LIN Li,LU Ying,LI Kongfei, et al. Network target prediction and mechanism confirmation of ginsenoside Rg1 in treating multiple myeloma[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2024, 54(8): 650-656，663.
Abstract：Objective: To explore the mechanism of ginsenoside Rg1 in the treatment of multiple myeloma (MM) by using network pharmacology and in vitro cell experiments. Methods: TTD, DisGeNet, GeneCards,PharmGKB, PubChem, Super-PRED and PharmMapper were used to predict the MM target. Ginsenoside Rg1 target was predicted by CTD and SymMap database. Protein-protein interaction network of MM and Rg1 intersection targets was constructed by STRING database. Gene Ontology (GO) and KEGG-pathway database were used to enrich the main biological functions and signal pathways of Rg1 in treating MM. Molecular docking was used to verify the binding activity of the core target with Rg1. CCK-8, flow cytometry and Western blot experiments were used to detect the cell activity, apoptosis rate, ROS level and the relative expression of core action targets Caspase3, Bax, Bcl-2 and NF-κB p65 in RPMI 8226 cell at different doses of ginsenoside Rg1 (5,10 and 20 μmol/L). Results: A total of 215 Rg1-MM targets were screened. The enrichment analysis of GO and KEGG pathway suggested that the mechanism of Rg1 in treating MM might involve oxidative stress, apoptosis and inflammation-related signaling pathways. Molecular docking suggested that Rg1 might play a role by regulating NFKB1, STAT3, AKT1, MAPK3, CASP3, BCL2 and other targets. In vitro experiments, compared with the control group, Rg1 (5, 10 and 20 μmol/L) significantly inhibited the proliferation (P<0.01) of RPMI 8226 cell,promoted apoptosis (P<0.01) and ROS production (P<0.01), and inhibited the activation of NF-κB signaling pathway (P<0.05). Conclusion: Ginsenoside Rg1 has a potential therapeutic effect on MM, which can regulate oxidative stress, apoptosis and proliferation of RPMI 8226 cell, and its mechanism involves the regulation of NF-κB signaling pathway.
