potential use for the prevention and treatment of NAFLD.



Eclipta alba


IN VIVO Hepatoprotective ACTIVITY OF ACTIVE FRACTION FROM ETHANOLIC EXTRACT OF ECLIPTA ALBA LEAVES


Abstract: The Alcoholic extract of fresh leaves of the plant Eclipta alba (Ea), previously reported for is Hepatoprotective activity was fractionated into three parts to chemically identify the most potent bioactive fraction. The Hepatoprotective potential of the fraction prepared from extract was studied in vivo in rats and mice against carbon tetrachloride induced hepatotoxicity. The Hepatoprotective activity was determined on the basis of their effects on parameters like hexobarbitone sleep time, zoxazolamine paralysis time, bromosulphaline clearance, serum transaminases and serum bilirubin.

Fraction EaII 00-80 mg/kg, p.o.) containing coumestan wedelolactone and desmethylwedelolactone as major components with apigenin, luteolin, 4-hydroxybenzoic acid and protocateuic acid as minor constituents exhibited maximum Hepatoprotective activity and is the active fraction for Hepatoprotective activity of Eclipta alba leave. The acute toxicity studies have shown that like Ea, Fraction EaII also high safety margin.


Hepatoprotective effect of ethanolic extract of Eclipta alba on experimental Liver damage in rats and mice


An Alcoholic extract of freshly collected Eclipta alba exhibited dose-dependent (62.5–500.0 mg/kg p.o.) significant Hepatoprotective activity against carbon tetrachloride-induced Liver injury in rats and mice. It indicated its protective role on parameters such as hexobarbitone-induced sleep, zoxazolamine-induced paralysis, bromosulphalen (BSP) clearance, serum levels of transaminases, bilirubin and protein. The extract did not show any signs of toxicity and the minimum lethal dose was greater than 2.0 g/kg when given orally and intraperitoneally in mice.


Hepatoprotective effects of Eclipta alba on subcellular levels in rats


The Hepatoprotective effect of the ethanol/water (1:1) extract of Eclipta alba (Ea) has been studied at subcellular levels in rats against CCl4-induced hepatotoxicity. Ea significantly counteracted CCl4-induced inhibition of the hepatic microsomal drug metabolising enzyme amidopyrine N-demethylase and membrane bound glucose 6-phosphatase, but failed to reverse the very high degree of inhibition of another drug metabolising enzyme aniline hydroxylase. The loss of hepatic lysosomal acid phosphatase and alkaline phosphatase by CCl4 was significantly restored by Ea.

Its effect on mitochondrial succinate dehydrogenase and adenosine 5′-triphosphatase was not significant. The study shows that Hepatoprotective activity of Ea is by regulating the levels of hepatic microsomal drug metabolising enzymes.


Hepatoprotective Activity of Taiwan Folk Medicine: Eclipta prostrata Linn. against Various Hepatotoxins Induced Acute Hepatotoxicity


The Hepatoprotective effects of Eclipta prostrata(Linn.) were studied on acute hepatitis induced in mice by a single dose of carbon tetrachloride (31.25 μL/kg, i.p.) or acetaminophen (600 mg/kg, i.p.) and in rats by a single dose of β-D-galactosamine (188 mg/kg, i.p.). The Hepatoprotective activity was monitored by estimating the serum transaminases (SGOT and SGPT) levels and histopathological changes in the Liver of experimental animals. The Eclipta prostrata extracts significantly inhibited the acute elevation of serum transaminases induced by carbon tetrachloride in mice and by β-D-GaLN in rats. However, in the experimental model of acetaminophen, although an inhibiting tendency was noticed, no statistical significance was observed.

Histopathologically, the crude E. prostrata extract significantly ameliorates either CCl4 or GaLN-induced histopathological changes in the Liver of experimental animals but no statistically significant improvement could be observed in acetaminophen induced Liver damage. All serological and histopathological effects of Eclipta prostrata were compared with that of Bupleurum chinense DC., which has been previously reported and used as a treatment criteria for hepatitis (Chiu et al., 1988; 1989; Lin et al., 1990a, b).


Comapartive Study on Hepatoprotective activity of Phyllanthus amarus
and Eclipta prostrata against Alcohol induced in albino rats


These results clearly suggest that, the Phyllanthus amarus and Eclipta prostrata have enormous Hepatoprotective value. Among the two plants Phyllanthus amarus has slightly high activity as compare to Eclipta prostrata. These herbal drugs have equivalent therapeutic value with the standards drug Silymarin. Moreover, it is very important to study the specific phytochemical compounds responsible for this Hepatoprotective effect.


Comparative study on Hepatoprotective activity of Aegle marmelos and
Eclipta alba against Alcohol induced in albino rats


These results clearly suggest that, the Aegle marmelos and Eclipta alba have enormous Hepatoprotective value. Among the two plants Aegle marmelos has slightly high activity as compare to Eclipta alba. These herbal drugs have equivalent therapeutic value with the standards drug Silymarin. Moreover, it is very important to study the specific phytochemical compounds responsible for this Hepatoprotective effect.



Epicatechin


Protective effect of Epicatechin on APAP-induced acute Liver injury of mice through anti-inflammation and apoptosis inhibition


Epicatechin (EC) is the most effective compound in Euonymus alatus (Thunb.)Sieb, and possesses a series of benefits, including anti-inflammatory, antioxidant, antiobesity and anticancer effects. In this study, we investigated the protective effects of EC in Acetaminophen(N-acetyl-p-aminophenol, APAP)-induced acute Liver injury in C57BL/6J mice and explored the possible mechanisms involved in these effects.


Hepatoprotective Effect of Green Tea (Camellia sinensis) Extract against Tamoxifen-induced Liver Injury in Rats


Tamoxifen citrate (TAM), is widely used for treatment of breast cancer. It showed a degree of hepatic carcinogenesis. The purpose of this study was to elucidate the antioxidant capacity of green tea (Camellia sinensis) extract (GTE) against TAM-induced Liver injury. A model of Liver injury in female rats was done by intraperitoneal injection of TAM in a dose of , i.p. for 7 successive days. GTE in the concentration of 1.5%, was orally administered 4 days prior and 14 days after TAM-intoxication as a sole source of drinking water. The antioxidant flavonoid; epicatechin (a component of green tea) was not detectable in Liver and blood of rats in either normal control or TAM-intoxicated group, however, TAM intoxication resulted in a significant decrease of its level in Liver homogenate of tamoxifen-intoxicated rats. The model of TAM-intoxication elicited significant declines in the antioxidant enzymes (glutathione-S-transferase,glutathione peroxidase, superoxide dismutase and catalase) and reduced glutathione concomitant with significant elevations transaminase) levels.

The oral administration of 1.5% GTE to TAM-intoxicated rats, produced significant increments in the antioxidant enzymes and reduced glutathione concomitant with significant decrements in TBARS and Liver transaminases levels. The data obtained from this study speculated that 1.5% GTE has the capacity to scavenge free radical and can protect against oxidative stress induced by TAM intoxication. Supplementation of GTE could be useful in alleviating tamoxifen-induced Liver injury in rats.


Hepatoprotective effects of litchi (Litchi chinensis) procyanidin A2 on carbon tetrachloride-induced Liver injury in ICR mice


Drug tolerance, lacking Liver regenerative activity and inconclusive inhibition of steatosis and cirrhosis by silymarin treatment during chronic Liver injury have increased the demand for novel alternative or synergistic treatments for Liver damage. Litchi fruit is abundant in polyphenolic compounds and is used in traditional Chinese medicine for treatments that include the strengthening of hepatic and pancreatic functions. Unique polyphenolic compounds obtained from litchi pericarp extract (LPE) were studied in vitro and in vivo for hepatoprotection. Epicatechin (EC) and procyanidin A2 (PA2) of LPE were obtained by fractionated‑extraction from pulverized litchi pericarps. All fractions, including LPE, were screened against silymarin in carbon tetrachloride (CCl4)‑treated murine embryonic Liver cell line (BNL). The effects of daily gavage‑feeding of LPE, silymarin (200 mg/kg body weight) or H2O in CCl4‑intoxicated male ICR mice were evaluated by studying serum chemicals, Liver pathology and glutathione antioxidative enzymes.

The effects of EC and PA2 on Liver cell regenerative activity were investigated using a scratch wound healing assay and flow cytometric cell cycle analysis; the results of which demonstrated that LPE protected BNL from CCl4‑intoxication. Gavage‑feeding of LPE decreased serum glutamic oxaloacetate transaminase and glutamic pyruvic transaminase levels, and exhibited superior retention of the hexagonal structure of hepatocytes and reduced necrotic cells following Liver histopathological examinations in CCl4‑intoxicated ICR mice.

Glutathione peroxidise and glutathione reductase activities were preserved as the normal control level in LPE groups. EC and PA2 were principle components of LPE. PA2 demonstrated Liver cell regenerative activity in scratch wound healing assays and Alcohol‑induced Liver cell injury in vitro. The present findings suggest that litchi pericarp polyphenolic extracts, including EC and PA2, may be a synergistic alternative to silymarin in hepatoprotection and Liver cell regeneration.


Hepatoprotective and Antioxidative Properties of Salacia reticulata: Preventive Effects of Phenolic Constituents on CCl4-Induced Liver Injury in Mice


These results suggest that the antioxidative activity of the principal phenolic compounds is involved in the Hepatoprotective activity of S. reticulata.


Hepatoprotective effects of Camellia nitidissima aqueous ethanol extract against CCl4-induced acute Liver injury in SD rats related to Nrf2 and NF-κB signalling


CONCLUSION: These results suggested that CNE is a promising agent for functional food and Hepatoprotective drug against ALI.

Hepatoprotective Effect of the Aqueous Extract of Camellia sinensis Against Methotrexate-induced Liver Damage in Rats


In CONCLUSION, treatment of rats with GTE protects hepatic tissue against MTX-induced Liver damage in dose dependent manner.



Forsythia suspensa extract


Forsythia suspensa extract attenuates lipopolysaccharide-induced inflammatory Liver injury in rats via promoting antioxidant defense mechanisms


Reactive oxygen species (ROS) have been shown to have a role in inflammation. We investigated whether Forsythia suspensa extract (FSE) could exert its antioxidant potential against lipopolysaccharide (LPS)-induced inflammatory Liver injury in rats. Rats were orally fed FSE once daily for 7 consecutive days prior to LPS (Escherichia coli, serotype O55:B5) injection. LPS treatment caused Liver dysfunction as evidenced by massive histopathological changes and increased serum alanine aminotransferase and aspartate aminotransferase activities which were ameliorated by FSE pretreatment. FSE attenuated LPS-induced depletion of cytosolic nuclear factor-erythroid 2-related factor 2 (Nrf2) and suppression of Nrf2 nuclear translocation in Liver, and the generation of ROS and malondialdehyde in serum and Liver.

FSE increased the Nrf2-mediated induction of heme oxygenase-1 in Liver, as well as superoxide dismutase and glutathione peroxidase activities in serum and Liver. Importantly, FSE attenuated LPS-induced nuclear factor-кB (NF-кB) nuclear translocation in Liver, and subsequently decreased tumor necrosis factor-α, interleukin (IL)-1β and IL-6 levels in serum and Liver, which were associated with FSE-induced activation of Nrf2 in Liver. These results indicate that the protective mechanisms of FSE may be involved in the attenuation of oxidative stress and the inhibition of the NF-кB-mediated inflammatory response by modulating the Nrf2-mediated antioxidant response against LPS-induced inflammatory Liver injury.


Hepatoprotective effect of Forsythiae Fructus water extract against carbon tetrachloride-induced Liver fibrosis in mice


CONCLUSION: FSE attenuates CCl4-induced Liver fibrosis in mice by inhibiting hepatic stellate cells (HSCs) activation, reducing hepatic extracellular matrix (ECM) disposition and reversing epithelial-mesenchymal transition (EMT).


Hepatoprotective effect of forsythiaside a against acetaminophen-induced Liver injury in zebrafish: Coupling network pharmacology with biochemical pharmacology


CONCLUSION: Our results indicated that FA could mitigate APAP-induced Liver injury through modulating the remolding of extracellular matrix and PI3K/AKT-mediated apoptosis.


New iridoid glycosides from the fruits of Forsythia suspensa and their Hepatoprotective activities


A novel iridoid glycoside trimer named forsydoitriside A (1) and five new iridoid glycosides (2–6) were isolated from the fruits of Forsythia suspensa together with two known compounds (7, 8). These new structures were elucidated by comprehensive spectroscopic data and the comparison of experimental and calculated electronic circular dichroism spectra. Compounds 18 were all assayed on acetaminophen-induced HepG2 cell damage. The results exhibited that compounds 2, 3, 5 and 6 possessed strong Hepatoprotective activities against the damage in HepG2 cell.


Eight new phenylethanoid glycoside derivatives possessing potential Hepatoprotective activities from the fruits of Forsythia suspensa


In our study to investigate components with Hepatoprotective activities, eight new phenylethanoid glycoside derivatives (1–8) were isolated from the 75% EtOH–H2O extract of the fruits of Forsythia suspensa along with six known compounds (9–14). These new structures were elucidated through HRESIMS and extensive NMR spectroscopic techniques. The absolute configurations of their sugars were determined by GC analysis. The pharmacological assay showed that compounds 2, 3, and 9–11 displayed remarkable Hepatoprotective activities against N-acetyl-p-aminophenol (APAP)-induced HepG2 cell damage at the concentration of 10 μM (Bicyclol as positive contrast).

Eight new phenylethanoid glycoside derivatives were isolated from the fruits of Forsythia suspensa. The bioactive assay suggested that some of them possessed potential Hepatoprotective activities.


Hepatoprotective effect of phillygenin on carbon tetrachloride-induced Liver fibrosis and its effects on short chain fatty acid and bile acid metabolism


CONCLUSION: Promoting the production of SCFAs in the gut and restoring the disturbance of BA metabolism may be the potential mechanisms by which PHI alleviated CCl4-induced Liver fibrosis.



Fructus schisandrae (Wuweizi in Chinese)


A Network Pharmacology-Based Study on the Hepatoprotective Effect of Fructus Schisandrae


Fructus schisandrae (Wuweizi in Chinese), a common traditional Chinese herbal medicine, has been used for centuries to treat chronic Liver disease. The therapeutic efficacy of Wuweizi has also been validated in clinical practice. In this study, molecular docking and network analysis were carried out to explore the Hepatoprotective mechanism of Wuweizi as an effective therapeutic approach to treat Liver disease. Multiple active compounds of Wuweizi were docked with 44 protein targets related with viral hepatitis, fatty Liver, Liver fibrosis, cirrhosis, and Liver cancer. A compound–target network was constructed through network pharmacology analysis, predicting the relationships of active ingredients to the targets.

Our results demonstrated that schisantherin, schisandrin B, schisandrol B, kadsurin, Wuweizisu C, Gomisin A, Gomisin G, and angeloylgomisin may target with 21 intracellular proteins associated with Liver diseases, especially with fatty Liver disease. The CYP2E1, PPARα, and AMPK genes and their related pathway may play a pivotal role in the Hepatoprotective effects of Wuweizi. The network pharmacology strategy used provides a forceful tool for searching the action mechanism of traditional herbal medicines and novel bioactive ingredients.


A Herbal Composition of Semen Hoveniae, Radix Puerariae, and Fructus Schisandrae Shows Potent Protective Effects on Acute Alcoholic Intoxication in Rodent Models


This study is designed to evaluate the effects of a herbal composition of Semen Hoveniae, Radix Puerariae and Fructus Schisandrae (SRF) against acute Alcoholic intoxication. The animals were treated with SRF extract (SRFE) for 14 days, and ethanol was conducted subsequent to the final treatment. The effects of SRFE on righting reflex, inebriety rates, kinetic parameters of blood ethanol and acetaldehyde were determined. In addition; levels of Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), the activities of cytochrome P450 2E1 (CYP2E1), selected antioxidative enzymes, and the contents of malonaldehyde (MDA) were measured. SRFE-pretreated rodents exhibited lower rates of intoxication, longer times to loss of righting reflex, and shortened times to recovery of righting reflex than in controls.

The peak concentrations and area under the time-concentration curves were lower in the pretreated animals than in controls, which corresponded to higher levels of ADH and ALDH in both gastrointestines and Livers of the SRFE-treated animals. The activities of CYP2E1 were lower in SRFE-pretreated animals, which also exhibited higher activities of some antioxidant enzymes and lower hepatic MDA levels. These findings suggest that the anti-inebriation effects of SRFE may involve inhibition of ethanol absorption, promotion of ethanol metabolism, and enhancing hepatic anti-oxidative functions.


The Hepatoprotective effect of the combination use of Fructus Schisandrae with statin – A preclinical evaluation


CONCLUSION: Taken together, these data suggested FSE has a potential beneficial effect on weight control and lipid metabolism in Sprague Dawley rats with diet-induced obesity, and the combination use of FSE with AS could significantly prevent Liver toxicity and anti-oxidative status induced by AS alone.



Galangin


Galangin Improved Non-Alcoholic Fatty Liver Disease in Mice by Promoting Autophagy


CONCLUSION: In vitro and in vivo studies showed that galangin cannot only improve pre-existing hepatic steatosis but also prevent the development of stenosis by promoting hepatocyte autophagy.

Galangin-loaded, Liver targeting liposomes: Optimization and Hepatoprotective efficacy


Collectively, these results indicated that the liposomes could serve as an effective deLivery system to achieve improved oral bioavailability and Liver targeting of galangin.


Hepatoprotective effect of galangin on carbon tetrachloride-induced hepatotoxicity via the LKB1/AMPK pathway


To investigate the protective effects of galangin on Liver toxicity induced by carbon tetrachloride (CCl4) in mice. Mouse hepatotoxicity model was established by intraperitoneal injection (i.p.) of 10 ml/kg body weight CCl4 that diluted with corn oil to a proportion of 1:500 on Kunming mice. The mice were randomly divided into five groups named control group, model group, and 1, 5, and 10 mg/kg galangin group. The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were analyzed by ELISA. Liver histopathological examination was observed via optical microscopy. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), and glutathion (GSSG) were analyzed to assess oxidative stress.

Finally, western blot assay was carried out to analyse the expression levels of total AMP-activated protein kinase (AMPK), phospho-AMPK (p-AMPK), total Liver kinase B1 (LKB1), and phospho-LKB1 (p-LKB1). Compared with the control group, in the model group, the levels of AST, ALT, MDA, and GSSG increased significantly (p < 0.01); the activity of SOD and GSH decreased significantly (p < 0.01); and the histopathological examination revealed Liver necrosis. However, treatment with galangin (5 and 10 mg/kg) significantly reversed these CCl4-induced Liver damage indicators.

