The potential of chrysophanol in protecting against high fat-induced cardiac injury through Nrf2-regulated anti-inflammation, anti-oxidant and anti-fibrosis in Nrf2 knockout mice
The potential of chrysophanol in protecting against high fat-induced cardiac injury through Nrf2-regulated anti-inflammation, anti-oxidant and anti-fibrosis in Nrf2 knockout mice
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DOI：
10.1016/j.biopha.2017.05.148
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发表时间：
2017-09-01
影响因子：
7.5
通讯作者：
Zhu, Yunfeng
中科院分区：
文献类型：
--
作者：
Lian, Yonggang;Xia, Xiangjun;Zhu, Yunfeng
高脂肪引起的心血管并发症是目前最具挑战性的健康问题之一。氧化应激、炎症和纤维化是糖尿病心肌病病理的主要组成部分。核因子红系2相关因子2(Nrf2)是多种疾病的重要治疗靶点，具有诱导抗氧化酶和其他保护酶的作用。此外，一些Nrf2激活剂显示出很强的抗炎特性。在这项研究中，我们计算了大黄酚在高脂饮食诱导的糖尿病心脏损伤中的NRF2依赖的抗氧化、抗炎和抗纤维化作用。用H9C2细胞体外实验探讨大黄酚的作用机制。体内实验采用高脂饮食诱发野生型(Nrf2(+/+))和Nrf2基因敲除(Nrf2(-/-))小鼠心脏损伤，高脂饲养2周后给予大黄酚。在Nrf2(+/+)小鼠，而不是Nrf2(-/-)小鼠，大黄酚通过调节不同的信号通路改善代谢紊乱，改善心功能，减少病理变化，减轻氧化损伤，下调炎症反应和纤维化进程。我们的研究结果表明大黄酚的抗氧化、抗炎和抗纤维化作用受Nrf2表达的调节。因此，我们认为大黄酚可以作为一种安全的治疗策略来减轻高脂饮食所致的心脏损伤。(C)2017年，爱思唯尔·马森公司出版。
Cardiovascular complications induced by high fat are one of the most challenging health problems presently. Oxidative stress, inflammation and fibrosis are major components included in the pathology of diabetic cardiomyopathy. Nuclear factor erythroid 2-related factor 2 (Nrf2) has been reported as an essential therapeutic target in various diseases for its induction of anti-oxidant enzymes, and other protective enzymes. Additionally, a number of Nrf2 activators showed strong anti-inflammatory properties. In the study, we calculated the Nrf2-dependent anti-oxidant, anti-inflammatory and antifibrosis effects of chrysophanol in high fat diet-induced diabetic heart injury. The underlying mechanisms of chrysophanol were explored using H9C2 cells in vitro. For the in vivo experiment, cardiac injury was triggered in wild type (Nrf2(+/+)) and Nrf2-knockout (Nrf2(-/-)) mice by high fat diet, and chrysophanol was administered after high fat feeding for two weeks. In Nrf2(+/+) mice, but not the Nrf2(-/-) animals, chrysophanol ameliorated metabolic disorders, improved cardiac function, reduced pathological changes, attenuated oxidative injury, down-regulated inflammatory response and fibrosis progression through regulating different signaling pathways. Our data indicated that the anti-oxidant, anti-inflammatory and anti-fibrosis effects of chrysophanol are regulated by Nrf2 expression. Thus, we supposed that chrysophanol could be used as a safe therapeutic strategy to ameliorate cardiac injury induced by high fat diet. (C) 2017 Published by Elsevier Masson SAS.