Comparative Kinetics of Acetyl- and Butyryl-Cholinesterase Inhibition by Green Tea Catechins|Relevance to the Symptomatic Treatment of Alzheimer's Disease.

Alzheimer's disease (AD) is characterised by the apoptosis of cholinergic neurons and the consequent attenuation of acetylcholine mediated neurotransmission, resulting in neurodegeneration. Acetyl-cholinesterase (AChE) and butyryl-cholinesterase (BuChE) are attractive therapeutic targets in the treatment of AD since inhibition of these enzymes can be used to restore synaptic concentrations of acetylcholine. Whilst inhibitors for these enzymes such as galantamine and rivastigmine have been approved for use, none are able to halt the progression of AD and are responsible for the production of troublesome side-effects. Efficacious cholinesterase inhibitors have been isolated from natural plant-based compounds with many demonstrating additional benefits beyond cholinesterase inhibition, such as antioxidation and anti-inflammation, which are key parts of AD pathology. In this study, five natural flavan-3-ol (catechin) compounds: ((-)-epicatechin (EC), catechin, (-)-epicatechin-3-gallate (ECG),) (-)-epigallocatechin (EGC), (-)-epigallocatechin-3-gallate (EGCG), isolated from green tea, were screened for their cholinesterase inhibitory activity using the Ellman assay. The kinetics of inhibition was determined using reciprocal Lineweaver-Burk plots. EGCG was the only compound found to produce statistically significant, competitive inhibition, of both AChE (p < 0.01) and BuChE (p < 0.01) with IC50 values of 0.0148 µmol/mL and 0.0251 µmol/mL respectively. These results, combined with previously identified antioxidative and anti-inflammatory properties, highlight the potential use of EGCG in the treatment of AD, provided it can be delivered to cholinergic neurons in therapeutic concentrations. Further testing of EGCG in vivo is recommended to fully characterise the pharmacokinetic properties, optimal method of administration and efficacy of this novel plant-based compound.

Effects of green and black tea consumption on brain wave activities in healthy volunteers as measured by a simplified Electroencephalogram (EEG): A feasibility study.

OBJECTIVES: Tea has been associated with many mental benefits, such as attention enhancement, clarity of mind, and relaxation. These psychosomatic states can be measured in terms of brain activity using an electroencephalogram (EEG). Brain activity can be assessed either during a state of passive activity or when performing attention tasks and it can provide useful information about the brain's state. This study investigated the effects of green and black consumption on brain activity as measured by a simplified EEG, during passive activity. METHODS: Eight healthy volunteers participated in the study. The EEG measurements were performed using a two channel EEG brain mapping instrument - HeadCoach™. Fast Fourier transform algorithm and EEGLAB toolbox using the Matlab software were used for data processing and analysis. RESULTS: Alpha, theta, and beta wave activities were all found to increase after 1 hour of green and black tea consumption, albeit, with very considerable inter-individual variations. DISCUSSION: Our findings provide further evidence for the putative beneficial effects of tea. The highly significant increase in theta waves (P < 0.004) between 30 minutes and 1 hour post-consumption of green tea may be an indication of its putative role in cognitive function, specifically alertness and attention. There were considerable inter-individual variations in response to the two teas which may be due genetic polymorphisms in metabolism and/or influence of variety/blend, dose and content of the selected products whose chemistry and therefore efficacy will have been influenced by 'from field to shelf practices'.

Determination of Lovastatin, ß-glucan, Total Polyphenols, and Antioxidant Activity in Raw and Processed Oyster Culinary-Medicinal Mushroom, Pleurotus ostreatus (Higher Basidiomycetes).

The objective of this study was to quantify a number of bioactive compounds and antioxidant activity of the oyster mushroom, Pleurotus. Ostreatus, and characterize the effects of processing, such as blanching, on these outcomes. Dry matter content was 8%. Lovastatin was not detected in this study. ß-glucan content of 23.9% and total polyphenol content of 487.12 mg gallic acid equivalent/100 g of dry matter were obtained in raw P. ostreatus. Antioxidant activities as evaluated by 1,1-diphenyl-2-picrylhydrazyl, Trolox equivalent antioxidant capacity, and ferric reducing antioxidant power assays in raw P. ostreatus were 14.46, 16.51, and 11.21 µmol/g, respectively. Blanching did not significantly affect ß-glucan content but caused significant decrease in dry matter content, polyphenol content, and antioxidant activities. Mushroom rolls produced from blanched mushrooms and blanching water contained significantly higher amounts of ß-glucan, total polyphenol content, and FRAP antioxidant activity compared to blanched mushrooms. In conclusion, P. ostreatus is a good source for ß-glucan, dietary polyphenols, and antioxidants. Although the blanching process could affect these properties, re-addition of the blanching water during the production process of mushroom rolls could potentially recover these properties and is therefore recommended.

