{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:36:44Z","timestamp":1791920204473,"version":"4.3.4"},"reference-count":44,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2016,7,8]],"date-time":"2016-07-08T00:00:00Z","timestamp":1467936000000},"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":["J Cardiovasc Pharmacol Ther"],"published-print":{"date-parts":[[2016,9]]},"abstract":"<jats:p>Preclinical and clinical studies have demonstrated that berberine (BBR) improves diabetic complications and reduces mortality of patients with congestive heart failure. The therapeutic effects of BBR have been reported to be mediated by its regulation of adenosine monophosphate (AMP)-activated protein kinase (AMPK). We previously reported that BBR protects against ischemia\u2013reperfusion injury via regulating AMPK activity in both ischemic and nonischemic areas of the rat heart. Since diabetic hearts are more sensitive to ischemia\u2013reperfusion injury, we examined whether BBR treatment exhibited cardioprotective effects in the diabetic heart. Type 2 diabetic rats were pretreated plus or minus BBR for 7 days and subjected to 30-minute ischemia followed by 120-minute reperfusion. Pretreatment of type 2 diabetic rats with BBR reduced ischemia\u2013reperfusion injury infarct size and attenuated arrhythmia compared to untreated diabetic controls. Subsequent to ischemia\u2013reperfusion, serum triglyceride, total cholesterol, and malondialdehyde levels were reduced by pretreatment of type 2 diabetic rats with BBR compared to untreated diabetic controls. In contrast, serum glucose and superoxide dismutase levels were unaltered. The mechanism for the BBR-mediated cardioprotective effect was examined. Pretreatment with BBR did not alter AMPK activity in ischemic areas at risk but increased AMPK activity in nonischemic areas compared to untreated diabetic controls. The increased AMPK activity in nonischemic areas was due an elevated ratio of AMP to adenosine triphosphate (ATP) and adenosine diphosphate to ATP. In addition, pretreatment with BBR increased protein kinase B (AKT) phosphorylation and reduced glycogen synthase kinase 3\u03b2 (GSK3\u03b2) activity in nonischemic areas compared to untreated diabetic controls. These findings indicate that BBR protects the diabetic heart from ischemia\u2013reperfusion injury. In addition, BBR may mediate this cardioprotective effect through AMPK activation, AKT phosphorylation, and GSK3\u03b2 inhibition in the nonischemic areas of the diabetic heart.<\/jats:p>","DOI":"10.1177\/1074248415627873","type":"journal-article","created":{"date-parts":[[2016,2,4]],"date-time":"2016-02-04T21:14:01Z","timestamp":1454620441000},"page":"486-494","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":58,"title":["Berberine Pretreatment Confers Cardioprotection Against Ischemia\u2013Reperfusion Injury in a Rat Model of Type 2 Diabetes"],"prefix":"10.1177","volume":"21","author":[{"given":"Wenguang","family":"Chang","sequence":"first","affiliation":[{"name":"Department of Pharmacology, College of Basic Medical Sciences, School of Nursing, Jilin University, Changchun, China"},{"name":"Department of Pharmacology and Therapeutics, Center for Research and Treatment of Atherosclerosis, University of Manitoba, 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