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整合网络药理学和实验验证方法研究豆甾醇治疗类风湿性关节炎的机制
Authors Xie W , Yang H, Guo C, Xie R, Yu G, Li Y
Received 25 August 2022
Accepted for publication 1 March 2023
Published 7 March 2023 Volume 2023:17 Pages 691—706
DOI https://doi.org/10.2147/DDDT.S387570
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Professor Manfred Ogris
Background: Rheumatoid arthritis (RA) is a chronic inflammatory disease of the joints associated with systemic comorbidities. Sinomenium acutum is regarded as an effective traditional Chinese medicine (TCM) for the treatment of RA.
Materials and Methods: Based on network pharmacology and Gene Expression Omnibus (GEO) database, 33 RA-related differentially-expressed genes (DEGs) targeting active compounds of Sinomenium acutum were initially screened in our investigation.
Results: Gene Ontology (GO) and Kyoto encyclopaedia of genes and genome (KEGG) analyses found the important involvement of these DEGs in osteoclast differentiation, and finally 5 core DEGs, including NCF4, NFKB1, CYBA, IL-1β and NCF1 were determined through protein–protein interaction (PPI) network. We also identified the related active component of Sinomenium acutum include Stigmasterol . Finally, in order to experimentally verify these results, a rat model of collagen-induced arthritis (CIA) was established, and subsequently treated with Stigmasterol solution.
Conclusion: Similar to the healing effect of Indomethacin, Stigmasterol was observed to reduce the levels of inflammatory factors (IL-6 and IL-1β) and osteoclast differentiation-related factors (RANKL, ACP5 and Cathepsin K), which can also reduce the arthritis index score and alleviate the degree of pathological injury of rat ankle joints. The predictions and experimental data uncover the involvement of Stigmasterol , an active component of Sinomenium acutum , in regulation of osteoclast differentiation, exerting great medicinal potential in the treatment of RA.
Keywords: rheumatoid arthritis, Sinomenium acutum , stigmasterol , network pharmacology, osteoclasts