Mechanisms of action underlying Shentong Zhuyu decoction based treatment of rheumatoid arthritis using systems biology and computer-aided drug design

Rheumatoid arthritis is an autoimmune disease characterized by chronic polyarticular pain, for which no cure currently exists. In Chinese medicine, rheumatoid arthritis (RA) is believed to be caused by phlegm and blood stagnation. Shentong Zhuyu decoction can be used to treat RA, as it promotes blood circulation, resolves blood stasis, and relieves pain. In our study, we used network pharmacology and computer-aided drug design to evaluate the components, active compounds, and targets of Shentong Zhuyu decoction (STZY). Our results suggest that STZY contains active compounds such as quercetin, luteolin, and formononetin that regulate immune network targets. RA associated genes are enriched in pathways including those associated with nuclear factor kappa B, phosphatidylinositol-3-kinase/AKT, and hypoxia inducible factor 1 signaling. The main active compounds in STZY (quercetin and luteolin) were derived from Achyranthis Bidentatae Radix, Carthami Flos, licorice, Cyperi Rhizoma, and Myrrha and targeted the pro-inflammatory cytokines interleukin 2, interleukin 1 alpha, interleukin 1 beta, and interleukin 6. In addition, the compounds quercetin, luteolin, and formononetin in these herbs can target the anti-inflammatory cytokines interleukin 4 and interleukin 10. Our results suggest that STZY can balance the immune network, promote an anti-inflammatory environment, and reduce the clinical symptoms of RA. Based on the close relationship between inflammatory response and osteoclast formation, we hypothesized that STZY may inhibit inflammation and alleviate bone destruction in RA. Our findings indicate that STZY can treat RA through multiple components, targets, and pathways. This study may provide a reference for the clinical application of STZY in RA treatment.