title: A single fraction from Uncaria sinensis exerts neuroprotective effects against glutamate-induced neurotoxicity in primary cultured cortical neurons.
abstract: We identified a neuroprotective single fraction among 62 ones of hexane extract from Uncaria sinensis (JGH43IA) and investigated its effects and mechanisms in primary cortical neurons. Pretreatment with JGH43IA showed a significantly increase cell viability in a dose-dependent manner with a decrease in the lactate dehydrogenase release. When we performed morphological assay and flow cytometry to determination of the type of cell death, pretreatment with JGH43IA showed a significant reduction of glutamate-induced apoptotic cell death. Then we explored the downstream signaling pathways of N-methyl-D-aspartate receptor (NMDAR) with calpain activation to elucidate possible pathways of neuroprotection by JGH43IA. Pretreatment with JGH43IA exhibited a significant attenuation of NMDAR GluN2B subunit activation and a decrease in active form of calpain 1 leading to subsequent cleavage of striatal-enriched protein tyrosine phosphatase (STEP). In addition, pretreatment with JGH43IA showed a marked increase of cAMP responsive element binding protein. These results suggest that JGH43IA may have neuroprotective effects through down-regulation of NMDAR GluN2B subunit and calpain 1 activation, and subsequent alleviation of STEP cleavage. This single fraction from U. sinensis might be a useful therapeutic agent for brain disorder associated with glutamate injury.
authors.affiliation: Department of Korean Medicine, School of Korean Medicine, Pusan National University, Yangsan, Korea.
authors.forename: Ha Neui
authors.initials: HN
authors.lastname: Kim
authors.affiliation: Division of Meridian and Structural Medicine, School of Korean Medicine, Pusan National University, Yangsan, Korea.
authors.forename: Ji Yeon
authors.initials: JY
authors.lastname: Jang
authors.affiliation: Department of Korean Medicine, School of Korean Medicine, Pusan National University, Yangsan, Korea. ; Division of Meridian and Structural Medicine, School of Korean Medicine, Pusan National University, Yangsan, Korea.
authors.forename: Byung Tae
authors.initials: BT
authors.lastname: Choi
keywords: Calpain; Glutamates; N-Methyl-D-aspartate receptors; STEP; Uncaria sinensis