异补骨脂素通过靶向 MIF 改善类风湿关节炎。

Isopsoralen ameliorates rheumatoid arthritis by targeting MIF.

机构信息

China Academy of Chinese Medical Sciences, Guang'anmen Hospital, Beijing, China.

Department of Orthopedics, Dezhou People's Hospital, Dezhou, Shandong, China.

出版信息

Arthritis Res Ther. 2021 Sep 17;23(1):243. doi: 10.1186/s13075-021-02619-3.

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSION

Our study demonstrates the antiarthritic effect of IPRN, which suggests the therapeutic potential of IPRN in RA.

背景

补骨脂素（IPRN）是补骨脂的一种活性成分，具有抗炎特性。我们试图研究 IPRN 对类风湿关节炎（RA）的抑制作用，并探讨其潜在的机制。

方法

RA 成纤维样滑膜细胞（FLSs）和胶原诱导性关节炎（CIA）小鼠被用作体外和体内模型，以分析 IPRN 的抗关节炎作用。使用微计算机断层扫描（micro-CT）和苏木精-伊红（HE）染色对 CIA 小鼠的炎症关节进行组织学分析。进行 RNA 测序（RNA-Seq）、网络药理学分析、分子对接、药物亲和反应靶标稳定性（DARTS）测定和细胞热转移测定（CETSA），以评估 IPRN 的作用靶点。

结果

IPRN 通过抑制 RA FLSs 的细胞因子产生、迁移、侵袭和促血管生成能力，改善了 RA FLSs 的炎症表型。IPRN 还通过降低爪厚度、关节炎评分、骨损伤和血清炎症细胞因子水平，显著减轻 CIA 小鼠的严重程度。机制研究表明，巨噬细胞移动抑制因子（MIF）是炎症过程中的关键蛋白，是 IPRN 在 RA FLSs 中发挥抗炎作用的特定靶点。