Strychni Semen Combined with Atractylodes Macrocephala Koidz Attenuates Rheumatoid Arthritis by Regulating Apoptosis

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease that can lead to joint pain and disability, and seriously impact patients' quality of life. Strychni Semen combined with Atractylodes Macrocephala koidz (SA) have pronounced curative effect on RA, and there is no poisoning of Strychni Semen (SS). However, its pharmacological mechanisms are still unclear. Objective: In this study, we aimed to investigate the pharmacological mechanisms of Strychni Semen combined with Atractylodes Macrocephala Koidz (SA) for the treatment of RA. Methods: We used network pharmacology to screen the active components of SA and predict the targets and pathways involved. Results originating from network pharmacology were then verified by animal experiments. Results: Network pharmacology identified 81 active ingredients and 141 targets of SA; 2640 disease- related genes were also identified. The core targets of SA for the treatment of RA included ALB, IL-6, TNF and IL-1β. A total of 354 gene ontology terms were identified by Gene ontology (GO) enrichment analysis. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis results showed that SA was closely associated with TNF signaling pathways in the treatment of RA. Furthermore, according to the predicted results of network pharmacology, we established a rat model of Adjuvant Arthritis (AA) for in vivo experiments. Analysis showed that each treatment group led to an improvement in paw swelling, immune organ coefficient and synovial tissue morphology in AA rats to different degrees, inhibit the expression levels of IL-1β, TNF-α and IL-6, upregulated the levels of Fas, Bax and Caspase 3, down-regulated the expression levels of Fas-L, Bcl-2 and p53. Conclusion: SA has an anti-RA effect, the mechanism underlying the therapeutic action of SA in AA rats was related to the regulation of apoptosis signaling pathways