Furthermore, treatment with galangin (10 mg/kg) significantly increased the p-AMPK and p-LKB1 expression levels (p < 0.01). This study supports the Hepatoprotective effect of galangin against hepatotoxicity, perhaps occurring mainly through the LKB1/AMPK-mediated pathway.


Galangin mitigates oxidative stress, inflammation, and apoptosis in a rat model of methotrexate hepatotoxicity


In CONCLUSION, Gal possesses a Hepatoprotective effect mediated by attenuating oxidative damage, inflammation, and apoptosis in rats.


Antioxidant and Hepatoprotective effects of Schisandra chinensis pollen extract on CCl4-induced acute Liver damage in mice


The results indicated that SCPE has strong antioxidant activities and significant protective effect against acute hepatotoxicity induced by CCl4, and have been supported by the evaluation of Liver histopathology in mice. The Hepatoprotective effect may be related to its free radical scavenging effect, increasing antioxidant activity and inhibiting lipid peroxidation.


Hepatoprotective activity of Achyrocline satureioides(Lam) D. C.


The results obtained with the aqueous extract of A. satureioides support its use in popular medicine as a Hepatoprotective and digestive agent, and the effects might be mediated through the antioxidant and choleretic activities.



Ganoderma lucidum


Hepatoprotective activity of Ganoderma lucidum triterpenoids in Alcohol
induced Liver injury in mice, an iTRAQ-based proteomic analysis


The Hepatoprotective activity of ethanol extract of Ganoderma lucidum (GLE) in Alcohol-induced Liver injury in mice was investigated. GLE, protected Alcohol-induced Liver injury through inhibiting lipid peroxidation, elevating activity of antioxidant enzymes, and suppressing apoptotic cell death and immune inflammatory response.


Hepatoprotective activity of Ganoderma lucidum triterpenoids in Alcohol-induced Liver injury in mice, an iTRAQ-based proteomic analysis


The Hepatoprotective activity of ethanol extract of Ganoderma lucidum (GLE) in Alcohol-induced Liver injury in mice was investigated. HPLC coupled with photo-diode array detector and electrospray ionization-mass spectrometry was used to analyze the major triterpenoids in GLE. The effects of GLE on hepatoprotection were evaluated through histopathology and biochemical analysis of serum enzymes. We used isobaric tag for relative and absolute quantitation (iTRAQ) coupled with tandem mass spectrometry to identify differentially expressed Liver proteome in mice.

There were more than 4000 differentially expressed proteins; 40 proteins with the most significant changed proteins were applied for further bioinformatics analysis. Expression levels of cytochrome P450 2E1 and Alcohol dehydrogenase 1, proteins that are closely associated with these processes, were validated by western blotting. Triterpenoids, major components of GLE, protected Alcohol-induced Liver injury through inhibiting lipid peroxidation, elevating activity of antioxidant enzymes, and suppressing apoptotic cell death and immune inflammatory response.


β-Glucuronidase-Inhibitory Activity and Hepatoprotective Effect of Ganoderma lucidum


These results suggest that the β-glucuronidase seems to be closely related to Liver injury, which could be prevented by β-glucuronidase inhibitors.


Hepatoprotective Evaluation of Ganoderma lucidum Pharmacopuncture: In vivo Studies of Ethanol-induced Acute Liver Injury


CONCLUSION: The present study suggests that GLP treatment is effective in protecting against ethanol-induced acute hepatic injury in SD rats by modulating the activities of ethanol-metabolizing enzymes and by attenuating oxidative stress.

Hepatoprotective effects of Ganoderma lucidum peptides against d-galactosamine-induced Liver injury in mice


The best Hepatoprotective effects of GLP were observed after treatment with the dose of 180 mg/kg as it was evidenced from biochemical parameters and Liver histopathological characters which were similar to those of normal control group. Results of this study revealed that GLP could afford a significant protection in the alleviation of d-GalN-induced hepatocellular injury.


Hepatoprotective role of ganoderma lucidum polysaccharide against BCG-induced immune Liver injury in mice


CONCLUSION: The present study indicates that NO participates in immune Liver injury induced by Mycobacterium bovis BCG infection. The mechanisms of protective roles by GLP for BCG-induced immune Liver injury may be due to influence NO production in mice.


Structural characterization and Hepatoprotective activity of an acidic polysaccharide from Ganoderma lucidum


In this study, Ganoderma lucidum crude polysaccharide (GLP) was found to have protective effect on Liver damage in mice caused by restraint stress through improving oxidative status. Two polysaccharides, including a neutral β-glucan (GLPB2) and an acidic β-glucan (GLPC2) were purified from GLP through anion-exchange chromatography (AEC) combined with gel permeation. GLPC2, with an average molecular weight of 20.56 kDa, exhibited stronger Hepatoprotective effect against H2O2-induced Liver injury in HepG2 cells compared to GLPB2.

Glycosidic residues and NMR analysis comprehensively revealed that GLPC2 contained d-Glcp-(1→, →3)-d-Glcp-(1→, →4)-d-Glcp-(1→, →6)-d-Glcp-(1→, →3, 6)-d-Glcp-(1 → and → 4)-d-GlcpA-(1 → . AEC can be an effective technique for separating β-glucans into neutral and acidic fractions by different ionic strength buffer. The findings provided a theoretical basis for the potential application of G. lucidum polysaccharides as a Hepatoprotective in food and pharmaceutical industry.


Triterpenoids and polysaccharide peptides-enriched Ganoderma lucidum: a randomized, double-blind placebo-controlled crossover study of its antioxidation and Hepatoprotective efficacy in healthy volunteers


CONCLUSION: The outcome of the present intervention demonstrated the antioxidation, anti-aging and Hepatoprotective nature of GL by effectively curbing oxidative stress.


Anti-Inflammatory and Hepatoprotective Effects of Ganoderma lucidum Polysaccharides against Carbon Tetrachloride-Induced Liver Injury in Kunming Mice


Key Message: These results suggested that GLPS may be a potential for the prevention and treatment of acute Liver injury with Liver inflammation. The possible mechanism may be related to the inhibition of free radical lipid peroxidation, NOS, and CYP2E1 activities and activation of Liver inflammatory factors.


Hepatoprotective Activity and the Mechanisms of Action of Ganoderma lucidum (Curt.:Fr.) P. Karst. (Ling Zhi, Reishi Mushroom) (Aphyllophoromycetideae)


G. lucidum could represent a promising approach for the management of various chronic hepatopathies. Further studies are needed to explore the kinetics and mechanisms of action of G. lucidum constituents with Hepatoprotective activities.


Hepatoprotective Effects of Aqueous Extract from Lingzhi or Reishi Medicinal Mushroom Ganoderma lucidum (Higher Basidiomycetes) on α-Amanitin−Induced Liver Injury in Mice


The results demonstrated that GLE induces Hepatoprotective effects on acute Liver injury induced by α-AMA; these protective effects may be related in part to the antioxidant properties of GLE.


Hepatoprotective Effects and Mechanisms of Action of Triterpenoids from Lingzhi or Reishi Medicinal Mushroom Ganoderma lucidum (Agaricomycetes) on α-Amanitin-Induced Liver Injury in Mice


The results demonstrated that triterpenoids have Hepatoprotective effects on a-AMA-induced Liver injury and that their Hepatoprotective mechanisms may be the result of their antioxidative and radical scavenging activities and their inhibition of apoptosis.


The Hepatoprotective Effects of Polysaccharides Isolated from Submerged Fermentation of Ganoderma lucidum


A neutral polysaccharide, GP, was isolated from a fermentation broth of Ganoderma lucidum Acid hydrolysis and a paper chromatography analysis indicated that the polysacchride was composed of glucose, xylose, and mannose. The molecular weight was estimated to be . The oral administration of GP to mice showed that it can inhibit Liver damage induced by GalN and .


Radical scavenger and antihepatotoxic activity of Ganoderma formosanum, Ganoderma lucidum and Ganoderma neo-japonicum


The results indicated that Ganoderma formosanum showed the greatest antihepatotoxic activity and the greatest free radical scavenging activity.



Garlic (aged black)


Hepatoprotective Effect of Aged Black Garlic on Chronic Alcohol-Induced Liver Injury in Rats


In CONCLUSION, ABG has strong antioxidative properties and may be a promising agent for protecting against chronic Alcohol-induced Liver damage.


Hepatoprotective effects of garlic against ethanol-induced Liver injury: A mini-review


Alcoholic Liver disease (ALD) is a progressively aggravated Liver disease with a diverse spectrum from steatosis to hepatitis, fibrosis, and cirrhosis. Epidemiological studies reveal that Alcohol is one of the major causes of advanced Liver disease in Europe, United States, and China. Despite the considerable harm, progression in ALD research is slow and the current therapies for ALD have less efficient.

Garlic (Allium sativum) has been used as a flavoring agent and also a folk medicine since ancient time. Along with the prosperity in the use of herbal medicines for the treatment of human diseases in recent decades, a series of studies have focused on the beneficial effects of garlic against ALD. This mini-review highlighted the protective roles of garlic against ALD and the potential mechanisms.


Hepatoprotective Effect of Aged Black Garlic Extract in Rodents


These results demonstrate that ABG has Hepatoprotective effects and suggest that ABG supplementation might be a good adjuvant therapy for the management of Liver injury.


Extracts from Fermented Black Garlic Exhibit a Hepatoprotective Effect on Acute Hepatic Injury


It was concluded that black garlic exhibited significant protective effects on CCl4-induced acute hepatic injury.


Transcriptome Analysis of Garlic-Induced Hepatoprotection against Alcoholic Fatty Liver


Fatty Liver induced by Alcohol abuse is a major worldwide health hazard leading to morbidity and mortality. Previous studies indicate antifatty Liver properties of garlic. This study investigated the molecular mechanisms of garlic oil (GO) or diallyl disulfide (DADS) imparted hepatoprotection against Alcohol induced fatty Liver in C57BL/6 mice using microarray-based global gene expression analysis. Alcohol liquid diet resulted in severe fatty Liver with increased levels of serum aspartate aminotransferease and alanine aminotransferease as well as triglycerides and decreased levels of Liver glutathione and antioxidant enzymes.

The major canonical pathways implicated by Alcohol treatment are the metabolisms of xenobiotics by cytochrome P450, glutathione, and arachidonic acid. Treatment with DADS or GO normalized the serum aminotransferease levels and Liver antioxidant enzymes and reduced the contents of triglycerides and cholesterol.

The canonical pathways involved in the amelioration of Liver include arachidonic acid metabolism, altered T cell and B cell signaling, tryptophan metabolism, antigen presentation pathway for DADS, metabolism of xenobiotics, mitotic roles of Polo-like kinase, fatty acid metabolism, LPS/IL-1 mediated inhibition of RXR function, and C21-steroid hormone metabolism for GO.


Effects of the Fermented Black Garlic Extract on Lipid Metabolism and Hepatoprotection in Mice


Therefore, black garlic extracts could be an ideal material as a dietary supplement in healthy functional foods to improve the effects on fatty Liver.


Amelioration of Single Clove Black Garlic Aqueous Extract on Dyslipidemia and Hepatitis in Chronic Carbon Tetrachloride Intoxicated Swiss Albino Mice


Single clove garlic is the product of atypical bulbing process of garlic under specific conditions. Therefore, the number of researches on single clove garlic bioactivity is limited. Recently, the Hepatoprotective effect of single clove garlic has been demonstrated. In this study, we investigated amelioration of single clove black garlic aqueous extract, a processed product from single clove garlic, on dyslipidemia and hepatitis induced by chronic administration of CCl4. Mice were randomly divided into four groups: control, extract control, CCl4 intoxication, and coadministrated CCl4 and extract group. Mice were orally given a dose of 1 ml/kg body weight of CCl4 for 28 days twice a week to establish chronic Liver injury model.

To evaluate the Hepatoprotective effect of single clove black garlic, mice were cotreated with CCl4 and single clove black garlic extract (200 mg/kg body weight) via gastric gauge for 30 days. Cotreatment with CCl4 and extract could improve the changes of body weight, Liver weight, and relative Liver weight as compared to CCl4 intoxicated mice. Single clove black garlic ameliorated dyslipidemia and the elevation of ALT and AST levels induced by chronic CCl4 intoxication. Histological studies revealed that single clove black garlic could prevent mononuclear cells infiltration and hepatocyte necrosis.



Genistein


Genistein and phycocyanobilin may prevent hepatic fibrosis by suppressing proliferation and activation of hepatic stellate cells


Hepatic fibrosis reflects hepatotoxin-mediated activation of hepatic stellate cells, resulting in their proliferation and transformation to myofibroblasts that secrete collagen. This activation is suppressed by estrogen, an effect which explains the decreased risk for hepatic fibrosis enjoyed by premenopausal women and by postmenopausal women receiving hormone replacement therapy. Since stellate cells have been found to express the beta but not the alpha isoform of the estrogen receptor, it can be predicted that nutritional intakes of the soy isoflavone genistein – a selective agonist for ERbeta in the low nanomolar plasma concentrations achievable with these intakes – have potential for suppressing hepatic fibrosis, in both men and women.

The antiproliferative impact of estrogen on stellate cells is mediated at least in part by suppression of NADPH oxidase activity; oxidant production by this enzyme complex plays a crucial role in stellate cell activation. Alternatively, it may be feasible to inhibit NADPH oxidase with phycocyanobilin (PCB), a biLiverdin homolog found in spirulina that has recently been shown to inhibit the NADPH oxidase activity of human cell cultures in low micromolar concentrations. Joint administration of soy isoflavones and PCB in appropriate doses might have considerable potential for prevention of hepatic fibrosis in at-risk subjects.


Protective Effects of Genistein and Puerarin against Chronic Alcohol-Induced Liver Injury in Mice via Antioxidant, Anti-inflammatory, and Anti-apoptotic Mechanisms


In CONCLUSION, both genistein and puerarin effectively alleviate hepatic damage induced by chronic Alcohol administration through potential antioxidant, anti-inflammatory, or anti-apoptotic mechanisms.


Hepatoprotective effect of genistein against dimethylnitrosamine-induced Liver fibrosis in rats by regulating macrophage functional properties and inhibiting the JAK2/STAT3/SOCS3 signaling pathway


CONCLUSION: Taken together, our results showed that genistein could be improved Liver fibrosis both in vivo and in vitro, probably through regulating the functional properties of macrophage and inhibiting the JAK2/STAT3/SOCS3 signaling pathway.


Chemopreventive and Hepatoprotective effects of genistein via inhibition of oxidative stress and the versican/PDGF/PKC signaling pathway in experimentally induced hepatocellular carcinoma in rats by thioacetamide


CONCLUSION: Genistein exerted antitumor and antioxidant effects and therefore suppress HCC development via inhibition of the PDGF/versican bidirectional axis, suppressing both ERK1 and PKC as downstream regulators. Therefore, genistein is a potential novel therapeutic candidate for improving the outcome of patients with HCC.

COMPARISON OF THE HEPATO-PROTECTIVE EFFECTS OF GENISTEIN AND GLUCURONE IN MICE TREATED WITH ACETAMINOPHEN


These findings suggest that genistein might prevent APAP-induced Liver toxicity by modulating the activities of antioxidant and metabolic enzymes, whereas glucurone did not exhibit protective activity in this study.


Genistein Ameliorates Cyclophosphamide – Induced Hepatotoxicity by Modulation of Oxidative Stress and Inflammatory Mediators


CONCLUSION: The present study demonstrated that the antioxidant and anti-inflammatory activities of GEN might contribute to its protective effects against CP-induced Liver damage.


Gentiana scabra Bunge extract


Hepatoprotection of Gentiana scabra Extract and Polyphenols in Liver of Carbon Tetrachloride-Intoxicated Mice


Histopathological studies further confirmed the Hepatoprotective activity of GS. Taken together, these results show that the antioxidant activities and polyphenolic compounds (kaempferol, ellagic acid, and quercetin) of GS may have contributed to its Hepatoprotective activity in CCl4-intoxicated mice, and its mechanism of action could be mediated through the reduction of oxidative stress in Liver tissue.


Gentiopicroside prevents Alcoholic Liver damage by improving mitochondrial dysfunction in the rat model


Results showed that the gentiopicroside exhibited good Hepatoprotective activity on rats with ALD by decreasing the transaminase levels, regulating the blood lipid levels, and increasing the antioxidant capacity. The potential mechanisms were related to regulating mitochondrial dysfunction by recovering mitochondrial membrane potential level, adenosine triphosphate concentration, activities of key enzymes in tricarboxylic acid cycle, and activities of complex I-V, regulating micromolecular metabolism and anti-apoptosis. These findings supported the further exploration of Gentianae Radix et Rhizoma as effective phytotherapy to prevent and treat ALD.


Longdan Xiegan Tang attenuates Liver injury and hepatic insulin resistance by regulating the angiotensin-converting enzyme 2/Ang (1–7)/Mas axis-mediated anti-inflammatory pathway in rats


CONCLUSION: The present results demonstrate that LXT attenuates Liver injury and hepatic insulin resistance by regulating the ACE2/Ang (1–7)/Mas axis-mediated anti-inflammatory pathway in rats. Our findings provide a better understanding of LXT for treatment of insulin resistance- and inflammation-associated Liver injuries.


Promising traditional Chinese medicine for the treatment of cholestatic Liver disease process (cholestasis, hepatitis, Liver fibrosis, Liver cirrhosis)


CONCLUSION

Yin Chen, Chi Shao, Fu Ling, HQD and YCHD have shown good clinical efficacy in controlling the development of CLD. Clinically, it is easier to curb the development of CLD by adopting graded diagnosis and treatment measures. We suggest that CLD should be risk stratified in clinical treatment to ensure personalized treatment for patients, so as to slow down the development of the disease.



Glycyrrhiza glabra


A review for discovering Hepatoprotective herbal
drugs with least side effects on kidney


The introduced medicinal plants can be used for production of new drugs via antioxidant-related properties, Hepatoprotective activities and least side effects on kidney for the prevention and treatment of Liver disorders.


Hepatoprotective effect of licorice, the root of Glycyrrhiza uralensis Fischer, in Alcohol-induced fatty Liver disease


CONCLUSION: Taken together, our data suggests that protective effect of licorice against Alcohol-induced Liver injury may be attributed to its anti-inflammatory activity and enhancement of antioxidant defense.


