Abstract
BackgroundSigesbeckia glabrescens Makino (SG) has been traditionally used for rheumatism and joint protection. However, the anti-arthritic effects and underling mechanisms of SG have not been demonstrated. In this study, we investigated the anti-arthritic effects and mechanisms of SG extract (SGE) on collagen-induced arthritic rats and interleukin (IL)-1β-stimulated human synovial SW982 cells.MethodsRats were induced to arthritis by collagen for 15 days and then received SGE treatment for 35 days. The body weight and arthritis severity score of the rats were monitored weekly. At the end of the experiment, the radiographic and histological changes of rats’ hind paw were obtained; the serum C-reactive protein was detected by enzyme-linked immunosorbent assay (ELISA); the expression levels of interleukin (IL)- 1β, IL6 and IL-10 in the joint muscles were determined by ELISA and immunohistochemical staining; and the level of regulatory T cells (Tregs) in the spleen was detected using flow cytometry. In addition, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and scratch wound healing assay were used to evaluate the proliferation of SW982 synovial cells. ELISA, western blot and immunofluorescence staining were used to investigate the anti-inflammatory mechanisms of SGE on IL-1β-induced SW982 cells and joint muscles of CIA rats.ResultsSGE attenuated the collagen-induced hind paw swelling, cartilage damage and bone erosion. SGE inhibited the synovial hyperplasia to the articular cavity in the toe joint and ankle. Moreover, SGE decreased the production of C-reactive protein in serum and the expression of IL-6, IL-1β, cyclooxygenase-2 (COX-2) and phosphorylation of NF-κB p65 in the joint muscles. SGE also recovered the decreased Tregs. Results from the in vitro experiments showed that SGE not only inhibited the proliferation and migration of human synovial cell but also inhibited the IL-1β-induced expression of IL-6 and IL-8. Similarly, SGE inhibited the activation of NF-κB and the expression of COX-2.ConclusionsSGE attenuated the collagen-induced arthritis through inhibiting the synovial hyperplasia and inflammation.
Highlights
Sigesbeckia glabrescens Makino (SG) has been traditionally used for rheumatism and joint protection
SG extract (SGE) attenuated the collagen-induced arthritis through inhibiting the synovial hyperplasia and inflammation
SGE moderated the inflammation‐related proteins in serum and joint muscles As shown in Fig. 2a, the expression of serum c-reactive protein was increased in collagen-induced arthritis (CIA) group, which could be reduced by SGE dose-dependently, decreased by IND
Summary
Sigesbeckia glabrescens Makino (SG) has been traditionally used for rheumatism and joint protection. The anti-arthritic effects and underling mechanisms of SG have not been demonstrated. We investigated the anti-arthritic effects and mechanisms of SG extract (SGE) on collagen-induced arthritic rats and inter‐ leukin (IL)-1β-stimulated human synovial SW982 cells. As an important component of synovial tissue, the synovial fibroblasts, called fibroblast-like synoviocytes (FLS), play critical role during the progress of joint destruction through secreting various cytokines, proteases and arachidonic acid metabolites [3]. Excessive proliferation and invasion of FLS have been reported to be involved in the pathogenesis of RA. Blocking the activation of FLS to reduce the production of cytokines has become a promising RA therapy [4]. FLS becomes a critical target cell for studying the treatment and pathogenesis of RA
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