Hepatoprotective effect of the extract and isocytisoside from Aquilegia vulgaris

The hepatoprotective effect of the ethanol extract (AvEE) and the main fl avonoid compound 4'-methoxy-5,7-dihydroxy fl avone 6-C-beta-glucopyranoside (isocytisoside, ISOC) from the leaves and stems of Aquilegia vulgaris L. were studied using the CCl(4)-induced hepatotoxicity test.The acute toxicity test in mice showed that AvEE can be classi fi ed as nontoxic since a dose of 3000 mg/ kg did not cause mortality.The barbiturate-induced sleeping time prolonged by CCl(4) administration to mice was signi fi cantly reduced after AvEE treatment proving the protective effect of the extract on microsomal drug-metabolizing enzymes.AvEE and ISOC administered to rats 48 h, 24 h and 2 h before, and 6 h after CCl(4) intoxication caused a signi fi cant decrease in the CCl(4)-induced elevation of hepatic enzymes activity in serum, i.e. sorbitol dehydrogenase (SDH), glutamate oxaloacetate and glutamate pyruvate transaminases (GOT, GPT).Both substances induced CCl(4)-diminished erythrocyte superoxide dismutase (SOD) and reduced the activities of glutathione peroxidase (GPx) and glutathione reductase (GR) preliminarily enhanced by CCl(4).The hepatoprotective properties of AvEE and ISOC were con fi rmed by pathomorphological examination of the liver.     

Protective Effect of Chlorogenic Acid against Carbon Tetrachloride-induced Acute Liver Damage in Rats

Objective To evaluate the protective effect of chlorogenic acid(CGA)on carbon tetrachloride(CCl4)-induced liver injury of rats.Methods The anti-oxidative activity of CGA was investigated with several established in vitro systems.The hepatoprotective activity of CGA against CCl4-induced acute liver injury in rats was studied.The levels of alanine aminotranferase(ALT),aspartate aminotransferase(AST),alkaline phosphatase(ALP),and total bilirubin(TB)were measured.The histopathological examination was carried out to supplement the biochemical results.Results CGA possessed strong anti-oxidative ability in vitro.The CCl4-induced liver toxicity experiment showed that the rats pretreated with CGA(300 or 500 mg/kg)had lower levels of ALT,AST,ALP,and TB than those of the CCl4-treated group.These data were supplemented with histopathological examination of rat liver sections.CGA did not show any mortality at the dose up to 5000 mg/kg.Conclusion CGA could protect the liver against CCl4-induced oxidative damage in rats,and the possible mechanism of the activity may be due to its free radical-scavenging and anti-oxidative activity.     

酒制山茱萸水煎液对四氯化碳诱导的小鼠急性肝损伤的保护作用研究

目标：观察研究酒制山茱萸水煎液对四氯化碳诱导的小鼠急性肝损伤的保护作用。方法：通过四氯化碳诱导昆明小鼠急性肝损伤,并连续给小鼠灌胃酒制山茱萸水煎液14 d后,测定小鼠血清谷丙转氨酶（ALT）、谷草转氨酶（AST）活性、肝组织SOD、MDA含量;并用HPLC法测定酒制山茱萸水煎液中主要指标成分的含量。结果：结果酒制山茱萸水煎液能保护四氯化碳所致小鼠肝损伤,表现为血清ALT,AST活力和肝脏MDA含量下降,SOD含量升高。结论：酒制山茱萸水煎液对四氯化碳所致小鼠肝损伤具有保护作用。     

Antioxidant and hepatoprotective effects of Orthosiphon stamineus Benth. standardized extract

Orthosiphon stamineus (OS), Benth. (Lamiaceae) is widely used in Malaysia for treatments of various kidney and liver ailments. In the experiment, DPPH* radicals scavenging, Fe(3+)-induced lipid peroxidation inhibiting activities and trolox equivalent antioxidant capacity (TEAC) of methanol/water extract of Orthosiphon stamineus (SEOS) were determined. The results indicated that SEOS exhibited antioxidant, lipid peroxidation inhibition and free radical scavenging activities. The hepatoprotective activity of the SEOS was studied using CCl(4)-induced liver toxicity in rats. The activity was assessed by monitoring liver function tests through the measurement of alanine transaminase (ALT) and aspartate transaminase (AST). Furthermore, hepatic tissues were also subjected to histopathological studies. Pretreatment of SEOS (125, 250, 500 and 1000 mg/kg p.o.) dose-dependently reduced the necrotic changes in rat liver and inhibited the increase of serum ALT and AST activities. The results of the present study indicated that the hepatoprotective effect of Orthosiphon stamineus might be ascribable to its antioxidant and free radical scavenging property.     

