title: Sinapic acid attenuates kainic acid-induced hippocampal neuronal damage in mice.
abstract: Excitotoxin induces neurodegeneration via glutamatergic activation or oxidative stress, which means that the blockade of glutamate receptors and the scavenging of free radicals are potential therapeutic targets in neurodegenerative diseases. Sinapic acid (SA) has a GABA(A) receptor agonistic property and free radical scavenging activity. We investigated the neuroprotective effects of SA on kainic acid (KA)-induced hippocampal brain damage in mice. SA (10 mg/kg) by oral administration has an anticonvulsant effect on KA-induced seizure-like behavior. Moreover, SA (10 mg/kg) significantly attenuated KA-induced neuronal cell death in the CA1 and CA3 hippocampal regions when administered as late as 6 h after KA. In addition, flumazenil, a GABA(A) antagonist, blocked the effect of SA administered immediately after KA but not the effect of SA administered 6 h after KA. This late protective effect of SA was accompanied by reduced levels of reactive gliosis, inducible nitric oxide synthase expression, and nitrotyrosine formation in the hippocampus. In the passive avoidance task, KA-induced memory impairments were ameliorated by SA. These results suggest that the potential therapeutic effect of SA is due to its attenuation of KA-induced neuronal damage in the brain via its anti-convulsive activity through GABA(A) receptor activation and radical scavenging activity.
authors.affiliation: Department of Life and Nanopharmaceutical Sciences, Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Dong Hyun
authors.initials: DH
authors.lastname: Kim
authors.forename: Byung Hoon
authors.initials: BH
authors.lastname: Yoon
authors.forename: Won Yong
authors.initials: WY
authors.lastname: Jung
authors.forename: Jong Min
authors.initials: JM
authors.lastname: Kim
authors.forename: Se Jin
authors.initials: SJ
authors.lastname: Park
authors.forename: Dong Hyun
authors.initials: DH
authors.lastname: Park
authors.forename: Youngbuhm
authors.initials: Y
authors.lastname: Huh
authors.forename: Chan
authors.initials: C
authors.lastname: Park
authors.forename: Jae Hoon
authors.initials: JH
authors.lastname: Cheong
authors.forename: Kyung-Tae
authors.initials: KT
authors.lastname: Lee
authors.forename: Chan Young
authors.initials: CY
authors.lastname: Shin
authors.forename: Jong Hoon
authors.initials: JH
authors.lastname: Ryu
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000737:chemistry / Q000627:therapeutic use; D001362:Avoidance Learning / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D003373:Coumaric Acids / Q000737:chemistry / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005442:Flumazenil / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007608:Kainic Acid / Q000633:toxicity*; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy; D051379:Mice; D008813:Mice, Inbred ICR; D019636:Neurodegenerative Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000737:chemistry / Q000627:therapeutic use*; D009498:Neurotoxins / Q000633:toxicity*; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy
chemical_list: D000927:Anticonvulsants; D003373:Coumaric Acids; D018755:GABA Agonists; D018756:GABA Antagonists; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D018696:Neuroprotective Agents; D009498:Neurotoxins; D005442:Flumazenil; C073734:sinapinic acid; D007608:Kainic Acid