Hepatoprotective liposomal glycyrrhizin in Alcoholic Liver injury


CONCLUSION: Liposomal glycyrrhizin treatment moderated the Alcohol-related negative changes, therefore glycyrrhizin and/or its derivatives may have further impact in the treatment of Alcoholic Liver diseases.


Hepatoprotective Effects of Silybum marianum (Silymarin) and Glycyrrhiza glabra (Glycyrrhizin) in Combination: A Possible Synergy


Oxidative stress, lipid peroxidation, and transaminase reactions are some of the mechanisms that can lead to Liver dysfunction. A time-dependent study was designed to evaluate the ability of silymarin (SLN) and glycyrrhizin (GLN) in different dosage regimens to lessen oxidative stress in the rats with hepatic injury caused by the hepatotoxin carbon tetrachloride. Wistar male albino rats ( = 60) were randomly assigned to six groups. Group A served as a positive control while groups B, C, D, E, and F received a dose of CCl4 (50% solution of CCl4 in liquid paraffin, 2 mL/kg, intraperitoneally) twice a week to induce hepatic injury.

Additionally, the animals received SLN and GLN in different doses for a period of six weeks. CCl4 was found to induce hepatic injury by significantly increasing serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and thiobarbituric acid reactive substances while decreasing total protein and the activities of reduced glutathione, superoxide dismutase, and catalase.

Treatment with various doses of SLN and GLN significantly reduced ALT, AST, ALP, and TBARS levels and increased GSH, SOD, and CAT levels. Our findings indicated that SLN and GLN have Hepatoprotective effects against oxidative stress of the Liver.


Hepatoprotective Effect of Glycyrrhiza Glabra L. Extracts Against Carbon Tetrachloride-Induced Acute Liver Damage in Rats


We can conclude that the QGG and EGG (250mg/kg and 500mg/kg) possesses dose dependent, significant protective activity against acute Liver injuries induced by CCl4 and this activity can be attributed to the antioxidant property of G. glabra.


A review on Hepatoprotective activity of medicinal plants


 Herbal remedies are focused in the pharmaceutical industry to evolve a safe route for Liver disorders. Therefore, Hepatoprotective natural products such as Boerhaavia diffusa, Baliospermum montanum, Tridax procumbens, Glycyrrhiza glabra, Phyllanthus niruri, Cochlospermum planchoni, Cordia macleodii, Piper chaba, Acacia catechu, Ginkgo biloba, Scoparia dulcis, Vitex trifolia, Trianthema decandra, Tylophora indica, Hoslundia opposite is reviewed.

The present review is aimed at compiling data on promising Phytochemical from medicinal plants that have tested in hepatotoxicity models using modern scientific system.



Glycyrrhiza uralensis Fisch. extract


Hepatoprotective effect of licorice, the root of Glycyrrhiza uralensis Fischer, in Alcohol-induced fatty Liver disease


CONCLUSION: Taken together, our data suggests that protective effect of licorice against Alcohol-induced Liver injury may be attributed to its anti-inflammatory activity and enhancement of antioxidant defense.


Hepatoprotective effect of licorice, the root of Glycyrrhiza uralensis Fischer, in Alcohol-induced fatty Liver disease


CONCLUSION: Taken together, our data suggests that protective effect of licorice against Alcohol-induced Liver injury may be attributed to its anti-inflammatory activity and enhancement of antioxidant defense.


Hepatoprotective Efficacy and Interventional Mechanism of Qijia Rougan Decoction in Liver Fibrosis


Liver fibrosis is a leading contributor to chronic Liver diseases such as cirrhosis and Liver cancer, which pose a serious health threat worldwide, and there are no effective drugs to treat it. Qijia Rougan decoction was modified from Sanjiasan, a traditional Chinese medicine (TCM) described in the “Wenyilun” manuscript. Qijia Rougan decoction possesses Hepatoprotective and antifibrotic effects for clinical applications.

Overall, Qijia Rougan decoction significantly mediated metabolism-associated processes, inhibited inflammatory reactions, and repressed fibrosis-related TGFβ signaling, which prevented Liver fibrosis deterioration. Our study deepens our understanding of TCM in the diagnosis and treatment of Liver fibrosis.



Glycyrrihizin


Protective Mechanism of Glycyrrhizin on Acute Liver Injury Induced by Carbon Tetrachloride in Mice


These results suggest that glycyrrhizin alleviates CCl4-induced Liver injury, and this protection is likely due to the induction of heme oxygenase-1 and the downregulation of proinflammatory mediators.


Hepatoprotective effect of licorice, the root of Glycyrrhiza uralensis Fischer, in Alcohol-induced fatty Liver disease


CONCLUSION: Taken together, our data suggests that protective effect of licorice against Alcohol-induced Liver injury may be attributed to its anti-inflammatory activity and enhancement of antioxidant defense.


Hepatoprotective Effects of a Proprietary Glycyrrhizin Product during Alcohol Consumption: A Randomized, Double-Blind, Placebo-Controlled, Crossover Study


These results suggest that consumption of the proprietary glycyrrhizin study product during Alcohol consumption may support improved Liver health compared with drinking Alcohol alone.


Hepatoprotective liposomal glycyrrhizin in Alcoholic Liver injury


CONCLUSION: Liposomal glycyrrhizin treatment moderated the Alcohol-related negative changes, therefore glycyrrhizin and/or its derivatives may have further impact in the treatment of Alcoholic Liver diseases.


Hepatoprotective and anti-hepatocarcinogenic effects of glycyrrhizin and matrine


The results showed that compared with Gly or Mat alone, Gly + Mat reduced the mortality of acetaminophen overdosed mice more effectively, attenuate acetaminophen-induced hepatotoxicity, and reduced the number and area of γ-GT positive foci, thus protecting Liver function and preventing HCC from occurring.

In addition, Gly + Mat had a protective effect on immunosuppression, a strong non-specific anti-inflammatory effect, and an effect of reducing the incidence of sodium and water retention.


Hepatoprotective Effects of Silybum marianum (Silymarin) and Glycyrrhiza glabra (Glycyrrhizin) in Combination: A Possible Synergy


Oxidative stress, lipid peroxidation, and transaminase reactions are some of the mechanisms that can lead to Liver dysfunction. A time-dependent study was designed to evaluate the ability of silymarin (SLN) and glycyrrhizin (GLN) in different dosage regimens to lessen oxidative stress in the rats with hepatic injury caused by the hepatotoxin carbon tetrachloride. Wistar male albino rats ( = 60) were randomly assigned to six groups. Group A served as a positive control while groups B, C, D, E, and F received a dose of CCl4 (50% solution of CCl4 in liquid paraffin, 2 mL/kg, intraperitoneally) twice a week to induce hepatic injury.

Additionally, the animals received SLN and GLN in different doses for a period of six weeks. CCl4 was found to induce hepatic injury by significantly increasing serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and thiobarbituric acid reactive substances while decreasing total protein and the activities of reduced glutathione, superoxide dismutase, and catalase.

Treatment with various doses of SLN and GLN significantly reduced ALT, AST, ALP, and TBARS levels and increased GSH, SOD, and CAT levels. Our findings indicated that SLN and GLN have Hepatoprotective effects against oxidative stress of the Liver.



Gossypin


Modulation of Liver P-Glycoprotien Expression May Contribute to Gossypin Protection against Methotrexate-Induced Hepatotoxicity


CONCLUSION: Gossypin may be a valuable adjuvant therapy that protects the Liver against MTX toxicity through antioxidant, anti-inflammatory, antiapoptotic mechanisms, and mediated P-gp expression reduction.


Hepatoprotective Activity of Isolated Gossypin,
a Novel Bioflavanoid from Thespesia Populnea Linn


CONCLUSION: The present study reveals the scientific evidence in order to support its traditional use in Liver diseases and concludes that gossypin was isolated from T. populnea flower for the first time and found to be promising Hepatoprotective agent from natural source.


Hepatoprotective effect of mulberry water extracts on ethanol-induced Liver injury via anti-inflammation and inhibition of lipogenesis in C57BL/6J mice


These results suggested that MWE prevents Alcohol-induced Liver injury through the activation of the AMPK and PPAR-α signal. This may be mediated by multiple pathways, including reduced lipid accumulation and lipid synthesis, increased fatty acid transport and fatty acid oxidation responses, decreased oxidative stress and facilitated anti-inflammation.


Hepatoprotective and Antioxidant activity of Root of Cadaba farinosa, Forsk. against Carbon
Tetra Chloride induced Hepatotoxicity in Rats


This study suggests that possible mechanism for Hepatoprotective activity may be due to free radical scavenging potential caused by the presence of flavonoids in the extracts

The antioxidant and Hepatoprotective potential of
Solanum nigrum against oxidative stress


Conclusively, Solanum nigrum has the ability to alleviate Liver toxicity in an animal model by reducing oxidative stress and downregulating the apoptosis genes



Halichrysin A and B


Evaluation of the Hepatoprotective and antioxidant properties of an aqueous extract of plant polyphenols (helichrysum maracandicum)


This study investigated in vivo and in vitro the effects of helmar 2 polyphenol extracts isolated from the plant Helichrysum maracandicum in the conditions of toxic hepatitis poisoned by carbon dioxide (CCl4) in rats. The experiments were performed on healthy male rats and grouped hepatitis model animals with CCl4. In toxic hepatitis, helmar 2 polyphenol extracts at a dose of 20 mg/kg showed an inhibitory effect on hepatic mitochondrial lipid peroxidation. Evidently, the inhibitory effect of polyphenol extracts on the peroxidation of hepatic mitochondrial lipids was very close to that of the Hepatoprotective drug silymarin.


Improved metabolic control and hepatic oxidative biomarkers with the periconception use of Helichrysum plicatum ssp. plicatum


In CONCLUSION, the beneficial effects we encountered with the periconception use of the studied herbal extract warrant further investigation.


Evaluation of the Hepatoprotective and antioxidant properties of an aqueous extract of plant polyphenols (helichrysum maracandicum)


This study investigated in vivo and in vitro the effects of helmar 2 polyphenol extracts isolated from the plant Helichrysum maracandicum in the conditions of toxic hepatitis poisoned by carbon dioxide (CCl4) in rats. The experiments were performed on healthy male rats and grouped hepatitis model animals with CCl4. In toxic hepatitis, helmar 2 polyphenol extracts at a dose of 20 mg/kg showed an inhibitory effect on hepatic mitochondrial lipid peroxidation.

Evidently, the inhibitory effect of polyphenol extracts on the peroxidation of hepatic mitochondrial lipids was very close to that of the Hepatoprotective drug silymarin.



Hedyotis diffusa extract


Screening of Antitumor and Hepatoprotective Activity Components from Hedyotis
diffusa


Therefore, it is concluded that the main active components ofHedyotis diffusaagainst cancer and
protect Liver are total flavonoids
and amentoflavone.


Anti-Inflammatory and Hepatoprotective Activity of Peh-Hue-Juwa-Chi-Cao in Male Rats


The results indicated that extracts of HC, HD and MP possess anti-inflammatory activity, and that MP has the greatest inhibition against carrageenan-induced paw edema. In the Hepatoprotective study, results indicated that the three plant extracts significantly reduced the acute elevation of serum glutamate oxalate transaminase (sGOT) and serum glutamate pyruvate transaminase (sGPT) concentration, and alleviated the degree of Liver damage 24 hours after the intraperitoneal administration of hepatotoxins.


Screening of Antitumor and Hepatoprotective Activity Components from Hedyotis


Therefore, it is concluded that the main active components ofHedyotis diffusaagainst cancer and
protect Liver are total flavonoids
and amentoflavone.


A Study of Hepatoprotective activity of Hedyotis corymbosa. Linn, in albino rats


The present study was aimed to investigate the Hepatoprotective activity of ethanolic extract of Hedyotis corymbosa which was separated in to different fractions against carbon tetrachloride intoxification. The results indicate that, Intoxification with CCl4 increase the levels of SGOT and SGPT. The elevated levels of SGOT and SGPTwere significantly decreased by ether and butanol fractions at P<0.001 and butanone and ethanol at p<0.05, where as petroleum ether and ethyl acetate did not shown any significant reduction in the level of SGOT and SGPT.


Effect of Hedyotis diffusa water extract on protecting human hepatocyte cells (LO2) from H2O2-induced cytotoxicity


CONCLUSION: WEHDW may help to improve the antioxidant defense system, resulting in prevention of oxidative stress-related fatty Liver diseases.



Hibiscus vitifolius root extract


Hibiscus vitifolius (Linn.) root extracts shows potent protective action against anti-tubercular drug induced hepatotoxicity


CONCLUSION: These findings suggest that the root extracts of Hibiscus vitifolius have potent Hepatoprotective activity, thereby justifying its ethnopharmacological claim


Hibiscus vitifolius (Linn.) root extracts shows potent protective action against anti-tubercular drug induced hepatotoxicity


CONCLUSION: These findings suggest that the root extracts of Hibiscus vitifolius have potent Hepatoprotective activity, thereby justifying its ethnopharmacological claim.


Hepatoprotective Activity of Moringa oleifera on Antitubercular Drug-Induced Liver Damage in Rats


We have evaluated the Hepatoprotective effect of an ethanolic extract of M. oleifera leaves on Liver damage induced by antitubercular drugs such as isoniazid (INH), rifampicin (RMP), and pyrazinamide (PZA) in rats. Oral administration of the extract showed a significant protective action made evident by its effect on the levels of glutamic oxaloacetic transaminase (aspartate aminotransferase), glutamic pyruvic transaminase (alanine aminotransferase), alkaline phosphatase, and bilirubin in the serum; lipids, and lipid peroxidation levels in Liver.

This observation was supplemented by histopathological examination of Liver sections. The results of this study showed that treatment with M. oleifera extracts or silymarin (as a reference) appears to enhance the recovery from hepatic damage induced by antitubercular drugs.


Hepatoprotective properties of oleanolic and ursolic acids in antitubercular drug-induced Liver damage


CONCLUSION: The triterpene mixture was able to prevent the steatosis induced by the anti-TB drugs.


Hepatoprotective effect of aqueous methanolic extract of Rumex dentatus in paracetamol-induced hepatotoxicity in mice


So, it is concluded that R. dentatus has Hepatoprotective effect against paracetamol Liver damage in mice.


Assessment of Hepatoprotective Activity of Hibiscus vitifolius leaves in CCL4 induced hepatotoxic rats


The objective of this study was to investigate the Hepatoprotective activity of Alcoholic extract of Hibiscus vitifolius leaves against carbon tetrachloride (CCl4) induced hepatotoxicity. The plant material were dried in shade then powdered and extracted with Alcohol. Preliminary phytochemical tests were done. Alcoholic extract showed presence of phenolic compound and flavanoids.

The Hepatoprotective activity of the Alcoholic extract was assessed in CCl4 induced hepatotoxic rats. Alteration in the levels of biochemical markers of hepatic damage like SGOT, SGPT, ALP, Billirubin and Protein were tested in both CCl4 treated and untreated groups. CCl4 (1ml) has enhanced the SGOT, SGPT, ALP and Total Billirubin where decrease in total protein level in Liver.

Treatment of Alcoholic extract of Hibiscus vitifolius (500mg/kg) has brought back the altered levels of biochemical markers to the near normal levels in the dose dependent manner. Our findings suggested that Hibiscus vitifolius Alcoholic leaves extract possessed Hepatoprotective activity.



Houttuynia cordata Thunb extract


Hepatoprotective Effect of Houttuynia cordata Thunb Extract against Carbon Tetrachloride-induced Hepatic Damage in Mice


Houttuynia cordata Thunb (Saururaceae) is a traditional medicinal herb used to treat several disease symptoms. The present study was focused on the Hepatoprotective effects of H. cordata ethyl acetate extract in experimental mice. Further the antioxidant potential of the extract was also evaluated to substantiate its Hepatoprotective properties. Carbon tetrachloride-induced hepatic damage in mice was used to measure the serum biochemical parameters.

Morphological changes in hepatocyte architecture were studied by haematoxylin and eosin staining. In vitro alkyl and hydroxyl free radical scavenging assays were performed to evaluate the antioxidant effect. Administration of H. cordata extract significantly reduced the elevated serum levels and regulated the altered levels of serum cholesterol in carbon tetrachloride-treated mice (P<0.05). The morphological changes in hepatocyte architecture were also reversed by H. cordata treatment.

Further, the extract showed significant antioxidant actions by scavenging the alkyl and hydroxyl free radicals. The concentration of the extract necessary for 50% scavenging of alkyl and hydroxyl radicals was 15.5 and 410 μg/ml, respectively. H. cordata extract exhibited significant Hepatoprotective property in carbon tetrachloride-induced hepatotoxicity in mice. The strong antioxidant activities possessed by the extract might be responsible for such actions.


Hepatoprotective Effect of Houttuynia cordata Thunb Extract against Carbon Tetrachloride-induced Hepatic Damage in Mice


Houttuynia cordata Thunb (Saururaceae) is a traditional medicinal herb used to treat several disease symptoms. The present study was focused on the Hepatoprotective effects of H. cordata ethyl acetate extract in experimental mice. Further the antioxidant potential of the extract was also evaluated to substantiate its Hepatoprotective properties. Carbon tetrachloride-induced hepatic damage in mice was used to measure the serum biochemical parameters.

Morphological changes in hepatocyte architecture were studied by haematoxylin and eosin staining. In vitro alkyl and hydroxyl free radical scavenging assays were performed to evaluate the antioxidant effect. Administration of H. cordata extract significantly reduced the elevated serum levels and regulated the altered levels of serum cholesterol in carbon tetrachloride-treated mice (P<0.05).

The morphological changes in hepatocyte architecture were also reversed by H. cordata treatment. Further, the extract showed significant antioxidant actions by scavenging the alkyl and hydroxyl free radicals. The concentration of the extract necessary for 50% scavenging of alkyl and hydroxyl radicals was 15.5 and 410 μg/ml, respectively. H. cordata extract exhibited significant Hepatoprotective property in carbon tetrachloride-induced hepatotoxicity in mice. The strong antioxidant activities possessed by the extract might be responsible for such actions.


