title: Luteolin rescues pentylenetetrazole-induced cognitive impairment in epileptic rats by reducing oxidative stress and activating PKA/CREB/BDNF signaling.
abstract: 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.
authors.affiliation: Department of Neurology, Key Laboratory of Neurology of Hebei Province, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China.
authors.forename: Jun-Li
authors.initials: JL
authors.lastname: Zhen
authors.affiliation: Department of Internal Medicine, The 54th Institute of CETC Worker's Hospital, Shijiazhuang, Hebei 050081, China.
authors.forename: Ying-Na
authors.initials: YN
authors.lastname: Chang
authors.affiliation: Department of Neurology, Key Laboratory of Neurology of Hebei Province, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China.
authors.forename: Zhen-Zhen
authors.initials: ZZ
authors.lastname: Qu
authors.affiliation: Department of Internal Medicine, The 54th Institute of CETC Worker's Hospital, Shijiazhuang, Hebei 050081, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Fu
authors.affiliation: Department of Neurology, Qianan People's Hospital, Tangshan, Hebei 064400, China.
authors.forename: Jian-Qun
authors.initials: JQ
authors.lastname: Liu
authors.affiliation: Department of Neurology, Key Laboratory of Neurology of Hebei Province, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, China. Electronic address: WWP_ZJL_456@163.com.
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Wang
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor; D003071:Cognition / Q000187:drug effects*; D060825:Cognitive Dysfunction / Q000188:drug therapy* / Q000523:psychology; D003292:Convulsants / Q000633:toxicity; D017362:Cyclic AMP Response Element-Binding Protein; D051699:Cyclic AMP Response Element-Binding Protein A; D004827:Epilepsy / Q000188:drug therapy; D047311:Luteolin / Q000494:pharmacology*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D010433:Pentylenetetrazole / Q000009:adverse effects*; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D012640:Seizures / Q000139:chemically induced; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000927:Anticonvulsants; D019208:Brain-Derived Neurotrophic Factor; D003292:Convulsants; D017362:Cyclic AMP Response Element-Binding Protein; D051699:Cyclic AMP Response Element-Binding Protein A; C579455:BDNF protein, human; D011494:Protein Kinases; D047311:Luteolin; D010433:Pentylenetetrazole
keywords: CREB; Cognitive impairment; Luteolin; Oxidative stress; Pentylenetetrazole