Original ArticleProtective Effects of Isorhamnetin on Cardiomyocytes Against Anoxia/Reoxygenation-induced Injury Is Mediated by SIRT1Huang, Liqing BD; He, Huan PhD; Liu, Zhantu BD; Liu, Dan PhD; Yin, Dong PhD; He, Ming PhD Author Information *Jiangxi Provincial Key Laboratory of Basic Pharmacology, Nanchang University School of Pharmaceutical Science, Nanchang, China; and †Jiangxi Provincial Key Laboratory of Molecular Medicine, The Second Affiliated Hospital, Nanchang University, Nanchang, China. Reprints: Ming He, PhD, Department of Pharmacology and Molecular Therapeutics, Nanchang University School of Pharmaceutical Science, Nanchang 330006, China (e-mail: [email protected]) or Dong Yin, PhD, Jiangxi Provincial Key Laboratory of Molecular Medicine, The Second Affiliated Hospital, Nanchang University, Nanchang 330006, China (e-mail: [email protected]). This study was supported by the Natural Scientific Foundations of China (81160402, 81072632). The authors report no conflicts of interest. Liqing Huang and Huan He have contributed equally to this work. Received December 02, 2015 Accepted January 21, 2016 Journal of Cardiovascular Pharmacology: June 2016 - Volume 67 - Issue 6 - p 526-537 doi: 10.1097/FJC.0000000000000376 Buy Metrics Abstract It has been reported that apoptosis plays a very important role on anoxia/reoxygenation (A/R)-induced injury, and human silent information regulator type 1 (SIRT1) can inhibit the apoptosis of cardiomyocytes. It has been proved that isorhamnetin (IsoRN), 3′-O-methyl-quecetin, can protect the cardiomyocytes, but the mechanism is still not clear. The aim of the study was to explore whether the protective effects of IsoRN on the cardiomyocytes against the A/R-induced injury are mediated by SIRT1. The effects of IsoRN on cardioprotection against A/R injury in neonatal rat cardiomyocytes were monitored by cell viability, the levels of mitochondrial membrane potential (Δψm), apoptosis, and intracellular reactive oxygen species (ROS), the levels of lactate dehydrogenase (LDH), creatine phosphokinase (CPK) and mitochondrial permeability transition pores (mPTP). The effects on protein expression were measured by western blot assay. The results showed that IsoRN can reduce A/R-induced injury by decreasing the level of lactate dehydrogenase and creatine phosphokinase release from the cardiomyocytes, increasing cell viability and expression of SIRT1, reducing the generation of reactive oxygen species, inhibiting opening of mitochondrial permeability transition pores and loss of Δψm and activation of caspase-3, and decreasing the release of cytochrome c, and reducing apoptosis. In addition, sirtinol, a SIRT1 inhibitor, drastically reduced the protective effects of IsoRN on cardioprotective effects in cardiomocytes. In conclusion, we firstly demonstrated that SIRT1 may be involved in the protective effects of IsoRN on cardiomocytes against the A/R-induced injury. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.