title: Hexane extract from Uncaria sinensis exhibits anti-apoptotic properties             against glutamate-induced neurotoxicity in primary cultured cortical neurons.
abstract: We explored the neuroprotective effects of a hexane extract from Uncaria             sinensis (HEUS) against glutamate-induced toxicity focusing on its anti-apoptotic             mechanism in primary cultured cortical neurons. Pretreatment with HEUS resulted             in significantly reduced glutamate-induced toxicity in a dose-dependent manner             with a decrease in the release of lactate dehydrogenase. Morphological assay and             flow cytometry were performed for determination of the type of cell death; according             to the results, treatment with HEUS resulted in a significant reduction of glutamate-induced             apoptotic cell death. We examined the anti-apoptotic mechanism of HEUS; treatment             with HEUS resulted in markedly decreased expression of death receptor (DR)4, which             was induced by glutamate stimulation. In contrast, treatment with HEUS resulted             in significantly enhanced levels of expression of glutamate-attenuated XIAP and             Bcl-2, as well as marked blockade of glutamate-induced Bid cleavage, which inhibits             both extrinsic and intrinsic apoptosis pathways. In addition, pretreatment with             HEUS resulted in almost complete blockade of glutamate-induced activation of caspases-8,             -9 and -3, as well as cleavage of poly (ADP-ribose) polymerase. These findings             suggest that the neuroprotective effects of HEUS against glutamate-induced toxicity             occur via inhibition of DR4 and expression of anti-apoptotic proteins XIAP and             Bcl-2 resulting in effective abrogation of the activation of caspase cascades             and promotion of cell survival.
authors.affiliation: Division of Meridian and Structural Medicine, Pusan National                     University, Yangsan 626-870, Republic of Korea.
authors.forename: Ji-Yeon
authors.initials: JY
authors.lastname: Jang
authors.forename: Ha-Neui
authors.initials: HN
authors.lastname: Kim
authors.forename: Yu-Ri
authors.initials: YR
authors.lastname: Kim
authors.forename: Jin-Woo
authors.initials: JW
authors.lastname: Hong
authors.forename: Young-Whan
authors.initials: YW
authors.lastname: Choi
authors.forename: Yung-Hyun
authors.initials: YH
authors.lastname: Choi
authors.forename: Hwa-Kyoung
authors.initials: HK
authors.lastname: Shin
authors.forename: Byung-Tae
authors.initials: BT
authors.lastname: Choi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004789:Enzyme Activation; D018698:Glutamic Acid / Q000494:pharmacology / Q000502:physiology*; D006586:Hexanes / Q000737:chemistry; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D018696:Neuroprotective Agents / Q000302:isolation & purification / Q000494:pharmacology*; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D061251:Primary Cell Culture; D051381:Rats; D017207:Rats, Sprague-Dawley; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism; D012997:Solvents / Q000737:chemistry; D032070:Uncaria / Q000737:chemistry*
chemical_list: D051017:Apoptosis Regulatory Proteins; D006586:Hexanes; D018696:Neuroprotective Agents; D010936:Plant Extracts; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D012997:Solvents; D018698:Glutamic Acid; D007770:L-Lactate Dehydrogenase; D020169:Caspases