Isopsoralen ameliorates rheumatoid arthritis by targeting MIF

Yi Han,Jihong Pan,Guanhua Song,Jinguang Wang,Haojun Shi,Shufeng Li,Yuang Zhang,Huancai Fan,Lin Wang,Luna Ge,Ruojia Zhang,Yongli Zhang,Yi Li

doi:10.1186/s13075-021-02619-3

Abstract

BackgroundIsopsoralen (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.MethodsRA 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.ResultsIPRN 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.ConclusionOur study demonstrates the antiarthritic effect of IPRN, which suggests the therapeutic potential of IPRN in RA.

Highlights

Rheumatoid arthritis (RA) is a chronic, autoimmune inflammatory disease characterized by synovial hyperplasia and joint destruction [1]
IPRN ameliorates the inflammatory phenotype of rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLSs) RA FLSs display an inflammatory phenotype characterized by the excessive production of inflammatory factors and the enhancement of invasive ability
RT-qPCR and enzyme-linked immunosorbent assay (ELISA) analysis showed that the induction of IL-6, IL-8, MMP1, MMP3, (C-X-C motif) ligand (CXCL)9, and CXCL10 production resulting from tumor necrosis factor-α (TNF-α) stimulation could be significantly attenuated by IPRN treatment (Fig. S1, Fig. 1a)

Summary

Introduction

Rheumatoid arthritis (RA) is a chronic, autoimmune inflammatory disease characterized by synovial hyperplasia and joint destruction [1]. Traditional Chinese medicine (TCM) has long been applied to treat chronic inflammatory diseases and shows efficacy in RA [9, 10]. Numerous studies have been carried out to study the anti-RA effect of ingredients from TCM [11]. Isopsoralen (IPRN, 2H-Furo[2,3-H] chromen-2-one, CAS Number: 523-50-2, Fig 3b), one of the main ingredients in the seeds of the Psoralea corylifolia Linn plant, has been reported to exert anti-inflammatory effects in inflammatory respiratory and neurodegenerative diseases [15, 16]. 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

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Discussion

Conclusion