Isopsoralen ameliorates rheumatoid arthritis by targeting MIF

Autor: Huancai Fan, Jihong Pan, Lin Wang, Yuang Zhang, Ruojia Zhang, Luna Ge, Yongli Zhang, Shufeng Li, Yi Li, Haojun Shi, Jinguang Wang, Yi Han, Guanhua Song
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Arthritis Research & Therapy, Vol 23, Iss 1, Pp 1-11 (2021)
Arthritis Research & Therapy
ISSN: 1478-6362
Popis: 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.
Databáze: OpenAIRE
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