title: Protective effects of Araloside C against myocardial ischaemia/reperfusion injury: potential involvement of heat shock protein 90.
abstract: The present study was designed to investigate whether Araloside C, one of the major triterpenoid compounds isolated from Aralia elata known to be cardioprotective, can improve heart function following ischaemia/reperfusion (I/R) injury and elucidate its underlying mechanisms. We observed that Araloside C concentration-dependently improved cardiac function and depressed oxidative stress induced by I/R. Similar protection was confirmed in isolated cardiomyocytes characterized by maintaining Ca2+transients and cell shortening against I/R. Moreover, the potential targets of Araloside C were predicted using the DDI-CPI server and Discovery Studio software. Molecular docking analysis revealed that Araloside C could be stably docked into the ATP/ADP-binding domain of the heat shock protein 90 (Hsp90) protein via the formation of hydrogen bonds. The binding affinity of Hsp90 to Araloside C was detected using nanopore optical interferometry and yielded KD values of 29 μM. Araloside C also up-regulated the expression levels of Hsp90 and improved cell viability in hypoxia/reoxygenation-treated H9c2 cardiomyocytes, whereas the addition of 17-AAG, a pharmacologic inhibitor of Hsp90, attenuated Araloside C-induced cardioprotective effect. These findings reveal that Araloside C can efficiently attenuate myocardial I/R injury by reducing I/R-induced oxidative stress and [Ca2+]ioverload, which was possibly related to its binding to the Hsp90 protein.
authors.affiliation: Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Yu-Yang
authors.initials: YY
authors.lastname: Du
authors.affiliation: Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Gui-Bo
authors.initials: GB
authors.lastname: Sun
authors.affiliation: Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Xu-Dong
authors.initials: XD
authors.lastname: Xu
authors.affiliation: Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.|Key Laboratory of Chinese Materia Medica (Ministry of Education), Heilongjiang University of Chinese Medicine, Harbin, Heilongjang, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Academy of Chinese Medical Sciences of Jilin Province, Changchun, Jilin, China.
authors.forename: Hui-Bo
authors.initials: HB
authors.lastname: Xu
authors.affiliation: Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Xiang-Bao
authors.initials: XB
authors.lastname: Meng
authors.affiliation: Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Jing-Yi
authors.initials: JY
authors.lastname: Zhang
authors.affiliation: Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Shi-Lan
authors.initials: SL
authors.lastname: Ding
authors.affiliation: Harbin University of Commerce, Harbin, Heilongjiang, China.
authors.forename: Miao-di
authors.initials: MD
authors.lastname: Zhang
authors.affiliation: Harbin University of Commerce, Harbin, Heilongjiang, China.
authors.forename: Ming-Hua
authors.initials: MH
authors.lastname: Yang
authors.affiliation: Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Xiao-Bo
authors.initials: XB
authors.lastname: Sun
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D019610:Cytoprotection / Q000187:drug effects; D018841:HSP90 Heat-Shock Proteins / Q000737:chemistry / Q000378:metabolism*; D006706:Homeostasis / Q000187:drug effects; D007700:Kinetics; D008297:Male; D051379:Mice; D062105:Molecular Docking Simulation; D009200:Myocardial Contraction / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D012503:Saponins / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D012518:Sarcomeres / Q000187:drug effects / Q000378:metabolism
chemical_list: D002316:Cardiotonic Agents; D018841:HSP90 Heat-Shock Proteins; D012503:Saponins
keywords: Araloside C; biomolecular interactions; heat shock protein 90; ischaemia/reperfusion