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ZYZ-772 Prevents Cardiomyocyte Injury by Suppressing Nox4-Derived ROS Production and Apoptosis.

ZYZ-772 Prevents Cardiomyocyte Injury by Suppressing Nox4-Derived ROS Production and Apoptosis.
Author Information (click to view)

Wang Y, Zhong L, Liu X, Zhu YZ,


Wang Y, Zhong L, Liu X, Zhu YZ, (click to view)

Wang Y, Zhong L, Liu X, Zhu YZ,

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Molecules (Basel, Switzerland) 2017 02 2122(2) pii E331
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 from Zanthoxylum 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.

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