{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T03:39:58Z","timestamp":1792467598496,"version":"4.5.0"},"reference-count":31,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T00:00:00Z","timestamp":1792368000000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["iubmb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["IUBMB Life"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial inflammation and progressive joint destruction, in which fibroblast\u2010like synoviocytes (FLSs) play a central pathogenic role. Ferroptosis and oxidative stress\u2010driven mitochondrial dysfunction have recently been implicated in synovial cell injury during RA progression. Sirtuin 1 (SIRT1), a nicotinamide adenine dinucleotide\u2010dependent deacetylase, is known to regulate inflammation, redox homeostasis, and cell survival; however, the upstream regulatory mechanisms controlling SIRT1 function and their relevance to ferroptosis in RA remain poorly defined. Primary rat FLSs and a complete Freund's adjuvant (CFA)\u2010induced adjuvant arthritis (AA) rat model were used. SIRT1 transcription, protein expression, subcellular localization, and enzymatic activity were assessed using quantitative real\u2010time PCR, Western blotting, immunofluorescence, and enzymatic assays. Oxidative stress, mitochondrial dysfunction, lipid peroxidation, and ferroptosis\u2010related parameters were evaluated using biochemical assays and fluorescence\u2010based probes. SUMO1 expression was manipulated by knockdown and overexpression approaches, and the interaction between SUMO1 and SIRT1 was examined by co\u2010IP.Inflammatory stimulation with IL\u20101\u03b2 impaired SIRT1 transcriptional expression, reduced its nuclear localization, and suppressed its enzymatic activity in FLSs, accompanied by enhanced reactive oxygen species accumulation, mitochondrial dysfunction, lipid peroxidation, and ferroptosis\u2010related changes. ICA treatment restored SIRT1 expression and activity while alleviating oxidative stress and ferroptotic injury. ICA upregulated SUMO1 expression, while Co\u2010IP analysis demonstrated an association between SUMO1 and SIRT1. SUMO1\u2010dependent regulation was associated with increased SIRT1 nuclear localization and enzymatic activity. Disruption of SUMO1 expression or pharmacological inhibition of SIRT1 suppressed the protective effects of ICA in FLSs. Consistent regulatory effects were observed in arthritic rats following ICA administration. These findings support the involvement of SUMO1\/SIRT1 regulation in ferroptosis\u2010related injury and mitochondrial dysfunction in RA\u2010associated synovial cells. ICA exerts protective effects by restoring coordinated SIRT1 regulation at multiple functional levels, highlighting SIRT1\u2010centered pathways as potential therapeutic targets for RA.<\/jats:p>","DOI":"10.1002\/iub.70136","type":"journal-article","created":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T03:06:46Z","timestamp":1792465606000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Icariin Protects Against Mitochondrial Damage and Ferroptosis\u2010Related Injury in Synovial Fibroblast\u2010Like Synoviocytes Through\n                    <scp>SUMO1<\/scp>\n                    \u2010Dependent Regulation of\n                    <scp>SIRT1<\/scp>"],"prefix":"10.1002","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0358-2769","authenticated-orcid":false,"given":"Zhiming","family":"Wu","sequence":"first","affiliation":[{"name":"Chinese Medicine Department, The First Affiliated Hospital Jiangxi Medical College, Nanchang University  Nanchang Jiangxi Province People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeqing","family":"Mao","sequence":"additional","affiliation":[{"name":"Jiangxi Medical College, Nanchang University  Nanchang Jiangxi Province People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Guo","sequence":"additional","affiliation":[{"name":"Chinese Medicine Department, The First Affiliated Hospital Jiangxi Medical College, Nanchang University  Nanchang Jiangxi Province People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingfeng","family":"Xiong","sequence":"additional","affiliation":[{"name":"Preventive Medicine Center, the First Affiliated Hospital Jiangxi Medical College, Nanchang University  Nanchang Jiangxi Province People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifen","family":"Zhou","sequence":"additional","affiliation":[{"name":"Chinese Medicine Department, The First Affiliated Hospital Jiangxi Medical College, Nanchang University  Nanchang Jiangxi Province People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4394-5733","authenticated-orcid":false,"given":"Xiaobo","family":"Zhu","sequence":"additional","affiliation":[{"name":"Preventive Medicine Center, the First Affiliated Hospital Jiangxi Medical College, Nanchang University  Nanchang Jiangxi Province People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,19]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"crossref","first-page":"1051082","DOI":"10.3389\/fimmu.2022.1051082","article-title":"Systemic Complications of Rheumatoid Arthritis: Focus on Pathogenesis and Treatment","volume":"13","author":"Wu D.","year":"2022","journal-title":"Frontiers in Immunology"},{"issue":"2","key":"e_1_2_10_3_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2165\/00019053-200422001-00002","article-title":"Epidemiology and Burden of Illness of Rheumatoid Arthritis","volume":"22","author":"Kvien T. 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