Simiao Pill Attenuates Collagen-Induced Arthritis in Rats through Suppressing the ATX-LPA and MAPK Signalling Pathways.

Pan Shen,Hui Wang,Shenghao Tu,Kai Qin,Zhe Chen

doi:10.1155/2019/7498527

Abstract

Objective Simiao pill (SM), a traditional Chinese formula, has been used as an antirheumatic drug in clinical practice for hundreds of years. Rheumatoid arthritis (RA) is characterized by chronic synovial inflammation and hyperplasia, cartilage destruction, and joint damage. This study was designed to investigate the protective effects of SM on collagen-induced arthritis (CIA) in rats. It also aimed to explore whether this protective effect of SM was related to the inhibition of the ATX-LPA and MAPK signalling pathways. Materials and Methods Rats were injected with a collagen II emulsion at the end of the tail and on the back to induce arthritis. Treatment with different doses of SM was conducted by intragastric administration. Then, body weights and arthritis scores were measured. The serum levels of tumour necrosis factor (TNF)-α, interleukin (IL)-1β, C-reactive protein (CRP), osteoprotegerin (OPG), autotaxin (ATX), and lysophosphatidic acid (LPA) were determined by ELISA. Pathological changes in the joints were measured by micro-CT and assessed via haematoxylin-eosin (H&E) staining. The expression of ATX, LPA receptor 1 (LPA1) was detected by immunohistochemical staining, and the expression of mitogen-activated protein kinase (MAPK) was detected by Western blotting. Results SM significantly alleviated arthritis symptoms, inhibited bone erosion, and decreased the levels of TNF-α, IL-1β, CRP, ATX, and LPA in the sera of CIA rats. Importantly, SM clearly reduced the protein expression of LPA1 and ATX. The activation of the MAPK signalling pathway was also inhibited by SM in the synovial tissues of CIA rats. Conclusions The antirheumatic effects of SM were associated with the regulation of the ATX-LPA and MAPK pathways, the suppression of proinflammatory cytokine production, and the alleviation of cartilage and bone injury. These findings suggest that SM might be a promising alternative candidate for RA therapy.

Highlights

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic systemic inflammation, synovial hyperplasia, cartilage destruction, and bone damage that leads to pain, swelling, and deformation of the joints [1]
We investigated the effect of Simiao pill (SM) on the severity of arthritis in collagen-induced arthritis (CIA) rats
CIA rats were in poor conditions with sapless hair and exhibited lower food intake and dull responses compared to the control rats

Summary

Introduction

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic systemic inflammation, synovial hyperplasia, cartilage destruction, and bone damage that leads to pain, swelling, and deformation of the joints [1]. The pathogenesis of RA is complicated; lymphocytes, plasma cells, and macrophages infiltrate the synovium form and cause synovial hyperplasia and the expression of proinflammatory cytokines such as IL-1β, IL-6, IL-17, and TNF-a, which have been reported to play a role in the pathogenesis of RA [3, 4]. The infiltration of these cytokines, immune cells, and fibroblast-like synoviocytes produces a pannus that leads to joint destruction. The suppression of proinflammatory mediators has been proposed as a therapeutic strategy against RA

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Conclusion