Mechanism of Salviae Miltiorrhizae Radix et Rhizoma-Angelicae Sinensis Radix in the Treatment of Cerebral Ischemic Stroke Based on Network Pharmacology
Objective To investigate the potential mechanism of Salviae Miltiorrhizae Radix et Rhizoma-Angelicae Sinensis Radix in the treatment of cerebral ischemic stroke(CIS).Methods The active ingredients and targets of Salviae Miltiorrhizae Radix et Rhizoma and Angelicae Sinensis Radix were obtained by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and Swiss TargetPrediction database,and relevant literature in the PubMed and CNKI were searched for supplementary analysis.The potential targets of CIS were obtained by the GeneCards,Online Mendelian Inheritance in Man(OMIM)and DisGeNET databases.The common targets of active ingredients in Salviae Miltiorrhizae Radix et Rhizoma-Angelicae Sinensis Radix and CIS were imported into the String 11.0 platform to construct a protein-protein interaction(PPI)network,and a disease-drug-active ingredient-target visualization network was constructed by the Cytoscape 3.8.2 software.The common targets were imported into the DAVID database for Gene Ontology(GO)functional enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis,and an active ingredient-core target-pathway network was constructed by the Cytoscape 3.8.2 software.The top six core targets and active ingredients with high degree in the disease-drug-active ingredient-target network were selected for molecular docking verification by the AutoDock software.Results A total of 82 active ingredients(65 from Salviae Miltiorrhizae Radix et Rhizoma,17 from Angelicae Sinensis Radix),787 potential targets,671 disease targets and 76 common targets were obtained.The top six active ingredients with high degree were tanshinol B,danshenxinkun D,luteolin,ferulic acid,ligustilide and tanshinone ⅡA,the top six core targets were MAPK14,MAPK1,AKT1,PTGS2,EGFR and JAK2.A total of 2 545 GO functional entries were obtained,including 2 244 biological processes,128 cellular compositions and 173 molecular functions,involving response to lipopolysaccharide,membrane raft,endopeptidase activity and so on respectively.A total of 152 KEGG signaling pathways were obtained,mainly involving PI3K-Akt signaling pathway,lipid and atherosclerosis,calcium signaling pathway and so on.The molecular docking showed that six active ingredients had good binding energies with their corresponding core targets.Conclusion Salviae Miltiorrhizae Radix et Rhizoma-Angelicae Sinensis Radix in the treatment of CIS has the characteristics of multiple-ingredients,multiple-targets and multiple-pathways regulation.Its mechanism may be related to the anti-inflammatory,antioxidant stress,anti-neuronal apoptosis and autophagy function regulation.