Hepatoprotective effect of the aqueous extract of Flemingia macrophylla on carbon tetrachloride-induced acute hepatotoxicity in rats through anti-oxidative activities

This study investigated the protective effect of the aqueous extract of Flemingia macrophylla (AFM) against hepatic injury induced by CCl(4). Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected as biomarkers in the blood to indicate hepatic injury. Product of lipid peroxidation (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and reduced glutathione (GSH) contents were evaluated for oxidative stress in hepatic injury. Moreover, histopathological observation was assayed for the degree of hepatic injury. After oral administration of AFM, 0.5 g/kg and 1.0 g/kg doses significantly decreased ALT and AST, attenuated the histopathology of hepatic injury, ameliorated oxidative stress in hepatic tissue, and increased the activities of CAT, SOD and GSH-Px. The hepatoprotective effect of daidzein and genistein were consistent to that of AFM. This study demonstrated for the first time that AFM has hepatoprotective effect on acute liver injuries induced by CCl(4), and the results suggested that the effect of AFM against CCl(4)-induced liver damage was related to antioxidant properties.     

Hepatoprotective effect of Vitis vinifera L. leaves on carbon tetrachloride-induced acute liver damage in rats

The hepatoprotective effect of ethanolic extract and its four different fractions (CHCl(3), EtOAc, n-BuOH, and remaining water fraction) of Vitis vinifera L. leaves was investigated against carbon tetrachloride (CCl(4))-induced acute hepatotoxicity in rats. The ethanolic extract was found active at 125mg/kg dose (per os). The ethanolic extract was fractionated through successive solvent-solvent extractions and the n-BuOH fraction in 83mg/kg dose possessed remarkable antioxidant and hepatoprotective activities. Liver damage was assessed by using biochemical parameters (plasma and liver tissue MDA [malondialdehyde], transaminase enzyme levels in plasma [AST-aspartate transaminase, ALT-alanine transferase] and liver GSH [glutathione] levels). Additionally, the pathological changes in liver were evaluated by histopathological studies. Legalon 70 Protect was used as standard natural originated drug.     

Evaluation of the effectiveness of Rosmarinus officinalis (Lamiaceae) in the alleviation of carbon tetrachloride-induced acute hepatotoxicity in the rat

The effect of oral administration of Rosmarinus officinalis L. (Lamiaceae) on CCl(4)-induced acute liver injury was investigated. Rats were daily treated with the plant extract at a dose of 200 mg/kg corresponding to 6.04 mg/kg of carnosol as determined by reverse phase high-performance liquid chromatography. The treatment was initiated 1 h after CCl(4) administration and Rosmarinus officinalis fully prevented CCl(4) effect on hepatic lipid peroxidation after 24 h of CCl(4) administration. The increase in bilirubin level and alanine aminotransferase activity in plasma induced by CCl(4) was completely normalized by Rosmarinus officinalis. The treatment also produced a significant recovery of CCl(4)-induced decrease in liver glycogen content. CCl(4) did not modify the activity of liver cytosolic glutathione S-transferase (GST) compared with that of control groups. However, Rosmarinus officinalis increased liver cytosolic GST activity and produced an additional increment in plasma GST activity in rats treated with CCl(4). Histological evaluation showed that Rosmarinus officinalis partially prevented CCl(4)-induced inflammation, necrosis and vacuolation. Rosmarinus officinalis might exert a dual effect on CCl(4)-induced acute liver injury, acting as an antioxidant and improving GST-dependent detoxification systems.     

Protective effects of total flavonoids of Bidens pilosa L. (TFB) on animal liver injury and liver fibrosis

