Bisdemethoxycurcumin Protection of Cardiomyocyte Mainly Depends on Nrf2/HO-1 Activation Mediated by the PI3K/AKT Pathway

被引：21

作者：

Li, Xing ^{[1
]}

Huo, Cong ^{[1
]}

Xiao, Yuan ^{[1
,2
]}

Xu, Rong ^{[1
]}

Liu, Yan ^{[1
]}

Jia, Xin ^{[1
]}

Wang, Xiaoming ^{[1
]}

机构：

[1] Fourth Mil Med Univ, Xijing Hosp, Dept Geriatr, Xian 710032, Shaanxi, Peoples R China

[2] Xi An Jiao Tong Univ, Hong Hui Hosp, Coll Med, Xian 710054, Shaanxi, Peoples R China

来源：

CHEMICAL RESEARCH IN TOXICOLOGY | 2019年 / 32卷 / 09期

基金：

中国国家自然科学基金; 国家重点研发计划;

关键词：

HEME OXYGENASE-1 EXPRESSION; GLUCOSE-INDUCED APOPTOSIS; NF-KAPPA-B; OXIDATIVE STRESS; RAW264.7; CELLS; IN-VITRO; INJURY; DYSFUNCTION; NRF2; INFLAMMATION;

D O I：

10.1021/acs.chemrestox.9b00222

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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.

引用

页码：1871 / 1879

页数：9

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