title: Neuroprotection of Ilex latifolia and caffeoylquinic acid derivatives against excitotoxic and hypoxic damage of cultured rat cortical neurons.
abstract: Ilex latifolia (Aquifoliaceae), one of the primary components of "Ku-ding-cha", has been used in Chinese folk medicine to treat headaches and various inflammatory diseases. A previous study demonstrated that the ethanol extract of I. latifolia could protect against ischemic apoptotic brain damage in rats. The present study investigated the protective activity of I. latifolia against glutamate-induced neurotoxicity using cultured rat cortical neurons in order to explain a possible mechanism related to its inhibitory effect on ischemic brain damage and identified potentially active compounds from it. Exposure of cultured cortical neurons to 500 μM glutamate for 12 h triggered neuronal cell death. I. latifolia (10-100 μg/mL) inhibited glutamate-induced neuronal death, elevation of intracellular calcium ([Ca(2+)](i)), generation of reactive oxygen species (ROS), the increase of a pro-apoptotic protein, BAX, and the decrease of an anti-apoptotic protein, BcL-2. Hypoxia-induced neuronal cell death was also inhibited by I. latifolia. 3,4-Dicaffeoylquinic acid (diCQA), 3,5-diCQA, and 3,5-diCQA methyl ester isolated from I. latifolia also inhibited the glutamate-induced increase in [Ca(2+)](i), generation of ROS, the change of apoptosis-related proteins, and neuronal cell death; and hypoxia-induced neuronal cell death. These results suggest that I. latifolia and its active compounds prevented glutamate-induced neuronal cell damage by inhibiting increase of [Ca(2+)](i), generation of ROS, and resultantly apoptotic pathway. In addition, the neuroprotective effects of I. latifolia on ischemia-induced brain damage might be associated with the anti-excitatory and anti-oxidative actions and could be attributable to these active compounds, CQAs.
authors.affiliation: College of Veterinary Medicine, Chungbuk National University, Cheongju 361-763, Korea.
authors.forename: Joo Youn
authors.initials: JY
authors.lastname: Kim
authors.forename: Hong Kyu
authors.initials: HK
authors.lastname: Lee
authors.forename: Bang Yeon
authors.initials: BY
authors.lastname: Hwang
authors.forename: SeungHwan
authors.initials: S
authors.lastname: Kim
authors.forename: Jae Kuk
authors.initials: JK
authors.lastname: Yoo
authors.forename: Yeon Hee
authors.initials: YH
authors.lastname: Seong
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D015687:Cell Hypoxia; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000302:isolation & purification / Q000494:pharmacology*; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D018698:Glutamic Acid / Q000633:toxicity*; D030017:Ilex / Q000737:chemistry; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000302:isolation & purification / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D018515:Plant Leaves; D010946:Plants, Medicinal; D011801:Quinic Acid / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors
chemical_list: D051017:Apoptosis Regulatory Proteins; D004365:Drugs, Chinese Herbal; D018690:Excitatory Amino Acid Agonists; D018696:Neuroprotective Agents; D010936:Plant Extracts; D017382:Reactive Oxygen Species; C472707:caffeoylquinic acid; D011801:Quinic Acid; D018698:Glutamic Acid; D002118:Calcium