Protective effects of matrine against progression of high-fructose diet-induced steatohepatitis by enhancing antioxidant and anti-inflammatory defences involving Nrf2 translocation

The present study was aimed to investigate the hepatoprotective effects of matrine against nonalcoholic steatohepatitis induced by a high-fructose diet. After being fed a high-fructose diet (HFD) for 4 weeks, male Wistar rats were orally administered matrine in three different doses (40, 80, or 160 mg/kg) once daily. Serum and liver samples were collected after treatment with matrine for 4 weeks. Lipid droplets within hepatocytes, infiltration of inflammatory cells, and necrotic foci in the liver were morphologically alleviated by matrine in a dose-dependent manner compared with the HFD group. ALT and AST in the blood and the triglyceride content in the liver also decreased. The increased malondialdehyde and depleted glutathione by HFD were ameliorated in a dose-related manner with matrine. Matrine promoted Nrf2 translocation to the nucleus with subsequently up-regulated antioxidative enzyme protein expression, and it enhanced antioxidant activities compared with the HFD group (p<0.05). The increased activity of nuclear factor-kappa B in the liver and the tumour necrosis factor-alpha levels in plasma induced by HFD were inhibited by matrine as well (p<0.05). In this study, we also found that matrine ameliorated HID-induced hyperglycaemia and insulin resistance. Taken together, our findings demonstrate that matrine is effective in preventing conversion of high-fructose diet-induced hepatic steatosis into nonalcoholic steatohepatitis in rats. (C) 2013 Elsevier Ltd. All rights reserved.