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Carnosol is a plant\u2010derived polyphenol that has been proven to exhibit several cell protective effects. In this study, we established hyperandrogenic PCOS models both in vitro and in vivo. In the human\u00a0ovarian\u00a0granulosa\u00a0cell\u00a0line,\u00a0KGN cells, decreased viability and mitochondrial membrane potential, and upregulated reactive oxygen species (ROS) level and apoptosis induced by DHT were partly reversed by carnosol. Western blotting results showed that carnosol treatment inhibited the DHT\u2010activated mitochondrial apoptotic pathway by activating nuclear factor\u2010erythroid 2\u2010related factor (Nrf2)\/heme oxygenase 1 (HO\u20101). Knockdown of\n                    <jats:italic>Nrf2<\/jats:italic>\n                    by transfecting with siRNA or inhibiting HO\u20101 by zinc protoporphyrin (ZnPP) blocked the protective effects of carnosol. Computational modeling and pull\u2010down assay results confirmed the direct binding of carnosol to kelch\u2010like ECH\u2010associated protein 1 (Keap1). In vivo results showed that the intraperitoneal administration of carnosol (50 and 100\u2009mg\/kg) improved estrous cycle disorders, polycystic ovary, and decreased elevated androgen in the PCOS mice. In summary, Carnosol has an effective role in inhibiting oxidative stress and apoptosis in DHT\u2010treated KGN cells and protecting against mouse PCOS phenotypes through the Keap1\u2010mediated activation of Nrf2\/HO\u20101 signaling.\n                  <\/jats:p>","DOI":"10.1002\/ptr.7749","type":"journal-article","created":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T07:45:55Z","timestamp":1676360755000},"page":"1405-1421","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["Carnosol inhibits\n                    <scp>KGN<\/scp>\n                    cells oxidative stress and apoptosis and attenuates\n                    <scp>polycystic ovary syndrome<\/scp>\n                    phenotypes in mice through Keap1\u2010mediated Nrf2\/\n                    <scp>HO<\/scp>\n                    \u20101 activation"],"prefix":"10.1002","volume":"37","author":[{"given":"Rui","family":"Ji","sequence":"first","affiliation":[{"name":"Reproductive Medical Center Renmin Hospital of Wuhan University  Wuhan China"},{"name":"Ascientific Research Platform Hubei Clinic Research Center for Assisted Reproductive Technology and Embryonic Development  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangyuan","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Vascular and Endovascular Surgery Henan Provincial People's Hospital  Zhengzhou City Henan China"},{"name":"Department of Aortic Surgery Central China Fuwai Hospital of Zhengzhou University  Zhengzhou Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Chen","sequence":"additional","affiliation":[{"name":"Reproductive Medical Center Renmin Hospital of Wuhan University  Wuhan China"},{"name":"Ascientific Research Platform Hubei Clinic Research Center for Assisted Reproductive Technology and Embryonic Development  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Gao","sequence":"additional","affiliation":[{"name":"Reproductive Medical Center Renmin Hospital of Wuhan University  Wuhan China"},{"name":"Ascientific Research Platform Hubei Clinic Research Center for Assisted Reproductive Technology and Embryonic Development  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3286-0772","authenticated-orcid":false,"given":"Jing","family":"Yang","sequence":"additional","affiliation":[{"name":"Reproductive Medical Center Renmin Hospital of Wuhan University  Wuhan China"},{"name":"Ascientific Research Platform Hubei Clinic Research Center for Assisted Reproductive Technology and Embryonic Development  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,2,14]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2019.12.007"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-44390-1"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2019.00743"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbt.20212"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aah4477"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1708854114"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep15482"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2015.11.003"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2013.01.140"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2010.181"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.202222"},{"key":"e_1_2_11_13_1","article-title":"Development and validation of an analytical method for carnosol, carnosic acid and rosmarinic acid in food matrices and evaluation of the antioxidant activity of rosemary extract as a food additive","volume":"8","author":"Choi S. 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