Exploring the Mechanism of Action of Xinfeng Capsule in Treating Hypercoagulable State of Rheumatoid Arthritis Based on Data Mining and Network Pharmacology

Abstract

Objective: To explore the effect of Xinfeng Capsule (XFC) on hypercoagulable state in patients with rheumatoid arthritis (RA) using data mining and network pharmacology. Methods: The data were collected of 524 inpatients with RA who were treated with XFC in the Department of Rheumatology and Immunology of the First Affiliated Hospital of Anhui University of traditional Chinese medicine (TCM) before October 2021. The changes of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), complement component 3 (C3), C4, platelet (PLT), fibrinogen (FBG), thrombin time (TT), prothrombin time (PT), and activated partial thromboplastin time (APTT) were observed before and after the treatment. By implementing the Apriori module, the association rules between XFC and immune-inflammation indexes and coagulation indexes were analyzed. XFC and disease targets were obtained through traditional chinese medicine systems pharmacology database and analysis platform, Genecards, OMIM, and other databases. The cross targets and core targets were screened, and the network diagram of TCM—active ingredients—potential targets was constructed using Cytoscape3.7.2 software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed through Database for Annotation, Visualization and Integrated Discovery (DAVID) database. AutoDock Vina software was used for molecular docking between active ingredients and core targets. The docking results were visualized using PyMOL2.3.0 software. Results: (1) Data mining results showed that the inflammation and coagulation indexes of RA patients were significantly improved after XFC treatment, and there was a strong correlation between XFC and the improvement of CRP, ESR, RF, C3, C4, PLT, FBG, TT, PT, and APTT. (2) Network pharmacology results showed that prostaglandin-endoperoxide synthase 2 (PTGS2), CASP3, tumor necrosis factor (TNF), AKT1, and JUN, the main targets of XFC in the treatment of RA, were closely related to apoptosis and were mainly involved in interleukin 17 (IL-17), TNF, and nuclear factor-κB (NF-κb), and other apoptotic and inflammatory signaling pathways. (3) Molecular docking results showed that the active components of XFC, β- sitosterol, and stigmasterol, had good docking with TNF and PTGS2, which might be the key active components of XFC in the treatment of RA-related hypercoagulable state. Conclusion: XFC can improve the hypercoagulable state of patients with RA by promoting cell apoptosis and improving immune inflammatory response.