title: Elatoside C protects against hypoxia/reoxygenation-induced apoptosis in H9c2 cardiomyocytes through the reduction of endoplasmic reticulum stress partially depending on STAT3 activation.
abstract: Endoplasmic reticulum (ER) stress-induced apoptosis has been suggested to contribute to myocardial ischemia-reperfusion (I/R) injury. Elatoside C is one of the major triterpenoid compounds isolated from Aralia elata that is known to be cardioprotective. However, its effects on I/R injury to cardiac myocytes have not been clarified. This study aimed to investigate the possible protective effect of Elatoside C against hypoxia/reoxygenation (H/R)-induced H9c2 cardiomyocyte injury and its underlying mechanisms. H9c2 cardiomyocytes were subjected to H/R in the presence of Elatoside C. Our results showed that Elatoside C (25 μM) treatment provided significant protection against H/R-induced cell death, as evidenced by improved cell viability, maintained mitochondrial membrane potential, diminished mitochondrial ROS, and reduced apoptotic cardiomyocytes (P < 0.05). These changes were associated with the inhibition of ER stress-associated apoptosis markers (GRP78, CHOP, Caspase-12 and JNK), as well as the increased phosphorylation of STAT3 and an increased Bcl2/Bax ratio. Moreover, these effects of Elatoside C were prevented by the STAT3 inhibitor Stattic. Taken together, these results suggested that Elatoside C can alleviate H/R-induced cardiomyocyte apoptosis most likely by activating the STAT3 pathways and reducing ER stress-associated apoptosis.
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 151, Malianwa North Road, Haidian District, Beijing, 100193, People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.forename: Xiang-bao
authors.initials: XB
authors.lastname: Meng
authors.forename: Ying-li
authors.initials: YL
authors.lastname: Yu
authors.forename: Gui-bo
authors.initials: GB
authors.lastname: Sun
authors.forename: Xu-dong
authors.initials: XD
authors.lastname: Xu
authors.forename: Xiao-po
authors.initials: XP
authors.lastname: Zhang
authors.forename: Xi
authors.initials: X
authors.lastname: Dong
authors.forename: Jing-xue
authors.initials: JX
authors.lastname: Ye
authors.forename: Hui-bo
authors.initials: HB
authors.lastname: Xu
authors.forename: Yi-fan
authors.initials: YF
authors.lastname: Sun
authors.forename: Xiao-bo
authors.initials: XB
authors.lastname: Sun
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D027983:Aralia; D002316:Cardiotonic Agents / Q000494:pharmacology*; D015687:Cell Hypoxia; D002460:Cell Line; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D012503:Saponins / Q000494:pharmacology*; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: D002316:Cardiotonic Agents; D050796:STAT3 Transcription Factor; D012503:Saponins; D014315:Triterpenes; C000601129:elatoside C