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

Amirul Nazhan Ilias,Mokrish Ajat,Taznim Begam Mohd Mohidin,Mohd Faiz Idris,Hazilawati Hamzah,Intan Safinar Ismail

doi:10.52547/rbmb.10.3.477

Abstract

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.

Highlights

An evidence-based phytotherapy pathway that relies on scientific and clinical data is a crucial approach before the establishment of plantbased derivatives in medical practice [1]
The highest value for Total cellular cholesterol (TCC) was recorded in HRA following PC> LRA> NC, while the lowest was observed in BC
Treatment of cells with LRA has little to no effects on TCC as the result is almost similar to NC

Summary

Introduction

An evidence-based phytotherapy pathway that relies on scientific and clinical data is a crucial approach before the establishment of plantbased derivatives in medical practice [1]. Rebaudioside A is one of the major diterpene glycosides found in Stevia had been reported to possess anti-hyperlipidemic effects. 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. To illustrate the effect of Rebaudioside A on cellular lipid droplets and low-density lipoprotein receptors, treated cells were subjected to immunofluorescence microscopy. 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. We proposed that Rebaudioside A offers a potential alternative to statins for atherosclerosis therapy

Methods

Results

Conclusion