In China, Wang Bi Granule (WBG)2, composed of 16 herbal and 1 animal-based compounds, is used for clinical treatment of the "Wang Bi" syndrome, commonly referred to as later rheumatoid arthritis (RA) in modern medicine. It is also used in the treatment of ankylosing spondylitis, tuberculous arthritis, and Kashin-Beck disease, which are characterized by joint pain and swelling deformation. However, its pharmacological mechanisms remain unknown. We aimed to characterize the chemical components in WBG and examine the underlying mechanism for RA treatment using integrative pharmacological strategy, including chemical composition detection, efficacy evaluation, and mechanism exploration. We employed UPLC-QTOF-MS/MS to describe the chemical profile of WBG. TNF-α-stimulated RAW264.7 cells were used to simulate the inflammatory processes in RA and evaluate the anti-inflammatory effects of WBG. Network pharmacology was used to determine the mechanism underlying WBG action in RA. A total of 278 chemical components were identified or tentatively characterized. The water extract of WBG improved the imbalance in inflammation in TNF-α-stimulated RAW264.7 cells by regulating 179 differential genes. 55 key active constituents were obtained based on the interactions among "components" targets, RA-related genes, and differential genes (WBG vs TNF-α group) which may ameliorate RA by regulating 161 hub genes primarily involved in inflammation-related pathways. The present study, for the first time, employed integrative pharmacology to characterize the chemical profile of WBG and elucidate its mechanism of action against RA through an inflammation-immune regulatory system.
Keywords: Integrative pharmacology; Rheumatoid arthritis; TCMIP; UPLC-QTOF-MS/MS; Wang Bi Granule.
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