{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T12:05:58Z","timestamp":1793880358708,"version":"4.7.0"},"reference-count":32,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,12,28]],"date-time":"2019-12-28T00:00:00Z","timestamp":1577491200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["iubmb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BioFactors"],"published-print":{"date-parts":[[2020,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The present study was designed to explore the biological role of resveratrol (RES) in rheumatoid arthritis (RA) and the underlying mechanism. The adjuvant\u2010induced arthritic rats were administered RES on the 12th day after model establishment, and then arthritis assessment, oxidative stress measurement, histological examination, and immunohistochemical staining were performed. The primary rat fibroblast\u2010like synoviocytes (FLS) were isolated and treated with RES in vitro and then cell proliferation and apoptosis assay were examined. Chromatin immunoprecipitation assay, luciferase reporter assay, intracellular reactive oxygen species (ROS) determination, western blot, and quantitative real time\u2010polymerase chain reaction (qRT\u2010PCR) were performed to investigate the mechanisms. RES administration decreased arthritis scores and serum levels of antioxidant enzymes, attenuated paw swelling, synovial hyperplasia, inflammatory cell infiltration, and cartilage degradation, as well as inhibited synoviocyte proliferation in synovial tissues. Further investigation indicated that RES inhibited ROS production and FLS proliferation through activating the silent information regulator 1 (SIRT1)\/nuclear factor erythroid 2\u2010related factor 2 (Nrf2) signaling pathway. NF\u2010\u03baB was confirmed to negatively regulate miR\u201029a\u20103p and miR\u201023a\u20103p expression by directly binding to its promoter. Mechanistic analyses further revealed that Kelch\u2010like erythroid cell\u2010derived protein with CNC homology (ECH)\u2010associated protein 1 (Keap1), a negative regulator of Nrf2, was a downstream target of miR\u201029a\u20103p, while miR\u201023a\u20103p directly targeted cullin3 (cul3), a master regulator of ubiquitination and degradation of Nrf2. Together, the present study provided evidence that RES ameliorated RA through activation of Nrf2\u2010ARE signaling pathway via SIRT1\/NF\u2010\u03baB\/miR\u201029a\u20103p\/Keap1 and SIRT1\/NF\u2010\u03baB\/miR\u201023a\u20103p\/cul3 signaling pathway.<\/jats:p>","DOI":"10.1002\/biof.1599","type":"journal-article","created":{"date-parts":[[2019,12,28]],"date-time":"2019-12-28T13:49:18Z","timestamp":1577540958000},"page":"441-453","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":118,"title":["Resveratrol ameliorates rheumatoid arthritis via activation of SIRT1\u2010Nrf2 signaling pathway"],"prefix":"10.1002","volume":"46","author":[{"given":"Gaoyuan","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Orthopaedics The First Affiliated Hospital of Anhui Medical University  Hefei 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