As major sources of reactive oxygen species (ROS), mitochondrial structures are exposed
to high concentrations of ROS and may therefore be particularly susceptible to oxidative
damage. Mitochondrial damage could play a pivotal role in the cell death decision.
A decrease in mitochondrial energy charge and redox state, loss of transmembrane potential
(depolarization), mitochondrial respiratory chain impairment, and release of substances
such as calcium and cytochrome c all contribute to apoptosis. These mitochondrial
abnormalities may constitute a part of the spectrum of chronic oxidative stress in
Alzheimer’s disease. Accumulation of amyloid beta (Aβ) in form of senile plaques is
also thought to play a central role in the pathogenesis of Alzheimer’s disease mediated
by oxidative stress. In addition, increasing evidence shows that Aβ generates free
radicals in vitro, which mediate the toxicity of this peptide.
In our study, PC12 cells were used to examine the protective features of EGb 761®
(definition see editorial) on mitochondria stressed with hydrogen peroxide and antimycin,
an inhibitor of complex III. In addition, we investigated the efficacy of EGb 761®
in Aβ-induced MTT reduction in PC12 cells. Moreover, we examined the effects of EGb
761® on ROS levels and ROS-induced apoptosis in lymphocytes from aged mice after in vivo administration.
Here, we will report that EGb 761® was able to protect mitochondria from the attack
of hydrogen peroxide, antimycin and Aβ. Furthermore, EGb 761® reduced ROS levels and
ROS-induced apoptosis in lymphocytes from aged mice treated orally with EGb 761® for
2 weeks.
Our data further emphasize neuroprotective properties of EGb 761®, such as protection
against Aβ-toxicity, and antiapoptotic properties, which are probably due to its preventive
effects on mitochondria.
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PD Dr. Anne Eckert
Dept. of Pharmacology
Biocenter
University of Frankfurt
Marie-Curie-Str. 9
D-60439 Frankfurt
Germany
Phone: (+49) 69 79829377
Fax: (+49) 69 79829374
Email: A.Eckert@em.uni-frankfurt.de