Changchun University of Chinese Medicine

Tumor is characterized by high morbidity and mortality rates, and are often poorly treated with a grim prognosis. Astragalus membranaceus (AM), a natural herb, plays significant roles in various biological processes. In recent years, increasing evidence has shown that the anti-tumor constituents of AM exhibit significant effects in preventing the development of various cancers, including colon, breast, lung, liver, and melanoma.

This paper provides theoretical support and serves as a reference for future research on the anti-tumor potential of AM by summarizing the mechanisms of its bioactive constituents.

Available literature on AM and anti-tumor by referring to the library and electronic searches in PubMed and Web of Science. Plant names are provided in accordance with "The Plant List" (www.theplantlist.org).

AM contains a range of bioactive constituents, with polysaccharides, saponins, and flavonoids playing a significant role in anti-tumor activities. These mechanisms include inhibiting the proliferation of tumor cells, promoting the apoptosis of tumor cells, regulating the body's immune function, inhibiting the migration and invasion of tumor cells, inhibiting angiogenesis in tumor cells, and enhancing the anti-tumor drug sensitivity.

AM possesses a potential anti-tumor mechanism, but research is mostly based on cell experiments and animal models currently, with extensive clinical studies lacking. In-depth research is expected to improve the life cycle and quality of life of tumor patients.

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.