Journal
MOLECULES
Volume 22, Issue 2, Pages -Publisher
MDPI
DOI: 10.3390/molecules22020331
Keywords
Apoptosis; Cardiac; Nox4; ROS
Funding
- Education Commission of Shanghai Municipality [ZDSYS14005]
- National Natural Science Foundation of China [81330080]
- National Major Scientific and Technology Special Project [2012ZX09103101i-064, 2012ZX09501001-001-003]
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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--l-rhamnopyransoyl)--d-glucopyranoside-7-O--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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