Affiliation:
1. General Manager Office, Jiangxi Hanhe Biotechnology Co., Ltd, Nanchang, China
2. General Manager Office, Shaanxi Wisdom Health Management Service Co., Ltd, Xi’an, China
3. Laboratory of Traditional Chinese Medicine, Jiangxi Institute For Drug Control, Jiangxi Provincial Engineering Research Center for Drug and Medical Device Quality, NMPA Key Laboratory for Quality Evaluation of Traditional Chinese Medicine, Nanchang, China
Abstract
Objective To systematically explore the targets and signaling pathways of sinomenine (SIN) in the treatment of osteoarthritis (OA) using integrated network pharmacology, molecular docking, and experimental validation. Methods The TCMSP, SwissADME, and Pharmmapper databases were used to predict SIN targets, while the databases of GeneCards, DisGeNET, OMIM, and DrugBank were selected to acquire OA targets. Subsequently, the intersection targets of SIN and OA disease were collected using the Veeny platform. Then, the protein-protein interaction (PPI) network map of “SIN-targets-OA” was established using String database and Cytoscape software. Additionally, the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed through the Database for Annotation, Visualization and Integrated Discovery (DAVID). Additionally, the potential proteins of SIN against OA were validated via molecular docking technique. Finally, the experimental validation was performed in SW1353 cells induced by interleukin (IL)-1β. Results A total of 315 potential targets of SIN and 4300 OA-associated targets were collected from public databases, and 42 intersecting potential targets of SIN and OA disease acquired. Then, the PPI network diagram of “SIN-targets-OA” was acquired that comprised a total of 43 nodes and 82 edges. Moreover, 173 GO and 21 KEGG pathway entries were screened with a P-value <.05. Among them, peroxisome proliferator-activated receptor (PPAR) and IL-17 are the core signaling pathways. Molecular docking technique indicated strong binding energies of SIN with PPAR (−6.1 kcal/mol) and IL-17 (−6.3 kcal/mol). Lastly, SIN at the concentration of 50 μmol/L has a significant effect on IL-1β-induced SW1353 cells by the inhibition of PPAR-γ and IL-17A proteins without cytotoxicity. Conclusion This work revealed the underlying targets and signaling pathways of SIN against OA using integrated network pharmacology molecular docking, and experimental validation. These findings provide scientific evidence for the clinical application of SIN for OA treatment.