Effects of thymoquinone rich fraction and thymoquinone on plasma lipoprotein levels and hepatic low density lipoprotein receptor and 3-hydroxy-3-methylglutaryl coenzyme A reductase genes expression

The hypocholesterolemic effect of thymoquinone rich fraction (TQRF) extracted from Nigella sativa seeds using supercritical fluid extraction (SFE) in comparison with commercial available thymoquinone (TQ) in male Sprague–Dawley rats was investigated. Rats were fed prepared diet supplemented with 1% (w/w) cholesterol and treated with TQRF at, 0.5, 1 and 1.5 g/kg and TQ at 20, 50 and 100 mg/kg for 8 weeks. Plasma total cholesterol levels (TC) and low density lipoprotein cholesterol (LDLC) were significantly decreased in the TQRF and TQ treated rats compared to untreated rats. mRNA level of low density lipoprotein receptor (LDLR) was significantly expressed and the mRNA level of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-COAR) was significantly suppressed in the TQRF and TQ treated rats at different doses compared to untreated rats. These new findings identify TQRF and TQ as natural cholesterol lowering agents, and our study provides a molecular basis for the mechanisms of action through regulation of cholesterol in two main mechanisms first, uptake of LDLC via up regulation of LDLR gene and second, inhibition the synthesis of cholesterol via suppressing the HMG-COAR gene.     

Vanillin rich fraction regulates LDLR and HMGCR gene expression in HepG2 cells

Vanillin and its analogs have been exploited for their various health benefits. This work aimed to investigate the antioxidant properties and regulatory effects of vanillin rich fraction (VRF) extracted from vanilla pods using the supercritical fluid extraction (SFE) and commercial vanillin on low density lipoprotein receptor (LDLR) and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) gene expression in HepG2 cells. The vanillin content in the VRF was 2.6% (w/w) obtained at a temperature of 80 °C and a pressure of 600 bar. The VRF exhibited better antioxidant activity compared to the vanillin in DPPH and BCB tests. LDLR mRNA level was increased significantly by 2, 3 and 1.3 fold in the VRF treated cells at 100, 200 and vanillin treated cells at 100, respectively, compared with untreated cells. On the other hand, the HMGCR mRNA level was decreased significantly by 14, 58 and 13% respectively, in the VRF treated cells at 100, 200 and V treated cells at 100, respectively, compared with untreated cells. The VRF showed potential antioxidant activity and regulated genes involved in cholesterol metabolism including LDLR and HMGCR in dose-dependent manner.