The hepatoprotective effects of total flavonoids of Bidens pilosa L. (TFB), a traditional Chinese medicine were evaluated in carbon tetrachloride (CCl(4))-induced liver injury in mice and rats. Total flavonoids of Bidens pilosa L. (25, 50 and 100mg/kg) were administered via gavage daily for 10 days to CCl(4)-treated mice as well as TFB (30, 60 and 90mg/kg) administered for 6 weeks to CCl(4)-treated rats. Liver index (liver weight/body weight), serum levels of transaminases (alanine aminotransferase, ALT and aspartate aminotransferase, AST), hepatic malondialdehyde (MDA) content, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were evaluated following the 10 days treatment in mice. In addition histopathologic changes and nuclear factor-kappaB (NF-kappaB) expression of the liver were detected with hematoxylin-eosin (HE) and immunohistochemistry methods, respectively. The results showed that TFB (50 and 100mg/kg) effectively reduced the CCl(4)-induced elevated liver index, serum ALT, AST levels, hepatic MDA content, and restored hepatic SOD, GSH-Px activities in acute liver injury mice. TFB (60 and 90mg/kg) treatment significantly inhibited NF-kappaB activation in liver fibrosis of rats. The histopathological analysis suggested that TFB reduced the degree of liver injury in mice and severity of liver fibrosis in rats. These results suggested that TFB had a protective and therapeutic effect on animal liver injury, which might be associated with its antioxidant properties and inhibition of NF-kappaB activation.     

Hepatoprotective effects of bergenin, a major constituent of Mallotus japonicus, on carbon tetrachloride-intoxicated rats

The hepatoprotective effects of bergenin, a major constituent of Mallotus japonicus, were evaluated against carbon tetrachloride (CCl(4))-induced liver damage in rats. Bergenin at a dose of 50, 100 or 200 mg/kg was administered orally once daily for successive 7 days and then a mixture of 0.5 ml/kg (ip) of CCl(4) in olive oil (1:1) was injected two times each at 12 and 36 h after the final administration of bergenin. The substantially elevated serum enzymatic activities of alanine/aspartate aminotransferase, sorbitol dehydrogenase and gamma-glutamyltransferase due to CCl(4) treatment were dose dependently restored towards normalization. Meanwhile, the decreased activities of glutathione S-transferase and glutathione reductase were restored towards normalization. In addition, bergenin also significantly prevented the elevation of hepatic malondialdehyde formation and depletion of reduced glutathione content in the liver of CCl(4)-intoxicated rats in a dose dependent fashion. The results of this study clearly indicate that bergenin has a potent hepatoprotective action against CCl(4)-induced hepatic damage in rats.     

Ameliorative effects of pycnogenol on carbon tetrachloride-induced hepatic oxidative damage in rats

This study evaluated the putative antioxidant activity of Pycnogenol (PYC) against CCl4-induced hepatic oxidative damage in Sprague-Dawley rats. A single oral dose of CCl4 (1.25 mL/kg) produced significantly increased levels of serum aminotransferase (AST) and alanine aminotransferase (ALT) activities. In addition, increased malondialdehyde (MDA) concentration, reduced glutathione (GSH) content, and decreased catalase, superoxide dismutase (SOD) and glutathione-S-transferase (GST) activities were observed in the hepatic tissues. However, concomitant administration with PYC (10 or 20 mg/kg) significantly improved CCl4-induced hepatic injury, as evidenced by the decline of serum AST and ALT activities in a dose dependent manner. Moreover, PYC reduced MDA concentration and increased GSH levels and catalase, SOD and GST activities in hepatic tissues, indicating that concomitant administration with PYC efficiently prevent the CCl4-induced oxidative damage in rats. The free radical scavenging assay showed that PYC has a dose-dependent scavenging activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals. These results indicate that PYC has an antioxidant effect against CCl4-induced hepatic oxidative damage and is useful as a hepatoprotective agent against various liver diseases induced by oxidative stress.     

Hepatoprotective activity of reduohanxiao-tang (yuldahanso-tang) is related to the inhibition of beta-glucuronidase

Beta-glucuronidase-inhibitory and hepatoprotective effects of Reduohanxiao-tang (Yuldahanso-tang), which has been used for liver diseases and stroke, on carbon tetrachloride (CCl4)-induced hepatotoxicity of rats were investigated. Reduohanxiao-tang potently inhibited beta-glucuronidases. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactic acid dehydrogenase (LDH) levels of the CCl4 group orally treated with Reduohanxiao-tang (100 mg/kg) were lowered to 54%, 71.5% and 66.1% of the CCl4-treated control group, respectively. Among the ingredients of the Reduohanxiao-tang, the rhizomes of Pueraria thunbergiana and Scutellaria baicalensis potently inhibited beta-glucuronidases and protected against CCl4-induced liver injury. Orally administered puerarin, which is a main component of Pueraria thunbergiana, showed potent hepatoprotective activity, but did not inhibit beta-glucuronidase. However, daidzein, which is produced from puerarin by human intestinal bacteria, potently inhibited beta-glucuronidase. These results suggest that beta-glucuronidase inhibition by herbal medicines may protect against CCl4-induced liver injury.     

