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Oxid Med Cell Longev. 2018 Jun 25;2018:4327901. doi: 10.1155/2018/4327901. eCollection 2018.

Aucubin Protects against Myocardial Infarction-Induced Cardiac Remodeling via nNOS/NO-Regulated Oxidative Stress.

Yang Z1,2,3, Wu QQ1,2,3, Xiao Y1,2,3, Duan MX1,2,3, Liu C1,2,3, Yuan Y1,2,3, Meng YY1,2,3, Liao HH1,2,3, Tang QZ1,2,3.

Author information

1
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China.
2
Cardiovascular Research Institute, Wuhan University, Wuhan 430060, China.
3
Hubei Key Laboratory of Cardiology, Wuhan 430060, China.

Abstract

Whether aucubin could protect myocardial infarction- (MI-) induced cardiac remodeling is not clear. In this study, in a mouse model, cardiac remodeling was induced by left anterior descending coronary artery ligation surgery. Mice were intraperitoneally injected with aucubin (10 mg/kg) 3 days post-MI. Two weeks post-MI, mice in the aucubin treatment group showed decreased mortality, decreased infarct size, and improved cardiac function. Aucubin also decreased cardiac remodeling post-MI. Consistently, aucubin protected cardiomyocytes against hypoxic injury in vitro. Mechanistically, we found that aucubin inhibited the ASK1/JNK signaling. These effects were abolished by the JNK activator. Moreover, we found that the oxidative stress was attenuated in both in vivo aucubin-treated mice heart and in vitro-treated cardiomyocytes, which caused decreased thioredoxin (Trx) consumption, leading to ASK1 forming the inactive complex with Trx. Aucubin increased nNOS-derived NO production in vivo and vitro. The protective effects of aucubin were reversed by the NOS inhibitors L-NAME and L-VINO in vitro. Furthermore, nNOS knockout mice also reversed the protective effects of aucubin on cardiac remodeling. Taken together, aucubin protects against cardiac remodeling post-MI through activation of the nNOS/NO pathway, which subsequently attenuates the ROS production, increases Trx preservation, and leads to inhibition of the ASK1/JNK pathway.

PMID:
30046377
PMCID:
PMC6036820
DOI:
10.1155/2018/4327901
[Indexed for MEDLINE]
Free PMC Article

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