Exploration of the molecular mechanism guiding Xinfeng capsule regulatory mechanism for rheumatoid arthritis inflammation.

Abstract

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of the joint synovium. The traditional Chinese medicine Xinfeng capsule (XFC) has a remarkable alleviating effect on inflammatory symptoms, such as joint pain and swelling, in patients with RA. However, the underlying mechanism of action remains to be elucidated. This study intended to conduct network pharmacology, animal experiments, data mining, and molecular docking to explore the molecular mechanism through which XFC can improve the inflammatory symptoms of RA. The Apriori association rules and a random walk model were employed to evaluate the effect of XFC on the clinical inflammatory indexes of RA. The active ingredients and the potential target genes of XFC were obtained from public databases. Based on the search tool for recurring instances of neighboring genes (STRING) database, the Database for Annotation, Visualization and Integrated Discovery (DAVID) database, Cytoscape software, and molecular docking method, the molecular mechanism by which XFC acts on RA was also analyzed. Finally, an adjuvant arthritis rat model was established to verify the effects of XFC on inflammation-related signaling pathways and inflammatory factors. XFC significantly reduced the level of C-reactive protein (CRP), vascular endothelial growth factor (VEGF), and the erythrocyte sedimentation rate (ESR). The docking space structures of the active ingredients in XFC, namely triptolide and quercetin, and the key targets were stable. Inflammation-related biological processes were identified as the key factors involved in the development of RA, and the regulation of the toll-like receptor (TLR) signaling pathway may be the key link for XFC toward improving the inflammatory state of RA. The expression levels of toll-like receptor 4 (TLR4), myeloid differentiation primary response protein MyD88 (MyD88), interleukin-1 receptor-associated kinase 1 (IRAK1), TNF receptor-associated factor 6 (TRAF6), TGF-beta-activated kinase 1 (TAK1), phospho-Inhibitor of NF-κB kinaseβ (p-IKKβ), phospho-Nuclear factor-k-gene binding (p-NF-κB), and interleukin-1β (IL-1β) can all be decreased by XFC. XFC improves joint inflammation symptoms by lowering pro-inflammatory factors tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interferon-γ (INF-γ) levels. XFC could effectively improve the clinical inflammatory indexes of RA. The active ingredients of XFC improved the inflammatory state of RA by regulating the TLR-signaling pathway.