| PurposeThis study was designed to investigate the protective effects of(Simiao formula)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.MethodsMale Wistar rats were injected with a collagen II emulsion at the end of the tail and on the back to induce arthritis.Among these rats,a total of 30 rats were picked out and divided into five groups(n=6/group)as CIA group,methotrexate(MTX)group,low-dose Simiao formula group(SM-L),medium-dose Simiao formula group(SM-M),and a high-dose Simiao formula group(SM-H)randomly.Treatment with different doses of SM was conducted by intragastric administration for 40 days.Control and CIA group rats were treated by saline.Then,body weights and arthritis scores were measured.The serum levels of tumour necrosis factor(TNF)-?,interleukin(IL)-1?,C reactive protein(CRP),osteoprotegerin(OPG),autotaxin(ATX)and lysophosphatidic acid(LPA)were determined by ELISA.Pathological changes inthe 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.ResultsSM significantly alleviated arthritis symptoms,inhibited bone erosion and decreased the levels of TNF-?,IL-1?,CRP,ATX and LPA in the sera of CIA rats.Importantly,SM clearly reduced the protein levels of LPA1 and ATX in ankle tissues.The activation of ERK1/2,p38,JNK was also inhibited by SM in the synovial tissues of CIA rats.ConclusionThe anti-rheumatic 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 treatment. |
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