Ginkgo biloba extract restores amyloid-beta induced mitochondrial deficits

Abstract

Aims: We investigated protective effects of standardized Ginkgo biloba extract (EGb LI1370) on induced energy metabolism defects in an Alzheimer cell culture model. Methods: We used a new high-resolution respiratory protocol (Rhein et al, Cell Mol Neurobiol 2009 Apr 7 [Epub ahead of print]) to investigate the respiratory capacity of mitochondrial electron transport system (ETS) under physiological condition in vital cells (human neuroblastoma SH-SY5Y cell lines either stably transfected with human wild-type amyloid precursor protein (APP) or empty vector). Activities of mitochondrial enzymes, ATP levels and mitochondrial DNA (mtDNA) were determined. Results: We observed an increase of the coupling state of mitochondria resulting in an improvement of efficiency of ETS after EGb pretreatment (24hr, 0.1mg/ml) in both cell lines with the strongest enhancement in APP cells that overproduce Abeta. The increase of oxygen consumption arose from the modulation of mitochondrial complex I, III and IV activities leading finally to an amelioration of ATP resourcing. In parallel, an up-regulation of mtDNA content was detected in cells treated with EGb. Conclusions: Although the definite biochemical pathways occurring inside cell as well as the molecular mechanisms acting on mitochondria remain to be determined, our study clearly highlights the beneficial effect of EGb on stabilization and restoration of mitochondrial function and energy metabolism in AD related to the toxicity cascade.