CCl4-induced Hepatic Damage In Rats Research Articles

Phenolic Content, Antioxidant and Hepatoprotective Activities of Sabah Hoya coronaria Blume

A common challenge that regularly results from oxidative stress is hepatic damage. This condition is characterised by a gradual progression from steatosis to chronic hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. The study proposed to assess the antioxidant activity and efficacy of Hoya coronaria aqueous extract in preventing CCl4-induced hepatic damage in rats. The DPPH technique was used in the study to assess the extract's antioxidant properties. The rats received dosages of 125 and 250 mg/kg body weight of H. coronaria extract for 14 days, followed by CCl4 exposure. After two weeks, the rats were euthanised for analysis. The results indicated that the extract showed significant antioxidant potential and decreased the impact of CCl4 on hepatic damage markers such as serum aspartate transaminase and alanine transaminase. Moreover, it increased hepatic reduced glutathione and various antioxidant enzymes while reducing malondialdehyde formation induced by CCl4. Additionally, the histopathological analysis demonstrated that H. coronaria extract protected the liver against fatty degeneration and necrosis induced by CCl4 toxicity. These outcomes suggest that H. coronaria extract could be used to prevent ROS-related hepatic damage.

Protective effect of Ceiba pentandra (L) Gaertn on CCl4-induced oxidative stress and liver damage in rats

BackgroundCeiba pentandra (L.) Gaertn, popularly known as the white silk-cotton tree and popularly used in Chinese and Indian traditional medicine. The bark is used to treat diarrhea, pain, fever, cardiac problems, asthma, and gastrointestinal problems. The present study aimed to evaluate the hepatoprotective and antioxidant effects of ethanol extract of C. pentandra bark (EECP-BK) against CCl4-induced hepatic damage in rats. MethodsPreliminary phytochemical analysis was performed to identify the bioactive compounds. CCl4 (40 mM) induced enzymatic changes at HepG2 cells were adopted for the in-vitro model. HepG2 cells were pretreated with EECP-BK (25, 50, 100, and 200 µg/ml) and standard (silymarin 12.5 µg/ml) respectively. Rat model of CCl4-induced liver damage for adopted for the in-vivo model. Rats were pretreated orally with EECP-BK 200 & 400 mg/kg and standard (silymarin 100 mg/kg) for 7 days. Rats were injected with 1 ml/kg of 50% CCl4 on day 8 to induce hepatic damage and were observed for antioxidant levels and serum biomarkers. In addition, in-silico studies have been performed to explore the binding properties of compounds from EECP-BK with tumor necrosis factor-alpha converting enzyme (TACE) targeting hepatic inflammation ResultsThe phytochemical analysis confirmed the presence of glycoside, steroids, phenols, tannins, and saponins. EECP-BK 200 µg/ml showed the highest protection against CCl4 in HepG2 cells. Similarly, silymarin 12.5 µg/ml showed good protection against CCl4. In rats, EECP-BK up to 2000 mg/kg did produce any toxic signs or mortality. CCl4 injection in rats showed elevated liver enzymatic and bilirubin levels and causes liver damage. It also decreased the SOD, CAT, and GSH levels. Pre-treatment with EECP-BK 400 mg/kg showed a significant reduction in SGPT, SGOT, ALP, and total bilirubin levels and increased SOD, CAT, and GSH levels. Similar results were observed with, silymarin treatment also. Furthermore, EECP-BK showed protection over hepatocyte necrosis induced by CCl4 in rats which is evident by histopathology. Molecular docking studies revealed that acacetin 7-rutinoside binds favorably with the active site of TACE with a binding affinity of -8.8 kJ/mol. ConclusionOur findings supported the antioxidative capability of EECP-BK by showing that it protected the liver from CCl4-induced hepatic damage. Additional research is needed to determine its safety profile and to find its molecular mechanism for therapeutic application.

Hepatoprotective and Anti-Oxidant Study of Mukta Bhasma (Calx of Cultured Pearls) Against CCl4-Induced Hepatic Damage in Rats (In-Vivo).

