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However, despite the potential benefits of antioxidants reported in clinical applications, few have proven effective in treating CIRI, particularly in the elderly. Epicatechin (EC) is a catechol flavonoid monomer derived from natural tea plants. Multiple phenolic hydroxyl groups give it strong antioxidant properties, which can not only degrade ROS through chemical reactions between hydroxyl and ROS but also enhance the activity of antioxidant enzymes in cells, and it is easy to penetrate the blood\u2013brain barrier. But its antagonistic effect on age\u2010related CIRI and potential medicinal value are still unknown. Nuclear factor erythroid 2\u2010related factor 2 (Nrf2) is the most important transcription factor regulating the expression of antioxidant proteins in the body. This study first compared the pathological differences of the Nrf2 system in CIRI between 2\u2010month\u2010old and 12\u2010month\u2010old Sprague\u2013Dawley (SD) rats. Subsequently, EC was administered to 12\u2010month\u2010old rat models of middle cerebral artery occlusion and reperfusion (MCAO\/R) and senescent SH\u2010SY5Y cell models subjected to oxygen glucose deprivation\/reoxygenation (OGD\/R). EC treatment improved cerebral morphology and function; increased p\u2010Nrf2, heme oxygenase\u20101 (HO\u20101), superoxide dismutase (SOD), and glutathione (GSH) expression; reduced infarct volume; and neuronal apoptosis in senescent rats. Moreover, EC enhanced cellular activity and the expression of p\u2010Nrf2, HO\u20101, and quinone oxidoreductase\u20101 (NQO\u20101) while decreasing ROS and malondialdehyde (MDA) levels and mitigating apoptosis in senescent SH\u2010SY5Y cells. These effects were reversed upon si\u2010Nrf2. In sum, we confirm that EC exerts neuroprotective effects by upregulating Nrf2\/ARE and reducing oxidative stress, suggesting that EC may be a promising drug for the treatment of senile cerebral apoplexy. This study also provides a scientific basis for the development and selection of new drugs for ischemic stroke in elderly patients.<\/jats:p>","DOI":"10.1002\/fsn3.4253","type":"journal-article","created":{"date-parts":[[2024,6,22]],"date-time":"2024-06-22T04:39:48Z","timestamp":1719031188000},"page":"6521-6533","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Epicatechin\u2010mediated modulation of the Nrf2\/<scp>HO<\/scp>\u20101 pathway alleviates senile cerebral ischemic\/reperfusion injury"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-5942-4527","authenticated-orcid":false,"given":"Changyue","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Physiology Guangxi Medical University  Nanning China"},{"name":"HIV\/AIDS Clinical Treatment Center of Guangxi (Nanning) and The Fourth Hospital of Nanning  Nanning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangzhen","family":"Zhuge","sequence":"additional","affiliation":[{"name":"Department of Physiology Guangxi Medical University  Nanning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deli","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Physiology Guangxi Medical University  Nanning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menghua","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cardiology Foresea Life Insurance Nanning Hospital  Nanning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanxiang","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Physiology Guangxi Medical University  Nanning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Physiology Guangxi Medical University  Nanning China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,6,21]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2020.111182"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.111729"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/8279851"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.11958\/20210388"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.121.021499"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom11030392"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.112610"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.12362"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox8080273"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27031049"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.Str.20.1.84"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010pharmtox\u2010011112\u2010140320"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.2174\/1381612826666200708133912"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0171161"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.13210\/j.cnki.jhmu.20230106.001"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.13098"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201802246RR"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2018.06.003"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2020.152525"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2019.10.088"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26237109"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11357\u2010019\u201000107\u2010w"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12868\u2010022\u201000740\u2010w"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1021\/jf301787f"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.15099"}],"container-title":["Food Science &amp; 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