Ferulic acid exerts neuroprotective effects against cerebral ischemia/reperfusion-induced injury via antioxidant and anti-apoptotic mechanisms in vitro and in vivo

被引:199
作者
Ren, Zhongkun [1 ]
Zhang, Rongping [2 ]
Li, Yuanyuan [1 ]
Li, Yu [1 ]
Yang, Zhiyong [1 ]
Yang, Hui [2 ]
机构
[1] Kunming Med Univ, Dept Neurosurg, Affiliated Hosp 1, 295 Xichang Rd, Kunming 650032, Yunnan, Peoples R China
[2] Kunming Med Univ, Biomed Engn Ctr, 1168 Chunrongxi Rd, Kunming 650500, Yunnan, Peoples R China
关键词
ferulic acid; neuroprotective effect; ischemia/reperfusion; oxidation; apoptosis; ISCHEMIA-REPERFUSION INJURY; OXIDATIVE STRESS; MEMORY IMPAIRMENT; NEURONAL DEATH; FREE-RADICALS; NITRIC-OXIDE; PC-12; CELLS; PC12; RATS; MODEL;
D O I
10.3892/ijmm.2017.3127
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
100103 [病原生物学]; 100218 [急诊医学];
摘要
Ferulic acid (FA) is a derivative of cinnamic acid. It is used in the treatment of heart head blood-vessel disease and exerts protective effects against hypoxia/ischemia-induced cell injury in the brain. This study investigated the potential neuroprotective effects of FA against ischemia/reperfusion (I/R)-induced brain injury in vivo and in vitro through hematoxylin and eosin (H&E) and Nissl staining assays, flow cytometry, Hoechst 33258 staining, quantitative PCR, western blot analysis and fluorescence microscopic analysis. In this study, models of cerebral I/R injury were established using rats and pheochromocytoma (PC-12) cells. The results revealed that treatment with FA significantly attenuated memory impairment, and reduced hippocampal neuronal apoptosis and oxidative stress in a dose-dependent manner. The results from in vitro experiments also indicated that FA protected the PC-12 cells against I/R-induced reactive oxygen species (ROS) generation and apoptosis by inhibiting apoptosis, Ca2+ influx, superoxide anion (O-2(-)), malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) production in a concentration-dependent manner. Moreover, FA inactivated the Toll-like receptor (TLR)/myeloid differentiation factor 88 (MyD88) pathway. MyD88 overexpression abolished the neuroprotective effects of FA. On the whole, we found that FA attenuated memory dysfunction and exerted protective effects against oxidative stress and apoptosis induced by I/R injury by inhibiting the TLR4/MyD88 signaling pathway. This study supports the view that FA may be a promising neuroprotective agent for use in the treatment of cerebral ischemia.
引用
收藏
页码:1444 / 1456
页数:13
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