title: ZYZ-772 Prevents Cardiomyocyte Injury by Suppressing Nox4-Derived ROS Production and Apoptosis.
abstract: Nox-dependent signaling plays critical roles in the development of heart failure, cardiac hypertrophy, and myocardial infarction. NADPH oxidase 4 (Nox4) as a major source of oxidative stress in the heart offers a new therapeutic target in cardiovascular disease. In the present work, a novel flavonoid was isolated fromZanthoxylum bungeanum.Its structure was elucidated as Quercetin-3-O-(6''-O-α-l-rhamnopyransoyl)-β-d-glucopyranoside-7-O-β-d-glucopyranoside (ZYZ-772) for the first time. ZYZ-772 exhibited significant cardio-protective property against CoCl₂ induced H9c2 cardiomyocyte cells injury. In CoCl₂ stimulated cardiomyocyte injury, ZYZ-772 inhibited expression of Nox4, and alleviated ROS overproduction. Importantly, ROS triggered MAPKs phosphorylation and P53 signaling mediated apoptosis were restored by ZYZ-772. Our findings present the first piece of evidence for the therapeutic properties of ZYZ-772 in preventing cardiomyocyte injury, which could be attributed to the suppression of Nox4/MAPKs/P53 axis. This will offer a novel therapeutic strategy for the treatment of cardiac ischemia disease.
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, China. tiantianwangying@126.com.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, China. 12211030038@fudan.edu.cn.
authors.forename: Liangjie
authors.initials: L
authors.lastname: Zhong
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, China. liuxinhua@fudan.edu.cn.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, China. yzzhu@must.edu.mo.|School of Pharmacy, Macao University of Science and Technology, Macao. yzzhu@must.edu.mo.
authors.forename: Yi Zhun
authors.initials: YZ
authors.lastname: Zhu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002316:Cardiotonic Agents / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D015394:Molecular Structure; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism*; D019255:NADPH Oxidases / Q000378:metabolism*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D002316:Cardiotonic Agents; D005419:Flavonoids; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D019255:NADPH Oxidases
keywords: Apoptosis; Cardiac; Nox4; ROS