{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T18:55:47Z","timestamp":1792090547094,"version":"4.4.0"},"reference-count":49,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2019,6,20]],"date-time":"2019-06-20T00:00:00Z","timestamp":1560988800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antioxidants &amp; Redox Signaling"],"published-print":{"date-parts":[[2019,7]]},"abstract":"<jats:sec>\n                    <jats:title>Aims:<\/jats:title>\n                    <jats:p>The management of myocardial ischemia has been challenged by reperfusion injury. Reactive oxygen species (ROS) production is the critical cause of reperfusion injury, but antioxidant treatment failed to gain satisfactory effects. We hypothesized that improvement of redox homeostasis by preconditioning regulation should potentiate the ability of antioxidants to protect the heart from reperfusion injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      By phenotype-based screening, we identified that dihydrotanshinone I (DT) and protocatechuic aldehyde (PCA) potently protected cardiomyocytes through preconditioning regulation and antioxidant activity, respectively. DT induced transient ROS generation\n                      <jats:italic toggle=\"yes\">via<\/jats:italic>\n                      reversible inhibition of mitochondrial respiratory complex I and thereby stabilizing HIF-1\u03b1, while PCA elevated the levels of reduced glutathione (GSH) by providing reducing equivalents to scavenge ROS. HIF-1\u03b1, stabilized by DT, transcriptionally upregulated Nrf2 and thereby activated antioxidant enzymes, potentiating PCA to protect cardiomyocytes from reperfusion injury by strengthening intrinsic ROS scavenging capacity. In rat ischemia\/reperfusion (I\/R) model, sequential administration of DT and PCA, but not in reverse, additively protected the heart from I\/R injury, manifested by reduced infarct size and improved cardiac function. These results were further supported by sequential administration of metformin and vitamin E in the rat and porcine I\/R models.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Innovation and Conclusion:<\/jats:title>\n                    <jats:p>Our work demonstrates that preconditioning regulation of redox state is essential for antioxidants to protect the heart from I\/R injury, providing a new direction for the treatment of myocardial injury.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/ars.2018.7624","type":"journal-article","created":{"date-parts":[[2019,2,23]],"date-time":"2019-02-23T06:18:53Z","timestamp":1550902733000},"page":"227-242","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":56,"title":["HIF-1\u03b1 Preconditioning Potentiates Antioxidant Activity in Ischemic Injury: The Role of Sequential Administration of Dihydrotanshinone I and Protocatechuic Aldehyde in Cardioprotection"],"prefix":"10.1177","volume":"31","author":[{"given":"Lifeng","family":"Jiang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Natural Medicines, Department of Pharmacognosy, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Zeng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines, Department of Pharmacognosy, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihong","family":"Ni","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines, Department of Pharmacognosy, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lifengrong","family":"Qi","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines, Department of Pharmacognosy, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanmin","family":"Xu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines, Department of Pharmacognosy, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludan","family":"Xia","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines, Department of Pharmacognosy, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinghua","family":"Yu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines, Department of Pharmacognosy, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baolin","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines, Department of Pharmacognosy, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines, Department of Pharmacognosy, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiping","family":"Hao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines, Department of Pharmacokinetics, College of Pharmacy, China Pharmaceutical University, Nanjing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural Medicines, Department of Pharmacognosy, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2019,6,20]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehq456"},{"key":"e_1_3_4_3_2","first-page":"620","article-title":"Additive effects of exenatide, glucose-insulin-potassium, and remote ischemic conditioning against reperfusion ventricular arrhythmias in pigs","volume":"69","author":"Alburquerque-Bejar JJ","year":"2016","unstructured":"Alburquerque-Bejar JJ, , Barba I, , Ruiz-Meana M, , Valls-Lacalle L, , Rodriguez-Sinovas A, , and Garcia-Dorado D. 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