6-Gingerol mitigates nutritional steatohepatitis through regulating key genes related to oxidative stress, inflammation and fibrogenesis

Abstract

The aim of the study was to investigate the effects of 6-gingerol, a bioactive ingredient of plants belonging to the Zingiberaceae family, on experimental models of non-alcoholic steatohepatitis (NASH). Male C57BL/6 mice were fed with a methionine and choline-deficient diet (MCDD) to induce steatohepatitis. After 8 weeks of feeding, the mice were treated orally with 6-gingerol (100 mg per kg per day). All mice were sacrificed after 4 weeks of treatment, and biochemical, pathological, and molecular analyses were performed. MCDD-fed mice showed severe hepatic injury including hepatic steatosis, necro-inflammation and fibrosis. 6-Gingerol possesses a repressive property on hepatic steatosis, which is associated with inhibition of acyl-CoA:diacylglycerol acyltransferase 2 and induction of peroxisome proliferator-activated receptor α. Administration of 6-gingerol significantly lowered plasma levels of alanine aminotransferase, aspartate aminotransferase, reduced hepatic oxidative stress and ameliorated hepatic inflammation and fibrosis. These effects were associated with down-regulation of cytochrome P450 2E1; reducing Jun N-terminal kinase-signaling; suppression of pro-inflammation genes and chemokines; and inhibition of pro-fibrotic genes. Our study demonstrated the protective role of 6-gingerol in ameliorating nutritional steatohepatitis. The effect was mediated through regulating key genes related to oxidative stress, inflammation and fibrogenesis.