acteoside and Chemical-and-Drug-Induced-Liver-Injury

Acanthus ilicifolius L. has been used as a folk medicine in the treatment of acute and chronic hepatitis in China for a long time. Phenylethanoid glycosides are one of main components in A. ilicifolius L.. The aim of present study was to assess the hepatoprotective activities of total phenylethanoid glycosides from A. ilicifolius L. (APhGs) against carbon tetrachloride (CCl. The APhGs was separated by resin column chromatography. The purity of total phenylethanoid glycosides was determined by UV-Vis spectrophotometry using acteoside as a standard. The hepatoprotective activities of APhGs against CCl. The results showed that pre-administration of APhGs to mice decreased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in serum, and improved superoxide dismutase (SOD) activity and decreased malondialdehyde (MDA) level in serum and liver tissue induced by CCl. Overall, total phenylethanoid glycosides from A. ilicifolius L. displayed promising hepatoprotective effects. These results offer a support for the medicine uses of A. ilicifolius L.

Topics: Acanthaceae; Alanine Transaminase; Animals; Antioxidants; Aspartate Aminotransferases; Carbon Tetrachloride; Chemical and Drug Induced Liver Injury; China; Female; Glucosides; Glutathione; Glycosides; Hepatocytes; Liver; Male; Malondialdehyde; Mice; Mice, Inbred C57BL; Phenols; Plant Extracts; Protective Agents

Wu-Chia-Pi medicated wine, composed nine Chinese medicines soaked in 35% alcohol, is widely used in Asia for its health-promoting functions. However, long-term consumption of alcohol could result in liver dysfunction. In this study, Wu-Chia-Pi solution (WCPS) and extract (WCPE) were prepared by modification of the principals given by the Committee on Chinese Medicine and Pharmacy in Taiwan. The aim of this study was to explore the protective effect of WCPS against carbon tetrachloride (CCl4)-induced liver injury and to clarify its active component(s). Antioxidative effects of the test samples were evaluated via MDA inhibition, catalase activity and DPPH-scavenging assays. HPLC was used to analysis the active components. Results showed that WCPS (1 and 5 mL/kg) significantly prevented CCl4-induced liver injury without chronic liver toxicity. Referring to the antioxidative activities, WCPE displayed significant MDA inhibitory and DPPH-scavenging activities with IC50 values of 0.91 ± 0.03 and 0.60 ± 0.04 mg/mL, respectively. Catalase activity was also enhanced by treatment of WCPE, acteoside and quercetin. Therefore, we suggest that acteoside and quercetin are the major contributors to the antioxidative and hepatoprotective activities of WCPS, and a possible mechanism could be mediated through reduction of oxidative stress.

Topics: Administration, Oral; Animals; Antioxidants; Carbon Tetrachloride; Catalase; Chemical and Drug Induced Liver Injury; Chromatography, High Pressure Liquid; Chronic Disease; Dose-Response Relationship, Drug; Glucosides; Lipid Peroxidation; Liver; Liver Diseases; Male; Mice; Mice, Inbred ICR; Oxidative Stress; Phenols; Plant Extracts; Quercetin; Taiwan

The methanolic extract from fresh stems of Cistanche tubulosa (Orobanchaceae) was found to show hepatoprotective effects against D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced liver injury in mice. From the extract, three new phenylethanoid oligoglycosides, kankanosides H(1) (1), H(2) (2), and I (3), were isolated together with 16 phenylethanoid glycosides (4-19) and two acylated oligosugars (20, 21). The structures of 1-3 were determined on the basis of spectroscopic properties as well as of chemical evidence. Among the isolates, echinacoside (4, IC(50)=10.2 microM), acteoside (5, 4.6 microM), isoacteoside (6, 5.3 microM), 2'-acetylacteoside (8, 4.8 microM), and tubuloside A (10, 8.6 microM) inhibited D-GalN-induced death of hepatocytes. These five isolates, 4 (31.1 microM), 5 (17.8 microM), 6 (22.7 microM), 8 (25.7 microM), and 10 (23.2 microM), and cistantubuloside B(1) (11, 21.4 microM) also reduced TNF-alpha-induced cytotoxicity in L929 cells. Moreover, principal constituents (4-6) exhibited in vivo hepatoprotective effects at doses of 25-100mg/kg, po.