Experimental inhibition of fibrillogenesis and neurotoxicity by amyloid-beta (Aß) and other disease-related peptides/proteins by plant extracts and herbal compounds.

Amyloid-ß (Aß) fibrillogenesis and associated cyto/neurotoxicity are major pathological events and hallmarks in diseases such as Alzheimer's disease (AD). The understanding of Aß molecular pathogenesis is currently a pharmacological target for rational drug design and discovery based on reduction of Aß generation, inhibition of Aß fibrillogenesis and aggregation, enhancement of Aß clearance and amelioration of associated cytotoxicity. Molecular mechanisms for other amyloidoses, such as transthyretin amyloidosis, AL-amyloidosis, as well as α-synuclein and prion protein are also pharmacological targets for current drug therapy, design and discovery. We report on natural herbal compounds and extracts that are capable binding to and inhibiting different targets associated with AD and other amyloid-associated diseases, providing a basis for future therapeutic strategies. Many herbal compounds, including curcumin, galantamine, quercetin and other polyphenols, are under active investigation and hold considerable potential for future prophylactic and therapeutic treatment against AD and other neurodegenerative diseases, as well as systemic amyloid diseases. A common emerging theme throughout many studies is the anti-oxidant and anti-inflammatory properties of the compounds or herbal extracts under investigation, within the context of the inhibition of cyto/neurotoxicity and anti-amyloid activity.

Inhibition of acetylcholinesterase by green and white tea and their simulated intestinal metabolites.

By 2034 it is forecast that 5% of the global population will be aged 85 years or over--approximately two and half fold increase on present day figures--which will inevitably lead to an increase in age-associated disorders such as Alzheimer's disease. There is mounting evidence that green tea (Camellia sinensis) possesses numerous health-promoting properties, and may potentially be beneficial to those suffering from Alzheimer's and other diseases, including cardiovascular disease and cancer. These beneficial properties are largely attributed to the high polyphenol content, particularly the catechins. In this study, we measured acetylcholinesterase inhibition by white and green teas and their simulated intestinal digests. We found that the potency with which the white and green tea extracts inhibited acetylcholinesterase varied through the simulated digestion procedure. Initially, in the undigested extract form, potency was high with IC50 values of 7.20 µg mL⁻¹ and 8.06 µg mL⁻¹ for green and white tea respectively.However, this decreased significantly after gastric digestion but activity was recovered after pancreatic digestion which could be related to relative increases in the levels of caffeine and specific phenolic components. Of the pure tea compounds tested, EGCG was the most potent with an IC50 of 0.0096 µmol mL⁻¹ but its breakdown product; γ-valerolactone was the least potent analyte. Particularly interesting were the results of caffeine,which exhibited a strong inhibitory activity and pyrogallol, which recorded a much stronger potency than its parent compound gallic acid, suggesting a pro-drug-like relationship. Overall, the results indicate that further research is necessary to determine the full potential of digestion of tea and its metabolites and how inter-individual variation may indicate that some sections of society could potentially benefit more from drinking tea as a strategy to prevent the development of dementia. We have also shown the activities of a number of metabolites,however, further research is required to determine their potential bioavailability.

An aqueous extract of Withania somnifera root inhibits amyloid ß fibril formation in vitro.

The ability of an aqueous extract of W. somnifera L. Dunal (Family: Solanaceae) roots to inhibit fibril formation by the amyloid-ß peptide in vitro was investigated. W. somnifera is used extensively in traditional Ayurvedic medicine as a nerve tonic with reputed memory enhancing properties. Inhibition of fibrillogenesis measured by transmission electron microscopy and ThT fluorescence assay showed that an aqueous extract of W. somnifera strongly inhibited Aß fibril formation in a concentration-dependent manner, when compared with control samples. These results suggest that the aqueous extract of W. somnifera root has an ability to inhibit the formation of mature amyloid-ß fibrils in vitro, which are known to lead to amyloid plaque formation in vivo.

