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FACT
Focus on Alternative and Complementary Therapies

Stabilisation of mitochondrial membrane potential by Ginkgo biloba EGb 761

Müller WE1, Keil U1, Scherping I1, Hauptmann S1, Eckert A2
1Department of Pharmacology, Biocenter, University of Frankfurt, Frankfurt, D-60439, Germany
2Department of Neurobiology, Psychiatric University of Basel, Basel, CH-4025, Switzerland

Objective

EGb 761 has been used for many years to treat age-related cognitive disorders, including Alzheimer disease (AD). Recent studies also indicate a therapeutic potential of EGb 761 in AD. Mitochondrial abnormalities have been identified in brain ageing and neurodegenerative dementia, leading to mitochondrial dysfunctions.

Materials and methods

Mitochondrial membrane potential is an important marker for the function of mitochondria and can be measured by specific membrane probes. Accordingly, we investigated the protective effects of EGb 761 on mitochondrial dysfunction. As cellular models the PC 12 cells and acutely dissociated brain cells of young and aged mice were investigated under a variety of conditions associated with impaired mitochondrial function and decreased membrane potential.

Results

EGb 761 given either before or shortly after initiating mitochondrial damage by H2O2, serum deprivation or sodium nitroprusside (SNP) improved mitochondrial membrane potential significantly and dose-dependently, with first effects seen at rather low concentration (10 μgl/ml). Moreover, when PC 12 cells were treated with SNP, washed and subsequently incubated with EGb 761, recovery was significantly enhanced by similar low EGb 761 concentrations. Under these conditions, EGb 761 also reversed the decrease of ATP production associated with SNP treatment. The effect of EGb 761 was specific, since protective effects were mainly seen after specifically impairing complexes II, IV and V of the respiratory chain. Comparable findings were made with dissociated brain cells from young and aged mice where usually aged brain cells were more sensitive for the protective effects of EGb 761.

Conclusion

Our findings clearly show the stabilisation and protection of mitochondrial dysfunction as a specific and very sensitive property of EGb 761 at rather low concentrations. This mechanism can explain many of the until now rather unrelated observations of EGb 761 in brain ageing and neurodegeneration.

Acknowledgement

Supported by Dr W. Schwabe Arzneimittel (Karlsruhe, Germany).

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