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In the current research, different doses of Nobiletin (7.5, 15 and 30\u00a0mg\/kg\/day) were administered to AMI rat model for 21\u00a0days. Survival rate, echocardiography, and histological analysis were assessed in vivo. In addition, MTT assay, flow cytometry, and Western blotting were conducted to explore Nobiletin's cytotoxicity and antiapoptotic effect on H9C2 cells. Mechanistically, the activation of MAPK effectors and p38 in vivo was studied. The results showed medium\u2010 and high\u2010dose Nobiletin could significantly improve survival rate and cardiac function and reduce the area of infarction and cardiac fibrosis. Medium dose showed the best protection on cardiac functions, whereas high dose showed the best protective effect on cellular apoptosis and histological changes. JNK activation was significantly inhibited by Nobiletin in vivo, which could help to explain the partial contribution of autophagy to AMI\u2010induced apoptosis and the discrepancy on dose\u2013effect relationships. Together, our study suggested that JNK inhibition plays an important role in Nobiletin\u2010induced antiapoptotic effect in myocardial infarction, and medium\u2010dose Nobiletin demonstrated the strongest effect in vivo.<\/jats:p>","DOI":"10.1002\/prp2.728","type":"journal-article","created":{"date-parts":[[2021,3,4]],"date-time":"2021-03-04T10:02:11Z","timestamp":1614852131000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Nobiletin ameliorates cardiac impairment and alleviates cardiac remodeling after acute myocardial infarction in rats via JNK regulation"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9465-0594","authenticated-orcid":false,"given":"Zumei","family":"Liu","sequence":"first","affiliation":[{"name":"Key Laboratory of Molecular Target &amp; Clinical Pharmacology and the State Key Laboratory of Respiratory Disease School of Pharmaceutical Sciences The Fifth Affiliated Hospital Guangzhou Medical University Guangzhou PR China"},{"name":"Department of Central Laboratory Guangdong Second Provincial General Hospital Guangzhou Guangdong PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhimin","family":"Gao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Target &amp; 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