Bauhinia championii Flavone Attenuates Hypoxia-Reoxygenation Induced Apoptosis in H9c2 Cardiomyocytes by Improving Mitochondrial Dysfunction.

Ping Liao,Xiaobo Sun,Chan Zhang,Yao Sun,Guibo Sun,Jie Jian,Yuehan Zhou,Min Wang

doi:10.3390/molecules21111469

Abstract

This study aimed to determine the effects of Bauhinia championii flavone (BCF) on hypoxia-reoxygenation (H/R) induced apoptosis in H9c2 cardiomyocytes and to explore potential mechanisms. The H/R model in H9c2 cardiomyocytes was established by 6 h of hypoxia and 12 h of reoxygenation. Cell viability was detected by CCK-8 assay. Apoptotic rate was measured by Annexin V/PI staining. Levels of mitochondria-associated ROS, mitochondrial transmembrane potential (∆Ψm) and mitochondrial permeability transition pores (MPTP) opening were assessed by fluorescent probes. ATP production was measured by ATP assay kit. The release of cytochrome c, translocation of Bax, and related proteins were measured by western blotting. Our results showed that pretreatment with BCF significantly improved cell viability and attenuated the cardiomyocyte apoptosis caused by H/R. Furthermore, BCF increased ATP production and inhibited ROS-generating mitochondria, depolarization of ΔΨm, and MPTP opening. Moreover, BCF pretreatment decreased Bax mitochondrial translocation, cytochrome c release, and activation of caspase-3, as well as increased the expression of p-PI3K, p-Akt, and the ratio of Bcl-2 to Bax. Interestingly, a specific inhibitor of phosphatidylinositol 3-kinase, LY294002, partly reversed the anti-apoptotic effect of BCF. These observations indicated that BCF pretreatment attenuates H/R-induced myocardial apoptosis strength by improving mitochondrial dysfunction via PI3K/Akt signaling pathway.

Highlights

Coronary artery disease is the largest contributor to cardiovascular diseases which has become a leading cause of death worldwide [1,2]
Early myocardial reperfusion using either thrombolytic or primary percutaneous coronary intervention can effectively salve the damaged myocardium, the process of reperfusion can itself lead to further injury such as cardiomyocyte death, which is known as myocardial ischemia/reperfusion (I/R) injury [3]
Multiple studies have demonstrated that apoptosis contributes to one of the important pathological mechanisms of I/R injury, while the mitochondrial dysfunction associated with intrinsic apoptosis is considered crucial in myocardial apoptosis [4,5,6]

Summary

Introduction

Coronary artery disease is the largest contributor to cardiovascular diseases which has become a leading cause of death worldwide [1,2]. Early myocardial reperfusion using either thrombolytic or primary percutaneous coronary intervention can effectively salve the damaged myocardium, the process of reperfusion can itself lead to further injury such as cardiomyocyte death, which is known as myocardial ischemia/reperfusion (I/R) injury [3]. Various studies have demonstrated that phospho-Akt can improve mitochondrial dysfunction by regulating Bcl-2 protein family [8,9,10]. It may be a possible target of improving I/R injury to inhibit apoptosis by activating Akt and improving mitochondrial function

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