Regulation of Low-Density Lipoprotein Receptor and 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Gene Expression by Thymoquinone-Rich Fraction and Thymoquinone in HepG2 Cells

Abstract

Background and Aim: Nigella sativa and its active constituent thymoquinone (TQ) have been exploited for their various health benefits. This work was aimed to investigate the regulatory effects of TQ-rich fraction (TQRF) and commercial TQ on the low-density lipoprotein receptor (LDLR) and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) genes in HepG2 cells. Methods and Results: TQRF was extracted from N. sativa seeds using supercritical fluid extraction. The regulatory effects of TQRF at 80 μg/ml and TQ at 2 μg/ml on LDLR and HMGCR gene expression were investigated in HepG2 cells using quantitative real-time PCR. The TQ content in TQRF was 2.77% (w/w) and was obtained at a temperature of 40°C and a pressure of 600 bar. Treatment of cells with TQRF and TQ resulted in a 7- and 2-fold upregulation of LDLR mRNA level, respectively, compared with untreated cells. The mRNA level of HMGCR was downregulated by 71 and 12%, respectively, compared with untreated cells. Conclusion: TQRF and TQ regulated genes involved in cholesterol metabolism by two mechanisms, the uptake of low-density lipoprotein cholesterol via the upregulation of the LDLR gene and inhibition of cholesterol synthesis via the suppression of the HMGCR gene.

Ameliorative effects of Nigella sativa on dyslipidemia

“…NS consumption can also up-regulate LDL receptors by decreasing intracellular cholesterol, an effect that leads to rapid clearance of LDL particles from circulation [76]. In addition, thymoquinone supplementation has been shown to enhance the expression of LDL receptor gene [80]. The choleretic activity of NS and increased biliary excretion of cholesterol are other possible causes of the observed hypolipidemic, in particular hypotriglyceridemic, effects of this plant [18,81].…”

Potential Protective Effects of Nigella Sativa and Allium Sativum Against Fructose-Induced Metabolic Syndrome in Rats

“…The cholesterol-lowering effect of NS was explained to be due to either stimulation of bile acid excretion 64 or inhibition of de novo cholesterol synthesis by down-regulating HMG-CoA genes 65 while the significant decrease in LDL-C was reported to be due to upregulation of LDL -receptor gene 66 .…”

Thymoquinone Improves Anti-Diabetic Activity of Metformin in Streptozotocin-Induced Diabetic Male Rats

“…Remarkably, the level of serum triglycerides and cholesterol was reduced and corrected to the normal values after the treating with TQ and MET. It was stated that plasma triglyceride and cholesterol levels diminished in the diabetic rats treated with TQ [41] due to its anti-oxidant activity [42]. Also, the anti-lipidemic action of TQ may be caused by its ability to stimulate insulin secretion and action.…”

“…Also, the anti-lipidemic action of TQ may be caused by its ability to stimulate insulin secretion and action. In addition, TQ generated a hypocholesterolemic effect in diabetic rats through regulation of cholesterol via up-regulation of hepatic LDL receptor gene and suppressing the HMG-CoA R gene [41].…”