Integrated Network Pharmacology and Metabolomics to Investigate the Effects and Possible Mechanisms of Ginsenoside Rg2 Glycine Ester Derivative Against Hypoxia

Abstract

Previous studies have suggested that ginsenoside Rg₂ glycine ester derivative (RG) exhibits therapeutic potential in mitigating hypoxia. This study aimed to elucidate the potential mechanism of RG in hypoxia injury through a combined approach of metabolomics and network pharmacology. Initially, a CoCl₂-induced cell hypoxia model was established, and the therapeutic impact of RG on biochemical indices was evaluated. Subsequently, metabolomics analysis of cell samples was conducted to identify biomarkers, and network pharmacology was employed to identify potential targets of RG for hypoxia treatment. Finally, the key target and pathway were verified. The study revealed that RG could reverse CoCl₂-induced abnormalities in biochemical indicators. Metabolomics analysis identified 13 biomarkers and seven metabolic pathways associated with RG treatment. Utilizing network pharmacology, five key targets and five metabolic pathways were identified, partially aligning with the metabolomics results. Molecular docking results demonstrated the effective binding of RG to the key targets. Enzyme linked immunosorbent assay verified that RG could exert antihypoxia effect by activated PI3K/Akt pathway. In conclusion, this integrated strategy, combining metabolomics with network pharmacology, sheds light on the protective mechanism of RG against hypoxia-induced cellular damage. The findings offer valuable insights for future research and potential applications of RG in the field.