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Effect of ginkgolides on beta-amyloid-suppressed acetylocholine release from rat hippocampal slices.

Abstract
As Ginkgo has been shown to improve age-related memory de fi cits and beta-amyloid-related peptides have been suggested to play a signi fi cant role in memory degeneration in Alzheimer's disease, the present study was carried out to examine the effect of two major ginkgolides, A and B, on beta-amyloid peptide-modulated acetylcholine (ACh) release from hippocampal brain slices. Addition of beta-amyloid fragment(25-35) (0.01-1 micro M) in the superfusion medium suppressed the K(+)-evoked [(3)H]-ACh release from the rat hippocampal slices in a concentration-related manner; a 40% reduction in ACh out fl ow was observed with the highest amyloid concentration used (1 micro M). Inclusion of ginkgolide B (GKB, 0.01-10 micro M) caused a concentration-related reversion of the inhibitory effect elicited by the effective concentration of beta-amyloid (1 micro M). The reversal of the beta-amyloid-inhibited ACh release by GKB (1 micro M) was not blocked by tetrodotoxin (1 micro M) indicating a direct interaction of GKB on the cholinergic nerve terminals. In contrast, addition of the same concentration range of ginkgolide A (GKA, 0.01-10 micro M) had no effect on beta-amyloid-inhibited ACh release. These results suggest that GKB may elicit its anti-amnesic effect by minimizing the inhibitory effect of beta-amyloid peptides on cholinergic transmission.
AuthorsTze-Fun Lee, Chieh-Fu Chen, Lawrence C H Wang
JournalPhytotherapy research : PTR (Phytother Res) Vol. 18 Issue 7 Pg. 556-60 (Jul 2004) ISSN: 0951-418X [Print] England
PMID15305316 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Amyloid beta-Peptides
  • Diterpenes
  • Ginkgolides
  • Lactones
  • Plant Extracts
  • ginkgolide B
  • Acetylcholine
  • ginkgolide A
Topics
  • Acetylcholine (metabolism)
  • Alzheimer Disease (prevention & control)
  • Amyloid beta-Peptides (drug effects, metabolism)
  • Animals
  • Diterpenes (administration & dosage, pharmacology, therapeutic use)
  • Dose-Response Relationship, Drug
  • Ginkgo biloba
  • Ginkgolides
  • Hippocampus (drug effects)
  • Lactones (administration & dosage, pharmacology, therapeutic use)
  • Male
  • Phytotherapy
  • Plant Extracts (administration & dosage, pharmacology, therapeutic use)
  • Rats
  • Rats, Sprague-Dawley

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