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The potential defense mechanism of PCs against cerebral ischemia\/reperfusion injury (CIRI) was investigated in this study. Pre\u2212administration for 7 days of a PC enhanced nerve function and decreased cerebellar infarct volume in a mouse middle cerebral artery embolization paradigm. In addition, mitochondrial ferroptosis was enhanced, exhibited by mitochondrial shrinkage and roundness, increased membrane density, and reduced or absent ridges. The level of Fe2+ and lipid peroxidation that cause ferroptosis was significantly reduced by PC administration. According to the Western blot findings, PCs altered the expression of proteins associated with ferroptosis, promoting the expression of GPX4 and SLC7A11 while reducing the expression of TFR1, hence inhibiting ferroptosis. Moreover, the treatment of PCs markedly elevated the expression of HO\u22121 and Nuclear\u2212Nrf2. The PCs\u2019 ability to prevent ferroptosis due to CIRI was decreased by the Nrf2 inhibitor ML385. Our findings showed that the protective effect of PCs may be achieved via activation of the Nrf2\/HO-1 pathway and inhibiting ferroptosis. This study provides a new perspective on the treatment of CIRI with PCs.<\/jats:p>","DOI":"10.3390\/molecules28083582","type":"journal-article","created":{"date-parts":[[2023,4,20]],"date-time":"2023-04-20T02:01:11Z","timestamp":1681956071000},"page":"3582","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Procyanidins Alleviated Cerebral Ischemia\/Reperfusion Injury by Inhibiting Ferroptosis via the Nrf2\/HO-1 Signaling Pathway"],"prefix":"10.3390","volume":"28","author":[{"given":"Lei","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy, Bengbu Medical College, Bengbu 233030, China"},{"name":"Anhui Engineering Technology Research Center of Biochemical Pharmaceutical, Bengbu 233030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy, Bengbu Medical College, Bengbu 233030, China"},{"name":"Anhui Engineering Technology Research Center of Biochemical Pharmaceutical, Bengbu 233030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi-Meng","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy, Bengbu Medical College, Bengbu 233030, China"},{"name":"Anhui Engineering Technology Research Center of Biochemical Pharmaceutical, Bengbu 233030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Rong","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy, Bengbu Medical College, Bengbu 233030, China"},{"name":"Anhui Engineering Technology Research Center of Biochemical Pharmaceutical, Bengbu 233030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu-Hui","family":"Tong","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy, Bengbu Medical College, Bengbu 233030, China"},{"name":"Anhui Engineering Technology Research Center of Biochemical Pharmaceutical, Bengbu 233030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy, Bengbu Medical College, Bengbu 233030, China"},{"name":"Anhui Engineering Technology Research Center of Biochemical Pharmaceutical, Bengbu 233030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy, Bengbu Medical College, Bengbu 233030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu-Ying","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Pharmacy, Bengbu Medical College, Bengbu 233030, China"},{"name":"Anhui Engineering Technology Research Center of Biochemical Pharmaceutical, Bengbu 233030, China"},{"name":"Key Laboratory of Cardiovascular and Cerebrovascular Diseases, Bengbu Medical College, Bengbu 233030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"59","DOI":"10.3389\/fphar.2020.00059","article-title":"Non-Mitogenic Fibroblast Growth Factor 1 Enhanced Angiogenesis Following Ischemic Stroke by Regulating the Sphingosine-1-Phosphate 1 Pathway","volume":"11","author":"Zou","year":"2020","journal-title":"Front. 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