Chemical Composition and Hepatoprotective Effects of Polyphenol-Rich Extract from Houttuynia cordata Tea


This study was designed to investigate the antioxidant activity, Hepatoprotective effect, and phenolic composition of the ethyl acetate fraction (EAF) extracted from Houttuynia cordata tea. These results combined with Liver histopathology indicate that EAF possesses a significant protective effect against acute hepatotoxicity induced by CCl4, which may be due to the strong antioxidant activity of phenolic components.


Protective Effects of Houttuynia cordata Thunb on Carbon Tetrachloride-induced Hepatotoxicity in Rats


These results suggest that butanol fiuction of Houttuynia cordata Thunb methanol extract have potent Hepatoprotective effect against carbon tetrachloride intoxicated rats.


Evaluation of Hepatoprotective Potential of Chromolaena odorata (L.) R.M. King & H.Rob. Against Methotrexate-induced Hepatic Toxicity in Rats


CONCLUSION: Thus, Ch. odorata (L.) offered protection to the Liver from damage caused by Methotrexate attributable to its active bioactive agents including flavonoids which scavenges free radicals, enhanced the antioxidant status and protected against oxidative damage and oxidative stress.


Effect of Houttuynia cordata Thunb and Herbs Mixture Extract on the Lipid Metabolism in the LPS-induced Hepatotoxicity


Lipopolysaccharide (LPS) induces the synthesis of several inflammatory cytokine, chemokine, NO and inflammation in the Liver of rats. These results showed that HCTM had the protective effect against the hepatotoxicity-inducing LPS in the lipid metabolism, and it suggest that HCTM could be used for functional beverage.



Hovenia dulcis extract


Hepatoprotective Effects of Hovenia dulcis Extract on Acute and Chronic Liver Injuries induced by Alcohol and Carbon Tetrachloride


CONCLUSION: The results show that H. dulcis extract has Hepatoprotective effect in acute and chronic Alcohol-induced Liver injury and acute -induced Liver injury. These findings suggest that H. dulcis could be a potent Hepatoprotective agent.


Preliminary characterization, antioxidant activity in vitro and Hepatoprotective effect on acute Alcohol-induced Liver injury in mice of polysaccharides from the peduncles of Hovenia dulcis


For Hepatoprotective activity in vivo, the administration of HDPS significantly decreased the serum levels of alanine aminotransferase and aspartate aminotransferase, significantly decreased the Liver level of malondialdehyde and remarkably restored the Liver activities of superoxide dismutase and glutathione peroxidase in Alcohol-induced Liver injury mice. The results suggested that HDPS had a significant protective effect against acute Alcohol-induced Liver injury possibly via its antioxidant activity to protect biological systems against the oxidative stress.


Hepatoprotective Effects of Hovenia dulcis Extract on Acute and Chronic Liver Injuries induced by Alcohol and Carbon Tetrachloride


CONCLUSION: The results show that H. dulcis extract has Hepatoprotective effect in acute and chronic Alcohol-induced Liver injury and acute -induced Liver injury. These findings suggest that H. dulcis could be a potent Hepatoprotective agent.


Hepatoprotective effects of Hovenia dulcis seeds against Alcoholic Liver injury and related mechanisms investigated via network pharmacology


CONCLUSION: The results of this study demonstrate that H. dulcis seeds could be a good natural antioxidant source with protective effects on oxidative diseases such as ALD.

Combined Water Extracts from Oxidation-Treated Leaves and Branches of Hovenia dulcis Has Anti-Hangover and Liver Protective Effects in Binge Alcohol Intake of Male Mice


Hovenia dulcis, known as the oriental raisin tree, is used for food supplements and traditional medicine for the Liver after Alcohol-related symptoms. However, little information exists about the use of its leaves and branches. In this study, we established a method to use the leaves and branches to develop anti-hangover treatment and elucidated the underlying mechanisms. Oxidation-treated leaves (OL) exhibited high antioxidant content comparable to that of the peduncles and showed an anti-hangover effect in male mice.

The branch extract (BE) was enriched in the flavonoid catechin, approximately five times more than OL extract. The mixture of OL and BE (OLB) was formulated in a 2:1 ratio with frozen-dried extract weight and was tested for anti-hangover effects and protective properties against binge Alcohol-induced Liver injury. OLB showed better anti-hangover effect than OL. In addition to this anti-hangover effect, OLB protected the Liver from oxidative/nitrosative damage induced by binge Alcohol intake.



hypophyllanthin


Thidiazuron-induced shoot organogenesis and production of Hepatoprotective lignan phyllanthin and hypophyllanthin in Phyllanthus amarus


Callus cultures from nodal and leaf explants of Phyllanthus amarus were established on Murashige and Skoog (MS) medium with various combinations of auxins and cytokinins. The leaf-derived callus induced on 2.26 μM 2,4-dichlorophenoxyacetic acid (2, 4-D) + 2.32 μM Kinetin (Kin) upon transfer to medium containing thidiazuron (TDZ) exhibited higher shoot regeneration (32.4 ± 1.3 shoots per culture). Four-week-old shoots rooted readily on 1.5 μM Indol acetic acid (IAA)-containing medium and were successfully acclimatized with 98% survival.

The lignans, Phyllanthin (PH) and Hypohyllanthin (HPH), of leaf extracts from naturally grown plants were identified by using TLC, HPLC and H1-NMR. The PH and HPH production in the regenerated shoots was compared to their production in callus cultures, plants under field conditions and in naturally grown plants. The regenerated shoots on MS + 2.27 μM TDZ produced about two times higher PH and HPH than the leaves of naturally grown plant.

The present study provides a useful system for further studies on in vitro morphogenesis, elicitor-assisted production of PH and HPH and A. rhizogenes-mediated genetic transformation in Phyllanthus amarus.


Enhancing Hepatoprotective Bioactive’s from Phyllanthus Amaraus Through Immobilization


The study revealed that increase in the content of phyllanthin and hypophyllanthin was precursor concentration dependent and cinnamic acid treatment give maximum yield of Hepatoprotective bioactives as compared to other precursor and phytohormones used.


Hepatoprotective activity of Indian Phyllanthus


CONCLUSION: The Hepatoprotective and antioxidant activities of P. indofischeri are demonstrated for the first time in literature. The study also confirms the Hepatoprotective and antioxidant activities of leaves of P. emblica and P. polyphyllus. The molecule(s) responsible for the activities is being investigated.


Hepatoprotective activity of the Phyllanthus species on tert-butyl hydroperoxide (t-BH)-induced cytotoxicity in HepG2 cells


CONCLUSIONP. urinaria and P. maderaspatensis demonstrated dose-dependent Hepatoprotective activity and hence, can provide promising therapeutic interventions against chemical–induced Liver damage.

 


Imperata cylindrica Beauv.var. major( Nees)C.E.Hubb. root extract


Hepatoprotective glycosides from the rhizomes of Imperata cylindrical


Three new C-methylated phenylpropanoid glycosides (1, 2), a new 8–4′-oxyneolignan (3), together with two known analogs (4, 5), were isolated from the rhizomes of Imperata cylindrical Beauv. var. major (Nees) C. E. Hubb. Their structures were determined by spectroscopic and chemical methods. Compounds 1, 2, and 5 (10 μM) exhibited pronounced Hepatoprotective activity against N-acetyl-p-aminophenol (APAP)-induced HepG2 cell damage in vitro assays. Furthermore, their antioxidant activities against Fe2+-cysteine-induced rat Liver microsomal lipid peroxidation and the effects on the secretion of TNF-α in murine peritoneal macrophages (RAW264.7) induced by lipopolysaccharides were evaluated.


Hepatoprotective glycosides from the rhizomes of Imperata cylindrical


Three new C-methylated phenylpropanoid glycosides (1, 2), a new 8–4′-oxyneolignan (3), together with two known analogs (4, 5), were isolated from the rhizomes of Imperata cylindrical Beauv. var. major (Nees) C. E. Hubb. Their structures were determined by spectroscopic and chemical methods. Compounds 1, 2, and 5 (10 μM) exhibited pronounced Hepatoprotective activity against N-acetyl-p-aminophenol (APAP)-induced HepG2 cell damage in vitro assays.

Furthermore, their antioxidant activities against Fe2+-cysteine-induced rat Liver microsomal lipid peroxidation and the effects on the secretion of TNF-α in murine peritoneal macrophages (RAW264.7) induced by lipopolysaccharides were evaluated.


Chemical Composition and Hepato-protective activity of Imperata cylindrica Beauv


Phytochemical study of the aerial parts of Imperata cylindricaBeauv. (Graminae), growing in Egypt afforded four methoxylated flavonoids 1-4 , β-sitosterol-3-0-β-D-glucopyranosyl-6 ‘ -tetradecanoate 5 , 3-hydroxy-4-methoxy­benzaldehyde 6 , together with daucosterol, β-sitosterol and α-amyrin 7-9. To the best of our knowledge, this is the first isolation of compounds 1-5 from the genus Imperata.

A significant hepato-protective activity had been observed upon co-administration of the methanolic extracts of I. cylindrica with CCl 4 . The structures were determined using spectroscopic data.



Isatis indigotica Fort.root extract


Antioxidation and protection against H2O2 induced oxidative stress on normal human hepatocytes cell line (LO2) by extracts and three compounds from the root of Isatis Indigotica


The results demonstrated that Banlangen contained Hepatoprotective compounds distributed in different extracts.


Antioxidation and protection against H2O2 induced oxidative stress on normal human hepatocytes cell line (LO2) by extracts and three compounds from the root ofb Isatis Indigotica


The results demonstrated that Banlangen contained Hepatoprotective compounds distributed in different extracts.


Isatidis Folium alleviates acetaminophen-induced Liver injury in mice by enhancing the endogenous antioxidant system


In Summary, IF could alleviate APAP-induced hepatotoxicity by reducing the content of NAPQI via enhancing the level of GSH and the followed generation of NAPQI-GSH which might be ascribed to the upregulation of GSH-associated enzymes.


The Potential Application of Chinese Medicine in Liver Diseases: A New Opportunity


CONCLUSION, CM is very likely to be a potential candidate for Liver disease treatment based on modern phytochemistry, pharmacology, and genomeproteomics, which needs more clinical trials to further clarify its importance in the treatment of Liver diseases.


Hugan tablets for the treatment of RUCAM based drug-induced Liver injury: a propensity score matching analysis using a nationwide database


CONCLUSION: Hugan tablets are safe and effective in DILI treatment. Large-scale randomized controlled studies are needed to explore the effects of Hugan tablets on DILI induced by different offending drugs.


Antiviral activity of a polysaccharide from Radix Isatidis (Isatis indigotica Fortune) against hepatitis B virus (HBV) in vitro via activation of JAK/STAT signal pathway


CONCLUSION: These results suggested that the HBV inhibitory effect of RIP was possibly due to the activation of IFN-α-dependent JAK/STAT signal pathway and induction of the anti-HBV protein expression.



Isoquercitrin


Isoquercitrin inhibits the progression of Liver cancer in vivo and in vitro via the MAPK signalling pathway


The present study confirmed that isoquercitrin could inhibit the progression of human Liver cancer in vivo and in vitro, and the molecular mechanism of isoquercitrin may be closely associated with the MAPK and PKC signalling pathways.


Comparison of antioxidant and anti-inflammatory activity of quercetin, isoquercitrin and rutin against Alcohol-induced Liver injury in HepG2 Cells


These results indicate that quercetin and its derivatives might be beneficial in mitigating Alcohol-induced Liver diseases through the enhancement of phase II and antioxidant gene expressions via Nrf2 activation; thereby modulating the oxidative stress and inflammatory responses in hepatocytes.

Furthermore, it was found that quercetin showed higher Hepatoprotective activity than quercetin glycosides.


Hepatoprotective activity of Ganoderma lucidum triterpenoids in Alcohol-induced Liver injury in mice, an iTRAQ-based proteomic analysis


The Hepatoprotective activity of ethanol extract of Ganoderma lucidum (GLE) in Alcohol-induced Liver injury in mice was investigated. HPLC coupled with photo-diode array detector and electrospray ionization-mass spectrometry was used to analyze the major triterpenoids in GLE. The effects of GLE on hepatoprotection were evaluated through histopathology and biochemical analysis of serum enzymes. We used isobaric tag for relative and absolute quantitation (iTRAQ) coupled with tandem mass spectrometry to identify differentially expressed Liver proteome in mice.

There were more than 4000 differentially expressed proteins; 40 proteins with the most significant changed proteins were applied for further bioinformatics analysis. Expression levels of cytochrome P450 2E1 and Alcohol dehydrogenase 1, proteins that are closely associated with these processes, were validated by western blotting. Triterpenoids, major components of GLE, protected Alcohol-induced Liver injury through inhibiting lipid peroxidation, elevating activity of antioxidant enzymes, and suppressing apoptotic cell death and immune inflammatory response.


Hepatoprotective effect of isoquercitrin against acetaminophen-induced Liver injury


Our data evidenced that isoquercitrin protected Liver from APAP induced injury though inhibition of oxidative stress, nitrosative stress and inflammation, as well as regulation of APAP metabolism, suggesting that isoquercitrin could be a potential Hepatoprotective agent.


Hepatoprotective potential of isoquercitrin against type 2 diabetes-induced hepatic injury in rats


These results indicated that treatment with isoquercitrin protects against hepatic injury by T2DM.


Hepatoprotective and antioxidant activity of ethanolic extracts of edible lotus (Nelumbo nucifera Gaertn.) leaves


Lotus (Nelumbo nucifera Gaertn.), an aquatic vegetable, is extensively cultivated in eastern Asia, particularly in China. An ethanolic extract of the leaves was studied for its Hepatoprotective activity against CCl4-induced Liver toxicity in rats. In vitro and in vivo antioxidant activity was also assessed.

The results showed the Hepatoprotective activity of lotus leaf extract (LLE) at doses of 300 and 500 mg/kg and in vivo antioxidant activity at 100 mg/kg that was comparable with that of a standard treatment comprising 100 mg/kg of silymarin, a known Hepatoprotective drug. These data were supplemented with histopathological studies of rat Liver sections.

The main flavonoids and phenolic compounds of LLE were analysed by HPLC-DAD-ESI/MS methods. Six of the compounds detected were tentatively characterised, one as catechin glycoside and five as flavonoid glycoside derivatives: miricitrin-3-O-glucoside, hyperin, isoquercitrin, quercetin-3-O-rhamnoside and astragalin.



Kaempferol


Hepatoprotective Effect of Kaempferol Against Alcoholic Liver Injury in Mice


Kaempferol is a biologically active component present in various plants. The Hepatoprotective effect of kaempferol in drug-induced Liver injury has been proven, while its effect against Alcoholic Liver injury (ALI) remains unclear. Hence, the present study aimed to evaluate the effect of kaempferol against ALI in mice. The experimental ALI mice model was developed and the mice were treated with different doses of kaempferol for 4 weeks. The Liver functions were observed by monitoring the following parameters: Aspartate aminotransferase (AST/GOT) and alanine aminotransferase (ALT/GPT) levels in serum; histopathological studies of Liver tissue; oxidative stress by hydrogen peroxide (H2O2), superoxide dismutase (SOD) and glutathione (GSH); the lipid peroxidation status by malondialdehyde (MDA) and lipid accumulation by triglyceride (TG) level in serum; and the expression levels and activities of a key microsomal enzyme cytochrome 2E1 (CYP2E1), by both in vitro and in vivo methods.

The ALI mice (untreated) showed clear symptoms of Liver injury, such as significantly increased levels of oxidative stress, lipid peroxidation and excessive CYP2E1 expression and activity. The mice treated with different kaempferol dosages exhibited a significant decrease in the oxidative stress as well as lipid peroxidation, and increased anti-oxidative defense activity. The kaempferol treatment has significantly reduced the expression level and activity of hepatic CYP2E1, thus indicating that kaempferol could down regulate CYP2E1.

These findings show the Hepatoprotective properties of kaempferol against Alcohol-induced Liver injury by attenuating the activity and expression of CYP2E1 and by enhancing the protective role of anti-oxidative defense system.


Hepatoprotective Effect of Kaempferol Against Alcoholic Liver Injury in Mice


Kaempferol is a biologically active component present in various plants. The Hepatoprotective effect of kaempferol in drug-induced Liver injury has been proven, while its effect against Alcoholic Liver injury (ALI) remains unclear. Hence, the present study aimed to evaluate the effect of kaempferol against ALI in mice. The experimental ALI mice model was developed and the mice were treated with different doses of kaempferol for 4 weeks. The Liver functions were observed by monitoring the following parameters: Aspartate aminotransferase (AST/GOT) and alanine aminotransferase (ALT/GPT) levels in serum; histopathological studies of Liver tissue; oxidative stress by hydrogen peroxide (H2O2), superoxide dismutase (SOD) and glutathione (GSH); the lipid peroxidation status by malondialdehyde (MDA) and lipid accumulation by triglyceride (TG) level in serum; and the expression levels and activities of a key microsomal enzyme cytochrome 2E1 (CYP2E1), by both in vitro and in vivo methods.

The ALI mice (untreated) showed clear symptoms of Liver injury, such as significantly increased levels of oxidative stress, lipid peroxidation and excessive CYP2E1 expression and activity. The mice treated with different kaempferol dosages exhibited a significant decrease in the oxidative stress as well as lipid peroxidation, and increased anti-oxidative defense activity. The kaempferol treatment has significantly reduced the expression level and activity of hepatic CYP2E1, thus indicating that kaempferol could down regulate CYP2E1.

These findings show the Hepatoprotective properties of kaempferol against Alcohol-induced Liver injury by attenuating the activity and expression of CYP2E1 and by enhancing the protective role of anti-oxidative defense system.


Hepatoprotective role of kaempferol during Alcohol– and ΔPUFA-induced oxidative stress


CONCLUSION: From the results obtained, we conclude that kaempferol protects the Liver against Alcohol– and ΔPUFA- induced oxidative stress.


Hepatoprotective effects of kaempferol 3-O-rutinoside and kaempferol 3-O-glucoside from Carthamus tinctorius L. on CCl4-induced oxidative Liver injury in mice


These findings demonstrate that K-3-R and K-3-G have protective effects against acute CCl4-induced oxidative Liver damage.


