Zhen Jun-Li, Chang Ying-Na, Qu Zhen-Zhen, Fu Tao, Liu Jian-Qun, Wang Wei-Ping
Department of Neurology, Key Laboratory of Neurology of Hebei Province, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China.
Department of Internal Medicine, The 54th Institute of CETC Worker's Hospital, Shijiazhuang, Hebei 050081, China.
Epilepsy Behav. 2016 Apr;57(Pt A):177-184. doi: 10.1016/j.yebeh.2016.02.001. Epub 2016 Mar 8.
Most antiepileptic drugs (AEDs) interfere with cognitive function, and there is therefore an urgent need for AEDs that are effective but do not have this side effect. Various studies have reported the antiinflammatory and cytoprotective properties of the natural flavonoid luteolin (LU); however, none has examined systematically its antiseizure potential. The current study investigated the effects of LU on pentylenetetrazole (PTZ)-induced cognitive impairment in rats and the underlying mechanisms. Seizures were induced in rats by daily injection of PTZ for 36 days. Two other groups were pretreated with LU (50 or 100 mg/kg/day by oral administration) 30 min prior to PTZ administration. Seizure severity was scored, and cognitive function was tested in the Morris water maze. Neuronal damage, mitochondrial generation of reactive oxygen species, oxidative stress, phosphoactivation of the protein kinase A (PKA)-cyclic AMP response element-binding protein (CREB) pathway, and brain-derived neurotrophic factor (BDNF) expression were measured in the hippocampus. Pretreatment with LU suppressed seizure induction, duration, and severity following PTZ injection, reversed cognitive impairment, reduced neuronal and oxidative stress damage, and increased phosphoactivation of PKA and CREB as well as BDNF expression. These results indicate that LU should be further investigated as a treatment for epilepsy.
大多数抗癫痫药物（AEDs）会干扰认知功能，因此迫切需要有效但无此副作用的AEDs。多项研究报道了天然黄酮类化合物木犀草素（LU）的抗炎和细胞保护特性；然而，尚无研究系统地考察其抗癫痫潜力。本研究调查了LU对戊四氮（PTZ）诱导的大鼠认知障碍的影响及其潜在机制。通过每天注射PTZ持续36天诱导大鼠癫痫发作。另外两组在给予PTZ前30分钟用LU（50或100毫克/千克/天，口服给药）预处理。对癫痫发作严重程度进行评分，并在莫里斯水迷宫中测试认知功能。检测海马中的神经元损伤、线粒体活性氧生成、氧化应激、蛋白激酶A（PKA）-环磷酸腺苷反应元件结合蛋白（CREB）途径的磷酸化激活以及脑源性神经营养因子（BDNF）表达。LU预处理可抑制PTZ注射后的癫痫发作诱导、持续时间和严重程度，逆转认知障碍，减少神经元和氧化应激损伤，并增加PKA和CREB的磷酸化激活以及BDNF表达。这些结果表明，LU作为癫痫治疗药物应进一步研究。
