Isopsoralen ameliorates rheumatoid arthritis by targeting MIF.
Isopsoralen ameliorates rheumatoid arthritis by targeting MIF.
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异补骨脂素通过靶向 MIF 改善类风湿性关节炎
DOI：
10.1186/s13075-021-02619-3
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发表时间：
2021-09-17
影响因子：
4.9
通讯作者：
Wang L
中科院分区：
文献类型：
--
作者：
Han Y;Wang J;Li S;Li Y;Zhang Y;Zhang R;Zhang Y;Fan H;Shi H;Pan J;Song G;Ge L;Wang L
异补骨脂素(IPRN)是补骨脂的有效成分之一，具有抗炎作用。我们试图研究IPRN对类风湿关节炎(RA)的抑制作用，并探讨其可能的机制。以RA成纤维样滑膜细胞(FLSS)和胶原性关节炎(CIA)小鼠为实验动物模型，分析IPRN的抗炎作用。采用显微计算机断层扫描(Micro-CT)和苏木精-伊红(HE)染色，对CIA小鼠致炎关节进行组织学观察。采用RNA测序(RNA-Seq)、网络药理分析、分子对接、药物亲和反应靶向稳定性(DARTS)和细胞热位移分析(CETSA)等方法对IPRN靶点进行评价。IPRN通过抑制细胞因子的产生、迁移、侵袭和促血管生成能力来改善RA Fls的炎症表型。IPRN还通过降低爪厚、关节炎评分、骨损伤和血清炎症细胞因子水平显著降低了小鼠CIA的严重程度。机制研究表明，炎症过程中的关键蛋白巨噬细胞移动抑制因子(MIF)是IPRN发挥抗炎作用的特异性靶点。我们的研究证实了IPRN的抗关节炎作用，这表明IPRN在RA中具有治疗潜力。网上版载有补充材料，可在10.1186/s13075-021-02619-3查阅。
Isopsoralen (IPRN), one of the active ingredients of Psoralea corylifolia Linn, has anti-inflammatory properties. We attempted to investigate the inhibitory effects of IPRN on rheumatoid arthritis (RA) and characterize its potential mechanism. RA fibroblast-like synoviocytes (FLSs) and mice with collagen-induced arthritis (CIA) were used as in vitro and in vivo models to analyze the antiarthritic effect of IPRN. Histological analysis of the inflamed joints from mice with CIA was performed using microcomputed tomography (micro-CT) and hematoxylin-eosin (HE) staining. RNA sequencing (RNA-Seq), network pharmacology analysis, molecular docking, drug affinity responsive target stability (DARTS) assay, and cellular thermal shift assay (CETSA) were performed to evaluate the targets of IPRN. IPRN ameliorated the inflammatory phenotype of RA FLSs by inhibiting their cytokine production, migration, invasion, and proangiogenic ability. IPRN also significantly reduced the severity of CIA in mice by decreasing paw thickness, arthritis score, bone damage, and serum inflammatory cytokine levels. A mechanistic study demonstrated that macrophage migration inhibitory factor (MIF), a key protein in the inflammatory process, was the specific target by which IPRN exerted its anti-inflammatory effects in RA FLSs. Our study demonstrates the antiarthritic effect of IPRN, which suggests the therapeutic potential of IPRN in RA. The online version contains supplementary material available at 10.1186/s13075-021-02619-3.
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影响因子：
3.7
作者：
Li L;Eun JS;Nepal M;Ryu JH;Cho HK;Choi BY;Soh Y
通讯作者：
Soh Y
DOI：
10.1158/1055-9965.epi-11-0279
发表时间：
2011-07
期刊：
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
影响因子：
--
作者：
Healy ZR;Liu H;Holtzclaw WD;Talalay P
通讯作者：
Talalay P
影响因子：
2.8
作者：
Liu, Minghui;Hu, Chunhe
通讯作者：
Hu, Chunhe
影响因子：
7.3
作者：
Orita, M;Yamamoto, S;Tanaka, A
通讯作者：
Tanaka, A
影响因子：
24.1
作者：
Liu, Yan;Pan, Yun Feng;Zheng, Song Guo
通讯作者：
Zheng, Song Guo