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Luteolin, a polyphenolic bioflavonoid, is known to confer cardioprotection, although the underlying mechanisms, especially the role of luteolin on the antioxidant enzymes, such as the peroxiredoxin family, remain unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>We measured the effects of luteolin on myocardial ischaemia\/reperfusion (MI\/R) injury <jats:italic>in vivo<\/jats:italic> (Sprague\u2010Dawley rats) and <jats:italic>in vitro<\/jats:italic>, together with the underlying mechanisms, with a focus on signalling by peroxiredoxins. H9c2 cells were used to assess the changes in peroxiredoxins and the other antioxidant enzymes. Oxidative stress, cardiac function, LDH release, ROS and infarct size were also assayed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Luteolin exerted significant cardioprotective effects <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro via<\/jats:italic> improving cardiac function, increasing the expression of anti\u2010apoptotic protein Bcl\u20102 and decreasing the pro\u2010apoptotic protein Bax and active caspases 3 and 9, associated with MI\/R. Mechanistically, luteolin markedly enhanced expression of peroxiredoxin II, without significant effects on other forms of peroxiredoxin, catalase or SOD1. Molecular docking showed that luteolin could indeed bind to the enzymic active pocket of peroxiredoxin II. Furthermore, down\u2010regulation of peroxiredoxin II by peroxiredoxin II\u2010antisense, administered by adenovirus infection of H9c2 cardiomyocytes, and inhibition of peroxiredoxin II <jats:italic>in vivo<\/jats:italic> significantly reversed the cardioprotective effects of luteolin.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>Our findings, for the first time, demonstrate that luteolin protects against MI\/R injury through promoting signalling through the endogenous antioxidant enzyme, peroxiredoxin II, indicating the important beneficial role of this antioxidant system in the heart.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.14367","type":"journal-article","created":{"date-parts":[[2018,5,21]],"date-time":"2018-05-21T20:09:23Z","timestamp":1526933363000},"page":"3315-3332","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":69,"title":["Luteolin ameliorates rat myocardial ischaemia\u2013reperfusion injury through activation of peroxiredoxin II"],"prefix":"10.1111","volume":"175","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7646-5600","authenticated-orcid":false,"given":"Bo","family":"Wei","sequence":"first","affiliation":[{"name":"Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Co\u2010innovation Center of Henan Province for New Drug R &amp; D and Preclinical Safety, School of Pharmace utical Sciences Zhengzhou University  Zhengzhou Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiao","family":"Lin","sequence":"additional","affiliation":[{"name":"Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Co\u2010innovation Center of Henan Province for New Drug R &amp; D and Preclinical Safety, School of Pharmace utical Sciences Zhengzhou University  Zhengzhou Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya\u2010Ge","family":"Ji","sequence":"additional","affiliation":[{"name":"Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, Co\u2010innovation Center of Henan Province for New Drug R &amp; D and Preclinical Safety, School of Pharmace utical Sciences Zhengzhou University  Zhengzhou Henan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi\u2010Can","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine\u2010Cardiology The Second Affiliated Hospital of Zhengzhou University  Zhengzhou Henan P.R. 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