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Protective effects of asiaticoside derivatives against beta‐amyloid neurotoxicity
Author(s) -
MookJung Inhee,
Shin JiEun,
Yun Sung Hwan,
Huh Kyoon,
Koh Jae Young,
Park Hyung Keun,
Jew SangSup,
Jung Min Whan
Publication year - 1999
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/(sici)1097-4547(19991101)58:3<417::aid-jnr7>3.0.co;2-g
Subject(s) - neurotoxicity , programmed cell death , pharmacology , nmda receptor , chemistry , long term potentiation , apoptosis , staurosporine , toxicity , biochemistry , receptor , biology , signal transduction , protein kinase c , organic chemistry
Asiaticoside (AS) derivatives were tested for potential protective effects against Aβ‐induced cell death. Of the 28 AS derivatives tested, asiatic acid (AA), asiaticoside 6 (AS6), and SM2 showed strong inhibition of Aβ‐induced death of B103 cells at 1 μM. 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 Aβ 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 Aβ‐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 Aβ toxicity. J. Neurosci. Res. 58:417–425, 1999. © 1999 Wiley‐Liss, Inc.