A study of the molecular mechanism of action of Jiawei Guizhishaoyaozhimu Decoction during rheumatoid arthritis therapy based on basic of network pharmacology and experimental verification

Rheumatoid arthritis (RA) is a chronic autoimmune disease, which primarily affects the joints. The aim of the present study was to predict the main active ingredients of Jiawei Guizhishaoyaozhimu Decoction (JWGZSYZMD) and potential targets of this treatment during RA therapy by using molecular docking and network pharmacology methods. In addition, another aim was to investigate the therapeutic effects and mechanism of JWGZSYZMD on joint inflammation in rat models of collagen Ⅱ-induced arthritis (CIA). JWGZSYZMD ingredients and targets and genes associated with RA first extracted from traditional Chinese medicine (TCM) Systems Pharmacology Database and Analysis Platform, Bioinformatics Analysis Tool of Molecular Mechanism-TCM and Genecards databases, which were then transferred to the STRING database to set up protein interaction networks. The crystal structures of target proteins were also downloaded from the Protein Data Bank before molecular docking of compounds onto the protein targets was performed using AutoDock Vina software. In addition, a drug compound target visualization network was constructed using Cytoscape 3.7.2 software, which was used to elucidate the main mechanism underlying the anti-RA effect of JWGZSYZMD. A CIA rat model was established and animals were divided into the control, CIA model, JWGZSYZMD treatment (low-, medium- and high-dose) and tripterygium glycoside groups. Compared with the rats in the CIA model group, the joint scores of the rats in the high-dose group of JWGZSYZMD were significantly lower after 21 days of treatment. The expression levels of IL-6, TNF-α, IL-1β and IL-17A in the synovial supernatant of the model rats were lower compared with those in the CIA group. Also, the expression of the aforementioned cytokines in the high-dose JWGZSYZMD group was significantly lower compared with those in the CIA model group. To conclude, using molecular docking combined with network pharmacology, the material basis and molecular mechanism underlying the effects of JWGZSYZMD during RA therapy were studied, which could potentially provide a reference for future clinical applications.