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Planta Med 2011; 77(10): 984-991
DOI: 10.1055/s-0030-1250718
Biological and Pharmacological Activity
Original Papers
© Georg Thieme Verlag KG Stuttgart · New York

Orientin-Induced Cardioprotection against Reperfusion Is Associated with Attenuation of Mitochondrial Permeability Transition

Na Lu1 , Yiguo Sun1 , Xiaoxiang Zheng1
  • 1Department of Biomedical Engineering, Key Laboratory of Biomedical Engineering, Ministry of Education, Zhejiang University, Hangzhou, P. R. China
Further Information

Publication History

received Sept. 10, 2010 revised Nov. 29, 2010

accepted Dec. 13, 2010

Publication Date:
31 January 2011 (online)

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Abstract

In this study, we provide new evidence that orientin from bamboo leaves (Phyllostachys nigra) protect H9c2 cardiomyocytes against ischemia/reperfusion (I/R) injury through the mitochondrial apoptotic pathway. A previous work has identified that orientin could protect myocardium against ischemia/reperfusion injury. Mitochondria are both critical determinants of cardioprotection and crucial targets of cardioprotective signaling. Their role during reperfusion is conspicuously critical because the conditions promote apoptosis through the mitochondrial pathway and necrosis though irreversible damage to mitochondria, which is in association with mitochondrial permeability transition (MPT). After myocardial ischemia, opening of the mPTP is a critical determinant of cell death. The relationship of orientin and mPTP in mediating reperfusion-induced cardiomyocytes injury is still elusive. Here, our results indicate that the protective effect of orientin in H9c2 cells subjected to I/R injury is associated with depression of the mPTP opening, resultant mitochondrial dysfunction, and apoptosis. Further investigation of cellular mechanisms revealed that these effects were associated with inhibition of reactive oxygen species (ROS) generation, repolarization of mitochondrial membrane potential (Δψ m), suppression of mitochondrial cytochrome c release, enhancement of the Bcl-2 level, and inhibition of Bax and Smac/DIABLO levels. Furthermore, these beneficial effects of orientin were blocked by the phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin, and orientin could enhance Akt phosphorylation. In summary, we demonstrate that orientin protects H9c2 cardiomytocytes against I/R-induced apoptosis by modulating the mPTP opening, and this role of orientin may involve the PI3K/Akt signaling pathway.

Key words

orientin - mitochondrial permeability transition - cardiomyocytes - ischemia/reperfusion (I/R) - apoptosis

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Prof. Xiaoxiang Zheng

Department of Biomedical Engineering
Key Laboratory of Biomedical Engineering, MOE
Zhejiang University (Yuquan Campus)

Zheda Road 38

310027 Hangzhou

P. R. China

Phone: +86 5 71 87 95 38 60

Fax: +86 5 71 87 95 16 76

Email: zxx@bme.zju.edu.cn

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