A single fraction from Uncaria sinensis exerts neuroprotective effects against glutamate-induced neurotoxicity in primary cultured cortical neurons.
- Author:
Ha Neui KIM
1
;
Ji Yeon JANG
;
Byung Tae CHOI
Author Information
- Publication Type:Original Article
- Keywords: Uncaria sinensis; Glutamates; N-Methyl-D-aspartate receptors; Calpain; STEP
- MeSH: Brain Diseases; Calpain; Carrier Proteins; Cell Death; Cell Survival; Down-Regulation; Flow Cytometry; Glutamates; Glutamic Acid; L-Lactate Dehydrogenase; N-Methylaspartate; Neurons*; Neuroprotective Agents*; Protein Tyrosine Phosphatases; Receptors, N-Methyl-D-Aspartate; Uncaria*
- From:Anatomy & Cell Biology 2015;48(2):95-103
- CountryRepublic of Korea
- Language:English
- 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.
