Ginkgo bilobaextract EGb761 protects against aging-associated mitochondrial dysfunction in platelets and hippocampi of SAMP8 mice

Abstract

Standardized Ginkgo biloba extract, EGb761, has been shown to possess polyvalent properties, such as anti-oxidation, anti-apoptosis and anti-inflammation. Recently, it has also been proposed to have direct protective effects on mitochondria. The effects of EGb761 make it a potential anti-aging drug. Despite that, the 'anti-aging' effect of EGb761, particularly its effect on the central nervous system, is still inconclusive. Using two age groups (3-week-old and 40-week-old) of SAMP8 mice (a senescence-accelerated strain of mice), the effects of EGb761 on mitochondrial function in platelets and hippocampi were investigated in this study. It was found that mitochondrial functions, evaluated as cytochrome c oxidase (COX) activity, mitochondrial ATP (adenosine-5'-triphosphate) content and mitochondrial glutathione (GSH) content, decreased with age. EGb761 protected against mitochondrial dysfunction in platelets of young and old mice, suggesting a peripheral effect of this herb in the prevention and treatment of age-associated degeneration. In contrast, in hippocampi, protective effects of EGb761 were observed only in the old mice, probably due to an age-associated increase in the permeability of the blood brain barrier (BBB). Therefore, while EGb761 has a potential anti-aging effect, its central effect can be affected by in vivo factors such as the BBB permeability. A better understanding of the in vivo pharmacological actions of EGb761 may contribute to a better understanding of the effectiveness and complexity of this drug.

Senescence-Accelerated Mice P8: A Tool to Study Brain Aging and Alzheimer's Disease in a Mouse Model

“…In SAMP8, impairment of mitochondrial functions, including a decrease in cytochrome c oxidase (COX) activity, mitochondrial ATP content, and the mitochondrial glutathione (GSH) level, has been shown in SAMP8 brain at a relatively early age compared to SAMR1 mice [29]. In addition, significant age-dependent mitochondrial dysfunction with diminished efficiency of the electron transport chain and reduced ATP production has been found, accompanied by increased oxidative/nitrosative stress [123,124].…”

“…Conversely, associative learning in the fear conditioning task is not affected in the SAMP8, but both passive and active avoidance (i.e., learning to escape by exiting the chamber in which an aversive stimulus was previously received) shows significant declines starting as early as 2 months of age [29,105,106]. It is interesting to note that the SAMP8 exhibits reduced anxiety-like behavior [107].…”

“…SAMP8 presented not only similar characteristics to aged humans, such as shorter lifespan, lordosis, reduced physical activity, and hair loss [46,47], but also some neurodegenerative features, such as early onset of learning and memory deficits [48], altered emotions and abnormal circadian rhythm [49,50], neuronal cell loss [51], and reduction in the release of neurotransmitters in the brain [52,53]. Besides, impairment of mitochondrial functions has been shown in SAMP8 brain at a relatively early age compared to SAMR1 mice [29]. The SAMR1 mice do not show these senescence-related neuronal phenotypes and can therefore be used as a control strain commonly.…”

Cognitive-enhancing effects of hydrolysate of polygalasaponin in SAMP8 mice

“…SAMP8 mice are a metabolic model which not only exhibits the cognitive deficits that erode acquisition and memory retention, as shown in AD (Flood and Morley, 1998;Armbrecht et al, 2014), but also displays pathological changes such as A peptide deposition (Takemura et al, 1993), cholinergic system dysfunction (Strong et al, 2003), disturbed synaptic plasticity (López-Ramos et al, 2012), and overexpression of amyloid precursor protein (APP) (Morley et al, 2012). Besides this, SAMP8 mice show neuroenergetic imbalances including a decrease in mitochondrial glutathione (GSH) content, Mn-superoxide dismutase (MnSOD), Cu/Zn-SOD, catalase activity, complex IV activity, and adenosine-5'-triphosphate (ATP) levels (Xu et al, 2007;Shi et al, 2010). On the other hand, senescenceaccelerated resistant mouse 1 (SAMR1) of normal aging exhibits no senescence-related neuronal phenotypes and has a genetic background similar to that of SAMP8; it has been used extensively as a control (Takeda, 2009;Bayod et al, 2015).…”

Mitochondrial effects of Ginkgo biloba extract

“…In comparison, brain cells from mice treated with Ginkgo biloba extract EGb 761 were protected from the effects of hydrogen peroxide, which had a reduced effect on ATP production. Shi et al (2010) also investigated the impact of EGb 761 on ATP production using SAMP8 mice (a senescence-accelerated strain of mouse). The hippocampi of two age groups of mice (3 weeks and 40 weeks) were isolated and the ATP content in the mitochondria was determined.…”