The Role of Mitochondria in Piperine Mediated Cardioprotection in Isoproterenol Induced Myocardial Ischemia.
The Role of Mitochondria in Piperine Mediated Cardioprotection in Isoproterenol Induced Myocardial Ischemia.
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DOI：
10.2174/1381612826666200909125750
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发表时间：
2020-09
影响因子：
3.1
通讯作者：
V. Viswanadha;V. Dhivya;Bharath Somasundaram;Narasimha M. Beeraka;Chih-Yang Huang;L. Mikhaleva;E. Achkasov;S. Bondarev;L. Gridin;V. Nikolenko;G. Aliev
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文献类型：
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作者：
V. Viswanadha;V. Dhivya;Bharath Somasundaram;Narasimha M. Beeraka;Chih-Yang Huang;L. Mikhaleva;E. Achkasov;S. Bondarev;L. Gridin;V. Nikolenko;G. Aliev
背景：一些药物治疗干预被用作治疗心肌梗死/缺血（MI）的药物，但它们的使用受到毒性和非选择性药理作用的限制。我们的初步报告描述了胡椒碱对异丙肾上腺素（ISO）诱导的心肌缺血的心脏保护作用。目的：目前的研究通过调节线粒体功能来确定胡椒碱在异丙肾上腺素（ISO）诱导的心肌缺血大鼠模型中的保护作用。方法通过分析线粒体抗氧化状态、线粒体钙、线粒体酶活性、ATP水平和细胞凋亡来实现上述目的。透射电镜观察心脏组织超微结构变化。采用RT-PCR、Western blotting分别检测细胞凋亡及促凋亡基因表达、凋亡蛋白表达。结果胡椒碱预处理可防止ISO诱导的线粒体抗氧化状态、克雷布斯循环和线粒体呼吸链酶活性（MRCEs）的改变。胡椒碱预处理后再注射ISO组心肌线粒体超微结构改变明显减少。胡椒碱维持线粒体钙稳态并抑制iso诱导的心肌凋亡。与对照组相比，ISO注射组细胞Bax、caspase （caspase 9、caspase 3）、细胞色素c等促凋亡基因表达水平显著升高，同时抗凋亡基因Bcl-2表达水平降低。胡椒碱预处理后给药ISO组的促凋亡基因表达谱明显低于注射ISO组，抗凋亡基因表达谱明显高于注射ISO组。ISO处理可使Bax、细胞色素c、caspase-3和cleaved PARP等凋亡蛋白表达上调，Bcl-2表达下调，而胡椒碱预处理可阻止ISO诱导的心肌细胞损伤过程中凋亡蛋白表达的变化。结论胡椒碱可通过增强线粒体功能减轻心肌缺血。本研究描述了胡椒碱可以作为一种营养干预来对抗iso诱导的心肌缺血。
BACKGROUND Several pharmacological therapeutic interventions are being used as therapeutic agents against myocardial infarction/ischemia (MI) but their usage is constrained by toxicity and nonselective pharmacological actions. Our preliminary report depicted the cardioprotective effect of piperine against isoproterenol (ISO)-induced MI. AIM Current study determined the protective efficacy of piperine by modulating mitochondrial function in rat models of isoproterenol (ISO)-induced myocardial ischemia. METHODS The above aim was achieved by analyzing mitochondrial antioxidant status, mitochondrial calcium, mitochondrial enzyme activity, ATP level, and apoptosis. Ultra-structural alterations in heart tissue were determined by TEM analysis. RT-PCR studies, Western blotting were executed to determine apoptotic & proapoptotic gene expression, and apoptotic protein expression respectively. RESULTS The results elucidate that piperine pre-treatment prevents ISO induced alterations in the mitochondrial antioxidant status, Krebs cycle as well as mitochondrial respiratory chain enzyme activities (MRCEs). ISO induced ultra-structural changes of heart mitochondria were significantly reduced in the group received piperine pretreatment followed by ISO injection. Piperine maintains mitochondrial calcium homeostasis and inhibits ISO-induced myocardial apoptosis. A significant increase in the expression levels of proapoptotic genes such as Bax, caspases (caspase 9, caspase 3), cytochrome-c with concomitant decrease in Bcl-2 expression (anti-apoptotic gene) was observed in ISO injected group compared to control group. Group received the piperine pretreatment followed by ISO administration has showed a significant decrease in the expression profile of proapoptotic genes with concomitant increase in the anti-apoptotic gene expression than ISO injected group. Apoptotic protein expressions including Bax, cytochrome-c, caspase-3, and cleaved PARP were upregulated & Bcl-2 was downregulated with ISO treatment whereas piperine pre-treatment prevented these changes in apoptotic protein expressions during ISO-induced myocardial cell damage. CONCLUSION Current results demonstrate the piperine efficacy for attenuating ISO-induced myocardial ischemia by enhancing mitochondria function. This study described that the piperine could be used as a nutritional intervention against ISO-induced myocardial ischemia.