Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
11007588 | The Journal of Nutritional Biochemistry | 2018 | 39 Pages |
Abstract
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 (HO-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.
Keywords
Heme oxygenase-1LVPWdLVESDLVEDdSOD1HO-1NACCATANPERK1/2JNK1/2MAPKN-acetylcysteineROSLeft ventricular end-diastolic dimensionAortic bandingLeft ventricular end-systolic dimensionOxidative stresssuperoxide dismutase 1phenylephrineFisetinheart failureCardiac hypertrophyextracellular signal-regulated protein kinase 1/2mitogen-activated protein kinaseatrial natriuretic peptideCatalaseejection fractionfractional shorteningReactive oxygen species
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Authors
Bin Dong, Chen Liu, Ruicong Xue, Yan Wang, Yu Sun, Zhuomin Liang, Wendong Fan, Jingzhou Jiang, Jingjing Zhao, Qiao Su, Gang Dai, Yugang Dong, Huiling Huang,