Elucidation of Potential Targets of San-Miao-San in the Treatment of Osteoarthritis Based on Network Pharmacology and Molecular Docking Analysis

Abstract

Background. To examine the potential therapeutic targets of Chinese medicine formula San-Miao-San (SMS) in the treatment of osteoarthritis (OA), we analyzed the active compounds of SMS and key targets of OA and investigated the interacting pathways using network pharmacological approaches and molecular docking analysis. Methods. The active compounds of SMS and OA-related targets were searched and screened by TCMSP, DrugBank, Genecards, OMIM, DisGeNet, TTD, and PharmGKB databases. Venn analysis and PPI were performed for evaluating the interaction of the targets. The topological analysis and molecular docking were used to confirm the subnetworks and binding affinity between active compounds and key targets, respectively. The GO and KEGG functional enrichment analysis for all targets of each subnetwork were conducted. Results. A total of 57 active compounds and 203 targets of SMS were identified by the TCMSP and DrugBank database, while 1791 OA-related targets were collected from the Genecards, OMIM, DisGeNet, TTD, and PharmGKB databases. By Venn analysis, 108 intersection targets between SMS targets and OA targets were obtained. Most of these intersecting targets involve quercetin, kaempferol, and wogonin. Moreover, intersecting targets identified by PPI analysis were introduced into Cytoscape plug-in CytoNCA for topological analysis. Hence, nine key targets of SMS for OA treatment were obtained. Furthermore, the potential binding conformations between active compounds and key targets were found through molecular docking analysis. According to the DAVID enrichment analysis, the main biological processes of SMS in the treatment of OA include oxidative stress, response to reactive oxygen species, and apoptotic signaling pathways. Finally, we found wogonin, the key compound in SMS, might play a pivotal role on Toll-like receptor, IL-17, TNF, osteoclast differentiation, and apoptosis signaling pathways through interacting with four key targets. Conclusions. Therefore, this study elucidated the potential active compounds and key targets of SMS in the treatment of OA based on network pharmacology.