The anti-inflammatory and hepatoprotective effects of fractions from Cudrania cochinchinensis var. gerontogea.

Various fractions of the ethanol extract from the root wood of Cudrania cochinchinensis var. gerontogea (Moraceae) were evaluated for their anti-inflammatory effects on carrageenan-induced edema and hepatoprotective activities on carbon tetrachloride (CCl4)-induced and D-galactosamine-(D-GalN) induced acute hepatotoxicity in rats. The fractions (n-hexane, CHCl3, EtOAc, n-BuOH, and H2O) displayed significant inhibitory activity against carrageenan-induced edema, and the active anti-inflammatory components were further localized in the n-BuOH fraction, which exhibited the greatest anti-inflammatory effect, an effect 5% greater than indomethacin (which was used as a standard reference substance). Each fraction exerted a significant hepatoprotective effect by reducing enzymatic alteration (sGOT and sGPT) and by improving hepatic lesions, including liver centrilobular inflammation, cell necrosis, fatty change, ballooning degeneration in CCl4-induced acute hepatitis; and necrosis of the portal area in D-GalN-induced acute liver injury. The n-BuOH and EtOAc fractions had the greatest hepatoprotective effects on CCl4-induced liver injury; in contrast, the CHCl3 fraction was most potent against D-GalN intoxication, which is comparable to silymarin, as a recognized hepatoprotective drug.     

Antioxidant and hepatoprotective effects of Acathopanax senticosus

Acathopanax senticosus (Rupr. et Maxim.) Harms. is a popular folk medicine used as a nutrient for hepatitis and cancer in Taiwan. In this study, the antioxidant activity of the crude extract and the hepatoprotective activities on CCl(4)- or acetaminophen-induced toxicity in the rat liver were evaluated. Our results suggest that A. senticosus exerts some antioxidant effects. On a CCl(4)- or acetaminophen-intoxicated -model, the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were increased by CCl(4) or acetaminophen administration and reduced by treatment with the plant extract. Histological changes around the hepatic central vein were also recovered by treatments. However, treatments with larger doses of the crude extract of A. senticosus enhanced liver damage. This result suggests that even if A. senticosus had hepatoprotective activity in small doses, treatment with larger doses would possibly induce some cell toxicity.     

北苍术炮制前后水提液和多糖部位保肝作用比较研究

目的 比较生苍术及麸炒苍术水提液和多糖部位的保肝作用.方法 提取制备生苍术和麸炒苍术水提液和多糖部位;采用四氯化碳(CCl4)复制急性肝损伤模型,观察不同组别药物对小鼠血清转氨酶以及摄食量、饮水量、体重、肝脏脏器系数的影响.结果 麸炒苍术水提液和多糖部位能显著降低小鼠血清AST和ALT水平.结论 麸炒苍术水提液和多糖部...     

Protection of Citrullus colocynthis Fruit Extracts on Carbon Tetrachloride-induced and Bacillus Calmette-Guerin plus Lipopolysaccharide-induced Hepatotoxicity in Mice

Objective To investigate the hepatoprotective activities of the extracts from Citrullus colocynthis(ECC),a native plant used as traditional Uigur Medicine on acute liver injury in mice.Methods The activities of ECC of petroleum ether(ECCPE),chloroform(ECCC),ethyl acetate(ECCEA),n-butyl alcohol(ECCBA),and water(ECCW)were evaluated in vivo using two experimental models,carbon tetrachloride(CCl4)-and bacillus calmette-guerin(BCG)plus lipopolysaccharide(LPS)-induced acute hepatotoxicity in mice.The contents of aspartate aminotransferase(AST)and alanine aminotransferase(ALT)in serum were determined and the liver histological examination was carried out,respectively.Results The pretreatment with ECC for 7 d obviously reduced the impact of CCl4toxicity on the serum markers of liver damage,ECCEA and ECCC with a significant difference of AST(P<0.01,0.05,respectively)and ALT(P<0.05,0.01,respectively).The protective activity was reconfirmed against BCG+LPS-induced injury and the serum enzymatic levels were obviously elevated,for ECCEA and ECCC with a significant difference of AST(P<0.05,0.01,respectively)and ALT(P<0.01,0.05,respectively).Conclusion That ECCEA and ECCC are the potent hepatoprotective extracts that could protect liver against the acute injury,and this ability might be attributed to their hepatoprotective potentials.     

