Role of Panax ginseng and ginsenosides in regulating cholesterol homeostasis

Background: Hypercholesterolemia is harmful for human health since it may favor atherosclerosis and increase the risk of cardiovascular disease. Panax ginseng is one of the most used species of ginseng, also known as Asian or Korean ginseng. Most of the research on Panax ginseng focuses on ginsenosides. Ginsenosides Rb1 and Rb2 are among the most abundant ginsenosides in ginseng roots. Previous studies have demonstrated properties for both ginsenosides Rb1 and Rb2 against aging, oxidation, inflammation, obesity, hyperglycemia, and diabetes (Miao et al., 2022; Zhou et al., 2019). No data are currently available on the direct interaction between ginsenosides and the cellular cholesterol biosynthesis. In this work, the role of the ginsenosides Rb1 and Rb2 and of a P. ginseng root extract (previous prepared and characterized by our group, manuscript submitted for publication) in regulating cholesterol homeostasis were investigated. Methods: To investigate the effect of a Panax ginseng extract and of some major components thereof (namely, ginsenosides Rb1 and Rb2) on cellular cholesterol homeostasis, we analyzed key mediators of cholesterol synthesis and clearance through biosensor-based, chromatographic and immunoblotting assays. Results: Individual treatments reduced intracellular cholesterol levels by modulating the SREBP-2-HMGCR and LXR-IDOL signaling pathways and promoted cholesterol excretion from cells by upregulating the expression of cholesterol 7α-hydroxylase (CYP7A1). Furthermore, both ginsenosides targeted HMGCR and inhibited its functionality via a statin-like mechanism. Conclusion: Globally, besides confirming the biological properties of ginseng, our findings aid in deciphering the role of a major class of ginseng components in the observed cholesterol- regulating effects and support the use of ginseng as a therapeutic adjuvant in the treatment of diseases associated with dyslipidemia.