title: Protection of apigenin against kainate-induced excitotoxicity by anti-oxidative effects.
abstract: Apigenin (5,7,4'-trihydroxyflavone) is a principal ingredient of Cirsium japonicum. These experiments were performed to determine whether apigenin has neuroprotective effects against kainic acid (KA)-induced excitotoxicity in vitro and in vivo. Intraperitoneal (i.p.) administration of apigenin (25, 50 mg/kg) decreased the seizure scores induced by KA injection (40 mg/kg, i.p.) in mice. In addition, the convulsion onset time was significantly delayed by apigenin administration. Moreover, we found that apigenin blocked KA-induced seizure-form electroencephalogram (EEG) discharge activity in the brain cortex. In hippocampal cells, apigenin inhibited KA-induced excitotoxicity in a dose-dependent manner as measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. To study the possible mechanisms underlying the in vitro neuroprotective effects of apigenin against KA-induced cytotoxicity, we also examined the effect of apigenin on intracellular reactive oxygen species (ROS) elevations in cultured hippocampal neurons and found that apigenin treatment dose-dependently inhibited intracellular ROS elevation. The remarkable reduction of glutathione (GSH) levels induced by KA in hippocampal tissues was reversed by apigenin in a dose-dependent manner. In addition, similar results were obtained after pretreatment with free radical scavengers such as trolox and dimethylthiourea (DMTU). Finally, after confirming the protective effect of apigenin in hippocampal CA3 region, we found apigenin is an active compound in KA-induced neuroprotection. These results collectively indicate that apigenin alleviates KA-induced excitotoxicity by quenching ROS as well as inhibiting GSH depletion in hippocampal neurons.
authors.affiliation: Research Institute of Veterinary Medicine, College of Pharmacy, Chungbuk National University, Cheongju, Korea.
authors.forename: Jin-Yi
authors.initials: JY
authors.lastname: Han
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Ahn
authors.forename: Chung-Soo
authors.initials: CS
authors.lastname: Kim
authors.forename: Sung-Kwang
authors.initials: SK
authors.lastname: Yoo
authors.forename: Si-Kwan
authors.initials: SK
authors.lastname: Kim
authors.forename: Hyoung-Chun
authors.initials: HC
authors.lastname: Kim
authors.forename: Jin Tae
authors.initials: JT
authors.lastname: Hong
authors.forename: Ki-Wan
authors.initials: KW
authors.lastname: Oh
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D047310:Apigenin / Q000494:pharmacology / Q000627:therapeutic use*; D031177:Carduus / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000187:drug effects; D018690:Excitatory Amino Acid Agonists / Q000009:adverse effects; D005978:Glutathione / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007608:Kainic Acid; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*
chemical_list: D000975:Antioxidants; D018690:Excitatory Amino Acid Agonists; D018696:Neuroprotective Agents; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D047310:Apigenin; D005978:Glutathione; D007608:Kainic Acid