Antioxidant and Hepatoprotective activity of kaempferol 3-O-β-d- (2,6-di-O-α-l-rhamnopyranosyl)galactopyronoside against carbon tetrachloride-induced Liver injury in mice


This study aims to investigate the antioxidant and Hepatoprotective effects of kaempferol 3-O-β-d– (2,6-di-O-α-l-rhamnopyranosyl)galactopyronoside (KG) isolated from unripe soybean leaves. Carbon tetrachloride (CCl4)-induced hepatotoxic ddY mice were used in the study. The mice were divided into three groups, namely the control group, the CCl4 group (CCl4, CCl4 injected), and the KG group (KG, CCl4 injected with KG administration). Hepatic injury markers of serum and Liver were analyzed. The results show that serum ALT, AST activities, hepatic glutathione, superoxide dismutase, catalase, and glutathione peroxidase activities were normalized in mice pretreated with KG.

Furthermore, the Liver thiobarbituric acid reactive substances levels were found to be improved by pretreatment with KG, indicating that KG is available to alleviate Liver injury, this may be due to its antioxidant properties. This study suggests that unripe soy leaves could be used as functional food materials.


Hepatoprotective Effects of Kaempferol-3-O-α-l-Arabinopyranosyl-7-O-α-l-Rhamnopyranoside on d-Galactosamine and Lipopolysaccharide Caused Hepatic Failure in Mice


Fulminant hepatic failure (FHF), associated with high mortality, is characterized by extensive death of hepatocytes and hepatic dysfunction. There is no effective treatment for FHF. Several studies have indicated that flavonoids can protect the Liver from different factor-induced injury. Previously, we found that the extracts of Elaeagnus mollis leaves had favorable protective effects on acute Liver injury.

However, the role and mechanisms behind that was elusive. This study examined the Hepatoprotective mechanisms of kaempferol-3-O-α-l-arabinopyranosyl-7-O-α-l-rhamnopyra-noside (KAR), a major flavonol glycoside of E. mollis, against d-galactosamine (GalN) and lipopolysaccharide (LPS)-induced hepatic failure. KAR reduces the mouse mortality, protects the normal Liver structure, inhibits the serum aspartate aminotransferase (AST) and alamine aminotransferase (ALT) activity and decreases the production of malondialdehyde (MDA) and reactive oxygen species (ROS) and inflammatory cytokines, TNF-α, IL-6, and IL-1β. Furthermore, KAR inhibits the apoptosis of hepatocytes and reduces the expression of TLR4 and NF-κB signaling pathway-related proteins induced by GalN/LPS treatment.

These findings suggest that the anti-oxidative, anti-inflammatory, and anti-apoptotic effects of KAR on GalN/LPS-induced acute Liver injury were performed through down-regulating the activity of the TLR4 and NF-κB signaling pathways.



Kolaviron


MECHANISMS FOR THE Hepatoprotective ACTION OF KOLAVIRON: STUDIES ON HEPATIC ENZYMES, MICROSOMAL LIPIDS AND LIPID PEROXIDATION IN CARBONTETRACHLORIDE-TREATED RATS


The present work examines the protective mechanisms of a biflavonoid fraction of an extract fromGarcinia kola seeds, kolaviron, in rats treated with carbontetrachloride (CCl4). CCl4administered at a dose of 1.2 g kg−1, three times a week for 2 weeks, significantly depressed the activities of microsomal aniline hydroxylase, aminopyrine N -demethylase, ethoxyresorufin O -demethylase and p -nitroanisole O -demethylase. Kolaviron (200 mg kg−1), administered for 14 days consecutively, inhibited (P<0.001) the CCl4mediated decrease in the activities of these enzymes by 60, 65, 55, and 63%, respectively. Kolaviron reduced the CCl4increase in the cholesterol/phospholipid ratio.

Similarly, kolaviron attenuated the toxic onslaught imposed by CCl4on 5′nucleotidase, glucose 6-phosphatase (microsomal marker enzymes) and malondialdehyde formation by 41, 54 and 77%, respectively. Kolaviron elicited 168% and 234% increases in the activity of UDP-glucuronosyl transferase and glutathione S -transferase. Simultaneous administration of kolaviron with CCl4modulated the effect of CCl4on the activities of these enzymes.

On the basis of the above data, it can be postulated that kolaviron exerts its protective action against carcinogen-induced Liver damage, first, by acting as an in vivo natural antioxidant and, second, by enhancement of drug-detoxifying enzymes.


MECHANISMS FOR THE Hepatoprotective ACTION OF KOLAVIRON: STUDIES ON HEPATIC ENZYMES, MICROSOMAL LIPIDS AND LIPID PEROXIDATION IN CARBONTETRACHLORIDE-TREATED RATS


The present work examines the protective mechanisms of a biflavonoid fraction of an extract fromGarcinia kola seeds, kolaviron, in rats treated with carbontetrachloride (CCl4). CCl4administered at a dose of 1.2 g kg−1, three times a week for 2 weeks, significantly depressed the activities of microsomal aniline hydroxylase, aminopyrine N -demethylase, ethoxyresorufin O -demethylase and p -nitroanisole O -demethylase. Kolaviron (200 mg kg−1), administered for 14 days consecutively, inhibited (P<0.001) the CCl4mediated decrease in the activities of these enzymes by 60, 65, 55, and 63%, respectively. Kolaviron reduced the CCl4increase in the cholesterol/phospholipid ratio.

Similarly, kolaviron attenuated the toxic onslaught imposed by CCl4on 5′nucleotidase, glucose 6-phosphatase (microsomal marker enzymes) and malondialdehyde formation by 41, 54 and 77%, respectively. Kolaviron elicited 168% and 234% increases in the activity of UDP-glucuronosyl transferase and glutathione S -transferase.

Simultaneous administration of kolaviron with CCl4modulated the effect of CCl4on the activities of these enzymes. On the basis of the above data, it can be postulated that kolaviron exerts its protective action against carcinogen-induced Liver damage, first, by acting as an in vivo natural antioxidant and, second, by enhancement of drug-detoxifying enzymes.


A review of natural products with Hepatoprotective activity


Liver diseases are a major worldwide health problem, with high endemicity in developing countries. They are mainly caused by chemicals and some drugs when taken in very high doses. Despite advances in modern medicine, there is no effective drug available that stimulates Liver function, offer protection to the Liver from damage or help to regenerate hepatic cells. There is urgent need, therefore, for effective drugs to replace/supplement those in current use. The plant kingdom is undoubtedly valuable as a source of new medicinal agents. The present work constitutes a review of the literature on plant extracts and chemically defined molecules of natural origin with Hepatoprotective activity.

The review shows 107 plants, their families, geographical distribution, plant parts utilized, type of assay and inducer of Liver damage. It also includes 58 compounds isolated from higher plants, classified into appropriate chemical groups. This work intends to aid researchers in the study of natural products useful in the treatment of Liver diseases.


Anticlastogenic and Hepatoprotective effects of Kolaviron on sodium valproate-induced oxidative toxicity in Wistar rats


CONCLUSION: Kolaviron offered protection against sodium valproate-induced genotoxicity, augmented antioxidant status and prevented hepatic oxidative stress in rats.


Hepatoprotection of D-Galactosamine-Induced Toxicity in Mice by Purified Fractions from Garcinia kola Seeds


Abstract: The Hepatoprotective effect of a biflavonoid complex, kolaviron, and its fractions from Garcinia kola seeds, together with the possible mechanisms involved was investigated in mice intoxicated with a single dose of D-galactosamine (GalNH2). Likewise, the ability of vitamin E to attenuate the toxicity was examined. Kolaviron, was separated by thin-layer chromatographic technique into three fractions; Fraction I, Fraction II and Fraction III with RF values of 0.48, 0.71 and 0.76, respectively. Pretreatment with kolaviron, fraction I and fraction II at a dose of 100 mg/kg for seven consecutive days before challenge with a single dose of GalNH2 (800 mg/ kg) significantly (P<0.05) decreased serum alanine (ALT) and aspartate (AST) aminotransferases by 67%, 70%, 71% and 39%, 35%, 46%, respectively over GalNH2-only intoxicated mice. Vitamin E elicited respectively 65% and 39% reduction in the GalNH2-induced increase in the activities of these enzymes. In addition, pretreatment with kolaviron and fraction II significantly (P<0.05) decreased the activity of microsomal γ-glutamyl transferase (γ-GT) by 42% and 46%, respectively.

Administration of kolaviron to GalNH2-intoxicated mice also restored glucose-6-phosphatase to level that was comparable to the control (P<0.05). These extracts except fraction III prevented the accumulation of serum and microsomal lipid peroxidation products, and also prevented the depletion of reduced glutathione (GSH) levels in the Liver of GalNH2-intoxicated mice. Kolaviron, fraction I and fraction II at a dose of 100 mg/kg caused an induction of glutathione-S-transferase (GSH transferase) and uridyl glucuronosyl transferase (UDPGT) activities by 31%, 34%, 35% and 29%, 65%, 56%, respectively. GalNH2-induced toxicity was essentially prevented as indicated by a Liver histopathologic study of Liver slices from mice pretreated with kolaviron, fraction I and fraction II.

This study shows that treatment with kolaviron, fraction I and fraction II (purified fractions from Garcinia kola) appeared to enhance the recovery from GalNH2-induced hepatotoxicity, and that the fractions I and II may therefore be responsible for the observed antihepatotoxic effect of kolaviron. This protection may be due to the ability of these extracts to induce the expression of phase II drug metabolizing enzymes.


Hepatoprotective Activity of Purified Fractions from Garcinia kola Seeds in Mice Intoxicated with Carbon Tetrachloride


The Hepatoprotective activity of kolaviron (KV), a biflavonoid complex from Garcinia kola seeds, and its purified fractions was investigated in mice intoxicated with carbon tetrachloride (CCl4). The ability of vitamin E to attenuate the toxicity was also examined. KV was extracted from powdered seeds of G. kola and then separated by thin-layer chromatography into three fractions—Fraction I (FI), Fraction II (FII), and Fraction III (FIII), with ratio of fronts values of 0.48, 0.71, and 0.76, respectively.

Pretreatment with KV, FI, and FII at a dose of 100 mg/kg of body weight for 2 weeks and then challenge with CCl4 at a dose of 1.2 g/kg of body weight, three times a week for 2 consecutive weeks, decreased the CCl4-induced increase in activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) by 31%, 30%, and 31% and 41%, 55%, and 42%, respectively. CCl4 intoxication also caused a significant (P < .05) accumulation of lipid peroxidation (LPO) products as revealed by the formation of the thiobarbituric acid-reactive substances: CCl4 induced LPO levels in serum and microsomes by 112% and 89%, respectively. However, pretreatment with KV, FI, and FII decreased LPO levels in serum by 31%, 41%, and 40% and in microsomes by 48%, 39%, and 35%, respectively. Vitamin E was protective in reducing the CCl4-induced increase in levels of AST, ALT, and γ-glutamyl transferase as well as LPO.

Furthermore, CCl4 intoxication significantly (P < .05) decreased the activities of microsomal glucose-6-phosphatase, aniline hydroxylase, and cytosolic glutathione-S-transferase (GST). While pretreatments with KV, FI, and FII were able to ameliorate the levels of glucose-6-phosphatase and GST, there were no significant (P > .05) effects on the levels of aniline hydroxylase and DT-diaphorase. This study confirms that FI and FII from KV enhanced recovery from CCl4-induced hepatotoxicity by decreasing the extent of LPO and also inducing the levels of phase II enzyme (GST). These fractions are responsible for the observed antihepatotoxic effect of KV.



kutkoside


Picroliv and its Components Kutkoside and Picroside I Protect Liver Against Galactosamine-Induced Damage in Rats


D-Galactosamine (800 mg/kg, intraperitoneally) caused significant decrease in the activities of 5′-nucleotidase, glucose-6-phosphatase and cytochrome P450 and increase in activities of γ-glutamyl transpeptidase, succinate dehydrogenase, acid phosphatase and acid ribonuclease in Liver after 24 hr. The levels of RNA, protein and glycogen decreased while total lipids, phospholipids, cholesterol and lipid peroxides increased. It also increased the serum levels of transaminases, alkaline phosphatase and bilirubin while protein concentration decreased significantly.

Oral administration of Picroliv (12 mg/kg/day for 7 days), a standardised iridoid glycoside fraction of Picrorhiza kurroa, significantly prevented the biochemical changes in Liver and serum of galactosamine-toxicated rats. Kutkoside (12 mg/kg/day for 7 days) also protected against changes in most of the hepatic and serum constituents studied. Another iridoid glycoside from Picroliv, Picroside I, at the same dose level could only prevent toxicant-induced changes in acid phosphatase, phospholipids and lipid peroxides in Liver and alkaline phosphatase in serum. Mixture of Picroside I and Kutkoside in the ratio of 1:1.5 at 12 mg/kg dose elicited lesser response than Picroliv.


Pharmacology and Chemistry of a Potent Hepatoprotective Compound Picroliv Isolated from the Roots and Rhizomes of Picrorhiza kurroa Royle ex Benth. (Kutki)


Natural products from plants are of major pharmaceutical and therapeutic importance, several of which are often obtained from the underground parts of the concerned plants. Deviation from standard rules in modern medicines, where instead of a single isolated fraction, a group of naturally occurring components exerts the desired therapeutic effect, was noted in case of Picroliv or Kutkin of Picrorhiza kurroa. “Picroliv” mainly a glucoside, is one such compound, normally obtained from 3 – 4 years old roots and rhizomes of an endangered medicinal plant – Picrorhiza kurroa (kutki) and constitute an important component of many Indian herbal preparations, used mainly for the treatment of a variety of Liver ailments.

It is an iridoid glycoside mixture containing 60% picroside I and kutkoside in the ratio of 1:1.5. Picroliv has shown efficacy comparable to silymarin in rodent models of galactosamine, paracetamol, thioacetamide and CCl4 induced hepatic damage. Picroliv has also shown cholerectic effect in rats and anti-cholestatic effect in rats, guinea pigs and cats treated with paracetamol and ethinyl estradiol. It has also anti-viral and immune-stimulant activities and is devoid of any significant CNS and CVS, autonomic and other systemic activity.

Because of its apparent ability as a strong Hepatoprotective and immune-modulatory compound, it is in high demand in both national and international markets. The review discusses the potential of Picrorhiza in various hepatic diseases as well as the chemistry and activity of individual compound of crude drug Picroliv.


Recent advances in plant Hepatoprotectives: A chemical and biological profile of some important leads


Medicinal plants have been traditionally used for treating Liver diseases since centuries. Several leads from plant sources have been found as potential Hepatoprotective agents with diverse chemical structures. Although, a big list of Hepatoprotective phytomolecules was reported in the scientific literature, only a few were potent against various types of Liver damages. Of which, silymarin, andrographolide, neoandrographolide, curcumin, picroside, kutkoside, phyllanthin, hypophyllanthin, and glycyrrhizin have largely attracted the scientific community. This review focuses discussion on the chemistry, biological activity, mode of action, toxicity, and future prospects of these leads.


A review for discovering Hepatoprotective herbal
drugs with least side effects on kidney


The Liver is a vital organ which plays a major role in the metabolism and excretion of xenobiotics from the body, and Liver disease is a worldwide health problem. The currently available synthetic drugs to treat Liver disorders cause further damage to the Liver and kidney so it is imperative to find new drugs with least side effects. There are a number of treatment combinations which are derived from medicinal plants and commonly administered as tonic for the Liver.

In this review, we have introduced most important medicinal plants that are used in Liver disorders and have least side effects on kidney. In this regards, we have focused on their active constituents, effects and trial studies, mechanisms of action, pharmacokinetic characteristics, dosages, and toxicity.Amaranthus spinosusL.,Glycyrrhiza glabra,CichoriuminthybusL., Phyllanthus species (amarus,niruri,emblica),Picrorhiza kurroa, andSilybum marianumhave been extensively administered for the treatment of Liver disorders. The introduced medicinal plants can be used for production of new drugs via antioxidant-related properties, Hepatoprotective activities and least side effects on kidney for the prevention and treatment of Liver disorders.


Medicinal plants with Hepatoprotective activity in Iranian folk medicine


There are a number of medicinal combinations in the Iranian traditional medicine which are commonly used as tonic for Liver. In this review, we have introduced some medicinal plants that are used mainly for the treatment of Liver disorders in Iranian folk medicine, with focus on their Hepatoprotective effects particularly against CC14 agent. In this study, online databases including Web of Science, PubMed, Scopus, and Science Direct were searched for papers published from January 1970 to December 2013.

Search terms consisted of medicinal plants, traditional medicine, folk medicine, Hepatoprotective, Iran, Liver, therapeutic uses, compounds, antioxidant, CC14, anti-inflammatory, and antihepatotoxic, hepatitis, alone or in combination. Allium hirtifolium Boiss., Apium graveolens L., Cynara scolymus, Berberis vulgaris L., Calendula officinalis, Nigella sativa L., Taraxacum officinale, Tragopogon porrifolius, Prangos ferulacea L., Allium sativum, Marrubium vulgare, Ammi majus L., Citrullus lanatus Thunb, Agrimonia eupatoria L. and Prunus armeniaca L. are some of the medicinal plants that have been used for the treatment of Liver disorders in Iranian folk medicine.

Out of several leads obtained from plants containing potential Hepatoprotective agents, silymarin, β-sitosterol, betalain, neoandrographolide, phyllanthin, andrographolide, curcumin, picroside, hypophyllanthin, kutkoside, and glycyrrhizin have been demonstrated to have potent Hepatoprotective properties. Despite encouraging data on possibility of new discoveries in the near future, the evidence on treating viral hepatitis or other chronic Liver diseases by herbal medications is not adequate.


Hepatoprotective activities of picroliv, curcumin, and ellagic acid compared to silymarin on carbon- tetrachloride-induced Liver toxicity in mice


CONCLUSION: This study supports the use of these active phytochemicals against toxic Liver injury, which may act by preventing lipid peroxidation, augmenting the antioxidant defense system or by regenerating the hepatocytes.



Ligularia fischeri


Protective Effects of Ligularia fischeri and Aronia melanocarpa Extracts on Alcoholic Liver Disease (In Vitro and In Vivo Study)


These results suggest that oral ingestion of LF and AM mixed composite is able to protect Liver against Alcohol-induced injury by increasing Alcohol metabolism activity and antioxidant system along with decreasing inflammatory responses.


Hepatoprotective effect of Handaeri-gomchi (Ligularia fischeri var. spiciformis Nakai) extract against chronic Alcohol-induced Liver damage in rats


CONCLUSION: LF extract has a protective effect against chronic Alcohol hepatotoxicity, suggesting it could be developed as a functional food or medicine for protection of Liver disease.


