Bisdemethoxycurcumin Protection of Cardiomyocyte Mainly Depends on Nrf2/HO-1 Activation Mediated by the PI3K/AKT Pathway
Bisdemethoxycurcumin Protection of Cardiomyocyte Mainly Depends on Nrf2/HO-1 Activation Mediated by the PI3K/AKT Pathway
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DOI：
10.1021/acs.chemrestox.9b00222
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发表时间：
2019-09-01
影响因子：
4.1
通讯作者：
Wang, Xiaoming
中科院分区：
文献类型：
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作者：
Li, Xing;Huo, Cong;Wang, Xiaoming
双脱甲氧基姜黄素（Bisdemethoxycurcumin，BDMC）是从姜黄中提取的三种姜黄素类化合物之一。与姜黄素不同，BDMC具有抗肿瘤、抗炎、抗动脉粥样硬化、抗肥胖和抗衰老等作用。考虑到其在炎症、动脉粥样硬化和肥胖中的药理作用，本研究旨在检查BDMC是否显示心脏保护特性。本研究采用星形孢菌素（STS）建立心肌细胞损伤模型。我们的数据显示，BDMC显着抑制心肌细胞凋亡，提高细胞存活率，降低caspase-3活性，减少活性氧（ROS）的产生。BDMC可增强蛋白激酶B（AKT）和细胞外信号调节激酶（ERK）的磷酸化，上调HO-1的表达。锡原卟啉（SnPPIX）抑制HO-1活性可抑制BDMC的抗凋亡作用。此外，Nrf2从细胞质到细胞核的易位被LY294002消融，尽管仅部分被PD98059消融。HO-1的上调被PD98059弱抑制，但被LY294002强烈抑制。与PD98059不同，LY294002否定了BDMC的保护作用。这些结果表明，BDMC具有良好的心脏保护作用，在Nrf2/HO-1依赖的方式。Nrf2/HO-1的激活主要依赖于PI3K/AKT信号通路而非MEK/ERK信号通路。
Bisdemethoxycurcumin (BDMC) is one of three curcuminoids extracted from turmeric. Unlike the dominant ingredient curcumin with some intensive investigations, BDMC was recently reported to possess potent antitumor, anti-inflammatory, antiatherosclerosis, antiobesity, and antiaging effects. Considering its pharmacological effects in inflammation, atherosclerosis, and obesity, this study was designed to examine if BDMC displays cardioprotective properties. In this study, staurosporine (STS) was used to establish the cardiomyocyte injury model. Our data revealed that BDMC significantly inhibited myocardial apoptosis, improved cell survival, reduced caspase-3 activity, and diminished reactive oxygen species (ROS) production. BDMC enhanced phosphorylation of protein kinase B (AKT) and extracellular signal-regulated kinase (ERK) and up-regulated the expression of HO-1. Inhibition of HO-1 activity by using tin-protoporphyrin (SnPPIX) can restrain the antiapoptotic effect of BDMC. Furthermore, translocation of Nrf2 from the cytoplasm to the nucleus was ablated by LY294002, although only partially by PD98059. Up-regulation of HO-1 was weakly suppressed by PD98059 but strongly inhibited by LY294002. Unlike PD98059, LY294002 negated the protective effect of BDMC. These findings indicated that BDMC possessed favorable cardioprotection in a Nrf2/HO-1-dependent manner. Activation of Nrf2/HO-1 mainly depended on PI3K/AKT but not MEK/ERK signaling.