[6]-Gingerol dampens hepatic steatosis and inflammation in experimental nonalcoholic steatohepatitis

The aim of the study was to investigate the effects of 16]-gingerol ((S)-5-hydroxy-1-(4 hydroxy-3-methoxyphenyl)-3-decanone) in experimental models of non-alcoholic steatohepatitis. HepG2 cells were exposed to 500 mu mol/l oleic acid (OA) for 24 h and preincubated for an additional 24 h with [6]-gingerol (25, 50 or 100 it mol/l). [6]-Gingerol (100 mu mol/l) inhibited OA-induced triglyceride and inflammatory marker accumulation in HepG2 cells. After being fed a high-fat diet (HFD) for 2 weeks, male golden hamsters were dosed orally with [6]-gingerol (25,50 or 100 mg/kg/day) once daily for 8 weeks while maintained on HFD.[6]Gingerol (100 mg/kg/day) alleviated liver steatosis, inflammation, and reversed plasma markers of metabolic syndrome in HFD-fed hamsters. The expression of inflammatory cytokine genes and nuclear transcription factor-kB (NF-KB) were increased in the HFD group; these effects were attenuated by [6]-gingerol. The hepatic mRNA expression of lipogenic genes such as liver X receptor-a, sterol regulating element binding protein-1c and its target genes including acetyl-CoA carboxylase, fatty acid synthase, stearoyl-CoA desaturase 1, and acyl-CoA:diacylglycerol acyltransferase 2 in HFD-fed hamsters was also blocked by H-gingerol. [6]-Gingerol may attenuate HFD-induced steatohepatitis by downregulating NF-kB-mediated inflammatory responses and reducing hepatic lipogenic gene expression. (C) 2015 Elsevier GmbH. All rights reserved.