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This study aimed to explore the mechanisms of the antioxidant and proapoptotic effects of Res in H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>\u2010treated rheumatoid arthritis fibroblast\u2010like synoviocytes (RA\u2010FLSs) by the Nrf2\u2013Keap1 signaling pathway. We found that 5\u00a0\u00b5M H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> promoted cell proliferation and increased intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) content in RA\u2010FLSs. However, Res could reverse these effects in 5 \u00b5MH2O2\u2010treated RA\u2010FLSs by (1) promoting expression of nuclear factor erythroid 2\u2013related factor 2 (Nrf2) and heme oxygenase\u20101 (HO\u20101), (2) reducing expression of Kelch\u2010like ECH\u2013related protein 1 (Keap1), (3) inhibiting production of ROS and MDA, (4) blocking activation of nuclear factor\u2010\u03baB (NF\u2010\u03baB) p65, (5) inhibiting cell proliferation and migration, and (6) activating Bcl\u20102\/Bax to induce apoptosis. After lentiviral silencing of Nrf2 (siNrf2) mRNA expression in RA\u2010FLSs, Res addition did not increase the expression of Nrf2 or HO\u20101 to reduce the production of mitochondrial ROS caused by 5\u00a0\u00b5M H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>. Res reduced the Bcl\u20102\/Bax ratio, but siNrf2 reduced the ability of Res to promote apoptosis. We conclude that Res inhibits ROS production by activating the Nrf2 pathway, thereby inhibiting activation of NF\u2010\u03baB and proliferation and migration of RA\u2010FLSs, to induce apoptosis. Targeting the Nrf2\u2013Keap1 pathway may be a relevant aim of using Res in the treatment of RA.<\/jats:p>","DOI":"10.1111\/nyas.14196","type":"journal-article","created":{"date-parts":[[2019,9,2]],"date-time":"2019-09-02T06:05:26Z","timestamp":1567404326000},"page":"166-178","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":100,"title":["Nrf2\u2013Keap1 pathway\u2013mediated effects of resveratrol on oxidative stress and apoptosis in hydrogen peroxide\u2013treated rheumatoid arthritis fibroblast\u2010like synoviocytes"],"prefix":"10.1111","volume":"1457","author":[{"given":"Ye","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Histology and Embryology Anhui Medical University  Hefei Anhui P. R. China"},{"name":"Microscopic Morphological Center Laboratory Anhui Medical University  Hefei Anhui P. R. 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