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Gentiopicroside attenuates collagen-induced arthritis in mice via modulating the CD147/p38/NF-κB pathway

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
出处
期刊:International Immunopharmacology [Elsevier]
卷期号:108: 108854-108854 被引量:20
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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