Ginkgo biloba extract (EGb761) has been used for many years to treat age-related cognitive disorders. Recent studies also indicate a therapeutic potential of EGb761 in Alzheimer disease (AD). Bolstered evidence indicates that mitochondrial abnormalities might be part of the spectrum of chronic oxidative stress occurring in aging and AD finally contributing to synaptic failure and neuronal degeneration.

We investigated the protective effects of EGb761 on mitochondrial function and ATP production.

As cellular models, PC12 cells and acutely dissociated brain cells from young and aged mice were investigated under a variety of conditions, e.g. oxidative and nitrosative stress, associated with impaired mitochondrial function and decreased membrane potential.

EGb761 alleviated mitochondrial functions in vitro at concentrations as low as 0.01mg/ml. The effect of EGb761 was specific, since protective effects were mainly seen after specifically impairing respiratory chain complexes II, IV, and V. 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 EGb761. In addition, PC12 cells bearing an AD-related mutation in the amyloid precursor protein, that leads to enhanced beta-amyloid production, showed a greater benefit from treatment with EGb761 than control cells.

Taking together, our finding clearly show stabilization and protection of mitochondrial function as a specific and very sensitive property of EGb761 at rather low concentrations. This mechanism can explain many of the until now rather unrelated observations of EGb761 in brain aging and neurodegeneration.