Elevation of oxidative free radicals in Alzheimer's disease models can be attenuated by Ginkgo biloba extract EGb 761.
The role of amyloid beta-peptide (Abeta) in the free-radical oxidative-stress model of neurotoxicity in Alzheimer's disease (AD) has received much attention recently. In this study, we have employed both in vitro and in vivo models displaying endogenous Abeta production to study the effects of Abeta on intracellular free radical levels. We employed a neuroblastoma cell line stably expressing an AD-associated double mutation, which exhibits both increased secretion and intracellular accumulation of Abeta when stimulated, as well as transgenic Caenorhabditis elegans constitutively expressing human Abeta. A rise in levels of hydrogen peroxide (H2O2) was observed in both in vitro and in vivo AD-associated transgenic models expressing the Abeta peptide compared with the wild type controls. Treatment of the cells or C. elegans with Ginkgo biloba extract EGb 761 significantly attenuated the basal as well as the induced levels of H2O2-related reactive oxygen species (ROS). Among individual EGb 761 components tested, kaempferol and quercetin provided maximum attenuation in both models. Furthermore, an age-dependent increase in H2O2-related ROS was observed in wild type C. elegans, which is accelerated in the AD-associated C. elegans mutant. These results support the hypothesis of the involvement of Abeta and ROS in association with AD.
Smith
Julie Vining
JV
Laboratory of Cellular and Molecular Neuroscience, Department of Biological Sciences, The University of Southern Mississippi, Hattiesburg, MS 39406, USA.
Luo
Yuan
Y
D000544:Alzheimer Disease / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000235:genetics; D000818:Animals; D030801:Animals, Genetically Modified; D000975:Antioxidants / Q000494:pharmacology*; D017173:Caenorhabditis elegans; D045744:Cell Line, Tumor / Q000187:drug effects; D004195:Disease Models, Animal; D005609:Free Radicals / Q000378:metabolism; D020441:Ginkgo biloba; D006801:Humans; D044949:Kaempferols / Q000494:pharmacology; D009447:Neuroblastoma; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D010936:Plant Extracts / Q000494:pharmacology*; D011794:Quercetin / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D000096983:Ginkgo Extract
D016229:Amyloid beta-Peptides; D000975:Antioxidants; D005609:Free Radicals; D044949:Kaempferols; D018696:Neuroprotective Agents; D010936:Plant Extracts; D011794:Quercetin; D017382:Reactive Oxygen Species; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract; C006552:kaempferol