The effectiveness of ethanolic extract of Amaranthus tricolor L.: A natural hepatoprotective agent

The ethanolic extract of Amaranthus tricolor L. (ATE) leaves was tested for its efficacy against CCl?-induced liver toxicity in rats. The hepatoprotective activity of ATE was evaluated via measuring various liver toxicity parameters, the lipid profile, and a histopathological evaluation. A sleeping time determination study and an acute toxicity test were performed in mice. The results clearly showed that oral administration of ATE for three weeks significantly reduced the elevated levels of serum GOT, GPT, GGT, ALP, bilirubin, cholesterol, LDL, VLDL, TG, and MDA induced by CCl?. Moreover, ATE treatment was also found to significantly increase the activities of NP-SH and TP in liver tissue. These biochemical findings have been supported by the evaluation of the liver histopathology in rats. The prolongation of narcolepsy induced by pentobarbital was shortened significantly by the extract. The acute toxicity test showed that no morbidity or mortality was caused by the extract. The observed hepatoprotective effect appears to be due to the antioxidant properties of A. tricolor, which may pave the way to finding a new drug to be used for fighting liver diseases.     

Hepatoprotective activity of indigtone--a bioactive fraction from Indigofera tinctoria Linn.

A bioactive fraction, indigtone (FA), obtained by fractionation of a petroleum ether extract of the aerial parts of Indigofera tinctoria, showed significant dose related hepatoprotective activity against CCl(4) induced liver injury in rats and mice. Hexobarbitone induced 'sleeptime', zoxazolamine induced 'paralysis time', levels of transaminases, bilirubin and total protein in serum were employed as indices of liver injury. Pre and post treatment with FA significantly reversed the majority of the parameters altered by the hepatotoxin. This indicated the preventive and restorative effect of FA in the process of CCl(4) induced liver damage. The fraction possessed a high therapeutic ratio, as no mortality was observed up to a dose of 2 g/kg p.o. in mice.     

Hepatoprotective effect of Hypericum japonicum extract and its fractions

OBJECTIVE: To investigate the hepatoprotective activity of different parts of Hypericum japonicum against carbon tetrachloride(CCl(4))-induced hepatitis and alpha-naphthyl-isothiocyanate (ANIT)-induced cholestasis. MATERIALS AND METHODS: Mice were divided into groups and then administrated orally with solutions extracted from herbs before they were modeled in the experiments. Levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (T-BIL) in serum were evaluated. HPLC fingerprint was used for phytochemical analysis of the extracts. RESULTS: The total aqueous extract of Hypericum japonicum had an obvious effect on the decreasing of AST, ALT and T-BIL levels in serum. The isolated fraction IV (F4) exhibited a preferable activity of ameliorating cholestasis, while Fraction V (F5) was more efficacious in protecting liver from injury. Chemical fingerprint indicated that F5 contained several flavonoids which might be the active chemicals against hepatotoxicity. CONCLUSION: Different fractions of Hypericum japonicum manifest different effect, indicating their different potentials as candidacies of new drugs.     

Protective effect of Lygodium flexuosum (L.) Sw. extract against carbon tetrachloride-induced acute liver injury in rats

The hepatoprotective potential of Lygodium flexuosum (L.) Sw. was evaluated in male Wistar rats against carbon tetrachloride-induced liver damage in preventive and curative models. Toxic control and n-hexane extract-treated rats received a single dose of CCl4 (150 microL/100g, 1:1 in corn oil). Pre-treated rats were given n-hexane extracts at 200 and 100 mg/kg dose 48, 24 and 2 h prior to CCl4 administration. In post-treatment groups, rats were treated with n-hexane extract at a dose of 200 and 100 mg/kg, 2, 24 and 48 h after CCl4 intoxication. Rats pre-treated with Lygodium flexuosum remarkably prevented the elevation of serum AST, ALT, LDH and liver lipid peroxides in CCl4-treated rats. Rats treated with the extract after the establishment of CCl4 induced liver injury showed significant (p < or = 0.05) protection of liver as evidenced from normal AST, ALT, LDH and MDA levels. Hepatic glutathione levels were significantly (p < or = 0.05) increased by the treatment with the extracts in both the experimental groups. Histopathological changes induced by CCl4 were also significantly (p < or = 0.05) reduced by the extract treatment in preventive and curative groups. Phytochemical studies revealed the presence of saponins, triterpenes, sterols and bitter principles in Lygodium flexuosumn-hexane extract which could be responsible for the possible hepatoprotective action.