title: Acacetin inhibits glutamate release and prevents kainic acid-induced neurotoxicity in rats.
abstract: An excessive release of glutamate is considered to be a molecular mechanism associated with several neurological diseases that causes neuronal damage. Therefore, searching for compounds that reduce glutamate neurotoxicity is necessary. In this study, the possibility that the natural flavone acacetin derived from the traditional Chinese medicine Clerodendrum inerme (L.) Gaertn is a neuroprotective agent was investigated. The effect of acacetin on endogenous glutamate release in rat hippocampal nerve terminals (synaptosomes) was also investigated. The results indicated that acacetin inhibited depolarization-evoked glutamate release and cytosolic free Ca(2+) concentration ([Ca(2+)]C) in the hippocampal nerve terminals. However, acacetin did not alter synaptosomal membrane potential. Furthermore, the inhibitory effect of acacetin on evoked glutamate release was prevented by the Cav2.2 (N-type) and Cav2.1 (P/Q-type) channel blocker known as ω-conotoxin MVIIC. In a kainic acid (KA) rat model, an animal model used for excitotoxic neurodegeneration experiments, acacetin (10 or 50 mg/kg) was administrated intraperitoneally to the rats 30 min before the KA (15 mg/kg) intraperitoneal injection, and subsequently induced the attenuation of KA-induced neuronal cell death and microglia activation in the CA3 region of the hippocampus. The present study demonstrates that the natural compound, acacetin, inhibits glutamate release from hippocampal synaptosomes by attenuating voltage-dependent Ca(2+) entry and effectively prevents KA-induced in vivo excitotoxicity. Collectively, these data suggest that acacetin has the therapeutic potential for treating neurological diseases associated with excitotoxicity.
authors: Department of Anesthesiology, Far-Eastern Memorial Hospital, New Taipei, Taiwan ; Department of Mechanical Engineering, Yuan Ze University, New Taipei, Taiwan.
authors: Tzu-Yu
authors: TY
authors: Lin
authors: Graduate Institute of Pharmacognosy, Taipei Medical University, Taipei, Taiwan.
authors: Wei-Jan
authors: WJ
authors: Huang
authors: Department of Anesthesiology, Far-Eastern Memorial Hospital, New Taipei, Taiwan.
authors: Chia-Chan
authors: CC
authors: Wu
authors: Department of Anesthesiology, Far-Eastern Memorial Hospital, New Taipei, Taiwan ; Department of Mechanical Engineering, Yuan Ze University, New Taipei, Taiwan.
authors: Cheng-Wei
authors: CW
authors: Lu
authors: Graduate Institute of Basic Medicine, Fu Jen Catholic University, New Taipei, Taiwan.
authors: Su-Jane
authors: SJ
authors: Wang
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D047309:Flavones / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007608:Kainic Acid / Q000633:toxicity*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D017628:Microglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009411:Nerve Endings / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D009498:Neurotoxins / Q000633:toxicity*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D047309:Flavones; D009498:Neurotoxins; D018698:Glutamic Acid; D011189:Potassium Chloride; D012964:Sodium; D015761:4-Aminopyridine; C023717:acacetin; D007608:Kainic Acid; D002118:Calcium