Abstract

Yunnan Baiyao (YNB) is a traditional Chinese medicine that possesses anti-inflammatory effects. Previously, we have demonstrated the effects of YNB in rheumatoid arthritis (RA) animal models; however, the underlying mechanisms are unclear. In the present study, we aimed to investigate the effects of YNB on the T-helper (Th)17/T-regulatory (Treg) cell balance in a collagen-induced arthritis rat model orally administrated YNB or methotrexate, a widely used therapeutic agent for treating RA. Our results showed that YNB treatment significantly decreased the voix pedis thickness and joint functionality scores and alleviated joint histopathology in these rats. These YNB-induced effects were achieved by decreasing the number of Th17 cells and increasing that of Treg cells in the spleen. Moreover, the interleukin- (IL-) 17 level considerably decreased in the serum of YNB-treated rats, whereas the IL-10 level significantly increased. Furthermore, YNB could inhibit RANKL-induced osteoclast formation by regulating the tumor necrosis factor receptor-associated factor 6/NF-κB/nuclear factor of the activated T-cell pathway. In summary, our study shows that YNB exhibits antiarthritic activity by decreasing the ratio of Th17/Treg cells, regulating the cytokine balance, and inhibiting osteoclast activation, providing an experimental basis that supports the use of this traditional Chinese medicine for the clinical treatment of RA.

Highlights

  • Rheumatoid arthritis (RA) is a systemic heterogeneous autoimmune disease of unknown etiology mainly manifested by chronic inflammatory polyarthritis [1]

  • As the ratio of 17/Treg cells is crucial for the pathogenesis of RA, we hypothesised that the antiarthritic effects of Yunnan Baiyao (YNB) may be mediated via the regulation of the 17/Treg cell balance. erefore, in the present study, we focused on the potential anti-RA mechanisms induced by YNB, comparing them with those induced by methotrexate (MTX), one of the most frequently prescribed medicines for treating RA, to provide an experimental basis for the clinical treatment of this disease

  • Aseptic 0.1 mol/L acetate solution containing 2 mg/mL C-II was settled at 4°C overnight and mixed with the same volume of Freund’s complete adjuvant (FCA). e fresh mixture was used as the model construction reagent (MCR). e tartrate resistant acid phosphatase (TRAP) staining kit was acquired from Sigma-Aldrich. e antinuclear factor of activated T cells 1 (NFATc1), anti-TNF receptor-associated factor 6 (TRAF6), anti-NF-κBp65, and antiphosphorylated-NF-κBp65 antibodies were purchased from Cell Signaling Technology (Beverly, MA, USA); antiosteoprotegerin, anti-receptor activator of nuclear factor kappa-B ligand (RANKL), and anti-beta actin antibody were purchased from Abcam (Shanghai)

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Summary

Introduction

Rheumatoid arthritis (RA) is a systemic heterogeneous autoimmune disease of unknown etiology mainly manifested by chronic inflammatory polyarthritis [1]. It is characterised by T-lymphocyte infiltration-based chronic synovitis that eventually leads to arthritis and bone destruction [2]. The proinflammatory effects of 17 cells, anti-inflammatory effects of regulatory T (Treg) cells, and balance of the 17/Treg cell ratio in RA have been the focus of several studies. Traditional Chinese medicine has a long history in the treatment of RA, for which diverse treatment methods have been used. Many kinds of traditional Chinese medicines have been proven to be effective in treating arthritis [6]. Yunnan Baiyao (YNB) is a widely used Chinese herbal medicine mainly composed of Radix Notoginseng, Forest Musk, Borneolum Synthcticum, Rhizoma Paridis (Chonglou), and Radix Aconiti Kusnezoffii

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