Integrative Pharmacology Powers the Active Components Detection and Mechanism Exploration of Wang Bi Granules Acting on Rheumatoid Arthritis

Wang Bi Granule (WBG), composed of 16 botanical drugs and 1 animal drug, is clinically used to treat “Wang Bi” syndrome, which mainly refers to later rheumatoid arthritis (RA) in modern medicine, as well as ankylosing spondylitis, tuberculous arthritis, and Kashin-Beck disease characterized by joint pain and swelling deformation. However, its chemical composition and pharmacological mechanisms have not been clarified. Therefore, in the present study we aimed to characterize the chemical components of WBG and explore its mechanism in treating RA using integrative pharmacology, including chemical composition detection, efficacy evaluation, and mechanism exploration. We employed UPLC-QTOF-MS/MS to describe the chemical profile of WBG, TNF-a-stimulated RAW264.7 cells to simulate inflammatory process of RA and evaluate the anti-inflammatory effect of WBG, and network pharmacology to mine the mechanism of WBG acting on RA. As a result, a total of 278 chemical components were identified or tentatively characterized and the water extract of WBG improved the imbalance of inflammation by regulating 179 differential genes in RAW264.7 cells induced by TNF-a. 55 key active constituents were obtained based on the interactions among “components' targets, RA-related genes, and differential genes (WBG vs TNF-a group)”, which may ameliorate RA conditions by regulating 161 hub genes that mainly involved in inflammation-immune related pathways. The present study, for the first time, employed integrative pharmacology to characterize the chemical profile of WBG and reveal its mechanism against RA through inflammation-immune regulation system. Overall design: Based on RAW264.7 cells (mouse origin), blank group, induction group (inflammatory factors), WBG group and and want to obtain differentially expressed genes among each group, and further analyze the mechanism of drug efficacy