Sinomenine Decreases MyD88 Expression and Improves Inflammation-Induced Joint Damage Progression and Symptoms in Rat Adjuvant-Induced Arthritis

Abstract

Sinomenine (SIN) is the active principle of the Chinese medical plant Sinomenium acutum which is widely used for the treatment of rheumatoid arthritis (RA) in China. Recently, several groups indicated that myeloid differentiation primary response protein 88 (MyD88) might be associated with disease progression of RA. Here, we observed the effect of SIN on MyD88 expression and showed its therapeutic role in RA. First, immunohistochemical staining in clinical specimens showed that MyD88 was mainly located in characteristic pathological structures of RA synovial tissues. Second, we found that MyD88 was overexpressed in the synovial tissues of the rats with adjuvant-induced arthritis (AIA). Treatment with SIN markedly decreased the expression of MyD88 in AIA rats. Finally, we provided evidences that SIN suppressed inflammation response and inflammation-induced joint destructive progression and arthritis symptoms in AIA rats. Therefore, SIN is an effective therapeutic agent for RA. Targeting MyD88 signaling may provide new methods for the treatment of RA.

Sinomenine suppresses collagen-induced arthritis by reciprocal modulation of regulatory T cells and Th17 cells in gut-associated lymphoid tissues

“…The satisfactory therapeutic efficacy and fewer side effects of SIN in patients have been confirmed in open clinical trials (Huang et al, 2007;Shi et al, 1985). When orally administered at the doses of 100 and 300 mg/kg, SIN could attenuate adjuvantinduced arthritis (AIA) in rat and collagen-induced arthritis (CIA) in mouse through suppressing the production of autoantibody and modulating Th1/Th2 response (Feng et al, 2007;Mu et al, 2013). In vitro mechanistic studies showed that SIN could suppress the activation of T lymphocytes, induce the apoptosis of macrophage, reduce antigen-induced activation of basophils, and hinder migration of synoviocytes at concentrations over 0.5 mM (He et al, 2005;Huang et al, 2008;Liu et al, 1994;Ou et al, 2011).…”

Sinomenine prevents the development of cardiomyopathy in diabetic rats by inhibiting inflammatory responses and blocking activation of NF-κB

“…As reported previously, the compound possesses a diversified set of bioactivities, including anti-arrhythmic, antianginal, analgesic, anti-inflammatory and sedative activities (Zhao et al 2012). In vivo studies, sinomenine effectively reduced the inflammatory response in animal models of arthritis and uveitis (Mu et al 2013;Song et al 2013). In an in vitro study, sinomenine blockaded activation of immune cells (T lymphocytes, dendritic cells, macrophages) and reduced production of pro-inflammatory cytokines (TNF-α, IL-1) (Wang and Li 2011;Tong et al 2015).…”

“…At the molecular level, sinomenine attenuates nuclear translocation of the NF-κB p65 subunit and the DNA-binding activity of NF-κB (Wang et al 2007;Cheng et al 2009;Zhao et al 2013). In addition, sinomenine also reduces the production of IL-1β and TNF-α in synovial cells of rats with adjuvant-induced arthritis (Anker and Coats 2002;Zhao et al 2012;Mu et al 2013;Zhao et al 2013).…”

Herbal compounds for rheumatoid arthritis: Literatures review and cheminformatics prediction

“…Apigenin, baicalin, clematichinenoside AR, madecassoside, matrine, paeoniflorin, triptolide, tripterine, sinomenine, shikonin, and scopolin reduce the levels of proinflammatory mediators in synovium of RA, such as ILs, tumor necrosis factor (TNF), and cyclooxygenases. (Zhai, Ma, Wang, Song, & Yi, ; Yang et al, ; Pu et al, ; Chang et al, ; Yang, Yang, & Zou, ; Mu et al, ; Han et al, ; Pan, Dai, Gao, & Xia, ; Li et al, ; Dai, Wang, & Zhang, ; Dai, Fang, & Zhang, ;Li, Zhang, Tan, Jia, & Li, ; Tu et al, ; Chen, Ye, Hu, Zhang, & Cheng, ). Cartilage is also the target site for the antiarthritic effects of triptolide and shikonin, both of which lower the expression of cartilage cytokines (e.g., TNF‐α, IL‐6, and cyclooxygenase‐2; Xiao et al, ; Dai, Fang, & Zhang, ).…”

“…Under the guidance of pathology, the lesion area can be examined by means of morphology, histology, X‐ray, and computed tomography scan, so as to intuitively analyze the damage of bone and cartilage. The joint morphology shows that sinomenine suppresses synovial hypertrophied and cartilage destruction (Mu et al, ). Through histopathological examination, tanshinone IIA, artemether, tripterine, (−)‐epicatechin‐3‐ O ‐β‐ d ‐allopyranoside, shikonin, daphnetin, and kinsenoside can effectively ameliorate the bone and cartilage destruction in the joints of RA model (Cuzzocrea et al, ; Dai, Wang, & Zhang, ; Gao et al, ; Hsiao et al, ; Hsiao et al, ; Li, Zhang, et al, ; Zhang, Huang, et al, ).…”