Integration of virtual screening and proteomics reveals potential targets and pathways for ginsenoside Rg against myocardial ischemia.

BACKGROUND

Ginsenoside Rg (Rg) is one of the main active components in Chinese medicines, and . Research has shown that Rg has a protective effect on the cardiovascular system, including anti-myocardial ischemia-reperfusion injury, anti-apoptosis, and promotion of myocardial angiogenesis, suggesting it a potential cardiovascular agent. However, the protective mechanism involved is still not fully understood.

METHODS

Based on network pharmacology, ligand-based protein docking, proteomics, Western blot, protein recombination and spectroscopic analysis (UV-Vis and fluorescence spectra) techniques, potential targets and pathways for Rg against myocardial ischemia (MI) were screened and explored.

RESULTS

An important target set containing 19 proteins was constructed. Two target proteins with more favorable binding activity for Rg against MI were further identified by molecular docking, including mitogen-activated protein kinase 1 (MAPK1) and adenosine kinase (ADK). Meanwhile, Rg intervention on H9c2 cells injured by HO showed an inhibitory oxidative phosphorylation (OXPHOS) pathway. The inhibition of Rg on MAPK1 and OXPHOS pathway was confirmed by Western blot assay. By protein recombination and spectroscopic analysis, the binding reaction between ADK and Rg was also evaluated.

CONCLUSION

Rg can effectively alleviate cardiomyocytes oxidative stress injury via targeting MAPK1 and ADK, and inhibiting oxidative phosphorylation (OXPHOS) pathway. The present study provides scientific basis for the clinical application of the natural active ingredient, Rg, and also gives rise to a methodological reference to the searching of action targets and pathways of other natural active ingredients.