[6]-gingerol dampens hepatic steatosis and inflammation in experimental nonalcoholic steatohepatitis.
The aim of the study was to investigate the effects of [6]-gingerol ((S)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-3-decanone) in experimental models of non-alcoholic steatohepatitis. HepG2 cells were exposed to 500 µmol/l oleic acid (OA) for 24 h and preincubated for an additional 24 h with [6]-gingerol (25, 50 or 100 µmol/l). [6]-Gingerol (100 µmol/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-κB (NF-κB) 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-α, 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 [6]-gingerol. [6]-Gingerol may attenuate HFD-induced steatohepatitis by downregulating NF-κB-mediated inflammatory responses and reducing hepatic lipogenic gene expression.
Department of Pharmacy and Graduate Institute of Pharmaceutical Technology, Tajen University, Yanpu Township, Pingtung County, Taiwan, ROC.
Thing-Fong
TF
Tzeng
Department of Pharmacy and Graduate Institute of Pharmaceutical Technology, Tajen University, Yanpu Township, Pingtung County, Taiwan, ROC.
Shorong-Shii
SS
Liou
Department of Pharmacy and Graduate Institute of Pharmaceutical Technology, Tajen University, Yanpu Township, Pingtung County, Taiwan, ROC.
Chia Ju
CJ
Chang
Department of Pharmacy and Graduate Institute of Pharmaceutical Technology, Tajen University, Yanpu Township, Pingtung County, Taiwan, ROC . Electronic address: iml@tajen.edu.tw.
I-Min
IM
Liu
D000818:Animals; D002396:Catechols / Q000494:pharmacology*; D002784:Cholesterol / Q000378:metabolism; D006224:Cricetinae; D016207:Cytokines / Q000378:metabolism; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D005233:Fatty Alcohols / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy*; D014280:Triglycerides / Q000378:metabolism
D002396:Catechols; D016207:Cytokines; D005233:Fatty Alcohols; D014280:Triglycerides; C007845:gingerol; D002784:Cholesterol
Inflammation; Lipogenesis; Nuclear transcription factor κB; Steatohepatitis; [6]-Gingerol