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2022, Vol. 26 ›› Issue (2): 245-252Potential molecular mechanism of Guizhi Shaoyao Zhimu Decoction in the treatment of gouty arthritis based on network pharmacology and molecular dockingZhang Xiaoyun1, 2, Li Huanan1, Chen Feng2, Chai Yuan2, Gan Bin1, Li Song1, Chen Dingpeng1
Abstract: BACKGROUND: Clinical studies have shown that Guizhi Shaoyao Zhimu Decoction is effective in treating gouty arthritis, but its pharmacological mechanism is not yet clear. OBJECTIVE: To explore the potential molecular mechanism of Guizhi Shaoyao Zhimu Decoction in the treatment of gouty arthritis based on network pharmacology and molecular docking. METHODS: The active components and corresponding targets of Guizhi Shaoyao Zhimu Decoction was screened by TCMSP database. The related targets of gouty arthritis were obtained by the query results of Gene Cards, OMIM and DigSee databases. The potential targets of Guizhi Shaoyao Zhimu Decoction in the treatment of gouty arthritis were obtained by mapping intersection by Venny platform. The network of “single drug-active target-potential target” and the protein interaction network of Guizhi Shaoyao Zhimu Decoction in the treatment of gouty arthritis were constructed by Cytoscape software. The action targets of Guizhi Shaoyao Zhimu Decoction were analyzed by David database including the gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Finally, molecular docking between key active ingredients and key targets was performed using Autodock software. RESULTS AND CONCLUSION: There were 180 active components and 24 targets related to the treatment of gouty arthritis by Guizhi Shaoyao Zhimu Decoction. The key active components were quercetin, formononetin, luteolin, 3'-methoxyglabridin, taxifolin. The key targets were P53, neurotrophic receptor tyrosine kinase 1, Cullin3, estrogen receptor 1, and ubiquitin C. Molecular docking results showed that the key active components showed good binding activity with the key targets of gouty arthritis treatment. GO analysis showed that the key targets were mainly involved in many biological processes such as lipopolysaccharide reaction, bacterial derived molecules response, cell response to biological stimulation, oxidative stress response, regulation of inflammatory response, and response to reactive oxygen species. KEGG pathway analysis showed that Guizhi Shaoyao Zhimu Decoction mainly acted on interleukin-17 pathway, tumor necrosis factor pathway, AGE-RAGE pathway, NOD like receptor pathway, nuclear factor-κB pathway, and Toll like receptor pathway. To conclude, Guizhi Shaoyao Zhimu Decoction could reduce immune-inflammatory reaction, inhibit chondrocyte apoptosis and improve the ability of anti-oxidation stress response by multi-component, multi-target and multi-pathway, so as to play a role in the treatment of gouty arthritis. The protein scaffold drug delivery system can be used orally or locally in the future by screening of effective components, which is conducive to the remission of the disease. Key words:joint, gout, arthritis, traditional Chinese medicine, hyperuricemia, molecular mechanism, network pharmacology, signaling pathway |