Effects of Ginkgo biloba Extract EGb 761, Donepezil and their Combination on Central Cholinergic Function in Aged Rats

Abstract

Purpose. Ginkgo extract EGb 761 and cholinesterase inhibitors have been shown to be effective in the treatment of dementia patients. In addition to neuroprotective effects, Ginkgo extract EGb 761 has been reported to elevate brain levels of certain neurotransmitters such as dopamine, noradrenaline, and acetylcholine. In the present study, we investigated the impact of EGb 761, donepezil and the combination of both drugs on the central cholinergic system in aged rats. Methods. 24 month old rats received EGb 761 (100 mg/kg/day), donepezil (1.5 mg/kg/day), the combination of both drugs or vehicle control by oral gavage for 14 days. We used microdialysis in rat hippocampus to monitor extracellular concentrations of acetylcholine (ACh), choline, glucose and lactate. Brain homogenates were prepared to measure activities of acetylcholinesterase (AChE), choline acetyltransferase (ChAT) and high affinity choline uptake (HACU). Results. While EGb 761 alone had no effect, donepezil and the combination of donepezil and EGb 761 increased basal ACh levels by 2- to 3-fold. Concomitantly, significant reductions of AChE and HACU were measured in both groups. No differences were seen between donepezil and the combination in these parameters. Treatment with EGb 761 decreased extracellular choline release and showed a tendency to moderately elevate ChAT activity. Conclusions. We found that donepezil and EGb 761 do not display a pharmacological interaction when given together. Adding EGb 761 did not modify the effects of donepezil on the hippocampal cholinergic system. Reduced choline levels indicate neuroprotective properties of EGb 761. Therefore, the combination of EGb 761 and donepezil may be beneficial in the treatment of Alzheimer’s disease (AD). This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

WITHDRAWN: Ginkgolide B reduces hepatic lipid accumulation and ameliorates nonalcoholic fatty liver disease in high-fat diet–induced obese mice

“…In addition, excess energy is mainly stored as glycogen in normal liver cells; however, because of metabolic abnormalities, fatty liver cells would accumulate more oil droplets rather than form glycogen [12,16]. PAS staining showed that HFD-induced obese mice had reduced glycogen accumulation in hepatocytes compared to normal-diet mice, whereas ginkgolide B exposure was associated with enhanced glycogen storage compared to HFD-induced obese mice.…”

“…When liver cells take up more fatty acids, transcription factors involved in fat synthesis, including PPAR, C/EBP, and SREBP-1c, will be activated to enhance lipid accumulation in hepatocytes [16]. Those transcription factors bind to promoters of lipogenesis-related genes to switch on synthesis of fatty acid chains and TGs [3].…”

“…Ginkgo leaf extract has been applied to treat brain blood circulation and improve memory and prevent dementia; the extract also can be used to boost peripheral blood circulation and promote blood vessel dilation for prevention of thrombosis [15]. G. biloba extract (EGb-761) additionally is used to treat cardiovascular and neurodegenerative disease in European countries [16]. Moreover, in Chinese medicine, its fruit is applied for improving asthma symptoms [17].…”

Cardioprotective Action of Ginkgo biloba Extract against Sustained β-Adrenergic Stimulation Occurs via Activation of M2/NO Pathway

“…In fact, our findings are strikingly similar to data obtained in vivo with rats subjected to treatment with pyridostigmine, a cholinesterase inhibitor (Gavioli et al, 2014). Along with these lines, previous studies have reported the anticholinesterase activity of GBE (Stein et al, 2015; Kim et al, 2016). Although the exact mechanism by which GBE alters cholinergic signaling is still unknown, it is plausible to assume that GBE acts, at least in part, through changes in cholinergic signaling.…”

Real-time changes in hippocampal energy demands during a spatial working memory task

“…However, as all these studies assume that hippocampal glucose concentration is usually around 1 mM based on results from zero-net-flux experiments [51], which may be an overestimation of the baseline hippocampal glucose concentration. Indeed, recent work suggests that the concentration is lower, perhaps as low as around 0.60 mM [25] or even 0.31 mM [52], similar to levels esti-mated for the nucleus accumbens (0.54 mM; see [53] and [54]) and striatum (0.35 mM; see [8]). Assuming a basal concentration of 1.00 mM would therefore call into question any deviations from baseline glucose levels identified using the microdialysis method described in multiple studies [30][31][32]48].…”