Topics: Animals; Caffeic Acids; Chemical and Drug Induced Liver Injury; Cistanche; Coumaric Acids; Glucosides; Hepatocytes; Lipopolysaccharides; Mice; Plant Stems; Trisaccharides

The hepatoprotective effects of acteoside from O. coerulescens were evaluated in BCG plus LPS-induced immunological liver injury (ILI) in mice. Acteoside (50, 150, or 300 mg/kg) was administered via gavage daily for 12 days. The liver index (liver weight/body weight), liver homogenate levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), hepatic nitric oxide (NO), malondialdehyde (MDA) content, superoxide dismutase (SOD) activity, production of tumor necrosis factor-gamma (TNF-gamma) and interleukin-2, 4, 10 (IL-2, 4, 10), as well as histopathological changes of the liver were evaluated following the 12-day treatment. Moreover, the modulation influence of acteoside on the expression of B cell lymphoma/leukemia-2 (Bcl-2, hepatocyte apoptosis inhibitor) and Bcl-2 associated X protein (Bax, hepatocyte apoptosis promoter) in the mice liver with immunological hepatic injury was studied also. Acteoside (50, 150, or 300 mg/kg) effectively reduced the BCG/LPS-induced elevated liver index, liver homogenate AST and ALT levels, hepatic NO and MDA contents, restored hepatic SOD activity and reduced the degree of liver injury in ILI mice. The expression of Bax was decreased (vs. BCG + LPS model group), while the expression of Bcl-2 increased (vs. BCG + LPS model group). These results are close to those of DDB (as a reference drug), and suggest that acteoside has a protective and therapeutic effect on ILI mice, which might be associated with its antioxidant properties, immunoregulatory function and regulation of hepatic apoptosis.

Topics: Alanine Transaminase; Animals; Antioxidants; Aspartate Aminotransferases; bcl-2-Associated X Protein; Chemical and Drug Induced Liver Injury; Glucosides; Immunologic Factors; Lipopolysaccharides; Liver; Liver Diseases; Male; Malondialdehyde; Mice; Mice, Inbred Strains; Mycobacterium bovis; Nitric Oxide; Phenols; Protective Agents; Superoxide Dismutase

This study investigated the protective effects of acteoside, a phenylethanoid glycoside, on the carbon tetrachloride-induced hepatotoxicity as well as the possible mechanisms involved in this protection in mice. Pretreatment with acteoside prior to the administration of carbon tetrachloride significantly prevented the increased serum enzymatic activities of alanine and aspartate aminotransferase in a dose-dependent manner. In addition, pretreatment with acteoside significantly prevented the increase in hepatic malondialdehyde formation and the depletion of the reduced glutathione content in the liver of carbon tetrachloride-intoxicated mice. Carbon tetrachloride-induced hepatotoxicity was also essentially prevented, as indicated by a liver histopathologic study. The effects of acteoside on cytochrome P450 (P450) 2E1, the major isozyme involved in carbon tetrachloride bioactivation were also investigated. Treatment of the mice with acteoside resulted in a significant decrease in the P450 2E1-dependent pnitrophenol and aniline hydroxylation in a dose-dependent manner. Consistent with these observations, the P450 2El protein levels were also lower. Acteoside exhibited anti-oxidant effects on FeCl2-ascorbate induced lipid peroxidation in a mouse liver homogenate, and on superoxide radical scavenging activity. These results suggest that the protective effects of acteoside against the carbon tetrachloride-induced hepatotoxicity possibly involve mechanisms related to its ability to block the P450-mediated carbon tetrachloride bioactivation and free radical scavenging effects.

Topics: Alanine Transaminase; Animals; Antioxidants; Ascorbic Acid; Aspartate Aminotransferases; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Chlorides; Cytochrome P-450 CYP2E1; Dose-Response Relationship, Drug; Ferric Compounds; Free Radical Scavengers; Glucosides; Glutathione; Immunoblotting; Lipid Peroxidation; Liver; Liver Function Tests; Male; Mice; Mice, Inbred ICR; Microsomes, Liver; Mixed Function Oxygenases; Phenols; Superoxides

We assessed the effect of acteoside, a naturally occurring antioxidative phenylethanoid, on hepatic apoptosis and the subsequent liver failure induced by D-Galactosamine (D-GalN) and lipopolysaccharide (LPS). A co-administration of D-GalN (700 mg/kg) and LPS (35 microg/kg) to mice evoked typical hepatic apoptosis characterized by DNA fragmentation and apoptotic body formation, resulting in fulminant hepatitis and lethality of mice. Pre-administration of acteoside at 10 or 50 mg/kg subcutaneously at 12 and 1 h prior to D-GalN/LPS intoxication significantly inhibited hepatic apoptosis, hepatitis and lethality. Tumor necrosis factor-alpha (TNF-alpha) secreted from LPS-stimulated macrophages is an important mediator of apoptosis in this model. Acteoside showed no apparent effect on the marked elevation of serum TNF-alpha, but it partially prevented in vitro TNF-alpha (100 ng/ml)-induced cell death in D-GalN (0.5 mM)-sensitized hepatocytes at the concentrations of 50, 100 and 200 microM. These results indicated that D-GalN/LPS-induced hepatic apoptosis can be blocked by an exogenous antioxidant, suggesting the involvement of reactive oxygen intermediates (ROIs) in TNF-alpha-dependent hepatic apoptosis.

Topics: Alanine Transaminase; Animals; Antioxidants; Apoptosis; Aspartate Aminotransferases; Cell Survival; Chemical and Drug Induced Liver Injury; DNA; Drug Synergism; Galactosamine; Glucosides; Lipopolysaccharides; Liver; Liver Failure; Male; Mice; Phenols; Plant Extracts; Tumor Necrosis Factor-alpha