Abstract

Wang-Bi capsule (WB) is a traditional Chinese medicine formula and has been applied for rheumatoid arthritis (RA) treatment for many years. However, its underlying molecular mechanisms still remain unclear. In this study, collagen-induced arthritis (CIA) rats were used to observe the therapeutic effect of WB used at different time points, and the proteomic analysis of synovial tissue was applied to reveal its basic molecular mechanisms. The results demonstrated that WB not only effectively ameliorated the symptoms and synovitis, but also downregulated the serum levels of inflammatory cytokines/chemokines in CIA rats. Furthermore, the proteomic analysis of synovial tissue showed that WB could regulate several signaling pathways associated with inflammation or cell migration, such as “IL-1 signaling,” “IL-8 signaling,” and “CXCR4 signaling.” The expression levels of proteins including matrix metalloproteinase 3 (MMP3), MMP19, lipopolysaccharide-binding protein (LBP), serine/threonine kinase interleukin-1 receptor-associated kinase 4 (IRAK4), and actin-related protein 2/3 complex subunit 5 (ARPC5) in these pathways were downregulated significantly by WB when compared with the model group. In sum, this study indicated that WB had obvious inhibitory effects on synovitis of CIA rats, and the mechanisms of which may be involved in downregulating the expression levels of several key proteins including MMP3, MMP19, LBP, IRAK4, and ARPC5.

Highlights

  • Rheumatoid arthritis (RA) is a common chronic inflammatory disease with high incidence and disability rate, and one of the main pathological characteristics of it is the inflammation of the synovial membrane [1, 2]

  • To determine the effect of Wang-Bi capsule (WB) on collagen-induced arthritis (CIA) rats, administration of WB started at day 10 or day 23 or day 36 after first immunization, respectively (Figure 1(a))

  • The hind paw features including swelling and malformation were markedly observed in rats of the model group, but the severity of which was relieved by some degrees in WB treatment groups (T1, T2, and T3 groups) at day 64 compared with the model group (Figure 1(b))

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Summary

Introduction

Rheumatoid arthritis (RA) is a common chronic inflammatory disease with high incidence and disability rate, and one of the main pathological characteristics of it is the inflammation of the synovial membrane [1, 2]. Amounts of infiltrated cells including granulocytes, monocytes/macrophages, B cells, and T cells have been found in the synovial tissue of patients with RA [7,8,9,10] These infiltrated cells secrete plentiful proinflammatory cytokines which can further aggravate inflammation response of synovium. We found that WB could ameliorate arthritis symptoms in CIA mice It could alleviate the synovial inflammation and bone destruction via modulating the OPG/RANKL system and inhibiting the activation of NF-κB [18]. In this study, we observed the therapeutic effect of WB administrated at different time points in CIA rats, and explored its molecular mechanisms by using proteomic analysis of synovium tissue, which hope to present fundamental research evidence for rational use of WB

Materials and Methods
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Conflicts of Interest

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