Ligularia fischeri extract attenuates Liver damage induced by chronic Alcohol intake


CONCLUSION: LF extract attenuated Liver damage induced by Alcoholic oxidative stress through inhibition of ROS generation, down-regulation of CYP2E1, and activation of hepatic antioxidative enzymes. Homeostasis of the antioxidative defence system in the Liver by LF extract mitigated hepatic disorder following chronic Alcohol intake.


UPLC-ESI-MS/MS profiling and Hepatoprotective activities of Stevia leaves extract, butanol fraction and stevioside against radiation-induced toxicity in rats


Stevioside is the major component of Stevia rebaudiana (Bertoni) leaves, family Asteraceae. UPLC-ESI-MS/MS analyses of leaves total methanol extract (TEx) and standardized butanol fraction (BF, 113.5 mg stevioside/g) were performed herein, revealing steviol glycosides, caffeoylquinic acid derivatives, flavonoids, and sesquiterpenoids. Their Hepatoprotective activities against radiation-induced toxicity were evaluated compared to pure stevioside.

Rats pretreatment with stevioside, TEx, and BF orally for 7 days before subjection to 6.5 Gy whole-body-gamma-irradiation reversed histopathological damages; improved Liver functions and restored depleted antioxidants. ALT and reduced-glutathione levels showed insignificant changes, compared to control, by (5.22%, 3.20%, 24.90%) and (−0.47%, −3.95%, −2.63%), respectively.

Glutathione-S-transferase, catalase, and MDA levels were significantly ameliorated. Liver tissue molecular profiling showed reduction in elevated TNF-α by 23.83%, 29.06%, 28.34%, respectively, and in NF-kB and COX-2 expression levels via immunohistochemical study. BF showed better Hepatoprotective activity than TEx which may be attributed to higher stevioside, flavonoids, and caffeoylquinic acid derivatives content.


Hepatoprotective effect of Ainsliaea acerifolia water extract on LPS/D-GalN-induced acute Liver injury in human HepG2 cells


These results suggest that AAWE treatment reduces hepatotoxicity by increasing antioxidant activities, reducing GGT, AST, and LDH activities, and inhibiting TNF-α secretion.


Hepatoprotective effect of fermented Chrysanthemum indicum L. water extract on ethanol-induced Liver injury in HepG2 cells


These results suggest that FCI can be useful for the development of an effective Hepatoprotective agent.



Ligusticum chuanxiong hort extract


Chemical constituents of Ligusticum chuanxiong and their anti-inflammation and Hepatoprotective activities


The results show that compounds 5, 6 and 7 showed excellent inhibition of NO production in LPS-induced RAW 264.7 cells stronger than curcumin, and compounds 5, 7 and 9 exhibited greater Hepatoprotective effect than that of bicyclol.


Chemical constituents of Ligusticum chuanxiong and their anti-inflammation and Hepatoprotective activities


Ligusticum chuanxiong Hort is a famous health promoting plant cultivated in China, and widely consumed due to its various curative effects.  The results show that compounds 5, 6 and 7 showed excellent inhibition of NO production in LPS-induced RAW 264.7 cells stronger than curcumin, and compounds 5, 7 and 9 exhibited greater Hepatoprotective effect than that of bicyclol.


The antioxidative and Hepatoprotective effects comparison of Chinese angelica polysaccharide(CAP)and selenizing CAP (sCAP) in CCl4 induced hepatic injury mice


These results indicate that selenylation modification can enhance the antioxidant and Hepatoprotective actions of Chinese angelica polysaccharide. A action mechanism of sCAP is suppressing the protein expression of MAPK signaling pathway.



Limonium tetragonum


The Standardized Extract of Limonium tetragonum Alleviates Chronic Alcoholic Liver Injury in C57Bl/6J Mice


CONCLUSION: Results provided direct experimental evidence for the Hepatoprotective effect of EALT in the NIAAA mouse model. Therapeutic attempts with the L. tetragonum extract might be useful in the management of Alcoholic Liver disease.

Hepatoprotective effects of Limonium tetragonum, edible medicinal halophyte growing near seashores


CONCLUSION: Collectively, the above results demonstrated that MELT suppressed HSCs proliferation but not in hepatocytes, implying that L. tetragonum may be useful candidates for developing therapeutic agents for the prevention and treatment of hepatic fibrosis.

The Extract of Limonium tetragonum Protected Liver against Acute Alcohol Toxicity by Enhancing Ethanol Metabolism and Antioxidant Enzyme Activities


this study suggests that EALT prevent hepatic injury induced by acute Alcohol which is likely related to its modulation on the Alcohol metabolism and antioxidant enzymes activities.


The Standardized Extract of Limonium tetragonum Alleviates Chronic Alcoholic Liver Injury in C57Bl/6J Mice


CONCLUSION: Results provided direct experimental evidence for the Hepatoprotective effect of EALT in the NIAAA mouse model. Therapeutic attempts with the L. tetragonum extract might be useful in the management of Alcoholic Liver disease.

Hepatoprotective Effects of the Cichorium intybus Root Extract against Alcohol-Induced Liver Injury in Experimental Rats


These results indicated that ingestion of Cii inhibited Alcohol-induced Liver damage, indicating Cii as a useful treatment for Alcohol-induced Liver injury.



Lithospermum erythrorhizon Sieb. et Zucc extract


Protective Effect of Lithospermum erythrorhizon on Galactosamine Induced Liver Injury


The present study was carried out to investigate the Hepatoprotective effect of water extract of Lithospermum erythrorhizon on acute hepatotoxicity induced in Sprague-Dawley (SD) rats. These results suggest that administration of water extract of Lithospermum erythrorhizon suppress or retard galactosamine induced acute Liver injury.


Screening of Hepatoprotective Activity of Medicinal Plant Extracts on Carbon Tetrachloride-induced Hepatotoxicity in Rats


The purpose of this study was to find the effect of 36 traditional medicinal plant species on Hepatoprotective activity screening. For this study, carbon tetrachloride intoxificated rats were used.  Test extracts were made with the traditional medicinal plants refluxed in 95% MeOH and orally administered to the rats. Sixteen species, such as Mentha arvensis, Sophora japonica, Benincasa hispida, Lonicera japonica (Lonicerae Flos), Agaricus blazei, Epimedium koreanum, Aralia continentalis, Lithospermum erythrorhizon, Cimicifuga foetida, Gastrodia elata, Sanguisorba officinalis, Cephalonoplos segetum, Bupleurum falcatum, Alisma plantago-aquatica var. orientale, Lonicera japonica (Lonicerae Folium) and Sinomenium acutum showed protective effect against increased serum alanine aminotransferase (ALT) and/or serum asparteate aminotransferase (AST) activities.


Antioxidant capacity and Hepatoprotective effect on Ethanol-injured Liver
cell of Lemon Juice concentrates and its comparison with commercial
Japanese Apricot Juice concentrates


Lemon is an important crop in Southern Taiwan, and its price sometimes decreases during harvest period. So, it is necessary to develop diversified products of lemon, such as lemon juice concentrate to utilize the overproduced lemons. To obtain lemon juice concentrate, lemon was processed by squeezing, filtering and evaporating, to obtain the sticky dark black lemon juice concentrate. Lemon concentrate was obtained by 10 hours evaporation followed by separation through solid phase extraction column.

Obtained lemon concentrate extract was compared with commercial Japanese apricot juice concentrate extract for its antioxidant capacity and Hepatoprotective activity on ethanol injured mouse hepatocytes FL83B. Antioxidant properties observed from lemon juice concentrate, which were DPPH radical scavenging activity, trolox equivalent antioxidant capacity, reducing power, ferric reducing ability of plasma and thiobarbituric acid reactive substances assay, was higher than Japanese apricot juice concentrate.

Moreover, this finding was also supported by higher total phenolic and flavonoid content found in lemon juice concentrate. Mumefural, compound reported to have bioactivity and found in Japanese apricot concentrate, was also found in lemon juice concentrate by using liquid chromatography-mass spectrometry determination. In the cell culture test, 600 μg/mL of lemon concentrate extract showed significant protective ability on ethanol injured cells, which was a little bit higher compared to Japanese apricot juice concentrate.

This ability may be related with antioxidant properties of lemon juice concentrate contributed by its compounds, which are phenolic, flavonoid and mumefural


Hepatoprotective Effects of Hovenia dulcis Extract on Acute and Chronic Liver Injuries induced by Alcohol and Carbon Tetrachloride


CONCLUSION: The results show that H. dulcis extract has Hepatoprotective effect in acute and chronic Alcohol-induced Liver injury and acute -induced Liver injury. These findings suggest that H. dulcis could be a potent Hepatoprotective agent.


Isolation, structure elucidation, antioxidant and Hepatoprotective effects of petroleum ether extract of Artemisia integrifolia L. against CCl4-induced Liver injury in rats


The aim of this study was to investigate the chemical constituents of petroleum ether extract from Artemisia integrifolia L (AIPEE) and to evaluate its Hepatoprotective potential and in vivo antioxidant effects. Six compounds, namely eugenol (1), linolenic acid (2), 6,7epoxylinolenic acid (3), linoleic acid (4), oleic acid (5) and hexadecanoic acid (6) were isolated from the AIPEE.

Oral administration of AIPEE significantly reduced carbon tetrachlorideinduced elevations in the levels of plasma markers of hepatic damage and lipid peroxidation. It also rescued histopathologic alterations observed in the Liver and levels of oxidative stress markers. AIPEE exhibited antioxidant and Hepatoprotective activities in vivowhich may be attributable to its chemical constituents such as five fatty acids and eugenol.



Lonicera japonica Thunb. extract


Novel flavonoids from Lonicera japonica flower buds and validation of their anti-hepatoma and Hepatoprotective activity in vitro studies


Lonicera japonica, a widely used traditional Chinese medicine, possessed antiviral, Hepatoprotective, anti-tumor and other activities. Meanwhile, L. japonica could be used as healthy food, cosmetics, and so on. Herein, four novel flavonoids, japoflavone A–D (23, 5, 12), together with ten known flavonoids, were isolated and identified on the basis of spectroscopic evidence from L. japonica. In addition, all isolates were assayed for their anti-hepatoma and Hepatoprotective activities in vitro. 5 and 8 showed significant anti-hepatoma activity in SMCC 7721 cell with IC50 values of 13.01 ± 2.62 and 16.69 ± 0.35 μg/ml; Compound 12 showed significant Hepatoprotective activity against H2O2-induced injury in SMCC 7721 and HepG 2 cells (p <  0.001).

Drop in the levels of catalase and superoxide dismutase caused by H2O2 were remarkably reversed in a dose-dependent manner after treatment with 12. This study provided a phytochemical evidence for further development and utilization of Lonicera japonica in health products.


Antioxidant Properties in Microbial Fermentation Products of Lonicera japonica Thunb. Extract


The purpose of this study is to investigate antioxidant properties in microbial fermentation products of Lonicera japonica Thunb extract. The bacterium Lactobacillus plantarum NHP1 was isolated from conventional fermented foods. Modern pharmacological studies show that Lonicera japonica Thunb and its active principles of wide pharmacological actions. For instance, they show a strong efficacy in antibacterial, anti-inflammatory, antiviral, anti-endotoxin, blood fat reducing, antipyretic, and antioxidant activities. The extract of Lonicera japonica Thunb was obtained by extracting dried Lonicera japonica Thunb using either hot water or 70% ethanol as a solvent.

Fermentation was performed in a 2L fermentor containing 1.2 L of extractat conditions of and 100 rpm for 48 hr. The amount of cholorogenic acid was in hot water extract. The total phenolic content (GAE, gallic acid equivalent) in hot water and 70% ethanol were GAE mg/g and GAE mg/g, respectively. After fermentation, the phenolic content increased to 30.2% in hot water and 12.9% in ethanol extract. In the same manner, flavonoid content increased to more than 75% regardless of extract solvent. ABTS (2,2-azino-bis-3-ethylbenzthiazoline-6-sulfonic acid) value noticeably increased to 50% after fermentation.


Lonicera japonica Thunb.: Ethnopharmacology, phytochemistry and pharmacology of an important traditional Chinese medicine


CONCLUSION: As an important traditional Chinese medicine, further studies on Lonicera japonica can lead to the development of new drugs and therapeutics for various diseases, and how to utilize it better should be paid more attentions.

Acute and subacute toxicity study of the ethanol extract from Lonicera japonica Thunb


The ethanol extract from the leaves of Lonicera japonica Thunb. was evaluated for acute and subacute toxicity. The single oral dose of the ethanol extract at 5000 mg/kg did not produce mortality or significant changes in the general behaviour and gross appearance of the internal organs of rats. In subacute toxicity study, the ethanol extract was administered orally at a dose of 1000 mg/kg/day for a period of 14 days. The satellite group was treated with the ethanol extract at the same dose and the same period and kept for another 14 days after treatment. There were no significant differences in the body and organ weights between the control and the treated group of both sexes. Hematological analysis and clinical blood chemistry revealed no toxicity effects of the extract. Pathologically, neither gross abnormalities nor histopathological changes were observed.



Luteolin


Dose- and time-dependent effects of luteolin on carbon tetrachloride-induced hepatotoxicity in mice


The Hepatoprotective effect of luteolin against CCl4 hepatotoxicity was higher in animals pretreated with luteolin for 2 consecutive days. This suggests that the protection might be due to induction of some adaptive mechanisms. The data indicate that luteolin could be effective in protecting mice from the hepatotoxicity produced by CCl4.


Protective effects of luteolin against acetaminophen-induced acute Liver failure in mouse


These results suggest the presence of anti-oxidative, anti-inflammatory and anti-ER stress properties of luteolin in response to acetaminophen-induced Liver injury in mice.


Protective effects of luteolin-7-glucoside against Liver injury caused by carbon tetrachloride in rats


These results obtained in vivo and in vitro suggest that LUTG had protective effects against hepatic oxidative injury induced by chemicals. Further studies on the pharmaceutical functions and immunological responses of LUTG may help in the development of a clinical application.


Antifibrotic effects of luteolin on hepatic stellate cells and Liver fibrosis by targeting AKT/mTOR/p70S6K and TGFβ/Smad signalling pathways


CONCLUSION: This study demonstrates that luteolin prevents the progression of Liver fibrosis through multiple mechanisms and indicates that luteolin has potential for effective treatment of Liver fibrosis.

Luteolin Alleviates Alcoholic Liver Disease Induced by Chronic and Binge Ethanol Feeding in Mice


Ethanol consumption can lead to hepatic steatosis that contributes to late-stage Liver diseases such as cirrhosis and hepatocellular carcinoma. In this study, we investigated the potential protective effect of a flavonoid, luteolin, on ethanol-induced fatty Liver development and Liver injury. Six-wk-old male C57BL/6 mice were divided into 3 groups: a control group; a group exposed to Alcohol by using a chronic and binge ethanol feeding protocol (EtOH); and a group that was administered daily 50 mg/kg of luteolin in addition to ethanol exposure (EtOH + Lut). A chronic and binge ethanol feeding protocol was used, including chronic ethanol consumption (1%, 2%, and 4% for 3 d, and 5% for 9 d) and a binge (30% ethanol) on the last day. Compared with the control group, the EtOH group had a significant elevation in serum concentrations of alanine aminotransferase (ALT) (561%), triglyceride (TG) (47%), and LDL cholesterol (95%), together with lipid accumulation in the Liver.

Compared with the EtOH group, the EtOH + Lut group had significant reductions in serum concentrations of ALT (43%), TG (22%), LDL cholesterol (52%), and lipid accumulation in the Liver. Ethanol elevated Liver expression of lipogenic genes including sterol regulatory element-binding protein 1c (Srebp1c) (560%), fatty acid synthase (Fasn) (190%), acetyl-CoA carboxylase (Acc) (48%), and stearoyl-CoA desaturase 1 (Scd1) (286%). Luteolin reduced ethanol-induced expression of these genes in the Liver: Srebp1c (79%), Fasn (80%), Acc (60%), and Scd1 (89%). In cultured hepatocytes, luteolin prevented Alcohol-induced lipid accumulation and increase in the expression of lipogenic genes.

The transcriptional activity of the master regulator of lipid synthesis, sterol regulatory element-binding protein (SREBP), was enhanced by ethanol treatment (160%) and reduced by luteolin administration (67%). In addition, ethanol-induced reduction of AMP-activated protein kinase and SREBP-1c phosphorylation was abrogated by luteolin. Collectively, our study indicates that luteolin is effective in ameliorating ethanol-induced hepatic steatosis and injury.


Modulatory effect of luteolin on redox homeostasis and inflammatory cytokines in a mouse model of Liver cancer


Liver cancer is one of the leading causes of cancer‑associated mortality worldwide. Due to changes in lifestyle and daily exposure to various chemicals, which may lead to chemical intoxication, Liver cancer has become a prominent disease in humans. Chemical‑induced carcinogenesis in experimental animals has become a reliable model for the investigation of Liver cancer‑associated biological alterations that may mimic human hepatic cancer. Liver cancer in BALB/c mice was induced by administering diethylnitrosamine (DN) in drinking water for 6 weeks. Luteolin (LUT) is a flavone that is found in the leaves of the majority of spice‑associated plants. In the present study, 20 µg/kg of body weight LUT was administered intraperitoneally every alternate day to treat the DN‑induced Liver cancer in mice.

LUT improved the host system by modifying the levels of α‑fetoprotein, enzymatic antioxidants, such as superoxide dismutase and catalase, marker enzymes, such as AST and ALT, and lipid peroxides in the plasma or Liver tissue. LUT also reduced the levels of glutathione and the inflammatory cytokines interleukin‑2 and interferon‑γ in the plasma or Liver tissue. These findings augmented the treatment against Liver cancer and supported the effective anticancer activity of LUT against DN‑induced Liver carcinogenesis in mice.



Lycium barbarum L. extract


Hepatoprotective effect of crude polysaccharide isolated from Lycium barbarum L. against Alcohol-induced oxidative damage involves Nrf2 signaling


In general, the results showed that the inhibition of Alcohol-caused Liver damage by LBPs is due at least in part to its antioxidant and antiapoptosis activity via Nrf2 signaling pathway.


Study on the synergistic protective effect of Lycium barbarum L. polysaccharides and zinc sulfate on chronic Alcoholic Liver injury in rats


The results showed that the combination of LBP and ZnSO4 could significantly decrease the levels of triglyceride (TG), total cholesterol (TC), tumor necrosis factor-α(TNF-ɑ), malondialdehyde (MDA), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and the activity of enzyme subtype 2E1 (CYP2E1). It also significantly increased the activities of total superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione peptide (GSH), and Alcohol dehydrogenase, effectively improved the Liver tissue lesion.

