Tzeng Thing-Fong, Liou Shorong-Shii, Chang Chia Ju, Liu I-Min
Department of Pharmacy and Graduate Institute of Pharmaceutical Technology, Tajen University, Yanpu Township, Pingtung County, Taiwan, ROC.
Department of Pharmacy and Graduate Institute of Pharmaceutical Technology, Tajen University, Yanpu Township, Pingtung County, Taiwan, ROC .
Phytomedicine. 2015 Apr 15;22(4):452-61. doi: 10.1016/j.phymed.2015.01.015. Epub 2015 Feb 26.
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.
本研究的目的是在非酒精性脂肪性肝炎的实验模型中研究[6]-姜酚（(S)-5-羟基-1-(4-羟基-3-甲氧基苯基)-3-癸酮）的作用。将HepG2细胞暴露于500 µmol/l油酸（OA）中24小时，然后再与[6]-姜酚（25、50或100 µmol/l）预孵育24小时。[6]-姜酚（100 µmol/l）抑制OA诱导的HepG2细胞中甘油三酯和炎症标志物的积累。雄性金黄仓鼠在高脂饮食（HFD）喂养2周后，每天口服一次[6]-姜酚（25、50或100 mg/kg/天），持续8周，同时维持高脂饮食。[6]-姜酚（100 mg/kg/天）减轻了高脂饮食喂养仓鼠的肝脏脂肪变性、炎症，并逆转了代谢综合征的血浆标志物。高脂饮食组炎症细胞因子基因和核转录因子-κB（NF-κB）的表达增加；[6]-姜酚减弱了这些作用。[6]-姜酚还阻断了高脂饮食喂养仓鼠中肝脏X受体-α、固醇调节元件结合蛋白-1c及其靶基因（包括乙酰辅酶A羧化酶、脂肪酸合酶、硬脂酰辅酶A去饱和酶1和酰基辅酶A：二酰甘油酰基转移酶2）等脂肪生成基因的肝脏mRNA表达。[6]-姜酚可能通过下调NF-κB介导的炎症反应和降低肝脏脂肪生成基因表达来减轻高脂饮食诱导的脂肪性肝炎。
