fraxetin and Liver-Cirrhosis

Liver fibrosis is a chronic lesion which ultimately results in cirrhosis and possible death. Although the high incidence and lethality, few therapies are effective for liver fibrosis. Fraxetin (7,8-dihydroxy-6-methoxy coumarin), a natural product extracted from cortex fraxini, has exhibited a significant hepatoprotective and anti-fibrotic properties. However, the underlying mechanism of the anti-hepatic fibrotic property remains unknown.. Our findings indicate that fraxetin is effective in preventing liver fibrosis through inhibiting inflammation and hepatocytes apoptosis which is associated with regulating NF-κB/IκBα, MAPKs and Bcl-2/Bax signaling pathways in rats.

Topics: Animals; Apoptosis; bcl-2-Associated X Protein; Carbon Tetrachloride; Coumarins; Inflammation; Liver; Liver Cirrhosis; Male; Mitogen-Activated Protein Kinase 1; NF-kappa B; NF-KappaB Inhibitor alpha; Oxidative Stress; Rats; Rats, Sprague-Dawley; Signal Transduction

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.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Cells, Cultured; Coumarins; Cytochrome P-450 CYP2E1; Ethanol; Heme Oxygenase-1; Inflammation Mediators; Interleukin-1beta; Lipid Peroxidation; Liver; Liver Cirrhosis; Male; Oxidative Stress; Rats; Rats, Wistar; Tumor Necrosis Factor-alpha

The aim of the study was to investigate the potentially protective effects of fraxetin on carbon tetrachloride (CCl4) induced oxidative stress and hepatic fibrosis in Sprague-Dawley rats. In this study, rats were divided into five groups, including normal controls, model, silymarin as the positive control, fraxetin 20 mg/kg and fraxetin 50 mg/kg. After 8 weeks, activities of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBIL) were checked. The levels of protein carbonyls, thiobarbituric acid-reactive substances (TBARS) and antioxidant enzymes such as catalase, SOD and glutathione peroxidase (GSH-Px) were determined after fraxetin administration. The hydroxyproline levels and histopathologic examinations of hepatocyte fibrosis were also determined. We found that fraxetin at doses of 20 and 50 mg/kg for 8 weeks significantly reduced the levels of TBARS and protein carbonyls compared with CCl4 group. Fraxetin significantly increased the activities of catalase, SOD and GSH-Px in the liver. We also found that fraxetin prevented CCl4 induced hepatic fibrosis by histological observations. These results indicate that fraxetin exhibits potent protective effects against CCl4 induced oxidative stress and hepatic fibrosis.

Topics: Animals; Carbon Tetrachloride; Catalase; Chemical and Drug Induced Liver Injury; Coumarins; Glutathione Peroxidase; Hydroxyproline; Lipid Peroxidation; Liver; Liver Cirrhosis; Male; Protective Agents; Rats; Rats, Sprague-Dawley; Superoxide Dismutase