Effect of ginkgolides on β‐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.

Protection against β-amyloid induced abnormal synaptic function and cell death by Ginkgolide J

“…In a previous study it has been shown that GB but not GA suppressed the K + -evoked acetylcholine release in rat hippocampal slices treated with the Aβfragment (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) [25]. Although we have found that higher concentrations of GB re-establish normal LTP and therefore this aspect of our work is consistent with these studies, GA in our experimental paradigm was also able to re-establish normal LTP.…”

Potential medicinal plants for CNS disorders: an overview

“…Given the limited therapeutic options for DAT, treatment with EGb still appears to be the method of choice compared with the ChE inhibitors (Schulz, 2003a). A few another studies also confirmed the role of Ginkgo biloba or its isolated constituents in dementia and other memory disorders (Pan, 2005;Haan and Horr, 2004;Yao et al, 2004;Lee et al, 2004;Kurz and Van Baelen, 2004;Evans et al, 2004;Williams et al, 2004;Colciaghi et al, 2004;Gertz and Kiefer, 2004;Kanowski and Hoerr, 2003;Stackman et al, 2003;Smith and Luo, 2003 Bars, 2003;Muller and Chatterjee, 2003;Andrieu et al, 2003;Birks et al, 2002;Nathan et al, 2002;Mix and Crews, 2002;Gasser and Gasser, 2001;Wettstein, 2000;van Dongen et al, 2000;Bastianetto et al, 2000). During recent years, several cases of hemorrhage have been reported to occur in coincidence with the use of Ginkgo products.…”

Plant Adaptogens: Natural Medicaments for 21stCentury?

“…In transgenic Caenorhabditis elegans , ginkgolide A ( 5.1 ) reduced Aβ‐induced adverse behavior, including paralysis . Ginkgolide B ( 5.2 ) inversed the Aβ‐induced reduction of ACh release from hippocampal brain slices, and caused substantial improvement in learning and memory worsening by Aβ . Ginkgolide J ( 5.3 ) was described as the most potent inhibitor of Aβ‐induced hippocampal neuronal cell death among the ginkgolides in the plant extract .…”