Integrating network pharmacology and in vivo pharmacological investigation for deciphering the mechanism of Simiao Yong’an decoction in alleviating rheumatoid arthritis

Objective: To investigate the mechanism of Simiao Yong’an Decoction in alleviating the damage of rheumatoid arthritis (RA), and accordingly provide pharmacological evidence and further experimental support for the application of Simiao Yong’an Decoction, as well as provide a reference direction for the development of new drugs for RA treatments. Materials and methods: Arthritis was induced in Balb/c mice. The animals were randomly divided into 4 groups: control, model, methotrexate (MTX), and Simiao Yong’an Decoction group (n = 6). The Simiao Yong’an Decoction group was orally administered 4.5 g·kg−1 of Simiao Yong’an Decoction every day, and the MTX group received a single intraperitoneal injection of 2 mg·kg−1 of MTX. The arthritis symptoms of joints were scored every day after injecting a cocktail antibody. The histopathology injuries and bone destruction of joints were measured by hematoxylin and eosin staining, Safranin-O fast green staining, tartrate-resistant acid phosphatase staining, and micro–computed tomography. The regulation of Simiao Yong’an Decoction on leukocytes was analyzed by flow cytometry. The expression of inflammatory cytokines, chemokines, and matrix metalloproteinases in joints was detected by quantitative real-time polymerase chain reaction. In the network pharmacology analysis, drug targets of Simiao Yong’an Decoction were obtained from Swiss Target Prediction. Disease targets of RA were obtained from the Therapeutic Target Database and Disgenet. The ingredients-targets network, protein-protein interaction network, and gene ontology function enrichment were performed and visualized by Cytoscape software. Results: In the collagen antibody-induced arthritis (CAIA) murine model, Simiao Yong’an Decoction effectively improved arthritis symptoms, decreased the expression of inflammatory cytokines, and reduced joint pathologic damage and bone destruction. In the network pharmacology analysis, multiple active ingredients of Simiao Yong’an Decoction were found to regulate genes related to inflammation, chemotaxis, and collagen degradation in RA, and reduce RA damage by regulating biological processes including leukocyte migration, myeloid cell homeostasis, and collagen degradation metabolism. We further verified that Simiao Yong’an Decoction effectively regulated the number of myeloid cells in CAIA mice. Moreover, Simiao Yong’an Decoction suppressed the expression of myeloid cell-associated chemokines and matrix metalloproteinases in inflamed joints of CAIA mice. Conclusion: Simiao Yong’an Decoction effectively reduces RA damage by regulating myeloid cells and reducing collagen degradation.