Mukta Bhasma (MB) is a traditional Ayurvedic preparation for upper respiratory and lower respiratory conditions, eye disorders, powerful cardiac tonic, immune-regulator, mood elevator and known to promote strength, intellect and semen production. Mukta bhasma is prepared using direct heat as a media of transformation. Mukta Bhasma was evaluated for its hepatoprotective and antioxidant activities against Carbon tetrachloride (CCl4) induced liver damage in wistar albino rats. Mukta Bhasma (100mg/kg, 200mg/kg and 300mg/kg) was administered to experimental rats for 10 days. Silymarin (25mg/kg) was given as the standard drug. The hepatoprotective activity was assessed using various serum biochemical parameters like (SGOT), (SGPT), Total and Direct bilirubin (TB and DB), Alkaline phosphatase (ALP), Total Triglycerides (TG) and Total Cholesterol (TC). Lipid peroxidation (LPO), Reduced Glutathione (GSH) and Catalase (CAT) were determined to explain the antioxidant activity of Mukta Bhasma. The substantially elevated levels of SGOT, SGPT, TB and DB, ALP, TG and TC due to CCl4 treatment were restored towards near normal by Mukta bhasma (MB) of 200mg/kg dose. Administration of MB 200mg has shown significant reduction in the biochemical parameters like SGOT, SGPT, ALP, Bilirubin, Total cholesterol and Total triglycerides with significance of p<0.001 in all the parameters when compared to CCl4 group. Also, they were near to the standard Silymarin group. Mukta bhasma 200mg has shown significant (p<0.001) reduction in the LPO level, increase in CAT and GSH representing significant antioxidant activity of Mukta bhasma. The histopathological study showed reduction in fatty degeneration of liver in MB 200mg/kg body weight. Thus, results revealed that Mukta bhasma afford significant hepatoprotective and antioxidant effects in CCl4 induced hepatic damage.

Preparation and Characterization of Silymarin-Conjugated Gold Nanoparticles with Enhanced Anti-Fibrotic Therapeutic Effects against Hepatic Fibrosis in Rats: Role of MicroRNAs as Molecular Targets.

Background: The main obstacles of silymarin (SIL) application in liver diseases are its low bioavailability, elevated metabolism, rapid excretion in bile and urine, and inefficient intestinal resorption. The study aimed to synthesize and characterize silymarin-conjugated gold nanoparticles (SGNPs) formulation to improve SIL bioavailability and release for potentiating its antifibrotic action. Methods: Both SGNPs and gold nanoparticles (GNPs) were prepared and characterized using standard characterization techniques. The improved formulation was assessed for in vitro drug release study and in vivo study on rats using CCl4 induced hepatic fibrosis model. SIL, SGNPs, and GNPs were administered by oral gavage daily for 30 days. At the end of the study, rats underwent anesthesia and were sacrificed, serum samples were collected for biochemical analysis. Liver tissues were collected to measure the genes and microRNAs (miRNAs) expressions. Also, histopathological and immunohistochemistry (IHC) examinations of hepatic tissues supported these results. Results: The successful formation and conjugation of SGNPs were confirmed by measurements methods. The synthesized nanohybrid SGNPs showed significant antifibrotic therapeutic action against CCl4-induced hepatic damage in rats, and preserved normal body weight, liver weight, liver index values, retained normal hepatic functions, lowered inflammatory markers, declined lipid peroxidation, and activated the antioxidant pathway nuclear factor erythroid-2-related factor 2 (NRF2). The antifibrotic activities of SGNPs mediated through enhancing the hepatic expression of the protective miRNAs; miR-22, miR-29c, and miR-219a which results in suppressed expression of the main fibrosis mediators; TGFβR1, COL3A1, and TGFβR2, respectively. The histopathology and IHC analysis confirmed the anti-fibrotic effects of SGNPs. Conclusions: The successful synthesis of SGNPs with sizes ranging from 16 up to 20 nm and entrapment efficiency and loading capacity 96% and 38.69%, respectively. In vivo studies revealed that the obtained nano-formulation of SIL boosted its anti-fibrotic effects.

