Mechanism of Salviae Miltiorrhizae Radix et Rhizoma in the Treatment of Knee Osteoarthritis Based on Network Pharmacology

Abstract

Objective The molecular mechanism of Salviae Miltiorrhizae Radix et Rhizoma (SMRR) in the treatment of knee osteoarthritis (KOA) was analyzed based on network pharmacology. Methods Active components and potential targets of SMRR were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. KOA targets were obtained from the OMIM, DisGeNET, DrugBank, PharmGKB, and GeneCards Databases. The potential targets of SMRR in the treatment of KOA were identified by the Venn diagram. A protein-protein interaction network was generated with the STRING database. Visualization of the interactions in a potential pharmacodynamic component-target network was accomplished with Cytoscape software. The Database for Annotation, Visualization, and Integrated Discovery database and R software were used for Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway annotation analyses of common targets. Molecular docking of the potential leading components, as determined by efficacy with the core target molecules, was performed with Discovery Studio. Results Fifty-seven potential pharmacodynamic components and 58 potential targets of SMRR in the treatment of KOA were found. Bioinformatics analyses showed that the interleukin (IL)-17, hypoxia-inducible factor-1 (HIF-1), and tumor necrosis factor (TNF) signaling pathways, as well as the advanced glycation end product-receptor for advanced glycation end product signaling pathway in cases of diabetic complications, are related to the molecular mechanism of SMRR in the treatment of KOA. Molecular docking results showed that luteolin, tanshinone IIA, cryptotanshinone, and other components of SMRR had a strong affinity for MYC, signal transducer and activator of transcription 3, caspase-3 (CASP3), JUN, cyclin D1, prostaglandin endoperoxide synthase 2 (PTGS2), epidermal growth factor receptor (EGFR), mitogen-activated protein kinase 1 (MAPK1), protein kinase B, vascular endothelial growth factor A, and other targets. Conclusion SMRR indirectly regulates IL-17, HIF-1, TNF, and other signal transduction pathways by regulating the expression of proteins, including PTGS2, MAPK1, EGFR, and CASP3, thus playing a role in promoting chondrocyte proliferation, improving microcirculation, eliminating free radicals, and inhibiting inflammatory factors.