Combining network pharmacology and bioinformatics to identify bioactive compounds and potential mechanisms of action of Sedum aizoon L in the treatment of atherosclerosis

Abstract

Sedum aizoon L (SL) is a medicinal plant containing several active components with anti-inflammatory, hemostatic, and blood pressure lowering effects. The aim of this research was to investigate the main pathways, mechanisms, and active components of SL to treat atherosclerosis (AS) through network pharmacology. The active ingredients and their targets of action were obtained by setting the active ingredient-screening conditions using SL as a keyword in the Traditional Chinese Medicine (TCM) System Pharmacology Database and Analysis Platform. The differentially expressed genes related to AS were obtained from the Gene Expression Omnibus database, and the targets related to the treatment of AS were retrieved from databases, such as DisGeNet and GENECARDs, and the targets of AS and SL were intersected using the Cytoscape software platform and applied to construct a drug–compound–target–pathway network map. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, and protein–protein interaction were performed to explore the mechanisms of action of SL against AS. In all, 12 active ingredients were screened from the chemical composition of SL, among which myricetin, oleanolic acid, ursolic acid, sitosterol, and beta-sitosterol were the major active ingredients for the anti-atherosclerotic effect of SL. Combining the active ingredient–target network and disease–target protein–protein interaction (PPI) network, GO and KEGG analysis, tumor necrosis factor signaling pathway, and interleukin-17 signaling pathway were the key pathways of action. SL acts as an anti-atherosclerotic agent through multiple chemical components, targets, and pathways. The active ingredients of SL mainly play the role of prevention and treatment of AS by inhibiting inflammatory response, as an antioxidant, and by lowering blood lipids, thereby providing the theoretical basis for its clinical use.