Use of plant-derived products to control arthropods of veterinary importance: a review.

The use of synthetic products in veterinary pest management is becoming increasingly problematic. Issues, including pest resistance, product withdrawal, undesirable environmental persistence, and high mammalian toxicity associated with synthetic pesticides, are driving research to identify new pest management approaches. One approach employs the repellent/toxic effects of plant-derived products (PDPs). Several pesticides based on PDPs are already available in some areas of pest management. This review highlights instances in which such products have been used with success against pests of domestic animals, livestock, apiculture, and poultry.

Effects of cholinesterase inhibiting sage (Salvia officinalis) on mood, anxiety and performance on a psychological stressor battery.

Salvia officinalis (sage) has previously been shown both to possess in vitro cholinesterase inhibiting properties, and to enhance mnemonic performance and improve mood in healthy young participants. In this double-blind, placebo-controlled, crossover study, 30 healthy participants attended the laboratory on three separate days, 7 days apart, receiving a different treatment in counterbalanced order on each occasion (placebo, 300, 600 mg dried sage leaf). On each day mood was assessed predose and at 1 and 4 h postdose. Each mood assessment comprised completion of Bond-Lader mood scales and the State Trait Anxiety Inventory (STAI) before and after 20 min performance of the Defined Intensity Stress Simulator (DISS) computerized multitasking battery. In a concomitant investigation, an extract of the sage leaf exhibited dose-dependent, in vitro inhibition of acetylcholinesterase and, to a greater extent, butyrylcholinesterase. Both doses of sage led to improved ratings of mood in the absence of the stressor (that is, in pre-DISS mood scores) postdose, with the lower dose reducing anxiety and the higher dose increasing 'alertness', 'calmness' and 'contentedness' on the Bond-Lader mood scales. The reduced anxiety effect following the lower dose was, however, abolished by performing the DISS, with the same dose also being associated with a reduction of alertness during performance. Task performance on the DISS battery was improved for the higher dose at both postdose sessions, but reduced for the lower dose at the later testing session. The results confirm previous observations of the cholinesterase inhibiting properties of S. officinalis, and improved mood and cognitive performance following the administration of single doses to healthy young participants.

In vitro anti-beta-secretase and dual anti-cholinesterase activities of Camellia sinensis L. (tea) relevant to treatment of dementia.

The primary target of licensed drugs for the treatment of Alzheimer's disease is the inhibition of the enzyme acetylcholinesterase, although preventing beta-amyloidosis is a prime target for drugs in development. The in vitro dual anti-cholinesterase and beta-secretase activities of Camellia sinensis L. extract (tea) is reported. Green and black tea inhibited human acetylcholinesterase (AChE) with IC(50) values of 0.03 mg/mL and 0.06 mg/mL respectively, and human butyrylcholinesterase (BuChE) with IC(50) values 0.05 mg/mL. Green tea at a final assay concentration of 0.03 mg/mL inhibited beta-secretase by 38%. These novel findings suggest that tea infusions contain biologically active principles, perhaps acting synergistically, that may be used to retard the progression of the disease assuming that these principles, yet to be identified, reach the brain.

Butyryl- and acetyl-cholinesterase inhibitory activities in essential oils of Salvia species and their constituents.

Extracts of Salvia (sage) species have been reported to have cholinergic activities relevant to the treatment of Alzheimer's disease. A lack of information on the inhibition of the enzyme butyrylcholinesterase, also considered to be a target in the treatment of the disease, prompted this in vitro investigation of the essential oils of S. fruticosa, S. lavandulaefolia, S. of ficinalis and S. of ficinalis var. purpurea for anti-butyrylcholinesterase activity. Dose-dependent inhibition of human cholinesterases by the extracts and constituents was determined using the method of Ellman. A time dependent increase in the inhibition of butyrylcholinesterase by the oils of S. fruticosa and S. of ficinalis var. purpurea was evident. IC(50) values decreased from 0.15 +/- 0.007 and 0.14 +/- 0.007 mg/mL after 5 min to 0.035 +/- 0.016 and 0.06 +/- 0.018 mg/mL after 90 min incubation time respectively. The slow onset of inhibition of butyrylcholinesterase was also shown by individual constituents, such as 3-carene and beta-pinene. Analyses of the chemical composition of the oils and anti-butyrylcholinesterase activity of their constituents revealed that none of the compounds tested would account for the total activity of the oils and that synergy is likely.