Hepatoprotective Activity of Martynia annua L. Leaves Against CCl4-induced Hepatic Damage in Rats

Hepatoprotective Activity of Martynia annua L. Leaves Against CCl4-induced Hepatic Damage in Rats

Dietary fiber of psyllium husk (Plantago ovata) as a potential antioxidant and hepatoprotective agent against CCl4-induced hepatic damage in rats

The antioxidant and hepatoprotective activities of psyllium husk mucilage (PHM) were studied in carbon tetrachloride induced hepatotoxicity rat model. Subsequently, biochemical hepatic parameters were evaluated alongside the assessment of glutathione reductase, superoxide dismutase and catalase potentials in the rats’ liver tissue. Moreover, histopathology and western blot techniques were employed for the assessment of TNF-α protein expression level in the current study. Our results demonstrated that oral administration of PHM at 100 mg/kg in rats significantly ameliorated the deleterious effects induced by CCl4 on the rats’ livers. This was manifested by the substantial results obtained from in vitro antioxidant assays, the reestablishment of the level of different liver biomarkers, the fortification of the liver architecture to close typical and reduction of the TNF-α expression level in comparison to that of CCl4- intoxicated control group. The current approach highlighted the special role of the dietary fiber of psyllium husk, as a promising natural hepatoprotective agent.

Antioxidant and hepatoprotective effects of Artemisia dracunculus against CCl4-induced hepatotoxicity in rats.

The present study was conducted to investigate the antioxidant and hepatoprotective activity of the hydro-alcoholic extract of aerial parts of Artemisiadracunculus (HAAD) against CCl4-induced hepatotoxicity in rats. The antioxidant activity was evaluated by reducing power, 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and 2, 20-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays. Rats were pre-treated with either 50, 100, and 200 mg/kg of HAAD or silymarin (100 mg/kg; served as the positive control group) for 15 days and they received a single dose of CCl4 on the last day. Hepatoprotective effects were investigated by assessment of serum biochemical enzymes such as alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), total protein (TP), total bilirubin (TB), malondialdehyde (MDA), and antioxidant enzymes (SOD, CAT, GST and GSH), along with histopathological studies. Total phenolic content was 197.22±3.73 mg gallic acid equivalent/g HAAD dry weight. HAAD indicated powerful activity in FRAP, DPPH and ABTS tests. Acute toxicity study showed that the extract had an LD50 of >5000 mg/kg. Oral treatment with HAAD exhibited a significant decrease in the levels of AST, ALT, ALP and TB and an increase in the level of TP. The extract significantly diminished MDA levels. The activities of the antioxidant enzymes were significantly augmented in rats pretreated with HAAD 200 mg/kg. Histopathological examination demonstrated lower liver damage in HAAD-treated groups as compared to CCl4 groups. Our findings indicated hepatoprotective effects of the hydro-alcoholic extract of A. dracunculus on CCl4-induced hepatic damage in rats and suggested that these effects may be produced by reducing oxidative stress.

Protective Effect of <i>Alpina nigra</i> Leaves Extract in Mouse Liver Injury Induced by Carbon Tetrachloride

The present study was aimed to evaluate the hepatoprotective activity of methanol extract against carbon tetrachloride (CCl4) induced hepatic damage in rats. CCl4 caused liver damage in rats manifested by significant rise in serum enzyme levels. To examine the effect of the extract male albino rats were used and extract was administered orally at a dose of 300 mg/kg once daily. The results obtained showed that there were reductions in the activities of serum SGOT, SGPT, ALP, total protein, total bilirubin from 97.67±1.78, 275.67±2.86, 934 ± 1.41, 1.13±0.227 and 7.50±0.707 in animals treated with toxic doses of CCl4 to 78.33±1.08, 53±1.41, 870±0.707, 0.67±0.04 and 6.47±0.356 in animal treated with extract before CCl4 intoxication. The extract could also repair the abnormal lipid profile. From these results, it is concluded that methanol extract of Alpina nigra leaves has hepatoprotective activity in CCl4-induced hepatic damage in rats.

Hepatoprotective effect of Rosa canina fruit extract against carbon tetrachloride induced hepatotoxicity in rat.

