title: Catalpol protects glucose-deprived rat embryonic cardiac cells by inducing mitophagy and modulating estrogen receptor.
abstract: Catalpol, a bioactive component from Rehmannia glutinosa (Di Huang), has been widely used to protect cardiomyocytes against myocardial ischemia. The aim of the present study was to investigate the anti-apoptotic and anti-oxidative effects of Catalpol on glucose-starved H9c2 cells for cardio-protection and to elucidate the underlying mechanisms. Here, we showed that Catalpol protected the glucose-starved H9c2 cells through reducing apoptosis and attenuating oxidative damage. Moreover, the increases of autophagic lysosomes, LC3, autophagic flux and autophagic vacuole were observed in Catalpol-treated cells using flow cytometer and fluorescence microscope. Western blotting analyses showed that the autophagy-related proteins (LC3, Beclin1 and ULK) were markedly increased in Catalpol-treated cells, suggesting that Catalpol up-regulated autophagy in glucose starved H9c2 cells. Mechanistic investigations revealed that the autophagy inhibitor 3-MA markedly abrogated Catalpol's anti-apoptotic and anti-oxidative effects and prevented Catalpol-induced mitophagy. Furthermore, the estrogen receptor inhibitor tamoxifen significantly abolished Catalpol up-regulation of mitophagic related proteins (LC3, Beclin 1, p62, ATG5). Collectively, these data revealed that Catalpol inhibited apoptosis and oxidative stress in glucose-deprived H9c2 cell through promoting cell mitophagy and modulating estrogen receptor, supporting the notion that Catalpol could be a novel drug candidate against myocardial ischemia for the treatment of cardiovascular diseases.
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Lin
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Changzhou Affiliated Hospital of Nanjing University of Chinese Medicine, Changzhou 213003, China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Yan
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Wu
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Meiyu
authors.initials: M
authors.lastname: Kuai
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Sun
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Chen
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Xueyun
authors.initials: X
authors.lastname: Kong
authors.affiliation: Department of Pharmacology, School of Pharmacy, Nantong University, Nantong, 226001, China.
authors.forename: Zhaoguo
authors.initials: Z
authors.lastname: Liu
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Yuping
authors.initials: Y
authors.lastname: Tang
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Jing
authors.affiliation: Department of Preclinical Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Qichun
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China; Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: hmbian@sina.com.
authors.forename: Huimin
authors.initials: H
authors.lastname: Bian
mesh_terms: D000818:Animals; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D057888:Iridoid Glucosides / Q000494:pharmacology*; D063306:Mitophagy / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress; D051381:Rats; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*
chemical_list: D057888:Iridoid Glucosides; D011960:Receptors, Estrogen; C078040:catalpol; D005947:Glucose
keywords: Apoptosis H9c2; Catalpol; Estrogen receptor; Mitophagy; Myocardial ischemia