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Abstract Title:

Berberine protects the heart from ischemia/reperfusion injury by attenuating endoplasmic reticulum stress via the JAK2/STAT3 signaling pathway.

Abstract Source:

Acta Pharmacol Sin. 2016 Jan 25. Epub 2016 Jan 25. PMID: 26806299

Abstract Author(s):

Guo-Long Zhao, Li-Ming Yu, Wen-Li Gao, Wei-Xun Duan, Bo Jiang, Xu-Dong Liu, Bin Zhang, Zhen-Hua Liu, Meng-En Zhai, Zhen-Xiao Jin, Shi-Qiang Yu, Yun Wang

Article Affiliation:

Guo-Long Zhao

Abstract:

AIM: Endoplasmic reticulum (ER) stress plays a pivotal role in mediating cellular apoptosis during myocardial ischemia/reperfusion (MI/R) injury. Berberine (BBR) exerts potential cardioprotective effects. However, whether BBR can modulate the myocardial ER stress level during MI/R injury and the underlying mechanisms for its effects are still unknown. This study was performed to determine whether BBR protects against MI/R injury by attenuating the ER stress-induced apoptosis and to define the role of JAK2/STAT3 signaling in this process.

METHODS: Male Sprague-Dawley rats were treated with BBR (200 mg·kg(-1)·d(-1), ig, 2 weeks) and then subjected to MI/R surgery. An in vitro study was performed on cultured H9C2 cells exposed to simulated ischemia/reperfusion (SIR) injury.

RESULTS: In vivo MI/R injury significantly impaired cardiac function and increased myocardial apoptosis, oxidative damage and the ER stress level. BBR treatment effectively reduced the myocardial apoptosis, infarct size, oxidative damage and ER stress induced by PERK/eIF2α/ATF4 signaling, thus improving myocardial function. Furthermore, BBR significantly activated JAK2/STAT3 signaling, and inhibition with AG490 (the inhibitor of JAK2/STAT3 signaling) blocked BBR's protective effects. BBR also markedly reduced the cardiac apoptosis, oxidative stress and ER stress induced by SIR treatment in H9C2 cells. Consistent with the other results, these effects were abolished by JAK2 siRNA administration.

CONCLUSION: We demonstrate that BBR ameliorates MI/R injury by attenuating endoplasmic reticulum stress-induced apoptosis via the JAK2/STAT3 signaling pathway.

Study Type : Animal Study

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