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Molecules 2017, 22(2), 331;

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

Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, China
School of Pharmacy, Macao University of Science and Technology, Macao
Author to whom correspondence should be addressed.
Academic Editor: David J. Newman
Received: 16 January 2017 / Revised: 10 February 2017 / Accepted: 13 February 2017 / Published: 21 February 2017
(This article belongs to the Special Issue Natural Product: A Continuing Source of Novel Drug Leads)
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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. View Full-Text
Keywords: Apoptosis; Cardiac; Nox4; ROS Apoptosis; Cardiac; Nox4; ROS

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Wang, Y.; Zhong, L.; Liu, X.; Zhu, Y.Z. ZYZ-772 Prevents Cardiomyocyte Injury by Suppressing Nox4-Derived ROS Production and Apoptosis. Molecules 2017, 22, 331.

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