Elevation of oxidative free radicals in Alzheimer's disease models can be attenuated by Ginkgo biloba extract EGb 761

Abstract

The role of amyloid β-peptide (Aβ) 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 Aβ production to study the effects of Aβ 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 Aβ when stimulated, as well as transgenic Caenorhabditis elegans constitutively expressing human Aβ. A rise in levels of hydrogen peroxide (H2O2) was observed in both in vitro and in vivo AD-associated transgenic models expressing the Aβ 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 Aβ and ROS in association with AD.

Hyperforin prevents β-amyloid neurotoxicity and spatial memory impairments by disaggregation of Alzheimer's amyloid-β-deposits

“…Inhibition of ROS production in human cell line culture 52 Inhibition of ROS production in neuroblastoma cell line culture 70 Anti inflammatory effect 71a Anti-inflammatory effect 51 pounds and hyperforin. The neurological effects evaluated are related to AD: antidepressant properties, effect over neurotransmission and anti-oxidant and anti-inflammatory properties.…”

Protective efficacy of selenite against lead-induced neurotoxicity in Caenorhabditis elegans

“…Subsequently, intracellular ROS in C. elegans were measured using 29,79-dichlorodihydrofluoroscein diacetate (H 2 DCFDA) (Sigma, St. Louis, MO, USA). One hundred nematodes were broken up using sonication after each treatment, and the worm lysates were collected for the ROS measurement [52]. The worm samples were incubated with H 2 DCFDA (at a final concentration of 50 mM in phosphate buffered saline (PBS) at 37uC in an FLx800 Microplate Fluorescent Reader (Bio-Tek Instruments, Winookski, VT, USA) for quantification of fluorescence with excitation at 485 nm and emission at 530 nm.…”

Amyloid-β-Induced Pathological Behaviors Are Suppressed byGinkgo bilobaExtract EGb 761 and Ginkgolides in TransgenicCaenorhabditis elegans

“…Substantial experimental data indicate that EGb 761 has neuroprotective and neuromodulatory effects (Luo, 2001;Watanabe et al, 2001;Yao et al, 2001;DeFeudis, 2002). Two of its major constituents, flavonoids (24%) and terpenoids (6%), have been actively investigated for their neuroprotective properties (DeFeudis, 1998;Smith and Luo, 2003). The ginkgolides, known as potent antagonists of platelet-N2 (Bristol) was from Caenorhabditis Genetics Center (University of Minnesota, Minneapolis, MN).…”

“…Intracellular ROS were measured in C. elegans using 2,7-dichlorofluorescein diacetate (DCF-DA) (Invitrogen, Eugene, OR) as described previously (Smith and Luo, 2003). Agesynchronized C. elegans were collected at 36 h after temperature upshift (CL4176/1175) into 100 l of PBS with 1% Tween 20 (PBST) in Eppendorf tubes in groups of 40 worms.…”