Effect Of Gingerols On Cholesterol Metabolism

Objective:In this study,the effectiveness of cholesterol regulation were compared among 6-GN,8-GN and 10-GN to screen out the key components of ginger in regulating cholesterol metabolism.HepG2 cells were used as model to simulate cholesterol metabolism in human liver.And 6-GN was used to analyze the molecular mechanism of gingerols affecting the metabolism of cholesterol.Methods:The effect of gingerols on growth of HepG2 cells was determined by MTT assay,and cell shape was observed by inverted microscope to select the gingerols' concentration for the following experiments.Then,cholesterol in cells(treated with the selected concentration)was detected by cholesterol quantitation kit to compare the ability of cholesterol lowering among 6-GN,8-GN and 10-GN.At last,6-GN with different concentrations and simvastatin,the positive control,were used to treat cells.Meanwhile,cholesterol quantitation kit was used for intracellular cholesterol,LDLR uptake kit was used for LDLR relative fluorescence intensity expression,and real-time PCR and western blot were used for the expression of related genes and proteins in cholesterol metabolism pathways.Results:1.Compared to the control,which remained viable with vehicle alone during the incubation period(24 h),HepG2 cells,cultured with 0 to 200 ?M 6-GN,had no effect on cell viability,but 6-GN,in the presence of 600-800 ?M,dose-dependently reduced cell viability.Generally,8-GN and 10-GN had the same cytotoxicity with 6-GN,and 6-SG was stronger than 6-GN,8-GN and 10-GN.2.Thanks to the change of total and free cholesterol in HepG2 cells,gingerols' influence on hypocholesterolemic was in a dose-dependent manner.At the same concentration,compared to 6-GN and 8-GN,10-GN had the strongest cholesterol lowering ability,which was related to the chemical structure of compounds.3.According to the effect of 6-GN 8-GN,and 10-GN on the engulfment capability to thefluorescence labeled LDL and LDLR relative fluorescence intensity in HepG2 cells with fluorescent microscopy,6-GN enhanced the fluorescence expression of LDLR in a dose-dependent manner.4.According to the analysis of SREBP2,LDLR,HMGCR and PCSK9 expression,both at mRNA and protein levels,the data showed that 6-GN upregulated SREBP2,LDLR and PCSK9 at mRNA level.Meanwhile,6-GN enhanced the expression of LDLR,and inhibited the expression of PCSK9 at the concentration of 100 ?M in protein level,respectively.Conclusion:Compared to the cholesterol lowering ability of 6-GN and 8-GN,10-GN had the strongest ability.According to the analysis of SREBP2,LDLR,HMGCR and PCSK9 expression both at mRNA and protein levels,6-GN inhibited the expression of PCSK9,which led to the degradation of LDLR,and increased the expression of LDLR at protein level through SREBP2 pathway.Thus,6-GN strengthened the effect of endocytosis to the plasma cholesterol,promoted the decomposition of cholesterol in cells,and resulted in the decrease of plasma cholesterol eventually.