hispidulin and Chemical-and-Drug-Induced-Liver-Injury

Effects of the methanol extract of Cirsium japonicum var. ussuriense and hispidulin 7-O-neohesperidoside isolated from the plant on hepatic alcohol-metabolizing enzymes and lipid peroxidation were studied in rats treated with ethanol. Rats treated with 10% alcohol solution for 6 weeks were orally administered with 250 or 500 mg of methanol extract or 10 or 20 mg of hispidulin 7-O-neohesperidoside per kg body weight daily during the last week of ethanol treatment. The administration of the methanol extract of herbal plant and hispidulin 7-O-neohesperidoside in ethanol-treated rats significantly enhanced the activities of hepatic alcohol dehydrogenase, microsomal ethanol-oxidizing system and aldehyde dehydrogenase in a dose-dependent manner. The extract and the compound decreased hepatic lipid peroxidation along with an increase in hepatic content of reduced glutathione. The methanol extract and hispidulin 7-O-neohesperidoside of C. japonicum var. ussuriense also increased the activity of glutathione reductase, but had no effect on gamma-glutamylcysteine synthase. The results suggest that C. japonicum var. ussuriense may alleviate alcoholic toxicity by enhancing ethanol oxidation as well as inhibiting lipid peroxidation, and hispidulin 7-O-neohesperidoside is one of the active substances responsible for the protective effects of this plant.

Topics: Administration, Oral; Animals; Chemical and Drug Induced Liver Injury; Cirsium; Dipeptides; Ethanol; Flavones; Flavonoids; Glutathione Reductase; Lipid Peroxidation; Mitochondria, Liver; Phytotherapy; Plant Components, Aerial; Plant Extracts; Protective Agents; Rats; Rats, Sprague-Dawley; Thiobarbituric Acid Reactive Substances

The effects of the natural flavonoid hispidulin (6-methoxy-5,7,4'-trihydroxyflavone) on bromobenzene-induced hepatotoxicity in mice were investigated. We found a correlation between liver injury and hepatic lipid peroxidation besides a strong liver glutathione depletion due to the toxicant. Hispidulin at doses between 50 and 150 mg/kg i.p. compared favourably with the reference compound N-acetyl-L-cysteine for inhibition of liver injury and lipid peroxidation. The flavonoid at the highest dose tested was also able to counteract reduced glutathione depletion induced by bromobenzene in starved mice. These hepatoprotective effects can be related to the antioxidant properties of hispidulin.

Topics: Acetylcysteine; Animals; Bromobenzenes; Chemical and Drug Induced Liver Injury; Flavones; Flavonoids; Glutathione; Lipid Peroxides; Liver Diseases; Male; Mice