POSTER PRESENTATION ABSTRACTS
Please note: All posters will be displayed in
Salons 10-12.
FRIDAY, 10:15-11:00 AM
Zhuang H, Doré S*.
Novel neuroprotective mechanism of action of Ginkgo biloba.
Johns Hopkins University, SOM, ACCM Dept & Neuroscience
Dept sdore@jhmi.edu *Presenting
author
PURPOSE: Ginkgo biloba extract (EGb 761) is
a well-standardized extract with origins in traditional Chinese medicine.
The constituents from the extract are likely to have synergistic effects
and have been shown to be protective against cell death. Although it
is often prescribed, the cellular mechanisms of protection of Ginkgo
biloba extract are still unclear. We tested the hypothesis that EGb-761
would afford neuronal protection by inducing the endogenous antioxidant
enzyme heme oxygenase (HO). We and others previously reported that modulation
of HO could have direct beneficial consequences in cerebral ischemia.
By using mouse primary neuronal cultures, we will first determine whether
Ginkgo biloba extract can induce HO-1 and whether this induction is
sufficient to provide neuroprotection against induced oxidative stress
and induced excitotoxicity.
METHODS: Cortical tissue was isolated from 17-day-old
embryos of timed pregnant mice. Experimental treatments were conducted
on neuronal cultures using serum-free high glucose Neurobasal medium.
After 10Ð14 days in culture, cells were incubated with fresh medium
containing EGb 761. In order to look at protein _expression profiles,
we performed Western blots. Hydrogen peroxide (H2O2) was used to induce
free radical damage, and excitotoxicity was induced by glutamate. Cell
survival was quantified by measuring mitochondria activity.
RESULTS: We found that Ginkgo induces HO1 in
a dose-dependent (10-500 µg/ml) and time-dependent (2-24 hrs) manner,
with a maximum effect after 8 hrs at 100 µg/ml. Individual components
present in the Ginkgo biloba extract, such as bilobalides and ginkgolides,
were also tested, and no significant effect was observed. Ginkgo selectively
induced HO1 and did not have any effect on HO2, cytochrome P450 reductase,
or actin. In addition, we observed that Ginkgo at 100 µg/ml can protect
mouse primary cultures against H2O2-induced oxidative damage and against
glutamate-induced toxicity by more than 80%. In order to address specificity,
sister cells were incubated with the HO inhibitor (SnPPIX), and the
neuroprotective biologic effect was completely abolished.
CONCLUSIONS: Ginkgo is already recognized as
a polyvalent therapeutic agent in the treatment of disturbances of multifactorial
origin, including cerebral insufficiency and mild cognitive impairments
in elderly patients. Interestingly, several clinical studies support
the potential usefulness of Ginkgo in age- and vascular-related dementia.
Our study reveals that the neuroprotective properties of Ginkgo appear
to be at least partially mediated by heme oxygenase activity.
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