Ramoji Kosuru1,2, Yin Cai2,3, Vidya Kandula2, Dan Yan2, Chunyan Wang2, Hong Zheng4, Yalan Li5, Michael G Irwin2, Sanjay Singh1, Zhengyuan Xia2,3. 1. Department of Pharmaceutics, Indian Institute of Technology (Banaras Hindu University), Varanasi, India. 2. Department of Anaesthesiology, Hong Kong, China. 3. State Key Laboratory of Pharmaceutical Biotechnology,Li KaShing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. 4. Department of Anaesthesiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China. 5. Department of Anaesthesiology, First Affiliated Hospital of Jinan University, Guangzhou, China.
Abstract
BACKGROUND/AIMS: Pterostilbene (PT) exerts antidiabetic effects by decreasing blood glucose and modulating lipid metabolism and has been shown to attenuate myocardial ischemia-reperfusion (IR) injury in non-diabetic subjects. However, whether PT can protect against myocardial IR injury in diabetes is unknown. AMPK stimulation is indispensable in offering cardioprotection against myocardial IR injury in diabetes by limiting cardiac apoptosis. Thus, we hypothesized that PT may confer protection against myocardial IR injury in diabetes via AMPK activation. METHODS: Sprague-Dawley rats at eight weeks of diabetes induction (induced by an intravenous dose of 65 mg/kg streptozotocin) were administered with vehicle or PT (20 and 40 mg/kg/day, p.o.) for four weeks (starting from week 9 to 12). At the end of week 12, myocardial IR injury was induced by subjecting the diabetic rats to 30 minutes of coronary artery ligation and followed by 2 hours of reperfusion. In in vitro studies, rat primary cardiomyocytes were incubated with low glucose (LG, 5.5 mM) or high glucose (HG, 30 mM) and exposed to 45 minutes hypoxia and 2 hours reoxygenation in the presence or absence of PT (0.5 µM) or the AMPK inhibitor compound C (CC, 5 µM). RESULTS: PT significantly reduced post-ischemic cardiac infarct size, oxidative stress, plasma lactate dehydrogenase (LDH), creatine kinase-MB levels and apoptosis in diabetic rats. In cardiomyocytes, PT decreased hypoxia/ reoxygenation-induced oxidative stress, attenuated LDH and cleaved caspase3/caspase3 ratio and increased Bcl-2/Bax ratio and AMPK phosphorylation. However, CC administration blunted the cardioprotective effects of PT both in vivo and in vitro. CONCLUSION: Suppressing cardiac oxidative stress and apoptosis via AMPK stimulation may represent a primary mechanism whereby pterostilbene attenuates diabetic myocardial IR injury.
BACKGROUND/AIMS: Pterostilbene (PT) exerts antidiabetic effects by decreasing blood glucose and modulating lipid metabolism and has been shown to attenuate myocardial ischemia-reperfusion (IR) injury in non-diabetic subjects. However, whether PT can protect against myocardial IR injury in diabetes is unknown. AMPK stimulation is indispensable in offering cardioprotection against myocardial IR injury in diabetes by limiting cardiac apoptosis. Thus, we hypothesized that PT may confer protection against myocardial IR injury in diabetes via AMPK activation. METHODS:Sprague-Dawley rats at eight weeks of diabetes induction (induced by an intravenous dose of 65 mg/kg streptozotocin) were administered with vehicle or PT (20 and 40 mg/kg/day, p.o.) for four weeks (starting from week 9 to 12). At the end of week 12, myocardial IR injury was induced by subjecting the diabeticrats to 30 minutes of coronary artery ligation and followed by 2 hours of reperfusion. In in vitro studies, rat primary cardiomyocytes were incubated with low glucose (LG, 5.5 mM) or high glucose (HG, 30 mM) and exposed to 45 minutes hypoxia and 2 hours reoxygenation in the presence or absence of PT (0.5 µM) or the AMPK inhibitor compound C (CC, 5 µM). RESULTS:PT significantly reduced post-ischemiccardiac infarct size, oxidative stress, plasma lactate dehydrogenase (LDH), creatine kinase-MB levels and apoptosis in diabeticrats. In cardiomyocytes, PT decreased hypoxia/ reoxygenation-induced oxidative stress, attenuated LDH and cleaved caspase3/caspase3 ratio and increased Bcl-2/Bax ratio and AMPK phosphorylation. However, CC administration blunted the cardioprotective effects of PT both in vivo and in vitro. CONCLUSION: Suppressing cardiac oxidative stress and apoptosis via AMPK stimulation may represent a primary mechanism whereby pterostilbene attenuates diabetic myocardial IR injury.
Authors: Jierong Luo; Dan Yan; Sisi Li; Shiming Liu; Fei Zeng; Chi Wai Cheung; Hong Liu; Michael G Irwin; Huansen Huang; Zhengyuan Xia Journal: J Cell Mol Med Date: 2019-12-19 Impact factor: 5.310