Protective effects of asiaticoside derivatives against beta-amyloid neurotoxicity

✍ Scribed by Inhee Mook-Jung; Ji-Eun Shin; Sung Hwan Yun; Kyoon Huh; Jae Young Koh; Hyung Keun Park; Sang-Sup Jew; Min Whan Jung

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 185 KB
• Volume: 58
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/(sici)1097-4547(19991101)58:3<417::aid-jnr7>3.0.co;2-g

✦ Synopsis

Asiaticoside (AS) derivatives were tested for potential protective effects against A␤-induced cell death. Of the 28 AS derivatives tested, asiatic acid (AA), asiaticoside 6 (AS6), and SM2 showed strong inhibition of A␤-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 A␤ 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 A␤-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 A␤ toxicity. J.