Study on the Mechanism of Buyang Huanwu Decoction for the treatment of Ischemic Stroke Based on Network Pharmacology

Abstract Background: Buyang Huanwu Decoction (BYHWD) is one of the representative prescriptions for tonifying qi and promoting blood circulation. This formula has been widely used in Chinese clinical practice for treatment and prevention of ischemic cerebral vascular diseases. However, the mechanism and active compounds of BYHWD used in clinical practice for ischemic stroke are not well understood. The purpose of this study was to understand the potential active components of BYHWD and further explore its mechanism of improving ischemic stroke. Methods: This study was based on network pharmacology and bioinformatics analysis. The compounds of BYHWD were obtained from public databases. Oral bioavailability as well as drug-likeness were screened by using absorption, distribution, metabolism, and excretion (ADME) criteria. Then, components of BYHWD, candidate targets of each component and known therapeutic targets of ischemic cerebral were collected. A network of compound-target genes and compound-ischemic cerebral was established by means of network pharmacology data sources. The enrichment of key targets and pathways was analyzed by using string database and DAVID database. In addition, we verified three key targets predicted by western blot analysis (IL6, VEGFA and HIF1A). Results: Network pharmacology analysis results of BYHWD identified 7 herbs, 42 compounds and 79 target genes associated to cerebral ischemia. The 10 key compounds were baicalein, beta-carotene, Baicalin, kaempferol, luteolin, quercetin, hydroxysafflor yellow A, isorhamnetin, Bifendate, formononetin,Calycosin, AstragalosideIV, Stigmasterol, sitosterol, Z-ligustilide, Dihydrocapsaicin. Core genes in this network were IL6, TNF, VEGFA, HIF1A, MAPK1, MAPK3, JUN, STAT3, IL1B and IL10. And pathways TNF, IL-17, Apoptosis, PI3K-Akt, Toll-like receptor, MAPK, NF-kappa B and HIF-1 signaling pathway, etc. related to ischemic stroke were identified. In vitro experiments, The results showed that compared with the control group (no treatment), BYHWD could significantly inhibit the expression of IL6 and increased the expression of HIF1A and VEGFA. Conclusions: Network pharmacology analysis can reveal close interactions between multi-components and multi-targets, and enhance our understanding of the potential effects of BYHWD in cerebral ischemia.