体内
滑膜炎
类风湿性关节炎
医学
p38丝裂原活化蛋白激酶
关节炎
软骨
体外
药理学
NF-κB
癌症研究
免疫学
信号转导
化学
炎症
生物
MAPK/ERK通路
生物化学
解剖
生物技术
作者
Na Jia,Hongfang Ma,Tiejun Zhang,Lei Wang,Jia Cui,Yuanyuan Zha,Yi Ding,Jingwen Wang
标识
DOI:10.1016/j.intimp.2022.108854
摘要
Gentiopicroside (GEN) is a secoiridoid glycosides isolated from a traditional Chinese medicine Gentiana macrophylla Pall.. It exhibits potential activities in the treatment of inflammatory diseases. Here, we investigated whether GEN had the anti-rheumatoid arthritic activities in a model of rheumatoid arthritis, and explored its molecular mechanism. In vivo, the male C57BL/6J mice were injected chicken type II collagen to induce the animal model (collagen-induced arthritis, CIA). In vitro, we performed the research in rheumatoid fibroblast-like synoviocytes (FLS). In our study, it was innovatively authenticated that GEN treatment could not only reduce synovitis and inhibit the proliferation of RA FLS, but also relieve cartilage damage in CIA modal. More importantly, we firstly demonstrated that GEN treatment lessened the pain behaviors of CIA mice. In vivo and in vitro experiments confirmed that CD147 was the main target of GEN in attenuating RA symptoms for the first time. Next, we identified the downstream signaling pathway of CD147, and proved that the anti-RA effects of GEN were mediated by down-regulating the expression of p38, IκBα and p65 in vivo and in vitro assays. In conclusion, the data of this manuscript suggested that GEN treatment attenuated synovitis and cartilage destruction in CIA mice; the inhibitory effects on MMP secretion and the anti-rheumatic effects of GEN might be regulated by the CD147/p38/ NF-κB pathway. Accordingly, we found that GEN has the potential therapeutic effects for RA.
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