Mechanism of Salvia miltiorrhiza Bge. for the Treatment of Ischemic Stroke Based on Bioinformatics and Network Pharmacology

Abstract

Background and Purpose. A large number of pharmacological experiments have proved that many components of Salvia miltiorrhiza Bge. have neuroprotective, anti-inflammatory, and antioxidant effects. Middle cerebral artery occlusion (MCAO) models treated with Salvia miltiorrhiza Bge. can significantly reduce the infarct size and change the pathological morphology of brain tissue. However, not only the internal mechanism but also the material basis is unclear to researchers. Our research aims to elucidate the potential effective material basis and molecular internal mechanism between Salvia miltiorrhiza Bge. and stroke. Methods. In this study, SymMap was used to screen the 50 bioactive scored components and 65 putative targets of Salvia miltiorrhiza Bge., and their targets were standardized using the UniProt platform. The disease targets related to stroke were collected by comparative toxicogenomics database (CTD), GeneCards, and quantitative structure-activity relationships-TargetNet (QSAR-TargetNet). Thereafter, the protein-protein interaction (PPI) network was constructed using the STRING platform and visualized by Cytoscape (3.8.2) software. Then, the Metascape platform was used to analyze the Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Cytoscape (3.7.2) software was also used to construct the network of the “herb-component-target-pathway.” We found that Tanshinol B, Tanshinol A, Przewaquinone C, Tanshinone II, and other main components of Salvia miltiorrhiza Bge. may regulate neurotransmitters and neurological function. Therefore, we speculate Salvia miltiorrhiza Bge. has a neuroprotective effect. For further verification, potential core targets (STAT3, MMP2, ESR1, TERT, and MMP9 proteins) for ischemic stroke and core active ingredients (Tanshinol A, Tanshinol B, Tanshinone II A, and Przewaquinone C) for Salvia miltiorrhiza Bge. were further verified by molecular docking. Results. Our findings revealed that Tanshinol A, Tanshinol B, Tanshinone II A, and Przewaquinone C as the main component of Salvia miltiorrhiza Bge. may have a neuroprotective effect against ischemic stroke, which provides a new understanding for the development of therapies for the prevention and treatment of ischemic stroke.