Rebaudioside A Enhances LDL Cholesterol Uptake in HepG2 Cells via Suppression of HMGCR Expression

Abstract

Background: Rebaudioside A is one of the major diterpene glycosides found in Stevia had been reported to possess anti-hyperlipidemic effects. In this study, we explore the potential cholesterol-regulating mechanisms of Rebaudioside A in the human hepatoma (HepG2) cell line in comparison with simvastatin. Methods: Cells were incubated with Rebaudioside A at several concentrations (0-10 µM) to determine the cytotoxicity by the MTT assay. Cells were treated with selected dosage (1 and 5 µM) in further experiments. Total cellular lipid was extracted by Bligh and Dyer method and subjected to quantitative colorimetric assay. To illustrate the effect of Rebaudioside A on cellular lipid droplets and low-density lipoprotein receptors, treated cells were subjected to immunofluorescence microscopy. Finally, we investigated the expression of experimental gene patterns of cells in response to treatment. Results: In this study, cytotoxicity of Rebaudioside A was determined at 27.72 µM. Treatment of cells with a higher concentration of Rebaudioside A promotes better hepatocellular cholesterol internalization and ameliorates cholesterol-regulating genes such as HMGCR, LDLR, and ACAT2. Conclusions:In conclusion, our data demonstrated that Rebaudioside A is capable to regulate cholesterol levels in HepG2 cells. Hence, we proposed that Rebaudioside A offers a potential alternative to statins for atherosclerosis therapy.

The Cardiometabolic Impact of Rebaudioside A Exposure during the Reproductive Stage

“…Saravanan and Ramachandran also observed a decrease in total plasma cholesterol upon administration of a higher dose of RebA treatment (200 mg/kg/day for 45 days) on diabetic animals [23]. Ilias et al suggested that RebA promotes the internalization of cholesterol by hepatocytes, modulating the expression of genes involved in cholesterol metabolism, such as HMGCR, LDLR, and ACAT2 [24], which may, in part, explain our results.…”

New insights into the suppression of inflammation and lipid accumulation by JAZF1

“…TR4 also directly promotes lipid accumulation by activating the Fatty acid transport protein 1 ( FATP1 ) and CD36 promoters, which suggests that FATP1 and CD36 are target genes of TR4 . 88 , 89 As mentioned previously, PPARs are also target genes of TR4 . JAZF1 is a corepressor of TR4 , which suggests that JAZF1 regulates lipid accumulation by regulating the TR4-PPAR , TR4-CREB-HMGCR , TR4-FATP1 , and TR4-CD36 axes.…”

Triterpenoids from Protorhus longifolia Exhibit Hypocholesterolemic Potential via Regulation of Cholesterol Biosynthesis and Stimulation of Low-Density Lipoprotein Uptake in HepG2 Cells

“…The activity of the compounds could partly be linked to their ability to upregulate the expression of the LDL-R and SREBP-2 genes (Figure A,B). SREBP-2 is known to control cholesterol homeostasis via transcriptional regulation of LDL-R gene and HMG-CoA reductase . Moreover, while the transcriptional expression of LDL-R is regulated by SREBP-2, in post-translational pathways, LDL-R is regulated by protein convertase subtilisin/kexin type 9 (PCSK 9).…”

“…SREBP-2 is known to control cholesterol homeostasis via transcriptional regulation of LDL-R gene and HMG-CoA reductase. 19 Moreover, while the transcriptional expression of LDL-R is regulated by SREBP-2, in post-translational pathways, LDL-R is regulated by protein convertase subtilisin/kexin type 9 (PCSK 9). PCSK 9 mediates LDL-R degradation and interferes with its receptor recycling.…”