What is more, the combination of LBP and ZnSO4 had a synergistic effect on the remission of alcoholic  fatty Liver, and alleviated chronic alcoholic Liver injury by promoting lipid metabolism, inhibiting oxidative stress, controlling inflammatory responses, and regulating the expression and activity of Alcohol-metabolizing enzymes in rats.


Hepatoprotective effect of crude polysaccharide isolated from Lycium barbarum L. against Alcohol-induced oxidative damage involves Nrf2 signaling


In general, the results showed that the inhibition of Alcohol-caused Liver damage by LBPs is due at least in part to its antioxidant and antiapoptosis activity via Nrf2 signaling pathway.



Hepatoprotective effect of crude polysaccharide isolated from Lycium barbarum L. against Alcohol-induced oxidative damage involves Nrf2 signaling


In the present work, we investigated the effect of Lycium barbarum L. polysaccharides (LBPs) on L-02 cells exposed to Alcohol exploring the potential molecular mechanisms. Our results suggested that LBPs significantly prevented Alcohol-induced hepatotoxicity with dose-dependent effect, indicated by both cell viability and diagnostic indicators of Liver damage. Moreover, Alcohol induced excessive oxidative stress, as evidenced by an increase of the malondialdehyde level and reactive oxygen species production, while reducing antioxidant enzymes (T-SOD, CAT, and GPx) in Liver, were inhibited by administration of LBPs. Furthermore, LBPs reversed the cell apoptosis and increased the mitochondrial membrane potential in Alcohol-treated Liver cell.

Studies of underlying mechanisms revealed that LBPs increased expression levels of Nrf2 expression, which in turn blocked proapoptotic signaling events, restoring the balance between proapoptotic Bax and antiapoptotic Bcl-2 proteins, suppressing activities of cytochrome C (Cyto c), caspase-3, and caspase-9 in L-02 cells stimulation by ethanol. In general, the results showed that the inhibition of Alcohol-caused Liver damage by LBPs is due at least in part to its antioxidant and antiapoptosis activity via Nrf2 signaling pathway.


Hepatoprotective effect of plant polysaccharides from natural resources: A review of the mechanisms and structure-activity relationship


Liver injury is a common pathological process, which can result in fatty Liver, cirrhosis, fibrosis and even cancer. Polysaccharides isolated from plants have been regarded as an important resource of anti-hepatic lesion due to widely distributed in nature and low toxicity. In order to have a better understand of the protective mechanism on Liver function, a comprehensive review of research into plant polysaccharides during recent five years was performed. In total, 66 types of polysaccharides from 58 kinds of plant have shown Hepatoprotective effect through the pathological process of inflammation, apoptosis and oxidative stress by regulating NF-κB, JAK/STAT, TGF-β, PI3K/AKT, MAPK, caspase cascade, p53 and Nrf2-Keap1 pathways, lipid metabolism as well as cytochrome P450 enzymes.

Moreover, correlations between structure and Hepatoprotective activities of plant polysaccharides including primary structure, conformation properties, structural modification and content of uronic acid were also preliminarily explored. This review will provide a comprehensive perspective for better understanding the mechanism and development of polysaccharides against Liver injury.



Lysimachia christinae Hance extract


Hepatoprotective effects of Lysimachia christinae Hanceextracts on acute Liver injury induced by tripterygium glycosides in mice


CONCLUSION: This study for the first time demonstrates that L. christinae can protect against TG-induced acute Liver injury in dose-dependent manners in vivo, the potential mechanism may be related to inhibiting Liver oxidative stress injury, and the Hepatoprotective activity may be correlated with the contents of quercetin and kaempferol.


Protective effect of Lysimachia christinae against acute Alcohol
induced Liver injury in mice


Lysimachia christinae Hance (Primulaceae) is a medicinal plant. The present study was undertaken to investigate protection of L. christinae against acute Alcohol-induced Liver injury in mice, the related mechanism of oxidative stress and its Hepatoprotective chemical compound for the first time. Mice were orally administered Alcohol at 6 g/kg 2 h after a 75% ethanol extract of L. christinae (ET) (100, 200, 400 mg/kg), quercetin (2, 4, 8 mg/kg) isolated from L. christinae, or bifendate (150 mg/kg) for seven consecutive days by intragastric administration (i.g.) except the normal group. Serum and Liver tissue samples were collected 6 h after Alcohol administration and the amount of quercetin in ET was analyzed by high-performance liquid chromatography (HPLC) with a diode array detector (DAD).

The results showed that Alcohol-induced elevated serum alanine transferase (ALT) and aspartate transaminase (AST) activities were significantly reduced by ET (200, 400 mg/kg), quercetin (4, 8 mg/kg) and bifendate (150 mg/kg), respectively. Further analysis demonstrated that lipid peroxidation (LPO) levels significantly decreased, while glutathione amounts, glutathione-s transferase (GST), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) activities all increased in Livers of ET-, quercetin-, and bifendate-treated mice. Besides, amount of quercetin in ET was 1.03%. 

Taken together, our results indicate that L. christinae can protect against acute Alcohol– induced Liver injury in mice, the potential mechanism can be related to inhibiting Liver oxidative stress injury, and its main Hepatoprotective compound is quercetin, for the first time.


Lysimachia christinae Hance regresses preestablished cholesterol gallstone in mice


CONCLUSION: L. christinae can be considered as non-toxic. It showed prominent efficiency of eliminating preexisted CGS in mice and indicated a hypolipidaemic effect.



Mangiferin


Mangiferin ameliorates fatty Liver via modulation of autophagy and inflammation in high-fat-diet induced mice


Non-Alcoholic fatty Liver disease (NAFLD) is the most common Liver disease globally. The progression of NAFLD is complex and associated with inflammation, oxidative stress, autophagy, endoplasmic reticulum stress, and insulin resistance. Mangiferin, a natural C-glucosyl xanthone, has been reported to show multiple biological activities. The aim of this study was to investigate the therapeutic effect of mangiferin on NAFLD and the underlying molecular mechanism. We established a mouse model of NAFLD using a high-fat diet (HFD), and injected the mice with different doses of mangiferin (15, 30, and 60 mg/kg, intraperitoneal) for 12 weeks.

Liver tissue was assessed to evaluate changes in inflammatory responses, autophagy, and glycolipid metabolism. We found that mangiferin decreased body weight, as well as the levels of triglycerides and total cholesterol in plasma and the Liver. It also increased glucose tolerance in HFD-fed mice. In addition, mangiferin decreased inflammatory responses by inhibiting the activities of nuclear factor kappa B and c-Jun N-terminal kinase, regulated autophagy via the AMP-activated protein kinase/mechanistic target of rapamycin signaling pathway, and improved glycolipid metabolism via modulation of the insulin receptor substrate/phosphoinositide 3-kinase/protein kinase B signaling pathway.

This study demonstrated that mangiferin significantly ameliorates NAFLD development in HFD-fed mice by inhibiting inflammatory responses, activating autophagy, and improving glycolipid metabolism.


Mangiferin alleviates lipopolysaccharide and D-galactosamine-induced acute Liver injury by activating the Nrf2 pathway and inhibiting NLRP3 inflammasome activation


CONCLUSION: mangiferin protected against LPS/GalN-induced Liver injury by activating the Nrf2 pathway and inhibiting NLRP3 inflammasome activation.


Mangiferin Attenuates LPS/D-GalN-Induced Acute Liver Injury by Promoting HO-1 in Kupffer Cells


Acute Liver injury and its terminal phase, hepatic failure, trigger a series of complications, including hepatic encephalopathy, systematic inflammatory response syndrome, and multiorgan failure, with relatively high morbidity and mortality. Liver transplantation is the ultimate intervention, but the shortage of donor organs has limited clinical success. Mangiferin (MF), a xanthone glucoside, has been reported to have excellent anti-inflammatory efficacy. Here, a lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced acute Liver injury mouse model was established to investigate the protective role of MF and the underlying mechanisms of action.

Pretreatment with MF improved survival, decreased serum aminotransferase activities, and inhibited hepatic TNF-α production in LPS/D-GalN-challenged mice. Through Kupffer cell (KC) deletion by GdCl3 and KC adoptive transfer, KCs were confirmed to be involved in these beneficial effects of MF. MF reduced LPS-mediated TNF-α production via the suppression of the TLR4/NF-κB signaling pathway in vitro. MF promoted HO-1 expression, but the knockdown of HO-1 prevented TNF-α inhibition, suggesting that the damage-resistance effects of HO-1 occurred via the suppression of TNF-α synthesis.

When HO-1-silenced KCs were transferred to the Liver with KC deletion, the protective effect of MF against LPS/D-GalN-induced acute Liver injury was reduced, illustrating the role of KC-derived HO-1 in the anti-injury effects of MF. Collectively, MF attenuated acute Liver injury induced by LPS/D-GalN via the inhibition of TNF-α production by promoting KCs to upregulate HO-1 expression.


Mangiferin treatment inhibits hepatic expression of acyl-coenzyme A:diacylglycerol acyltransferase-2 in fructose-fed spontaneously hypertensive rats: a link to amelioration of fatty Liver


Mangiferin, a xanthone glucoside, and its associated traditional herbs have been demonstrated to improve abnormalities of lipid metabolism. However, its underlying mechanisms remain largely unclear. This study investigated the anti-steatotic effect of mangiferin in fructose-fed spontaneously hypertensive rat (SHR)s that have a mutation in sterol regulatory element binding protein (SREBP)-1. The results showed that co-administration of mangiferin (15 mg/kg, once daily, by oral gavage) over 7 weeks dramatically diminished fructose-induced increases in hepatic triglyceride content and Oil Red O-stained area in SHRs. However, blood pressure, fructose and chow intakes, white adipose tissue weight and metabolic parameters (plasma concentrations of glucose, insulin, triglyceride, total cholesterol and non-esterified fatty acids) were unaffected by mangiferin treatment.

Mechanistically, mangiferin treatment suppressed acyl-coenzyme A:diacylglycerol acyltransferase (DGAT)-2 expression at the mRNA and protein levels in the Liver.  In contrast, mangiferin treatment was without effect on hepatic mRNA and/or protein expression of SREBP-1/1c, carbohydrate response element binding protein, Liver pyruvate kinase, fatty acid synthase, acetyl-CoA carboxylase-1, stearoyl-CoA desaturase-1, DGAT-1, monoacyglycerol acyltransferase-2, microsomal triglyceride transfer protein, peroxisome proliferator-activated receptor-alpha, carnitine palmitoyltransferase-1 and acyl-CoA oxidase. Collectively, our results suggest that mangiferin treatment ameliorates fatty Liver in fructose-fed SHRs by inhibiting hepatic DGAT-2 that catalyzes the final step in triglyceride biosynthesis.

The anti-steatotic effect of mangiferin may occur independently of the hepatic signals associated with de novo fatty acid synthesis and oxidation.


Mangiferin protects against Alcoholic Liver injury via suppression of inflammation-induced adipose hyperlipolysis


Adipose dysfunction is closely associated with Alcoholic Liver disease. The impact of mangiferin on ethanol-induced Liver injury and the probable underlying molecular mechanism has not been sufficiently addressed. In the present study, mice were subjected to a chronic plus a single binge ethanol feeding to induce Liver injury.

In addition, the differentiated adipocytes from primary mouse adipocytes were isolated and used for the mechanism studies. Our study demonstrated that mangiferin protects against ethanol induced adipose hyperlipolysis by restoring PDE3B stability, which is associated with activating the AMPK/TBK1 signaling and suppressing the noncanonical NF-κB activation, leading to the reduction of free fatty acid release and the amelioration of ethanol-induced Liver injury.

Our findings identify that mangiferin ameliorates Alcoholic Liver injury via suppression of inflammation-induced adipose hyperlipolysis, suggesting that mangiferin might be a potential effective agent for the management of Alcoholic Liver injury.



Murraya koenigii


Combined Hepatoprotective Activity of Murraya koenigii and Phyllanthus niruri Extracts Against Paracetamol Induced Hepatotoxicity in Alcoholic Rats


The present study elucidated the Hepatoprotective activity of combination of Alcohol water extracts (AWEs) of Murraya koenigii (AWEMK) and Phyllanthus niruri (AWEPN) leaves against paracetamol induced hepatic damage in ethanol exposed rats. Phytochemical analysis of AWEs determined the presence of flavonoids and phenols, followed by high performance liquid chromatography determination of an important antioxidant tannic acid in AWEMK and a major bioactive lignan phyllanthin in AWEPN. Gas chromatography mass spectrometric analysis revealed the presence of carbazole alkaloids in AWEMK whereas AWEPN was found rich in sterols. Prolonged consumption of ethanol has been reported to enhance the hepatic damage caused by paracetamol overdose by induction of cytochrome P450 (CYP450) and depletion of reduced glutathione (GSH) in Alcohol abusers.

Oral administration of Alcohol (5 ml/kg/day) for three days followed by paracetamol (500 mg/kg, b.i.d.) for another 3 days produced Liver damage in rats as manifested by the significant (P < 0.01) rise in levels of Liver function tests and a marked increase in lipid peroxidation associated with significant reduction of the hepatic GSH and superoxide dismutase activity as compared with respective control values.

Post-treatment of rats with silymarin (200 mg/kg), AWEMK (500 mg/kg), AWEPN (500 mg/kg) and combination of AWEMK and AWEPN (250 mg/kg each) for one week significantly (P < 0.01) inhibited these biochemical alterations which were confirmed by histopathological examination of the Liver. Among all the treatment groups, the combination of extracts showed significant reversal of hepatic damage thus accentuating its Hepatoprotective potential and immense value for use as a hepatoprotectant.


Hepatoprotective ACTIVITY OF MURRAYA KOENIGII AGAINST ETHANOL-
INDUCED Liver TOXICITY MODEL IN EXPERIMENTAL ANIMALS


Murraya koenigii (Linn) Spreng (Indian curry leaf) is a highly valued culinary plant with the aqueous extract of its leaves which are reported to exhibit diverse biological activities. Considering free radical mechanism in hepatotoxicity, dietary antioxidants could provide protection in conditions including Alcoholic Liver disease. The objective of this study was to investigate its effects on biochemical markers of Liver function affected in diseased state. Two high doses of 1 g/kg and 2 g/kg were evaluated for its hepatoprotection on ethanol induced Liver toxicity in Wistar rats.

The aqueous extract showed potent antioxidant activity, and at both doses produced a significant increase in reduced glutathione levels with comparable reduction in serum glutamate pyruvate transaminase and alkaline phosphatase levels. Only 1 g/kg dose depleted malondialdehyde levels in comparison to ethanol. Histopathology of Liver samples confirmed the above findings.

The results suggested significant benefits of nutritive antioxidant compounds in M. koenigii contribute to its potential Hepatoprotective activity.


Hepatoprotective potential of polyphenol rich extract of Murraya koenigii L.: An in vivo study


The present study investigates Hepatoprotective effects of polyphenol rich Murraya koenigii L. (MK) hydro-ethanolic leaf extract in CCl4 treated hepatotoxic rats. Plasma markers of hepatic damage, lipid peroxidation levels, enzymatic, and non-enzymatic antioxidants in Liver and histopathological changes were investigated in control and treated rats. MK pretreated rats with different doses (200, 400 and 600 mg/kg body weight) showed significant decrement in activity levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total protein, and bilirubin. Also, MK treated rats recorded a dose dependent increment in hepatic super oxide dismutase, catalase, reduced glutathione and ascorbic acid and, a decrement in lipid peroxidation.

Microscopic evaluations of Liver revealed CCl4-induced lesions and related toxic manifestations that were minimal in Liver of rats pretreated with MK extract. These results demonstrate that hydro-ethanolic leaf extract of MK possesses Hepatoprotective potentials.


Hepatoprotective Sesquiterpenes and Rutinosides from Murraya koenigii (L.) Spreng


Three new sesquiterpenes (13) and two new rutinosides (4 and 5) along with 17 known compounds (622) were isolated from the leaves of Murraya koenigii (L.) Spreng. The new compounds were elucidated as (3R,5S,6R)-3,5,6-trihydroxy-1,1,5-trimethylcyclohexyl-8-butyn-9-one (1), (8E,9R)-ethyl-7-(3S,5R,6S)-3,6-dihydroxy-1,1,5-trimethylcyclohexyl-9-hydroxybut-8-enoate (2), (3R)-3-O-β-d-glucoside-6′-d-apiose-β-ionone (3), 4-O-β-d-rutinosyl-3-methoxyphenyl-1-propanone (4), and 1-O-β-d-rutinosyl-2(R)-ethyl-1-pentanol (5) based on their spectroscopic data. Compounds 1, 4, 5, 18, and 21 (10 μM) exhibited moderate Hepatoprotective activities.


Combined Hepatoprotective Activity of Murraya koenigii and Phyllanthus niruri Extracts Against Paracetamol Induced Hepatotoxicity in Alcoholic Rats


The present study elucidated the Hepatoprotective activity of combination of Alcohol water extracts (AWEs) of Murraya koenigii (AWEMK) and Phyllanthus niruri (AWEPN) leaves against paracetamol induced hepatic damage in ethanol exposed rats. Phytochemical analysis of AWEs determined the presence of flavonoids and phenols, followed by high performance liquid chromatography determination of an important antioxidant tannic acid in AWEMK and a major bioactive lignan phyllanthin in AWEPN. Gas chromatography mass spectrometric analysis revealed the presence of carbazole alkaloids in AWEMK whereas AWEPN was found rich in sterols. Prolonged consumption of ethanol has been reported to enhance the hepatic damage caused by paracetamol overdose by induction of cytochrome P450 (CYP450) and depletion of reduced glutathione (GSH) in Alcohol abusers.

Oral administration of Alcohol (5 ml/kg/day) for three days followed by paracetamol (500 mg/kg, b.i.d.) for another 3 days produced Liver damage in rats as manifested by the significant (P < 0.01) rise in levels of Liver function tests and a marked increase in lipid peroxidation associated with significant reduction of the hepatic GSH and superoxide dismutase activity as compared with respective control values. Post-treatment of rats with silymarin (200 mg/kg), AWEMK (500 mg/kg), AWEPN (500 mg/kg) and combination of AWEMK and AWEPN (250 mg/kg each) for one week significantly (P < 0.01) inhibited these biochemical alterations which were confirmed by histopathological examination of the Liver.

