Network-pharmacology-based study on the mechanism of fibrates regulating HIF-1A in the treatment of ischemic stroke

Abstract

Ischemic stroke (IS) is a serious threat to people's health, its occurrence risk is closely related to lipid levels and genes. Fibrates are commonly used as adjunctive therapy for IS in clinical practice, some studies have reported that hypoxia-inducible factor (HIF1A) is associated with the occurrence risk of various diseases, so it is important to explore the mechanism of fibrates regulate HIF1A in the treatment of IS. Firstly, the potential targets of fibrates, IS, HIF1A and HIF1A-related genes were obtained through various databases, then their common targets were obtained through Venny 2.1.0. The PPI network of fibrates and HIF1A-related genes was plotted by String platform and Cytoscape3.8.1 software. KEGG pathways of drugs, diseases, HIF1A and HIF1A related genes were obtained by Metascape platform. Finally, molecular docking of fibrates and HIF1A was performed by AutoDock software. In this study, the structure of five fibrates were obtained by reviewing the literature and pharmacopoeia. The common targets of five fibrates and IS showed that only 3 fibrates contained HIF1A. KEGG pathway analysis and molecular docking results showed that fibrates can better regulate HIF1A to treat IS, its main action pathways are pathways in cancer, kaposi sarcoma-associated herpesvirus infection and HIF-1 signaling pathway.