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Abstract

In the present study, we investigated the effect of Ginkgo biloba extract, EGb 761, and one of its components, bilobalide, on gene expression of subunit 1 of mitochondrial NADH dehydrogenase (ND1) in PC12 cells. By Northern blot analysis we found a approximately 2-fold significant increase in NDI mRNA level, after 48 and 72 h exposure to 100 microg/ml EGb 761 and to 10 microg/ml bilobalide. We also evaluated, by oxygraphy measurements, mitochondrial respiration during state 3 and state 4. In cells treated with EGb 761 and bilobalide for 48 and 72 h, state 4 respiration was significantly decreased, and the respiratory control ratio was increased. These results provide evidence that EGb 761 and bilobalide exert their protective effects by up-regulating mitochondrial ND1 gene expression and by decreasing state 4 respiration, whose increase is thought to be responsible for oxidative damage.

Ginkgo Biloba Extract Ameliorates Oxidative Phosphorylation Performance and Rescues Aβ-Induced Failure

“…Although further studies are necessary, we can speculate that a GBE treatment may not only enhance mtDNA as an early event after acute treatment, but may instigate mitochondria biogenesis as a long-term effect after chronic exposure [42]. In line with this idea, recent studies showed that GBE induced hippocampal neurogenesis, a very energy demanding process, in young and old transgenic AD mouse model (TgAPP/PS1) after receiving a diet supplemented with GBE for 1 month [43].…”

Antiapoptotic Effects of EGb 761

“…These events may increase stress resistance and stabilize the cellular redox state in living organisms [40, 88, 89]. Bilobalide upregulates two mitochondrial DNA-encoded genes: subunit III of cytochrome c oxidase (complex IV) and subunit ND1 of NADH dehydrogenase (complex I) of the respiratory chain, indicating a fundamental mechanism that may underline EGb 761 induced neuroprotection [90, 91]. Enhancement of the respiratory control ratio, improving ATP synthesis, and preserving the mitochondrial outer membrane integrity prevent cyt c release, thereby blocking the formation of the apoptosome and the apoptotic caspase cascade [89].…”

“…Enhancement of the respiratory control ratio, improving ATP synthesis, and preserving the mitochondrial outer membrane integrity prevent cyt c release, thereby blocking the formation of the apoptosome and the apoptotic caspase cascade [89]. Tendi et al [91] suggest that EGb 761 and bilobalide might indirectly increase ND1 transcription by modulating the expression and/or the binding of transcription factors in the promoters of genes involved in mitochondrial transcription. In addition, both flavonoid and terpenoid constituents of EGb 761 decrease the expression of iNOS, which might oppose the deleterious effects of excessive production of NO • [92], which inhibit the complex I of respiratory chain by S-nitrosation, tyrosine nitration, and damage to FeS centers [93] and could increase Bax expression and decrease Bcl-2 expression subsequently leading to neural death [94].…”

Promising Therapeutics with Natural Bioactive Compounds for Improving Learning and Memory — A Review of Randomized Trials

“…This extract increases the rate of acetylcholine turnover and stimulates binding activity of ligands to muscarinic receptors in the hippocampus [ 88 ]. G. biloba cures cognitive deficits and dementia [ 31 , 89 ] and also has antioxidant and free radical scavenging activity in animals [ 90 , 91 , 92 ]. The multiple effects G. biloba can be attributed to the different components of the extract, which may act independently or synergistically.…”