Fisetin inhibits cardiac hypertrophy by suppressing oxidative stress
Fisetin inhibits cardiac hypertrophy by suppressing oxidative stress
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非瑟酮通过抑制氧化应激来抑制心脏肥大。
DOI：
10.1016/j.jnutbio.2018.08.010
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发表时间：
2018-12-01
影响因子：
5.6
通讯作者：
Huang, Huiling
中科院分区：
文献类型：
--
作者：
Dong, Bin;Liu, Chen;Huang, Huiling
心脏肥大是对各种病理应激的病理生理反应，并最终导致心力衰竭。氧化应激是参与肥大发展的关键过程之一。非瑟酮是一种小分子黄酮类化合物，具有抗氧化、抗增殖和抗炎作用。然而，非瑟酮对心肌肥厚的影响仍不清楚。在我们目前的研究中，我们表明，非瑟酮抑制压力超负荷诱导的心肌肥大，改善心功能在体内和抑制苯肾上腺素（PE）诱导的心肌细胞肥大在体外。非瑟酮处理后，肥大心脏和心肌细胞的活性氧（ROS）水平均显著降低。此外，非瑟酮显着上调抗氧化基因的表达，包括过氧化氢酶（CAT），超氧化物歧化酶1（SOD 1）和血红素加氧酶1（H 0 -1）。此外，用N-乙酰半胱氨酸（NAC; ROS清除剂）和非瑟酮共处理对PE诱导的心肌细胞肥大没有协同抑制作用，表明非瑟酮的抗肥大作用主要与阻断氧化应激有关。最后，促肥大信号通路，丝裂原活化蛋白激酶（MAPK）和哺乳动物雷帕霉素靶蛋白（mTOR）激酶，被发现在压力超负荷和PE治疗后被非瑟酮抑制。总之，我们的研究表明，非瑟酮对心肌肥厚的保护和氧化应激抑制可能是参与的关键机制之一。(C)2018爱思唯尔公司All rights reserved.
Cardiac hypertrophy is a pathophysiological response to various pathological stresses and ultimately leads to heart failure. Oxidative stress is one of the critical processes involved in hypertrophy development. Fisetin, a small molecular flavonoid, has been shown to have anti-oxidative, anti-proliferative and anti-inflammatory properties. However, the effect of fisetin on cardiac hypertrophy remains unknown. In our present study, we showed that fisetin inhibited pressure overload-induced cardiac hypertrophy, improved cardiac function in vivo and suppressed phenylephrine (PE)-induced cardiomyocyte hypertrophy in vitro. Reactive oxygen species (ROS) levels were markedly decreased by fisetin treatment in both hypertrophic hearts and cardiomyocytes. Moreover, fisetin significantly up-regulated the expression of antioxidative genes, including catalase (CAT), superoxide dismutase 1 (SOD1) and heme oxygenase 1 (H0-1). Furthermore, co-treatment with N-acetylcysteine (NAC; ROS scavenger) and fisetin did not have synergistic inhibitory effects on PE -induced cardiomyocyte hypertrophy, indicating that the anti-hypertrophic effects of fisetin are mainly associated with the blockade of oxidative stress. Finally, the pro-hypertrophic signaling pathways, mitogen-activated protein kinase (MAPK) and mammalian target of rapamycin (mTOR) kinase, were found to be suppressed by fisetin after pressure overload and PE treatment. In conclusion, our study revealed that fisetin protects against cardiac hypertrophy and that oxidative stress inhibition may be one of the pivotal mechanisms involved. (C) 2018 Elsevier Inc. All rights reserved.