2. Academic Validation
  3. Isopsoralen ameliorates rheumatoid arthritis by targeting MIF

Isopsoralen ameliorates rheumatoid arthritis by targeting MIF

  • Arthritis Res Ther. 2021 Sep 17;23(1):243. doi: 10.1186/s13075-021-02619-3.
Yi Han 1,  Jinguang Wang 2,  Shufeng Li 3,  Yi Li 4,  Yongli Zhang 5,  Ruojia Zhang 5,  Yuang Zhang 5 6 7,  Huancai Fan 5,  Haojun Shi 8,  Jihong Pan 5 6 7,  Guanhua Song 9,  Luna Ge 10 11 12,  Lin Wang 13 14 15
Affiliations

Affiliations

  • 1 China Academy of Chinese Medical Sciences, Guang'anmen Hospital, Beijing, China.
  • 2 Department of Orthopedics, Dezhou People's Hospital, Dezhou, Shandong, China.
  • 3 Department of Orthopedic Surgery, The First Affiliated Hospital of Shandong First Medical University, Jinan, China.
  • 4 Department of Joint Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.
  • 5 Biomedical Sciences College & Shandong Medicinal Biotechnology Centre, Key lab for Biotech-Drugs of National Health Commission, Key Lab for Rare & Uncommon Diseases of Shandong Province, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China.
  • 6 Department of Rheumatology and Autoimmunology, The First Affiliated Hospital of Shandong First Medical University, Jinan, China.
  • 7 Biomedical Sciences College & Shandong Medicinal Biotechnology Center, Key lab for Biotech-Drugs of National Health Commission, Key Lab for Rare & Uncommon Diseases of Shandong Province, Shandong First Medical University & Shandong Academy of Medical Sciences, #18877, Jingshi Road, Jinan, 250062, China.
  • 8 The Second Clinical Medical College, Henan University of Chinese Medicine, Jinan, China.
  • 9 Institute of Basic Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China.
  • 10 Biomedical Sciences College & Shandong Medicinal Biotechnology Centre, Key lab for Biotech-Drugs of National Health Commission, Key Lab for Rare & Uncommon Diseases of Shandong Province, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China. geluna606@163.com.
  • 11 Department of Rheumatology and Autoimmunology, The First Affiliated Hospital of Shandong First Medical University, Jinan, China. geluna606@163.com.
  • 12 Biomedical Sciences College & Shandong Medicinal Biotechnology Center, Key lab for Biotech-Drugs of National Health Commission, Key Lab for Rare & Uncommon Diseases of Shandong Province, Shandong First Medical University & Shandong Academy of Medical Sciences, #18877, Jingshi Road, Jinan, 250062, China. geluna606@163.com.
  • 13 Biomedical Sciences College & Shandong Medicinal Biotechnology Centre, Key lab for Biotech-Drugs of National Health Commission, Key Lab for Rare & Uncommon Diseases of Shandong Province, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, China. kecheng1216@163.com.
  • 14 Department of Rheumatology and Autoimmunology, The First Affiliated Hospital of Shandong First Medical University, Jinan, China. kecheng1216@163.com.
  • 15 Biomedical Sciences College & Shandong Medicinal Biotechnology Center, Key lab for Biotech-Drugs of National Health Commission, Key Lab for Rare & Uncommon Diseases of Shandong Province, Shandong First Medical University & Shandong Academy of Medical Sciences, #18877, Jingshi Road, Jinan, 250062, China. kecheng1216@163.com.
PMID: 34535196 DOI: 10.1186/s13075-021-02619-3
Abstract

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.

Keywords

Collagen-induced arthritis; Isopsoralen; MIF; RA FLSs; Rheumatoid arthritis.

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