Genistein Attenuates Nonalcoholic Steatohepatitis and Increases Hepatic PPAR gamma in a Rat Model

摘要

Nonalcoholic steatohepatitis (NASH) has become a global chronic liver disease, but no effective medicine has been proven to cure it. This study investigated the protective effects of genistein, a phytoestrogen, on NASH and examined whether it has any effect on hepatic PPAR gamma. Male Sprague-Dawley rats were divided into four groups: control group fed ad libitum with standard rat diet, NASH group fed ad libitum with high-fat diet to induce NASH and NASH + Gen8 group and NASH + Gen16 group fed with high-fat diet plus intragastric administration of 8 or 16mg/kg genistein once daily. After 6 weeks, liver samples were collected to determine MDA, TNF-alpha, PPAR gamma, and histopathology. The findings were that levels of hepatic MDA and TNF-alpha increased in NASH group, but 16mg/kg genistein reduced these levels significantly. Downregulation of hepatic PPAR gamma was observed in NASH group, but genistein significantly upregulated the expression of PPAR gamma in both NASH + Gen groups. The histological appearance of liver in NASH group presented pathological features of steatohepatitis which were diminished in both NASH + Gen groups. The results suggest that genistein attenuates the liver histopathology of NASH with upregulation of hepatic PPAR gamma, reduction of oxidative stress, and inhibition of inflammatory cytokine.