Mechanism of ginsenoside Rg1 on myocardial ischemia-reperfusion injury based on network phar-macology,molecular docking and in vitro experiments
Objective Network pharmacology,molecular docking technology and experiments in vitro were applied to explore the potential mechanism of ginsenoside Rg1 on Myocardial ischemia-reperfusion injury(MIRI).Methods The databases of Swiss Target Prediction,Drug Bank,Pharm Mapper were used to identify potential targets of ginsenoside Rg1.The databases of Disgenet,Genecard and OMIM were used to identify disease targets of MIRI.Both common targets were obtained by Wayne diagram.The visual protein-protein interaction(PPI)network model was constructed by STRING database and Cytoscape v.3.7.0 software,and core targets were screened out.The core targets were imported into DAVID database for GO function and KEEG pathway enrichment analysis for the potential mechanism of ginsenoside Rg1 in treating MIRI.The core targets were docked with ginsenoside Rg1 by AutoDock vina software.H9c2 cells were deoxygenated for 6 hours and reoxygenated for 18 hours to simulate the MIRI in vivo.Cells apoptosis rates were detected by flow cytometry.The expressions of serine/threonine-protein kinase(Akt),heat shock protein HSP 90-alpha(HSP90AA1)and B-cell lymphoma-2(Bcl-2)proteins were detected by Western blot.Results 47 potential targets of ginsenoside Rg1 and 2357 disease targets of MIRI were obtained.38 common targets were screened out.Core targets selected by PPI results were signal transducer and activator of transcription 3(STAT3),Akt1,HSP90AA1,Akt2,nitric oxide synthase,inducible(NOS2),basic fibroblast growth factor(FGF2),suppressor of cytokine signaling 3(SOCS3),Bcl-2-like protein 1(BCL2L1),72 kDa type Ⅳ collagenase(MMP2);there are 183 enrichment items in GO analysis including 30 molecular functions,130 biological processes and 23 cell components.Enrichment analysis of KEEG pathway involves PI3K/Akt signaling pathway,pathways in cancer,Rap1 signaling pathway,Kaposi sarcoma-associated herpesvirus infection,chemical carcinogenesis-receptor activation,proteoglycans in cancer,relaxin signaling pathway,toxoplasmosis etc.The results of Molecular docking showed that ginsenoside Rg1 docks stably with STAT3,Akt1,HSP90AA1,Akt2 and NOS2.Compared with the model group,cells apoptosis rate of the ginsenoside Rg1 group were decreased significantly(P＜0.05)in vitro;compared with the model group,expressions of Akt and anti-apoptotic protein Bcl-2 in ginsenoside Rg1 group were increased while HSP90AA1 were decreased(P＜0.05).Conclusion The mechanism of ginsenoside Rg1 in the treatment of MIRI is mainly related to the activation of PI3K/Akt signaling pathway and the regulation of Akt,HSP90AA1,BCL2L1 protein expressions.
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