Abstract
Gingerols, the pungent ingredients in ginger, are reported to possess a cholesterol-lowering activity. However, the underlying mechanism remains unclear. The present study was to investigate how 6-gingerol (6-GN), the most abundant gingerol in fresh ginger, regulates hepatic cholesterol metabolism. HepG2 cells were incubated with various concentrations of 6-GN ranging from 50 to 200 μM for 24 h. Results showed that both cellular total cholesterol and free cholesterol decreased in a dose-dependent manner. Besides, 6-GN ranging from 100 to 200 μM increased the LDLR protein and uptake of fluorescent-labeled LDL. Moreover, the mRNA and protein expressions of cholesterol metabolism-related genes were also examined. It was found that 6-GN regulated cholesterol metabolism via up-regulation of LDLR through activation of SREBP2 as well as up-regulation of cholesterol efflux-related genes LXRα and ABCA1.
Highlights
Cardiovascular diseases (CVDs) are a major health hazard across the world, and high blood cholesterol level is closely related to CVD
In order to estimate the effect of 6-GN on cell viability, HepG2 cells were incubated with 6-GN ranging from 0 to 800 μM for 24 h. 6-GN ranging from 50 to 400 μM had no effect on HepG2 cell viability, but 6-GN ranging from 600 to 800 μM significantly inhibited cell viability compared with control (Figure 1A)
Real-time PCR was used to assess relative changes in the expression of selected genes related to cholesterol metabolism (Figure 4). 6-GN up-regulated the gene expression of SREBP2, low-density lipoprotein receptor (LDLR), proprotein convertase subtilisin/kexin type 9 (PCSK9), LXRα, and ABCA1, and had no significant effect on gene expression of HMG-CoA reductase (HMGCR) and CYP7A1 in HepG2 cells
Summary
Cardiovascular diseases (CVDs) are a major health hazard across the world, and high blood cholesterol level is closely related to CVD. The low-density lipoprotein (LDL) is a main carrier of blood cholesterol. It is well known that high level of low-density lipoprotein cholesterol (LDL-C) increases the risk of CVD, such as hyperlipidemia, atherosclerosis, and myocardial infarction (Ridker, 2014). Statins are the most commonly used drugs to lower cholesterol levels via inhibition of HMG-CoA reductase (HMGCR) which is the rate-limiting enzyme for cholesterol de novo synthesis. Many people on the brink of abnormal blood cholesterol level can return to normal blood cholesterol level without cholesterol-lowering medications. The bioactive ingredients from functional foods have attracted much attention due to their potential as nutraceuticals to treat hypercholesterolemia (Chen et al, 2008)
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