An integrated approach to explicate the anti-cerebral ischemia-reperfusion injury mechanisms of Ginsenoside Re action through autophagy

Background: Targeting neuronal functional restoration can be an efficacious regimen for treating neurological diseases, including cerebral ischemia-reperfusion injury (CIRI). Then, there is great significance for screening natural ingredient-played neuroprotection with therapeutical safety. Ginsenoside Re (Re), a nutraceutical molecule isolated from Panax ginseng, is previously proven to possess the neuroprotective benefit against CIRI. However, anti-CIRI regulatory mechanisms of Re action have not been totally explicated. Methods: In present study, we performed a network pharmacology approach accompanied with molecular docking analysis to illustrate the neuroprotective activity and biological mechanism of Re in the treatment of CIRI, characterized with bioinformatics findings by using gene ontology (GO) functional assay, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Results: Data from integrated bioinformatics analysis exhibited that 60 candidate genes were identified as the therapeutic potentials of Re against CIRI related to autophagy. Most of these genes were found to be regulated functionally for CIRI after Re treatment. According to topological parameter analysis, total 30 core targets in Re against CIRI relating autophagy were discovered. The molecular pathways enriched from core targets might be implicated in neural regeneration, neural restoration and immunoregulation. Further computational assay identified 3 key proteins including protein kinase B (AKT1), phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) and heat shock protein 90 AA1 (HSP90AA1), in which these proteins' functions were related to the actions and pathways of autophagy. Conclusion: Current findings from this study combine network pharmacology approach and molecular docking analysis to uncover the core targets and molecular mechanisms of Re in the treatment of CIRI related to autophagy, and then we extrapolate that Ginsenoside Re may be used for the potential application for treating CIRI.