Objective  To study the potential target and mechanism of Shiwei Jiegu formulation in the treatment of osteoarthritis based on network pharmacology and molecular docking technology.

Methods  The active constituents and corresponding targets of Shiwei Jiegu formulation were screened using pharmacology database of the traditional Chinese medicine systems, and the disease targets of osteoarthritis were obtained from GeneCards, Digsee and DisGeNET databases. Then, the intersection of drug active ingredient targets and disease targets was input into STRING database to construct the interaction network. The intersection target information was enriched by GO and KEGG using clusterProfiler 3.8.1. AutoDock 4.2.6 software was used to verify the molecular docking between important active ingredients and targets. The cell viability of chondrocytes and the RNA expression of key genes of osteoarthritis were detected by CCK-8 kit and RT-PCR.

Results  A total of 679 active ingredients and 2 411 targets were obtained. The main active ingredients were luteolin, ursolic acid, wogonin, etc. The main related targets were AKT1, TNF, IL-6, VEGFA, IL-1B, TP53, CASP3, PTGS2, EGFR, MMP-9, etc. The results of enrichment analysis showed that the key pathway of inhibiting osteoarthritis by Shiwei Jiegu formulation was lipid and atherosclerosis signaling pathway. The results of molecular docking indicated that the main active components of Shiwei Jiegu formulation, that luteolin, ursolic acid and wogonin had good binding energy with TNF, IL-6 and VEGFA of the key targets of osteoarthritis. The results of cell viability and cell proliferation indicated that Shiwei Jiegu formulation could effectively promote the growth and proliferation of chondrocytes. The results of gene and protein expression showed that Shiwei Jiegu formulation could significantly down-regulate the expression of TNF, IL-6 and VEGFA of the key genes in osteoarthritis.

Conclusion   Shiwei Jiegu formulation may regulate the expression of key proteins such as TNF, VEGFA and IL-6 in lipid and atherosclerotic pathway through the main active components such as luteolin, ursolic acid and wogonin, and inhibit the development of osteoarthritis.

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