Ginsenoside Re

Atherosclerosis (AS) is a major cause of severe cardiovascular disease and stroke. Ginsenoside Re (Re) has been shown to significantly alleviate AS in mice. Our study demonstrates for the first time that Re can reduce endothelial cell (EC) glycolysis, although the specific mechanism remains unclear.

The effects of Re on lipid levels, aortic wall thickness, inflammation, and aortic fibrosis in AS mice were assessed by measuring serum lipids, carotid artery intima-media thickness, Hematoxylin-Eosin, Masson, and Oil Red O staining, and enzyme-linked immunosorbent assay. The effects of Re on EC proliferation and migration were examined using CCK-8 and wound healing assays in a human umbilical vein endothelial cell model stimulated with oxidized low-density lipoprotein. Furthermore, immunohistochemistry, Western blotting, and real-time quantitative polymerase chain reaction were used to investigate the PFKFB3-HIF-1α-VEGFA-VEGFR2 pathways in vivo and in vitro.

Re demonstrated strong anti-AS activity, evidenced by improved blood lipid profiles, reduced inflammatory factors, and decreased levels of glycolysis-related products and enzymes. In vivo, Re protected against AS by inhibiting glycolysis. In vitro, Re suppressed EC migration through inhibition of the glycolysis-related PFKFB3-HIF-1α-VEGFA-VEGFR2 pathways.

Re may benefit AS mice by inhibiting EC glycolysis and migration through suppression of the PFKFB3-HIF-1α-VEGFA-VEGFR2 pathways. This work broadens the theoretical basis for the therapeutic use of Re in AS.

Ginseng exhibits pharmacological efficacy in the treatment of female postmenopausal osteoporosis (PMOP), although its specific active constituents remain unidentified. This study aims to identify the anti-PMOP active components of ginseng by screening against the ESR2 enzyme. Using osteoprotegerin (OPG) as a biomarker, the most effective ESR2-active components of ginseng were determined through experiments with MC3T3-E1 cells. The potential active components within ginseng were analyzed using ultra-high-performance liquid chromatography coupled with quadrupole-exactive orbitrap mass spectrometry (UHPLC-QE Orbitrap-MS) and further validated through molecular docking and molecular dynamics simulations. The single-target affinity ultrafiltration method was employed to assess the affinity rate (AR%) of the ESR2 enzyme by analyzing peak areas, leading to the identification of key active components of ginseng effective against PMOP through molecular docking analysis. Experimental findings indicated that ginseng extract exhibits compatibility with the ESR2 enzyme, with the 95 % ethanol extract demonstrating the highest activity. A total of 35 potential active components were identified through UHPLC-QE Orbitrap-MS analysis. Following a comprehensive evaluation of molecular docking binding energy and AR% results, Ginsenoside Rf, Ginsenoside Re, and Ginsenoside Rb1 were confirmed as the principal active components of ginseng effective against PMOP. The survival rate, OPG content, and alkaline phosphatase (ALP) activity index, a marker of osteogenic differentiation, were utilized to confirm the final key active components. In this study, the ESR2 enzyme was identified as the active target, and a combination of cell experiments, molecular docking, kinetic simulations, and affinity ultrafiltration was employed to effectively screen the active anti-PMOP constituents of ginseng.