title: Effect and mechanism of Sorbus pohuashanensis (Hante) Hedl. flavonoids protect against arsenic trioxide-induced cardiotoxicity.
abstract: The cardiotoxicity of arsenic trioxide (ATO) limits its clinical application in cancer treatment. Evidences suggest that sorbus has antioxidant activity and its consumption has been linked with improved cardioprotection. In this study, we investigated the cardio-protective effect and mechanisms of Sorbus pohuashanensis (Hante) Hedl. flavonoids (SPF) against ATO in BALB/c mice and H9c2 cells. Eleven major flavonoids were confirmed by ultra-performance liquid chromatography electrospray ionization quadrupole time of flight mass spectrometry (UPLC-ESI-Q-TOF-MS). SPF recovered the ATO-induced disordered electrocardiogram (ECG) and abnormal cardiac structure in the heart of mice. At the same time, SPF significantly reduced levels of creatine kinase (CK), creatine kinase-MB (CK-MB) lactate dehydrogenase (LDH), and glutamic oxaloacetic transaminase (GOT) against ATO-induced injury and inhibited ATO-induced apoptosis both in vivo and in vitro. In addition, SPF regulated ATO-induced oxidative stress damage by increasing the levels of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in vivo and in vitro, and reducing reactive oxygen species (ROS). Analysis of the oxidative stress pathways showed that SPF prevented the ATO-induced downregulation of phosphorylated protein kinase B (p-Akt) in vivo and in vitro. Pre-treatment of H9c2 cells with SPF inhibited attenuation of nuclear factor (Nrf2) and heme oxygenase (HO-1). Hence, SPF could be used as a preventive and therapeutic plant ingredient against ATO-induced cardiotoxicity.
authors.affiliation: School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin 150090, China; College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin 150040, China.
authors.forename: Xiaojin
authors.initials: X
authors.lastname: Yu
authors.affiliation: School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin 150090, China. Electronic address: wangzhenyu2017@126.com.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Wang
authors.affiliation: School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006,China.
authors.forename: Zunpeng
authors.initials: Z
authors.lastname: Shu
authors.affiliation: College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin 150040, China.
authors.forename: Zhengqing
authors.initials: Z
authors.lastname: Li
authors.affiliation: College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin 150040, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Ning
authors.affiliation: School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin 150090, China.
authors.forename: Keli
authors.initials: K
authors.lastname: Yun
authors.affiliation: School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin 150090, China.
authors.forename: Haina
authors.initials: H
authors.lastname: Bai
authors.affiliation: School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin 150090, China; Department of Food Science, Cornell University, Ithaca, NY 14853-7201, USA.
authors.forename: Ruihai
authors.initials: R
authors.lastname: Liu
authors.affiliation: College of Chemistry and Environmental Engineering, Shenzhen University, Shenzhen 518060, China.
authors.forename: Wenli
authors.initials: W
authors.lastname: Liu
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D000077237:Arsenic Trioxide; D001152:Arsenicals; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D066126:Cardiotoxicity / Q000188:drug therapy* / Q000473:pathology; D020169:Caspases / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology / Q000627:therapeutic use*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008807:Mice, Inbred BALB C; D009206:Myocardium / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D010087:Oxides / Q000633:toxicity*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D031994:Sorbus / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D000975:Antioxidants; D001152:Arsenicals; D002316:Cardiotonic Agents; D005419:Flavonoids; D010087:Oxides; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D007770:L-Lactate Dehydrogenase; D020169:Caspases; D000077237:Arsenic Trioxide
keywords: Apoptosis; Arsenic trioxide; Cardiotoxicity; Flavonoids; Oxidative stress