title: In vitro antioxidant and in vivo prophylactic effects of two gamma-lactones isolated from Grewia tiliaefolia against hepatotoxicity in carbon tetrachloride intoxicated rats.
abstract: Grewia tiliaefolia is widely used in traditional Indian medicines to cure jaundice, biliousness, dysentery and the diseases of blood. Bioassay-guided fractionation of methanolic extract of the G. tiliaefolia bark has resulted in the isolation of D-erythro-2-hexenoic acid gamma-lactone (EHGL) and gulonic acid gamma-lactone (GAGL). Hepatoprotective activity of the methanolic extract and the isolated constituents were evaluated against CCl(4)-induced hepatotoxicity in rats. The treatment with methanolic extract, EHGL and GAGL at oral doses of 100, 150 and 60 mg/kg respectively with concomitant CCl(4) intraperitoneal injection (1 ml/kg) significantly reduced the elevated plasma levels of aminotransferases, alkaline phosphatase and the incidence of liver necrosis compared with the CCl(4)-injected group without affecting the concentrations of serum bilirubin and hepatic markers. EHGL and GAGL significantly inhibited the elevated levels of thiobarbituric acid reactive substances and glutathione in liver homogenates. Histology of the liver tissues of the extract and isolated constituents treated groups showed the presence of normal hepatic cords, absence of necrosis and fatty infiltration as similar to the normal control. The results revealed that the hepatoprotective activity of EHGL is significant as similar to the standard drug silymarin. To clarify the influence of the extract and isolated constituents on the protection of oxidative-hepatic damage, we examined in vitro antioxidant properties of the test compounds. The extract and the constituents showed significant free radical scavenging activity. These results suggest that the extract as well as the constituents could protect the hepatocytes from CCl(4)-induced liver damage perhaps, by their anti-oxidative effect on hepatocytes, hence eliminating the deleterious effects of toxic metabolites from CCl(4).
authors.affiliation: Department of Genetics, School of Ecology and Conservation Genetics, GKVK Campus, University of Agricultural Science, Bangalore-560 065, Karnataka, India.
authors.forename: Mohamed B
authors.initials: MB
authors.lastname: Khadeer Ahamed
authors.forename: Venkatarangaiah
authors.initials: V
authors.lastname: Krishna
authors.forename: Chethan J
authors.initials: CJ
authors.lastname: Dandin
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D002208:Caproates; D002251:Carbon Tetrachloride / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005942:Gluconates / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D032382:Grewia / Q000737:chemistry*; D007783:Lactones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use*; D007928:Lethal Dose 50; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008519:Medicine, Traditional; D015394:Molecular Structure; D018384:Oxidative Stress / Q000187:drug effects; D008517:Phytotherapy; D024301:Plant Bark / Q000737:chemistry; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D018547:Plant Stems / Q000737:chemistry; D020011:Protective Agents / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D002208:Caproates; C549373:D-erythro-2-hexenoic acid gamma-lactone; D005942:Gluconates; D007783:Lactones; D010936:Plant Extracts; D020011:Protective Agents; D002251:Carbon Tetrachloride; C010730:beta-glucono-1,5-lactone