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

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.

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.

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.

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.