Effect of Siegesbeckiae Herba on immune-inflammation of rheumatoid arthritis: Data mining and network pharmacology

Introduction: Rheumatoid arthritis (RA) is an autoimmune disease resulting in an overall poor prognosis. Sie-gesbeckiae Herba is a natural botanical herb that possesses a variety of biological activities, particularly anti-rheumatism properties.Methods: This study collected the clinical data of 7657 patients with RA who received treatment with traditional Chinese medicine prescriptions before December 2021 in the Department of Rheumatology, The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine. The levels of immune-inflammatory indicators including Hs-CRP, ESR, RF, C3, C4, IgA, IgG, and IgM were observed before and after the treatment. Association rules between Siegesbeckiae Herba and immune-inflammatory indicators were analyzed by Apriori algorithm. Protein-protein interaction network diagram, core gene and drug-active ingredient-target diagram were drawn by Cytoscape3.7.2 software. GO and KEGG analysis was performed by DAVID database. Autodock software was used to conduct molecular docking and in vitro experiments were performed to verify the action mechanism of Siegesbeckiae Herba on RA. Results: Data mining results showed that the use of Siegesbeckiae Herba was strongly associated with the improvement of immune-inflammatory markers of RA. The results of network pharmacology and molecular docking showed that the main target proteins including Bax, CASP3, CASP8, CASP9, COX2, TNF, and IL-17 of Siegesbeckiae Herba were closely related to apoptosis and inflammatory signaling pathways in the treatment of RA. In vitro cell experiments results showed that Kirenol, the main active ingredient of Siegesbeckiae Herba, up-regulated the expressions of pro-apoptotic proteins Bax, caspase3, caspase8, and caspase9 in RA-fibroblast-like synoviocytes (RA-FLSs) and down-regulated the expressions of COX2, TNF, and IL-17.Conclusion: Siegesbeckiae Herba promoted the apoptosis of RA-FLSs and alleviated immune-inflammatory re-sponses in RA.