Hui Li1, Xin-Yue Cao2, Wen-Zhen Dang2, Bing Jiang2, Jun Zou3, Xiao-Yan Shen4. 1. School of Kinesiology, Shanghai University of Sport, No. 188, Hengren Road, Yangpu Aera, Shanghai 200438, China; Department of Pharmacology, School of Pharmaceutical Sciences, Fudan University, No. 826, Zhangheng Road, Pudong New Area, Shanghai 201203, China. 2. Department of Pharmacology, School of Pharmaceutical Sciences, Fudan University, No. 826, Zhangheng Road, Pudong New Area, Shanghai 201203, China. 3. School of Kinesiology, Shanghai University of Sport, No. 188, Hengren Road, Yangpu Aera, Shanghai 200438, China. Electronic address: zoujun777@126.com. 4. School of Kinesiology, Shanghai University of Sport, No. 188, Hengren Road, Yangpu Aera, Shanghai 200438, China; Department of Pharmacology, School of Pharmaceutical Sciences, Fudan University, No. 826, Zhangheng Road, Pudong New Area, Shanghai 201203, China. Electronic address: shxiaoy@fudan.edu.cn.
Abstract
BACKGROUND: The development of rheumatoid arthritis (RA) is related to germinal center (GC) response and autoreactive T cells, which mediate adaptive immunity and play an important role in stimulating the production of autoantibodies and pro-inflammatory cytokines by B cells and macrophages. Total Glucosides of Paeony (TGP) has anti-inflammatory, immunomodulatory and analgesic effects and is widely used to treat RA. However, few studies investigated whether the therapeutic effect of TGP is associated with the inhibition of autoimmune response. PURPOSE: The aim of this study was to investigate the effects and mechanisms of TGP on RA. STUDY DESIGN: Type II collagen-induced arthritis (CIA) mouse model was used, and TGP and paeoniflorin were intragastrically treated. METHODS: DBA/1 mice were divided into 5 groups: control, model, positive drug (paeoniflorin) and high- and low-dose TGP group. After 21 days of intragastric administration, the pathological change, inflammation expression and molecular mechanism of each group of mice were detected by Micro-CT, histochemical analysis, ELLSA, Western blot, RT-qPCR and flow cytometry. RESULTS: Our study found that TGP treatment effectively improved inflammation and joint destruction in CIA mice. It reduced the production of serum IgG2a and pro-inflammatory cytokines, including serum interleukin (IL)-21, tumor necrosis factor (TNF)-α and IL-6, and the phosphorylation of NF-κB p65 and STAT3 in a dose-dependent manner. More importantly, TGP could suppress the frequency of germinal center B cells and Tfh cells in the spleen. CONCLUSION: TGP can not only improve symptoms, but also inhibit bone destruction. The therapeutic effect of TGP on CIA is mainly achieved by inhibiting spleen Tfh cell differentiation and GC formation through STAT3 signaling pathway.
BACKGROUND: The development of rheumatoid arthritis (RA) is related to germinal center (GC) response and autoreactive T cells, which mediate adaptive immunity and play an important role in stimulating the production of autoantibodies and pro-inflammatory cytokines by B cells and macrophages. Total Glucosides of Paeony (TGP) has anti-inflammatory, immunomodulatory and analgesic effects and is widely used to treat RA. However, few studies investigated whether the therapeutic effect of TGP is associated with the inhibition of autoimmune response. PURPOSE: The aim of this study was to investigate the effects and mechanisms of TGP on RA. STUDY DESIGN: Type II collagen-induced arthritis (CIA) mouse model was used, and TGP and paeoniflorin were intragastrically treated. METHODS: DBA/1 mice were divided into 5 groups: control, model, positive drug (paeoniflorin) and high- and low-dose TGP group. After 21 days of intragastric administration, the pathological change, inflammation expression and molecular mechanism of each group of mice were detected by Micro-CT, histochemical analysis, ELLSA, Western blot, RT-qPCR and flow cytometry. RESULTS: Our study found that TGP treatment effectively improved inflammation and joint destruction in CIA mice. It reduced the production of serum IgG2a and pro-inflammatory cytokines, including serum interleukin (IL)-21, tumor necrosis factor (TNF)-α and IL-6, and the phosphorylation of NF-κB p65 and STAT3 in a dose-dependent manner. More importantly, TGP could suppress the frequency of germinal center B cells and Tfh cells in the spleen. CONCLUSION:TGP can not only improve symptoms, but also inhibit bone destruction. The therapeutic effect of TGP on CIA is mainly achieved by inhibiting spleen Tfh cell differentiation and GC formation through STAT3 signaling pathway.
Authors: Hui Li; Yan You; Bing Jiang; Haidong Li; Xiang Li; Wei Wu; Hong Cao; Xiaoyan Shen; Jun Zou Journal: Evid Based Complement Alternat Med Date: 2021-08-13 Impact factor: 2.629