A Network Pharmacology Approach to Uncover the Key Ingredients in Chuanxiong Rhizoma and Their Anti-Ischemic Stroke Mechanism

Abstract

Nowadays, ischemic stroke (IS) threatens millions of people’s lives. In traditional Chinese medicine, Chuanxiong Rhizoma(CR) has a good effect and is used most frequently in treaing IS. This study aimed to investigate the active ingredients and mechanism of CRagainst IS through network pharmacology and molecular docking technology. Firstly, TCMSP database was used to obtain main chemical active components of Chuanxiong Rhizome, and the targets of chemical active components were retrieved from the SwissTargetPrediction database. The targets of IS were searched from Genecards and PALM-IST, and then the protein-protein interaction network of the targets was constructed by String 11.0. Gene ontology (GO) enrichment analysis and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis of targets were based on Metascape. The molecular docking verification was carried out by SwissDock. A total of 6 chemical active components were screened from Chuanxiong Rhizoma. GO enrichment analysis showed that the biological processes act on 67 IS targets. The key targets were PTGS2, SRC, MAPK8, MMP9 and PPARG, mainly involved in circulatory system process, regulation of inflammatory response, positive regulation of cell death and metal ion homeostasis. KEGG pathway enrichment analysis showed that CR played a therapeutic role in IS by regulating EGFR tyrosine kinase inhibitor resistance, neuroactive ligand-receptor interaction, arachidonic acid metabolism, platelet activation and HIF-1 signaling pathway. The molecular docking results showed that the active components had the strong binding effect with core targets. GEO dataset analysis showed that CR’s therapeutic effects might be exerted via the core targets such as PTGS2, MMP9 and STAT3. This study reveals CR against IS may be related to its multiple targets, multiple biological functions and multiple signaling pathways, provides theoretical basis for further experimental and clinical research.