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Molecules 2017, 22(2), 331; doi:10.3390/molecules22020331

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

1
Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, China
2
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)
View Full-Text   |   Download PDF [3502 KB, uploaded 21 February 2017]   |  

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. View Full-Text
Keywords: Apoptosis; Cardiac; Nox4; ROS Apoptosis; Cardiac; Nox4; ROS
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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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