期刊
FRONTIERS IN PHARMACOLOGY
卷 11, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fphar.2020.547913
关键词
rheumatoid arthritis; synovial hyperplasia; inflammation; Sigesbeckia orientalisL; SW982; MH7A
资金
- National Natural Science Foundation of China [NSFC] [81470170]
- Science and Technology Development Fund of Macau SAR [0096/2019/A2]
- Research Committee of the University of Macau [MYRG2017-00178-ICMS, MYRG2018-00043-ICMS]
- international Cooperation Department of National Administration of traditional Chinese Medicine [GZYYGJ2019042]
Excessive proliferation and inflammation of synovial fibroblasts accelerate and decorate the pathological process of rheumatoid arthritis (RA).Sigesbeckia orientalisL. (SO) is one of the main plant sources for Sigesbeckiae Herba (SH) which has been used traditionally in treating various forms of arthritis and rheumatic pain. However, the anti-arthritic mechanisms of SO are still not clearly understood. In this study, we investigated the therapeutic effects and the underlying mechanisms of SO against collagen type II (C II)-induced RA in rats as well as the interleukin (IL)-1 beta-induced human synovial SW982 and MH7A cells. For thein vivostudies, thirty-six Wistar male rats were randomly arranged to six groups based on the body weight, and then C II-induced to RA model for 15 days, followed by treatment with the 50% ethanolic extract of SO (SOE, 0.16, 0.78, and 1.56 g/kg) for 35 days. The results suggested that SOE significantly inhibited the formation of pannus (synovial hyperplasia to the articular cavity) and attenuated the cartilage damaging and bone erosion in the CIA-induced rats' hind paw joints. Moreover, SOE decreased the production of C-reactive protein (CRP) in the serum and the expression of IL-6 and IL-1 beta in the joint muscles, as well as recovered the decreased regulatory T lymphocytes. The results obtained from thein vitrostudies showed that SOE (50, 100, and 200 mu g/ml) not only inhibited the proliferation, migration, and invasion of human synovial SW982 cells but also decreased the IL-1 beta-induced expression of IL-6 and IL-8 both in SW982 and MH7A cells. Besides, SOE reduced the expression of COX-2, NLRP3, and MMP9, and increased the expression of MMP2 in the IL-1 beta-induced SW982 cells. Furthermore, SOE blocked the activation of NF-kappa B and reduced the phosphorylation of MAPKs and the expression of AP-1. In conclusion, SOE attenuated the C II-induced RA through inhibiting of MAPKs/NF-kappa B/AP-1-mediated synovial hyperplasia and inflammation.
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