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胀果甘草对血管紧张素II诱导的H9c2心肌母细胞肥大中线粒体功能障碍的保护作用。

Protective effect of Boerhaavia diffusa L. against mitochondrial dysfunction in angiotensin II induced hypertrophy in H9c2 cardiomyoblast cells.

作者信息

Prathapan Ayyappan, Vineetha Vadavanath Prabhakaran, Raghu Kozhiparambil Gopalan

机构信息

Agroprocessing and Natural Products Division, CSIR-National Institute for Interdisciplinary Science and Technology (NIIST), Thiruvananthapuram, Kerala, India.

出版信息

PLoS One. 2014 Apr 30;9(4):e96220. doi: 10.1371/journal.pone.0096220. eCollection 2014.

Abstract

Mitochondrial dysfunction plays a critical role in the development of cardiac hypertrophy and heart failure. So mitochondria are emerging as one of the important druggable targets in the management of cardiac hypertrophy and other associated complications. In the present study, effects of ethanolic extract of Boerhaavia diffusa (BDE), a green leafy vegetable against mitochondrial dysfunction in angiotensin II (Ang II) induced hypertrophy in H9c2 cardiomyoblasts was evaluated. H9c2 cells challenged with Ang II exhibited pathological hypertrophic responses and mitochondrial dysfunction which was evident from increment in cell volume (49.09±1.13%), protein content (55.17±1.19%), LDH leakage (58.74±1.87%), increased intracellular ROS production (26.25±0.91%), mitochondrial superoxide generation (65.06±2.27%), alteration in mitochondrial transmembrane potential (ΔΨm), opening of mitochondrial permeability transition pore (mPTP) and mitochondrial swelling. In addition, activities of mitochondrial respiratory chain complexes (I-IV), aconitase, NADPH oxidase, thioredoxin reductase, oxygen consumption rate and calcium homeostasis were evaluated. Treatment with BDE significantly prevented the generation of intracellular ROS and mitochondrial superoxide radicals and protected the mitochondria by preventing dissipation of ΔΨm, opening of mPTP, mitochondrial swelling and enhanced the activities of respiratory chain complexes and oxygen consumption rate in H9c2 cells. Activities of aconitase and thioredoxin reductase which was lowered (33.77±0.68% & 45.81±0.71% respectively) due to hypertrophy, were increased in BDE treated cells (P≤0.05). Moreover, BDE also reduced the intracellular calcium overload in Ang II treated cells. Overall results revealed the protective effects of B. diffusa against mitochondrial dysfunction in hypertrophy in H9c2 cells and the present findings may shed new light on the therapeutic potential of B. diffusa in addition to its nutraceutical potentials.

摘要

线粒体功能障碍在心脏肥大和心力衰竭的发展中起关键作用。因此,线粒体正成为治疗心脏肥大及其他相关并发症的重要可药物作用靶点之一。在本研究中,评估了一种绿叶蔬菜白花蛇舌草乙醇提取物(BDE)对血管紧张素II(Ang II)诱导的H9c2心肌成纤维细胞肥大中线粒体功能障碍的影响。用Ang II刺激的H9c2细胞表现出病理性肥大反应和线粒体功能障碍,这从细胞体积增加(49.09±1.13%)、蛋白质含量增加(55.17±1.19%)、乳酸脱氢酶泄漏增加(58.74±1.87%)、细胞内活性氧生成增加(26.25±0.91%)、线粒体超氧化物生成增加(65.06±2.27%)、线粒体跨膜电位(ΔΨm)改变、线粒体通透性转换孔(mPTP)开放和线粒体肿胀中明显可见。此外,还评估了线粒体呼吸链复合物(I-IV)、乌头酸酶、NADPH氧化酶、硫氧还蛋白还原酶的活性、氧消耗率和钙稳态。用BDE处理可显著防止细胞内活性氧和线粒体超氧自由基的产生,并通过防止ΔΨm的耗散、mPTP的开放、线粒体肿胀来保护线粒体,并增强H9c2细胞中呼吸链复合物的活性和氧消耗率。由于肥大而降低的乌头酸酶和硫氧还蛋白还原酶的活性(分别为33.77±0.68%和45.81±0.71%)在BDE处理的细胞中增加(P≤0.05)。此外,BDE还降低了Ang II处理细胞中的细胞内钙超载。总体结果揭示了白花蛇舌草对H9c2细胞肥大中线粒体功能障碍的保护作用,本研究结果可能为白花蛇舌草除营养保健潜力外的治疗潜力提供新的线索。

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