The present study was conducted to investigate the hepatoprotective activity of hydro-ethanolic fruit extract of Rosa canina (R. canina) against carbon tetrachloride (CCl4)-induced hepatotoxicity in rats. Male Wistar albino rats were randomly divided into six groups of 8 animals of each, including control, toxic (CCl4), R. canina 250, 500, and 750 mg/kg + CCl4 and R. canina 750 mg/kg alone. R. canina (p.o., daily) and CCl4 (1 ml/kg twice a week, 50% v/v in olive oil, i.p.) were administered to animals for six weeks. Serum analysis was performed to assay the levels of aspartate aminotransferase (AST), alanine amino transaminase (ALT), alkaline phosphatase (ALP), albumin (ALB), total protein (TP) and malondialdehyde (MDA). Biochemical observations were also supplemented with histopathological examination (haematoxylin and eosin staining) of liver section. Hepatotoxicity was evidenced by considerable increase in serum levels of AST, ALT, ALP, and lipid peroxidation (MDA) and decrease in levels of ALB and TP. Injection of CCL4 also induced congestion in central vein, and lymphocyte infiltration. Treatment with hydro-alcoholic fruit extract of R. canina at doses of 500 and 750 mg/kg significantly reduced CCl4-elevated levels of ALT, AST, ALP and MDA (p<0.01). The extract also increased the serum levels of ALB and TP compared to CCl4 group (p<0.01) at the indicated dose Histopathological studies supported the biochemical finding. Our finding indicated hepatoprotective effects of the hydro-alcoholic fruit extract of R. canina on CCl4-induced hepatic damage in rats and suggested that these effects may be produced through reducing oxidative stress.

Hepatoprotective Effect of the Aqueous Extract of Simarouba amara Aublet (Simaroubaceae) Stem Bark against Carbon Tetrachloride (CCl4)-Induced Hepatic Damage in Rats

Simarouba amara stem bark decoction has been traditionally used in Brazil to treat malaria, inflammation, fever, abdominal pain, diarrhea, wounds and as a tonic. In this study, we investigate the hepatoprotective effects of the aqueous extract of S. amara stem bark (SAAE) on CCl4-induced hepatic damage in rats. SAAE was evaluated by high performance liquid chromatography. The animals were divided into six groups (n = 6/group). Groups I (vehicle—corn oil), II (control-CCl4), III, IV, V and VI were pretreated during 10 consecutive days, once a day p.o, with Legalon® 50 mg/kg b.w, SAAE at doses 100, 250 and 500 mg/kg b.w, respectively. The hepatotoxicity was induced on 11th day with 2 mL/kg of 20% CCl4 solution. 24 h after injury, the blood samples were collected and their livers were removed to biochemical and immunohistochemical analyzes. The SAAE decreased the levels of liver markers and lipid peroxidation in all doses and increased the catalase levels at doses 250 and 500 mg/kg. Immunohistochemical results suggested hepatocyte proliferation in all doses. These results may be related to catechins present in SAAE. Thus, SAAE prevented the oxidative damage at the same time that increased regenerative and reparative capacities of the liver.

Hepatoprotective effects of Lycium chinense Miller fruit and its constituent betaine in CCl4-induced hepatic damage in rats

The hepatoprotective activities of Lycium chinense Miller (LC) fruit extract and its component betaine were investigated under carbon tetrachloride (CCl4)-induced hepatotoxicity in rats. The treatment of LC fruit extract significantly suppressed the increase of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the sera of CCl4 injured rats, and restored the decreased levels of anti-oxidant enzymes such as total antioxidant capacity (TAC), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) and suppressed the expression of inflammatory mediators including inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-1 and -2. To visualize the potential activity of betaine, a component of LC fruit, betaine was substituted for LC extract in CCl4 injured rats. The biochemical profile in CCl4 injured rats co-treated with betaine matched those of LC fruit treated CCl4 injured rats. The ameliorative effects of LC extract, as well as betaine, were also confirmed by histopathological examination. Collectively, the present findings imply that LC fruit, via its component betaine, mitigate CCl4-induced hepatic injury by increasing antioxidative activity and decreasing inflammatory mediators including iNOS and COX-1/COX-2.

Pharmacological evaluation of Ipomoea asarifolia (Desr.) against carbon tetrachloride-induced hepatotoxicity in rats

