Mechanism of Cordyceps sinensis in atherosclerosis treatment based on network pharmacology and molecular docking analysis

Abstract

Background: The present study intented to delve into the molecular mechanism of Cordyceps sinensis ( C. sinensis ) in treating atherosclerosis by combining network pharmacology and molecular docking analysis. Methods: We searched the databases including Traditional Chinese Medicines Systems Pharmacology Database and Analysis Platform, PubChem, and PharmMapper to screen out the active chemical ingredients of C. sinensis and the corresponding targets. The String database was used for the matching normalization of results, and the software Cytoscape 3.7.2 was adopted to establish the C. sinensis -active components-targets of action-disease network. The databases of Online Mendelian Inheritance in Man database, GeneCards, Therapeutic Target Database, and DisGNET were searched to yield the major targets of atherosclerosis (AS), which were matched with the active component targets of C. sinensis to identify the potential therapeutic targets. The String database was utilized to set up the protein-protein interaction network, and Cytoscape software was applied for topological analysis, which was followed by the Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes signaling pathway analysis based on the DAVID database. Finally, the core components of C. sinensis and the targets of action were confirmed via molecular docking on AutoDock Vina and PyMOL. Results: In total, 7 bioactive ingredients of C. sinensis were identified from Traditional Chinese Medicines Systems Pharmacology Database and Analysis Platform database and 319 predicted targets were obtained, 231 of which were associated with AS. The core targets involved in AS treatment with C. sinensis included MAPK1, SRC, PIK3R1, AKT1, and HSP90AA1. The enrichment analysis unveiled the primary pathways involved in these processes, such as pathways in cancer and lipid and atherosclerosis. Moreover, through molecular docking, it was found that the active ingredients of C. sinensis presented with strong binding capacities with their corresponding targets, and the strongest binding capacity was observed between peroxyergosterol and SRC. Conclusions: The present study revealed at the molecular level that C. sinensis played its role in AS treatment through multiple drug active components, targets of action and pathways, which would point out the direction and provide theoretic basis for future research.