Reversal of chemical-induced liver fibrosis in Wistar rats by puerarin.
Puerarin is a major isoflavonoid compound isolated from Pueraria lobata, an edible vine used widely for various medicinal purposes. It has been used for centuries in China to counteract alcohol intoxication. However, the effects of puerarin on chemical-induced liver fibrosis have not been reported. In the present study, we investigated the effects of puerarin on liver fibrosis in Wistar rats induced by alcohol plus carbon tetrachloride administration. Liver fibrosis was produced in rats by treatment with a mixture (50% alcohol, 8 g/kg per day; corn oil, 2 g/kg per day; pyrazole, 24 mg/kg per day; ig) once a day and by intraperitoneal injection of 0.25 ml/kg of a 25% solution of carbon tetrachloride in olive oil twice a week for 8 weeks. After 8 weeks, treatment with puerarin (0.4 and 0.8 g/kg ig, daily for 4 weeks) was conducted to examine its therapeutic effects. At the same time, the model group and treatment group continued to receive the chemical mixture, while the control group received saline instead of the chemical mixture. Upon pathological examination, the puerarin-treated rats significantly reversed the symptoms of liver fibrosis and other hepatic lesions. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), as indexes of hepatic cell disruption, were reduced with puerarin treatment, whereas no significant effect was discovered in the levels of alkaline phosphatase (ALP) and gamma-glutamyltransferase (GGT) activities. A significant increase in apoptosis of activated hepatic stellate cell (HSC) was found by flow cytometric analysis of the hepatic tissues. And the expression of bcl-2 mRNA was down-regulated after puerarin administration. Consequently, all these results showed that puerarin could effectively reverse chemical-induced liver fibrosis in experimental rats, via the recovery of hepatic injury as well as the induction of apoptosis in activated HSC.
Zhang
Shuihua
S
School of Pharmacy, East China University of Science and Technology, Mailbox 268, Shanghai 200237, China.
Ji
Guang
G
Liu
Jianwen
J
D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001219:Aspartate Aminotransferases / Q000097:blood; D002252:Carbon Tetrachloride Poisoning / Q000188:drug therapy; D005434:Flow Cytometry; D007529:Isoflavones / Q000627:therapeutic use*; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008104:Liver Cirrhosis, Alcoholic / Q000188:drug therapy; D008106:Liver Cirrhosis, Experimental / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D005723:gamma-Glutamyltransferase / Q000097:blood
D007529:Isoflavones; D019253:Proto-Oncogene Proteins c-bcl-2; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; C033607:puerarin