Exploring the Mechanism of Zanthoxylum Bungeanum Maxim in the Treatment of Osteoarthritis Based on Network Pharmacology, Molecular Docking and Molecular Dynamics Simulation

Abstract

Zanthoxylum bungeanum Maxim (ZBM) is a traditional Chinese seasoning, and is often used as a Chinese herbal medicine in treating osteoarthritis (OA) and other diseases, but its active ingredients and pharmacological mechanisms are still unclear. We used network pharmacology, molecular docking, and molecular dynamics simulation (MDS) to explore the potential mechanisms of ZBM for the treatment of OA. A total of three potential active ingredients of ZBM, including quercetin, diosmetin, and beta-sitosterol, were screened from the TCMSP. The active ingredient targets were intersected with the OA-related targets obtained from GeneCards, OMIM, PharmGkb, and TTD databases, 43 common ZBM-OA targets were obtained. Hub genes (HIF1A, EGFR, CASP3, IL6, FOS and VEGFA) were obtained in the key target PPI network. GO and KEGG enrichment analysis showed that ZBM is involved in oxidative stress, inflammation, and apoptosis of chondrocytes mainly through regulating AGE-RAGE signaling pathway in diabetic complications, and thus plays a role in the treatment of OA; Molecular docking results showed that the key active compounds in ZBM could bind tightly to key target proteins; the MDS results showed that the active ingredient diosmetin could bind stably to EGFR. This study reveals the potential active ingredients and molecular mechanisms of ZBM for the treatment of OA.