Amirul Nazhan Ilias - Department of Veterinary Preclinical Science, Faculty of Veterinary Medicine, Universiti Putra Malaysia, ۴۳۴۰۰ UPM, Selangor, Malaysia.
Intan Safinar Ismail - Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, ۴۳۴۰۰ UPM, Selangor, Malaysia.
Hazilawati Hamzah - Department of Veterinary Pathology and Microbiology, Faculty of Veterinary Medicine, Universiti Putra Malaysia, ۴۳۴۰۰ UPM, elangor, Malaysia.
Taznim Begam Mohd Mohidin - Institute of Biological Sciences, Faculty of Science, University of Malaya, ۵۰۶۰۳ Kuala Lumpur, Malaysia.
Mohd Faiz Idris - Pusat Bahasa dan Pengajian Umum, Universiti Pendidikan Sultan Idris, ۳۵۹۰۰ Tanjong Malim, Perak, Malaysia.
Mokrish Ajat - Department of Veterinary Preclinical Science, Faculty of Veterinary Medicine, Universiti Putra Malaysia, ۴۳۴۰۰ UPM, Selangor, Malaysia.

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 (HepG۲) cell line in comparison with simvastatin. Methods: Cells were incubated with Rebaudioside A at several concentrations (۰-۱۰ μM) to determine the cytotoxicity by the MTT assay. Cells were treated with selected dosage (۱ and ۵ 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 ۲۷.۷۲ 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 ACAT۲. Conclusions: In conclusion, our data demonstrated that Rebaudioside A is capable to regulate cholesterol levels in HepG۲ cells. Hence, we proposed that Rebaudioside A offers a potential alternative to statins for atherosclerosis therapy.

Rebaudioside A, Anti-hypercholesterolemia, Lipid droplets, Low-density lipoprotein, HMGCR.