The therapeutic effect of fraxetin on ethanol-induced hepatic fibrosis by enhancing ethanol metabolism, inhibiting oxidative stress and modulating inflammatory mediators in rats

Publication date: March 2018
Source:International Immunopharmacology, Volume 56
Author(s): Xiaowei Chen, Xiaozhou Ying, Weiming Sun, Huijia Zhu, Xin Jiang, Bin Chen
The present study was designed to investigate the possible protective effects of fraxetin against ethanol induced liver fibrosis in rats. Rats were underwent intragastric administration of ethanol (5.0–9.5 g/kg) once a day for 24 weeks. Effect of fraxetin against ethanol induced liver fibrosis was investigated by giving 20 or 50 mg/kg fraxetin. At the end of experiment, the livers were collected for histopathological analyses, protein extraction, and enzymatic activities. Our results indicated that fraxetin significantly corrected ethanol-induced hepatic fibrosis, as evidenced by the decrease in serum ALT and AST, the attenuation of histopathological changes. Fraxetin also expedited ethanol metabolism by enhancing the alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activities. Besides, fraxetin alleviated lipid peroxidation, enhanced hepatic antioxidant capabilities, inhibited CYP2E1 activity, and reduced the inflammatory mediators, including TNF-α and IL-1β via up-regulation of hemeoxygenase-1 (HO-1) protein. In summary, the hepatoprotection of fraxetin is mostly attributed to its antioxidant capability, alcohol metabolism, and anti-inflammation effect.



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