Identification of the Main Active Components and Mechanism of Wang Bi Tablet in Treating Rheumatoid Arthritis Based on Integrative Pharmacology.

Yuanyuan Jiao,Jia Xu,Chenjing Shi,Jingbo Zhang,Xiaofang Deng,Qiuyan Guo,Ping Wang,Hong Chen,Tong Zhang

doi:10.3389/fphar.2021.669551

Abstract

Wang Bi tablet (WBT) is used to treat rheumatoid arthritis (RA) in China. We employed integrative pharmacology, including rapid analysis of chemical composition, pharmacological experiment, and network pharmacology analysis, to elucidate the active components and mechanism underlying the effect of WBT against RA. The chemical fingerprint of WBT was revealed by UPLC-QTOF-MS/MS, and the chemical composition was identified. The anti-inflammatory effect of WBT was evaluated in TNF-α-stimulated RAW264.7 cells by ELISA and transcriptome sequencing. Network pharmacology analysis, functional enrichment analysis, and network visualization were performed. A total of 293 chemical constituents were preliminarily identified or tentatively characterized in WBT extract, and they effectively inhibited inflammatory response in TNF-α-stimulated RAW264.7 cells. Forty-eight key active constituents were identified based on high-frequency binding to hub targets and their corresponding targets number. Next, 135 corresponding hub genes, which may be the putative targets of WBT in treating RA, were selected. Functionally, the putative targets were significantly associated with the inflammatory immune response regulation module, energy metabolism regulation module, and cell function regulation module, corresponding to the traditional efficacy of WBT. In summary, this study revealed, for the first time using integrative pharmacology, that WBT may attenuate RA through the inflammation-immune regulation system.

Highlights

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial hyperplasia, inflammatory cell infiltration, pannus formation, and destruction of articular cartilage and bone matrix, and this disease develops symmetrically and destructively, eventually leading to articular deformity and loss of function (Smolen et al, 2016; Burmester and Pope, 2017; McInnes and Schett, 2017; Aletaha and Smolen, 2018)
A total of 48 key active constituents were obtained based on their high-frequency binding to hub targets and contents in Wang Bi tablet (WBT), and 135 hub corresponding genes were selected, which may be the putative targets of WBT in treating rheumatoid arthritis (RA)
The 135 putative targets were significantly associated with the inflammatory immune response regulation module, energy metabolism regulation module, and cell function regulation module, corresponding to their traditional efficacy

Summary

Introduction

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial hyperplasia, inflammatory cell infiltration, pannus formation, and destruction of articular cartilage and bone matrix, and this disease develops symmetrically and destructively, eventually leading to articular deformity and loss of function (Smolen et al, 2016; Burmester and Pope, 2017; McInnes and Schett, 2017; Aletaha and Smolen, 2018). Between 2005–2014, the overall incidence of RA was stable compared with that in the previous decade, possibly owing to the changing prevalence of lifestyle factors, such as smoking and obesity (Myasoedova et al, 2020). The development of effective biologics and small-molecule kinase inhibitors has markedly improved both the management and long-term prognosis of RA. These treatments are mainly used to relieve symptoms, and they cause adverse side effects including vomiting, rash, leukopenia, and liver and kidney damage.

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