Ethnopharmacological relevanceIpomoeaasarifolia (Desr.) Roem. and Schult. is used traditionally in some parts of Africa for the treatment of a variety of diseases. This study attempts to validate its hepatoprotective activity by evaluating the prophylactic and curative properties of the methanolic extract of Ipomoea asarifolia (IA) leaves. Materials and MethodsLiver damage was induced by administering 0.5ml/kg of an equal mixture of carbon tetrachloride (CCl4) in olive oil intraperitoneally on alternate days, for 5 days and the plant extract was given orally daily, for 7 days at doses of 100, 200 and 400mg/kg. ResultsPre-treatment with the extract significantly (P<0.05) decreased CCl4-induced elevation in serum levels of alanine transaminase, aspartate transaminase, alkaline phosphatase, triglycerides, bilirubin and cholesterol, better than the standard drug silymarin at 100mg/kg. In the curative study, IA significantly (P<0.05) reversed CCl4-induced liver damage, comparable to silymarin. Hepatoprotective potential was further supported by decrease in pentobarbitone sleeping time and improved hepatic tissue histopathology. ConclusionThese results indicate that I. asarifolia leaves have potent hepatoprotective activity against CCl4-induced hepatic damage in rats.

Reversal of Carbon Tetrachloride-Induced Hepatic Injury by Aqueous Extract of Artemisia absinthium in Sprague-Dawley Rats

In the present study, we evaluated the protective activity of an aqueous extract of Artemisia absinthium against CCl4-induced hepatic damage in rats. The protective activity of this extract at three doses (2.5, 5, and 10 ml/ kg, once orally) against CCl4-induced oxidative damage (1.5 ml/kg, once intraperitoneally) in rats was analyzed. Various blood and tissue biochemical studies were performed, and the administration of the toxicant significantly altered blood biochemical variables. Hepatic lipid peroxidation (LPO) was significantly elevated, whereas glutathione (GSH) level was considerable depleted after intoxication. Remarkable decreases in the activities of adenosine triphosphatase (ATPase) and glucose-6-phosphatase (G-6-Pase) after intoxication were observed. Treatment with all three doses reversed altered tissue biochemical values, but the greatest protection was observed at the lowest dose (2.5 ml/kg). The results of this study show that A. absinthium induces strong hepatoprotective activity. It decreased the hexobarbitone-induced sleep time and improved cholerectic activity (bile flow and bile solids) and excretory capacity, and it also stimulated bile secretion. The potent antioxidant activity of A. absinthium was indicated by scavenging effects on 1,1-diphenyl-2-picryl-hydrazyl (DPPH) and hydrogen peroxide (H2O2). Thus, be considered for use in reducing hepatic damage and may serve as an alternative medicine in hepatic etiologies.

Hepatoprotective effects of Ficus racemosa stem bark against carbon tetrachloride-induced hepatic damage in albino rats

In the present study, the hepatoprotective effects of petroleum ether (FRPE) and methanol (FRME) extract of Ficus racemosa Linn. (Moraceae) stem bark were studied using the model of hepatotoxicity induced by carbon tetrachloride (CCl4) in rats. CCl4 administration induced a significant decrease in serum total protein, albumin, urea and a significant increase (P ≤ 0.01) in total bilirubin associated with a marked elevation in the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) as compared to control rats. Further, CCl4 intoxication caused significant increase in the TBARS and decrease in glutathione (GSH) levels in serum, liver and kidney. Pretreatment with FRPE and FRME restored total protein and albumin to near normal levels. Both the extracts resulted in significant decreases in the activities of AST, ALT and ALP, compared to CCl4-treated rats. However, a greater degree of reduction was observed in FRME pretreated group (FRPE 43%, 38%, and 33%; FRME 55%, 73%, and 38%). Total bilirubin content decreased from 2.1 mg/dL in CCl4-treated rats to 0.8 and 0.3 mg/dL in FRPE and FRME pretreated rats, respectively. The extracts improved the antioxidant status considerably as reflected by low TBARS and high GSH values. FRME exhibited higher hepatoprotective activity than a standard liver tonic (Liv52), while the protective effect of FRPE was similar to that of Liv52. The protective effect of F. racemosa was confirmed by histopathological profiles of the liver. The results indicate that F. racemosa possesses potent hepatoprotective effects against CCl4-induced hepatic damage in rats.

