Journal
DRUG DESIGN DEVELOPMENT AND THERAPY
Volume 12, Issue -, Pages 4095-4105Publisher
DOVE MEDICAL PRESS LTD
DOI: 10.2147/DDDT.S175763
Keywords
rheumatoid arthritis; curcumin; rapamycin; mammalian target of rapamycin; collagen-induced arthritis
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Funding
- Medical Science and Technology Project of Zhejiang Province [2014KYB166, 2017KY503]
- Traditional Chinese Medical Science and Technology Project of Zhejiang Province of China [2017ZB032, 2014ZA028]
- Educational Commission of Zhejiang Province of China [Y201431280]
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Purpose: Rheumatoid arthritis (RA) is a chronic, progressive autoimmune disease characterized by aggressive and symmetric polyarthritis. Mammalian target of rapamycin (mTOR) was reported to be a new target for RA therapy and its inhibitor rapamycin can significantly reduce the invasive force of fibroblast-like synoviocytes. Here, we determined the effect of curcumin to alleviate inflammation and synovial hyperplasia for the therapy of RA. Materials and methods: Collagen-induced arthritis (CIA) was developed in Wistar rats and used as a model resembling RA in humans. Rats were treated with curcumin (200 mg/kg) and the mTOR inhibitor rapamycin (2.5 mg/kg) daily for 3 weeks. Effects of the treatment on local joint, peripheral blood, and synovial hyperplasia in the pathogenesis of CIA were analyzed. Results: Curcumin and rapamycin significantly inhibited the redness and swelling of ankles and joints in RA rats. Curcinnin inhibited the CIA-induced mTOR pathway and the RA-induced infiltration of inflammatory cells into the synovium. Curcumin and rapamycin treatment inhibited the increased levels of proinliammatory cytokines including IL-1 beta, TNF-alpha, MMP-1, and MMP-3 in CIA rats. Conclusion: Our findings show that curcumin alleviates CIA-induced inflammation, synovial hyperplasia, and the other main features involved in the pathogenesis of CIA via the mTOR pathway. These results provide evidence for the anti-arthritic properties of curcumin and corroborate its potential use for the treatment of RA.
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