Among all the treatment groups, the combination of extracts showed significant reversal of hepatic damage thus accentuating its Hepatoprotective potential and immense value for use as a hepatoprotectant.



Naringenin


The flavonoid naringenin inhibits dimethylnitrosamine-induced Liver damage in rats


CONCLUSION: these results demonstrate that naringenin exhibited in vivo Hepatoprotective and anti-fibrogenic effects against DMN-induced Liver injury. It suggests that naringenin may be useful in preventing the development of hepatic fibrosis.


Naringenin-Loaded Nanoparticles Improve the Physicochemical Properties and the Hepatoprotective Effects of Naringenin in Orally-Administered Rats with CCl4-Induced Acute Liver Failure


CONCLUSION: NARN effectively improved the release of NAR which resulted in more Hepatoprotective effects mediated by its antioxidant and antiapoptotic properties. These observations also suggest that nanoformulation can improve the free drug’s bioactivity on oral administration.


Naringenin-Loaded Nanoparticles Improve the Physicochemical Properties and the Hepatoprotective Effects of Naringenin in Orally-Administered Rats with CCl4-Induced Acute Liver Failure


CONCLUSION: NARN effectively improved the release of NAR which resulted in more Hepatoprotective effects mediated by its antioxidant and antiapoptotic properties. These observations also suggest that nanoformulation can improve the free drug’s bioactivity on oral administration.


Influence of Naringenin on Oxytetracycline Mediated Oxidative Damage in Rat Liver


Our results demonstrate that naringenin exhibited antioxidant property and decrease the lipid peroxidation against oxytetracycline-induced oxidative stress in Liver.


Naringenin Regulates Doxorubicin-Induced Liver Dysfunction: Impact on Oxidative Stress and Inflammation


Doxorubicin (Dox) is an operational and largely used anticancer drug, used to treat an array of malignancies. Nonetheless, its beneficial use is constrained due to its renal and hepatotoxicity dose dependently. Numerous research findings favor the use of antioxidants may impact Dox-induced Liver injury/damage. In the current study, Wistar rats were given naringenin (50 and 100 mg/kg b.wt.) orally for 20 days as prophylactic dose, against the hepatotoxicity induced by single intraperitoneal injection of Dox (20 mg/kg b.wt.).

Potency of naringenin against the Liver damage caused by Dox was assessed by measuring malonyl aldehyde (MDA) as a by-product of lipid peroxidation, biochemical estimation of antioxidant enzyme system, reactive oxygen species (ROS) level, and inflammatory mediators. Naringenin-attenuated ROS production, ROS-induced lipid peroxidation, and replenished reduced antioxidant armory, namely, catalase (CAT), glutathione reductase (GR), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione (GSH). Naringenin similarly diminished expression of Cox-2 and levels of NF-κB and other inflammatory molecules induced by the Dox treatment.

Histology added further evidence to the defensive effects of naringenin on Dox-induced Liver damage. The outcomes of the current study reveal that oxidative stress and inflammation are meticulously linked with Dox-triggered damage, and naringenin illustrates the potential effect on Dox-induced hepatotoxicity probably through diminishing the oxidative stress and inflammation.


In vitro inhibition of dihydropyridine oxidation and aflatoxin B1 activation in human Liver microsomes by naringenin and other flavonoids


Recent in vivo studies in humans have shown a dramatic effect of grapefruit juice in blocking the oxidation of dihydropyridine calcium channel blockers. The flavonold naringin is the most abundant natural product specific for grapefruit and related citrus-the aglycone naringenin, known to be readily formed from naringin in humans, was found to inhibit the oxidation of the dlhydropyridines nifedipine and felodipine in human Liver microsomal preparations. These observations were of interest in light of the knowledge that the same human Liver cytochrome P450 (IIIA4) appears to be a major catalyst in both nifedipine oxidation and aflatoxin B1 activation.

Several flavones inhibited the in vitro activation of alfatoxin B1 in a system employing umuC gene activation due to DNA damage in Salmonlla typhimurium TA1535/pSK1OO2, with naringenin being as effective as any. The high concentration of derivatives of naringenin in certain citrus fruits may be of relevance to cancer chemoprevention involving those carcinogens that are activated by cytochrome P-450IIIA4.



Nelumbo nucifera Gaertn.


Hepatoprotective and antioxidant activity of ethanolic extracts of edible lotus (Nelumbo nucifera Gaertn.) leaves


The results showed the Hepatoprotective activity of lotus leaf extract (LLE) at doses of 300 and 500 mg/kg and in vivo antioxidant activity at 100 mg/kg that was comparable with that of a standard treatment comprising 100 mg/kg of silymarin, a known Hepatoprotective drug. These data were supplemented with histopathological studies of rat Liver sections. The main flavonoids and phenolic compounds of LLE were analysed by HPLC-DAD-ESI/MS methods.

Six of the compounds detected were tentatively characterised, one as catechin glycoside and five as flavonoid glycoside derivatives: miricitrin-3-O-glucoside, hyperin, isoquercitrin, quercetin-3-O-rhamnoside and astragalin.


Hepatoprotective Activity of Nelumbo nucifera Gaertn. Seedpod Extract Attenuated Acetaminophen-Induced Hepatotoxicity


The aim is to investigate the effect of lotus (Nelumbo nucifera Gaertn.) seedpod extract (LSE) on acetaminophen (APAP)-induced hepatotoxicity. LSE is rich in polyphenols and has potent antioxidant capacity. APAP is a commonly used analgesic, while APAP overdose is the main reason for drug toxicity in the Liver. Until now, there has been no in vitro test of LSE in drug-induced hepatotoxicity responses. LSEs were used to evaluate the effect on APAP-induced cytotoxicity, ROS level, apoptotic rate, and molecule mechanisms. The co-treatment of APAP and LSEs elevated the survival rate and decreased intracellular ROS levels on HepG2 cells. LSEs treatment could significantly reduce APAP-induced HepG2 apoptosis assessed by DAPI and Annexin V/PI. The further molecule mechanisms indicated that LSEs decreased Fas/FasL binding and reduced Bax and tBid to restore mitochondrial structure and subsequently suppress downstream apoptosis cascade activation.

These declines in COX-2, NF-κB, and iNOS levels were observed in co-treatment APAP and LSEs, which indicated that LSEs could ameliorate APAP-induced inflammation. LSE protected APAP-induced apoptosis by preventing extrinsic, intrinsic, and JNK-mediated pathways. In addition, the restoration of mitochondria and inflammatory suppression in LSEs treatments indicated that LSEs could decrease oxidative stress induced by toxic APAP. Therefore, LSE could be a novel therapeutic option for an antidote against overdose of APAP.


Hepatoprotective activity of aerial parts of Nelumbo nucifera Gaertn. in Paracetamol and Isoniazid-Rifampicine induced hepatotoxicity in rats


The results suggest that the ethanolic and aqueous extracts (NNE and NNA) of Nelumbo nucifera aerial parts possess significant Hepatoprotective activity.


Improvement for High Fat Diet-Induced Hepatic Injuries and Oxidative Stress by Flavonoid-Enriched Extract from Nelumbo nucifera Leaf


These results suggested that the flavonoid-enriched N. nucifera leaf extract supplement may significantly improve the high fat diet-induced abnormal blood lipids and Liver damage as significantly as the common drugs.

Consequently, it is suggested that the flavonoid-enriched N. nucifera leaf extract supplement is beneficial for the improvement of lipid metabolisms and the alleviation of Liver damage in high fat diet treatment.


Hepatoprotective Activity of Nelumbo nucifera Gaertn. Seedpod Extract Attenuated Acetaminophen-Induced Hepatotoxicity


LSE protected APAP-induced apoptosis by preventing extrinsic, intrinsic, and JNK-mediated pathways. In addition, the restoration of mitochondria and inflammatory suppression in LSEs treatments indicated that LSEs could decrease oxidative stress induced by toxic APAP. Therefore, LSE could be a novel therapeutic option for an antidote against overdose of APAP.



neoandrographolide


High-Performance Thin-Layer Chromatographic analysis of Hepatoprotective diterpenoids from Andrographis paniculata


A rapid and simple high-performance thin-layer chromatographic (HPTLC) method has been developed for the simultaneous quantitative estimation of the biologically active diterpenoids, 14-deoxy-11,12-didehydroandrographolide, andrographolide, neoandrographolide and andrographiside in Andrographis paniculata.

The assay combines the isolation and separation of andrographolide derivatives on silica gel 60 F254 HPTLC plates with spot visualization and scanning at 540 nm. Methanol was found to be the most appropriate solvent for the exhaustive extraction of andrographolide derivatives.


Recent advances in plant Hepatoprotectives: A chemical and biological profile of some important leads


Medicinal plants have been traditionally used for treating Liver diseases since centuries. Several leads from plant sources have been found as potential Hepatoprotective agents with diverse chemical structures. Although, a big list of Hepatoprotective phytomolecules was reported in the scientific literature, only a few were potent against various types of Liver damages.

Of which, silymarin, andrographolide, neoandrographolide, curcumin, picroside, kutkoside, phyllanthin, hypophyllanthin, and glycyrrhizin have largely attracted the scientific community. This review focuses discussion on the chemistry, biological activity, mode of action, toxicity, and future prospects of these leads.


Medicinal plants with Hepatoprotective activity in Iranian folk medicine


There are a number of medicinal combinations in the Iranian traditional medicine which are commonly used as tonic for Liver. In this review, we have introduced some medicinal plants that are used mainly for the treatment of Liver disorders in Iranian folk medicine, with focus on their Hepatoprotective effects particularly against CC14 agent. In this study, online databases including Web of Science, PubMed, Scopus, and Science Direct were searched for papers published from January 1970 to December 2013. Search terms consisted of medicinal plants, traditional medicine, folk medicine, Hepatoprotective, Iran, Liver, therapeutic uses, compounds, antioxidant, CC14, anti-inflammatory, and antihepatotoxic, hepatitis, alone or in combination.

Allium hirtifolium Boiss., Apium graveolens L., Cynara scolymus, Berberis vulgaris L., Calendula officinalis, Nigella sativa L., Taraxacum officinale, Tragopogon porrifolius, Prangos ferulacea L., Allium sativum, Marrubium vulgare, Ammi majus L., Citrullus lanatus Thunb, Agrimonia eupatoria L. and Prunus armeniaca L. are some of the medicinal plants that have been used for the treatment of Liver disorders in Iranian folk medicine. Out of several leads obtained from plants containing potential Hepatoprotective agents, silymarin, β-sitosterol, betalain, neoandrographolide, phyllanthin, andrographolide, curcumin, picroside, hypophyllanthin, kutkoside, and glycyrrhizin have been demonstrated to have potent Hepatoprotective properties.

Despite encouraging data on possibility of new discoveries in the near future, the evidence on treating viral hepatitis or other chronic Liver diseases by herbal medications is not adequate.


High-Performance Thin-Layer Chromatographic analysis of Hepatoprotective diterpenoids from Andrographis paniculata


A rapid and simple high-performance thin-layer chromatographic (HPTLC) method has been developed for the simultaneous quantitative estimation of the biologically active diterpenoids, 14-deoxy-11,12-didehydroandrographolide, andrographolide, neoandrographolide and andrographiside in Andrographis paniculata.

The assay combines the isolation and separation of andrographolide derivatives on silica gel 60 F254 HPTLC plates with spot visualization and scanning at 540 nm. Methanol was found to be the most appropriate solvent for the exhaustive extraction of andrographolide derivatives.


Hepatoprotective Diterpenoids Isolated from Andrographis paniculata


Andrographis paniculata (Burm.f.) Nees (Acanthaceae), a plant widely used as traditional herbal medicine in many countries, has drawn attention of the researchers in recent years. Its major constituents are diterpenoids and flavonoids. This article reviews the anti-hepatotoxic effects of A. paniculata extract and derivative compounds, such as andrographolide, the major active compound, most studied for its bioactivities. Neoandrographolide shows anti-inflammatory and anti-hepatoxic properties. 14-deoxy-11,12-didehydroandrographolide and 14-deoxyabdrographolide have immunostimulatory, anti-atherosclerotic, and anti-hepatotoxic activities. The Hepatoprotective activities include 1) inhibiting carbontetrachloride (CCl4), tert-butylhydroperoxide (t-BHP)-induced hepatic toxicity; 2) acting as cytochrome P450 enzymes (CYPs) inducers; 3) modulating glutathione (GSH) content; 4) influence glutathione S-transferase (GSTP) activity and phosphatidylinositol-3-kinase/Akt (PI3k/Akt) pathway; 5) synergistic effect with anti-cancer drugs induced apoptosis contributing to the bioactivities of A. paniculata extracts and isolated bioactive compounds. The articles reviewed suggest that the above compounds could be candidates for research and development as potential Hepatoprotective drugs.


Lead finding from medicinal plants with Hepatoprotective potentials


CONCLUSION: An attempt has been made through this article to review the most potential medicinal plants with pharmacologically established Hepatoprotective activity. Further, this article highlights their phytochemical profile and finds the effective leads from natural resources for the desired therapeutic benefit.


Nepenthes khasiana Hook. F


Mitotic Chromosome Studies in Nepenthes khasiana, An Endemic Insectivorous Plant of Northeast India


Chromosome counts were carried out in root tip cells of Nepenthes khasiana (Nepenthaceae), a threatened insectivorous plant of Northeast India. N. khasiana has become threatened in its natural habitat due to overexploitation for its medicinal uses as well as its ornamental importance. Plantlets of Nepenthes khasiana collected from Jarain, Meghalaya were cytologically analyzed. All the root tip cells analyzed showed the chromosomenumber of 2n=80 without any variations. Karyomorphological studies were not plausible in this species due to the relatively small size of the chromosomes.


Endophytic fungal diversity of endemic carnivorous plant Nepenthes khasiana in Meghalaya, India


So, with the help of the present finding, we conclude that the distribution of fungal endophytes and their % colonization frequencies vary within different tissues of the host plant and thus, this confirms tissue specificity nature of endophytic fungi.


Pollen morphology of Nepenthes khasiana Hook. f. (Nepenthaceae), an endemic insectivorous plant from India


The pollen morphology of Nepenthes khasiana (the pitcher plant) from India, was investigated using both light microscopy and scanning electron microscopy. This was to investigate fine details that may contribute to the taxonomic characterisation of species, as well as to utilise the knowledge of its morphology in order to correlate it with Bornean Nepenthes species. The size of the tetrad is the defining feature. The pollen grain is non-aperturate, the sexine is spinuliferous and thicker than the nexine. The study indicates that the species is similar in shape, aperture and ornamentation, and can be discriminated by the size of the tetrad, the length of the spines and the exine thickness. The size of the tetrad (30.7 μm) is closer to two Bornean species such as N. rafflesiana and N. mirabilis (30.5 and 31.0 μm respectively). These observations will be helpful in morphotaxonomy for accurate identification. This will help in finding these taxa from modern and sub-surface soils in order to study the present status of pollen preservation and decipher the palaeovegetation and past climate of the region.



Onitin


Hepatoprotective and free radical scavenging activities of phenolic petrosins and flavonoids isolated from Equisetum arvense


Hepatoprotective activity-guided fractionation of the MeOH extract of Equisetum arvense L. (Equisetaceae) resulted in the isolation of two phenolic petrosins, onitin (1) and onitin-9-O-glucoside (2), along with four flavonoids, apigenin (3), luteolin (4), kaempferol-3-O-glucoside (5), and quercetin-3-O-glucoside (6). Among these, compounds 1 and 4 exhibited Hepatoprotective activities on tacrine-induced cytotoxicity in human Liver-derived Hep G2 cells, displaying EC50 values of 85.8 ± 9.3 μM and 20.2 ± 1.4 μM, respectively. Silybin, used as a positive control, showed the EC50 value of 69.0 ± 3.3 μM. Compounds 1 and 4 also showed superoxide scavenging effects (IC50 = 35.3 ± 0.2 μM and 5.9 ± 0.3 μM, respectively) and DPPH free radical scavenging effect (IC50 of 35.8 ± 0.4 μM and 22.7 ± 2.8 μM, respectively). These results support the use of this plant for the treatment of hepatitis in oriental traditional medicine.

 


Review on plants having Hepatoprotective activity


Liver breakdown and neutralizes an array of substances that enter our body. Natural substances like hormones are also broken down by the Liver. Drugs like Nimesulide causes hepatic failure as a side effect.


Extraction, identification, fractionation and isolation of phenolic compounds in plants with Hepatoprotective effects


The Liver is one of the most important organs of human body, being involved in several vital functions and regulation of physiological processes. Given its pivotal role in the excretion of waste metabolites and drugs detoxification, the Liver is often subjected to oxidative stress that leads to lipid peroxidation and severe cellular damage. The conventional treatments of Liver diseases such as cirrhosis, fatty Liver and chronic hepatitis are frequently inadequate due to side effects caused by hepatotoxic chemical drugs. To overcome this problematic paradox, medicinal plants, owing to their natural richness in phenolic compounds, have been intensively exploited concerning their extracts and fraction composition in order to find bioactive compounds that could be isolated and applied in the treatment of Liver ailments. The present review aimed to collect the main results of recent studies carried out in this field and systematize the information for a better understanding of the Hepatoprotective capacity of medicinal plants in in vitro and in vivo systems. Generally, the assessed plant extracts revealed good Hepatoprotective properties, justifying the fractionation and further isolation of phenolic compounds from different parts of the plant. Twenty-five phenolic compounds, including flavonoids, lignan compounds, phenolic acids and other phenolic compounds, have been isolated and identified, and proved to be effective in the prevention and/or treatment of chemically induced Liver damage. In this perspective, the use of medicinal plant extracts, fractions and phenolic compounds seems to be a promising strategy to avoid side effects caused by hepatotoxic chemicals.


Revisiting Hepatoprotective Natural Products from a Biological Point of View


Naturally occurring small molecules from plants, microorganisms, and animals allow the design of drugs that can be beneficial in virtually all kinds of human diseases. Liver diseases with diverse etiologies such as viral infection, chemical intoxication, and metabolic fat accumulation are one of the leading causes of human mortality. Unfortunately, however, there are few effective drugs available capable of stopping or reversing the progress of Liver disease. Here, we discuss the current advances in developing Hepatoprotective natural products for several arrays of Liver disease pathogenesis.



ornithine aspartate


Hepatoprotection by L-Ornithine L-Aspartate in Non-Alcoholic Fatty Liver Disease

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