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Protective effects of asiaticoside derivatives against beta-amyloid neurotoxicity.

Authors
Mook-Jung, I; Shin, JE; Yun, SH; Huh, K; Koh, JY; Park, HK; Jew, SS; Jung, MW
Citation
Journal of neuroscience research, 58(3):417-425, 1999
Journal Title
Journal of neuroscience research
ISSN
0360-40121097-4547
Abstract
Asiaticoside (AS) derivatives were tested for potential protective effects against Abeta-induced cell death. Of the 28 AS derivatives tested, asiatic acid (AA), asiaticoside 6 (AS6), and SM2 showed strong inhibition of Abeta-induced death of B103 cells at 1 microM. The three AS derivatives were further tested for their effects on free radical injury and apoptosis. All three AS derivatives reduced H(2)O(2)-induced cell death and lowered intracellular free radical concentration, but AA showed the strongest protection. In contrast, SM2 was the most effective blocker of staurosporine-induced apoptosis. These results suggest that the three AS derivatives block Abeta toxicity by acting through different cellular mechanisms. When applied to hippocampal slices, AA, SM2, and AS6 did not alter n-methyl-D-aspartic acid (NMDA) or non-NMDA receptor-mediated synaptic transmission, paired-pulse facilitation or induction of long-term potentiation in the field CA1. These results indicate that the three AS derivatives do not alter physiological properties of the hippocampus at the concentration that blocks Abeta-induced cell death. Therefore AS6, AA, and SM2 can be regarded as reasonable candidates for a therapeutic Alzheimer's disease drug that protects neurons from Abeta toxicity.
MeSH terms
6-Cyano-7-nitroquinoxaline-2,3-dione/pharmacologyAmyloid beta-Peptides/toxicity*Analysis of VarianceAnimalsApoptosis/drug effectsCell Death/drug effectsCell LineElectric StimulationExcitatory Amino Acid Antagonists/pharmacologyFree Radicals/metabolismHippocampus/drug effects*Hippocampus/physiologyLipid Peroxidation/drug effectsMaleMolecular StructureNeurons/cytologyNeurons/drug effects*Neurons/physiologyNeurotoxins/toxicityPeptide Fragments/toxicity*RatsRats, Sprague-DawleyReceptors, N-Methyl-D-Aspartate/physiologyStaurosporine/pharmacologyStructure-Activity RelationshipSynaptic Transmission/drug effectsTriterpenes/chemistryTriterpenes/pharmacology*
DOI
10.1002/(SICI)1097-4547(19991101)58:3%3C417::AID-JNR7%3E3.0.CO;2-G
PMID
10518115
Appears in Collections:
Journal Papers > Research Organization > Brain Disease Research Center
Journal Papers > School of Medicine / Graduate School of Medicine > Neurology
Journal Papers > Research Organization > Institute for Medical Sciences
AJOU Authors
묵, 인희허, 균정, 민환
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