title: Astragaloside IV protects cardiomyocytes from anoxia/reoxygenation injury by upregulating the expression of Hes1 protein.
abstract: Astragaloside IV (ASI), a traditional Chinese medicine, is a main active ingredient of Astragalus membranaceus. Many clinical studies have found that ASI protects cardiomyocytes in cardiovascular diseases, but the underlying mechanisms remain obscure. The aim of this study was to investigate the molecular mechanisms responsible for the protective effects of ASI in cardiomyocytes from anoxia/reoxygenation (A/R) injury. According to the previous studies, we hypothesized that the cardioprotective effects of ASI against A/R injury might be associated with Notch1/Hes1 signaling pathway. In this study, neonatal rat primary cardiomyocytes were preconditioned with ASI prior to A/R injury. Our results showed that ASI effectively increased the cell viability, decreased the content of MDA, decreased the activities of CPK and LDH, increased the activities of GSH-Px and SOD, and reduced the reactive oxygen species (ROS) generation and the loss of mitochondrial membrane potential (Δψm). ASI inhibited the mitochondrial permeability transition pore (mPTP) opening and activation of caspase-3, and finally decreased the cell apoptosis in cardiomyocytes. Furthermore, ASI upregulated Hes1 protein expression. However, pretreatment with DAPT, a Notch1 inhibitor, effectively attenuated the cardioprotective effects of ASI against A/R injury, except MDA, SOD, GSH-Px, and the ROS generation. Taken together, we demonstrated that ASI could protect against A/R injury via the Notch1/Hes1 signaling pathway.
authors.affiliation: a Department of Cardiac Surgery, The First Affiliated Hospital of Nanchang University, No. 17, Yong Wai Zheng Street, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Huang
authors.initials: H
authors.lastname: Huang
authors.affiliation: a Department of Cardiac Surgery, The First Affiliated Hospital of Nanchang University, No. 17, Yong Wai Zheng Street, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Songqing
authors.initials: S
authors.lastname: Lai
authors.affiliation: b Department of Pharmacy, The First Affiliated Hospital of Nanchang University, No. 17, Yong Wai Zheng Street, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Wan
authors.affiliation: a Department of Cardiac Surgery, The First Affiliated Hospital of Nanchang University, No. 17, Yong Wai Zheng Street, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Wanghong
authors.initials: W
authors.lastname: Qi
authors.affiliation: a Department of Cardiac Surgery, The First Affiliated Hospital of Nanchang University, No. 17, Yong Wai Zheng Street, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Jichun
authors.initials: J
authors.lastname: Liu
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D027885:Astragalus propinquus / Q000737:chemistry; D002316:Cardiotonic Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D053148:Caspase 3 / Q000737:chemistry / Q000378:metabolism; D002478:Cells, Cultured; D003959:Diamines / Q000494:pharmacology; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D033681:Mitochondrial Membrane Transport Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D051881:Receptor, Notch1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D012503:Saponins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013844:Thiazoles / Q000494:pharmacology; D000072056:Transcription Factor HES-1 / Q000819:agonists* / Q000378:metabolism; D014315:Triterpenes / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: C000612000:24-diamino-5-phenylthiazole; D002316:Cardiotonic Agents; D003959:Diamines; D004365:Drugs, Chinese Herbal; C489735:Hes1 protein, rat; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; C497763:Notch1 protein, rat; D017382:Reactive Oxygen Species; D051881:Receptor, Notch1; D012503:Saponins; D013844:Thiazoles; D000072056:Transcription Factor HES-1; D014315:Triterpenes; C052064:astragaloside A; C505410:Casp3 protein, rat; D053148:Caspase 3
keywords: Hes1; Notch1 signaling pathway; anoxia/reoxygenation; anoxie/réoxygénation, préconditionnement, cardiomyocytes primaires de rats nouveau-nés; astragaloside IV; astragaloside IV, voie de signalisation Notch1, Hes1, cardioprotection; cardioprotection; neonatal rat primary cardiomyocytes; precondition