Hepatoprotective and Antioxidant Effect of Pisonia aculeata L. against CCl4-Induced Hepatic Damage in Rats

Ethanol extract of Pisonia aculeata (EPA) was evaluated for hepatoprotective and antioxidant activities in rats. The plant extract (250 and 500 mg/kg, p.o.) showed a remarkable hepatoprotective and antioxidant activity against carbon tetrachloride (CCl4)induced hepatotoxicity as judged from the serum marker enzymes and antioxidant levels in liver tissues. CCl4-induced a significant rise in aspartate amino transferase (AST), alanine amino transferase (ALT), alkaline phosphatase (ALP), total bilirubin, gamma glutamate transpeptidase (GGTP), lipid peroxidase (LPO) with a reduction of total protein, superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) and glutathione S-transferase (GST). Treatment of rats with different doses of plant extract (250 and 500 mg/kg) significantly (P<0.001) altered serum marker enzymes and antioxidant levels to near normal against CCl4-treated rats. The activity of the extract at dose of 500 mg/kg was comparable to the standard drug, silymarin (50 mg/kg, p.o.). Histopathological changes of liver sample

Hepatoprotective effect of a protein-enriched fraction from the maggots (Musca domestica) against CCl4-induced hepatic damage in rats

The hepatoprotective potential of a protein-enriched fraction (PEF) isolated from the maggots of housefly (Musca domestica) was evaluated in rats against carbon tetrachloride (CCl4)-induced acute hepatic damage. Activities of serum aspartate aminotransferase and alanine aminotransferase increased by 4- and 13-fold induced by CCl4, were significantly inhibited by pretreatment with 50, 100 and 200 mg PEF/kg. The formation of malondialdehyde was also significantly decreased in PEF-treated group compared with CCl4-treated group. The treatments with PEF also elevated total protein levels significantly. These results were further supplemented by histopathological examination of liver sections. Hyperplasia of kupffer cells was observed after treatment with PEF (100 and 200 mg/kg). We conclude that PEF is effective in this model of liver damage.

Protective Effect of Indigofera aspalathoides Against CCl4-Induced Hepatic Damage in Rats

The alcoholic extract of stem of Indigofera aspalathoides was evaluated for its antihepatotoxic activity against CCl(4)-induced hepatic damage in rats. The activity was evaluated by using biochemical parameters, such as serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT), alkaline phosphatase (ALP), total bilirubin and gama glutamate transpeptidase (GGTP). The histopathological changes of liver sample were compared with respective control. The extract showed remarkable hepatoprotective effect.

Protective Effect of Enicostemma littorale. against CCl4-Induced Hepatic Damage in Rats

The alcohol extract of the whole plant of Enicostemma littorale. Blume was evaluated for its antihepatotoxic activity against CCl4-induced hepatic damage in rats. The activity was evaluated by using biochemical parameters, such as serum glutamate pyruvate transaminase, serum glutamate oxaloacetate transaminase, alkaline phosphatase, total bilirubin, and γ.-glutamate transpeptidase. The histopathological changes of liver sample were compared with respective controls. The extract showed a remarkable hepatoprotective effect.

Protective effects of acetylbergenin against carbon tetrachloride-induced hepatotoxicity in rats

The present study was undertaken to investigate whether or not the hepatoprotective activity of acetylbergenin was superior to bergenin in carbon tetrachloride (CCl4)-intoxicated rat. Acetylbergenin was synthesized by acetylating bergenin, which was isolated from Mallotus japonicus. The hepatoprotective effects of acetylbergenin were examined against CCl4-induced liver damage in rats by means of serum and liver biochemical indices. Acetylbergenin was administered orally once daily for 7 successive days, then a 0.5 ml/kg mixture of CCl4 in olive oil (1:1) was intraperitoneally injected at 12 h and 36 h after the final administration of acetylbergenin. Pretreatment with acetylbergenin reduced the elevated serum enzymatic activities of alanine/aspartate aminotransferase, sorbitol dehydrogenase and gamma-glutamyltransferase in a dose dependent fashion. Acetylbergenin also prevented the elevation of hepatic malondialdehyde formation and depletion of glutathione content dose dependently in CCl4-intoxicated rats. In addition, the decreased activities of glutathione S-transferase and glutathione reductase were restored to almost normal levels. The results of this study strongly suggest that acetylbergenin has potent hepatoprotective activity against CCl4-induced hepatic damage in rats by glutathione-mediated detoxification as well as having free radical scavenging activity. In addition, acetylbergenin doses of 50 mg/kg showed almost the same levels of hepatoprotective activity as 100 mg/kg of bergenin, indicating that lipophilic acetylbergenin is more active against the antihepatotoxic effects of CCl4 than those of the much less lipophilic bergenin.