title: Neuroprotection of the leaf and stem of Vitis amurensis and their active compounds against ischemic brain damage in rats and excitotoxicity in cultured neurons.
abstract: Vitis amurensis (Vitaceae) has been reported to have anti-oxidant and anti-inflammatory activities. The present study investigated a methanol extract from the leaf and stem of V. amurensis for neuroprotective effects on cerebral ischemic damage in rats and on excitotoxicity induced by glutamate in cultured rat cortical neurons. Transient focal cerebral ischemia was induced by 2h middle cerebral artery occlusion followed by 24h reperfusion (MCAO/reperfusion) in rats. Orally administered V. amurensis (25-100 mg/kg) reduced MCAO/reperfusion-induced infarct and edema formation, neurological deficits, and neuronal death. Depletion of glutathione (GSH) level and lipid peroxidation induced by MCAO/reperfusion was inhibited by administration of V. amurensis. The increase of phosphorylated mitogen-activated protein kinases (MAPKs), cyclooxygenase-2 (COX-2), and pro-apoptotic proteins and the decrease of anti-apoptotic protein in MCAO/reperfusion rats were significantly inhibited by treatment with V. amurensis. Exposure of cultured cortical neurons to 500 μM glutamate for 12h induced neuronal cell death. V. amurensis (1-50 μg/ml) and (+)-ampelopsin A, γ-2-viniferin, and trans-ε-viniferin isolated from the leaf and stem of V. amurensis inhibited glutamate-induced neuronal death, the elevation of intracellular calcium ([Ca(2+)](i)), the generation of reactive oxygen species (ROS), and changes of apoptosis-related proteins in cultured cortical neurons, suggesting that the neuroprotective effect of V. amurensis may be partially attributed to these compounds. These results suggest that the neuroprotective effect of V. amurensis against focal cerebral ischemic injury might be due to its anti-apoptotic effect, resulting from anti-excitotoxic, anti-oxidative, and anti-inflammatory effects and that the leaf and stem of V. amurensis have possible therapeutic roles for preventing neurodegeneration in stroke.
authors.affiliation: College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea.
authors.forename: Joo Youn
authors.initials: JY
authors.lastname: Kim
authors.forename: Ha Yeon
authors.initials: HY
authors.lastname: Jeong
authors.forename: Hong Kyu
authors.initials: HK
authors.lastname: Lee
authors.forename: SeungHwan
authors.initials: S
authors.lastname: Kim
authors.forename: Bang Yeon
authors.initials: BY
authors.lastname: Hwang
authors.forename: KiHwan
authors.initials: K
authors.lastname: Bae
authors.forename: Yeon Hee
authors.initials: YH
authors.lastname: Seong
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry; D000975:Antioxidants / Q000737:chemistry; D017209:Apoptosis; D001929:Brain Edema / Q000188:drug therapy / Q000473:pathology; D001930:Brain Injuries / Q000188:drug therapy*; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000737:chemistry; D005260:Female; D018698:Glutamic Acid / Q000633:toxicity; D005978:Glutathione / Q000737:chemistry; D015227:Lipid Peroxidation; D008297:Male; D000432:Methanol / Q000737:chemistry; D015394:Molecular Structure; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology*; D020258:Neurotoxicity Syndromes / Q000473:pathology; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D018515:Plant Leaves / Q000737:chemistry; D018547:Plant Stems / Q000737:chemistry; D011247:Pregnancy; D061251:Primary Cell Culture; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000737:chemistry; D015427:Reperfusion Injury / Q000188:drug therapy / Q000473:pathology; D027843:Vitis / Q000737:chemistry*
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D018696:Neuroprotective Agents; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D018698:Glutamic Acid; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D005978:Glutathione; D000432:Methanol