Therefore, regular green tea consumption may gunction cognitive function by increasing antioxidant capacity. PLoS One e Green tea contains a type of polyphenol called a catechin.

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Green tea extract for cognitive function -

In the search for a natural anti-AD functional agent, green tea extract GTE has been widely reported to have beneficial effects on cognitive function.

According to human cohort studies, interventions with GTE showed positive effects on the cognitive function of healthy volunteers and MCI patients [ 5 — 7 ].

In addition, the consumption of green tea was closely related to a reduced risk of MCI and dementia [ 8 — 10 ]. These positive effects of GTE have been attributed mainly to its most abundant catechin component, epigallocatechin gallate EGCG.

Indeed, EGCG administration has shown positive effects on AD model mice. EGCG treatment lowered amyloid β Aβ levels, secretase activity, and expression levels of age-related genes [ 11 — 15 ].

Although EGCG is abundant in dried green tea leaves, approximately half of the catechins are epimerized to catechin C2 epimers during food processing, such as brewing tea or pasteurizing tea drinks [ 16 ].

Consequently, a significant proportion of the catechin ingested during the consumption of green tea actually consists of catechin epimers. In the present study, we investigated the in vitro neuroprotective effects of heat-epimerized green tea phytochemicals and their in vivo effects on cognitive decline.

Specifically, we investigated the protective effects of high-temperature-processed green tea extract HTP-GTE against Aβ-induced neurotoxicity and Aβ aggregation in vitro and cognitive decline in presenilin 2 PS2 and Tg mice.

Camellia sinensis CS leaves were obtained from Osulloc Garden in Jeju, South Korea. The preparation of HTP-GTE was performed as previously described [ 17 ]. This extract was decaffeinated by filtration with activated clay and then subjected to aqueous conditions at °C, 1.

After heat treatment, HTP-GTE was concentrated with a rotary evaporator Buchi R in vacuo. The injection volume was 20 μL. The UV wavelength was set at nm. Mass spectra were carried out by using an LCQ fleet with ESI-MS. A total of 2 × 10 4 cells were seeded in well plates and allowed to adhere for 1 day before the addition of Aβ aggregates.

Then, aggregate solution was added to the PC12 cells to a final concentration of 1 μM. Using the SensoLyte® Thioflavin T Beta-Amyloid Aβ42 Aggregation Kit AnaSpec, Fremont, USA , the kinetics of amyloid formation was monitored by the fluorescent, amyloid-specific dye ThT. The aggregation of Aβ42 was measured in the presence of GCG, EGCG, and a combination of the two.

Samples were plated in triplicate on uncoated black well polystyrene plates. The plate was placed on a TECAN Infinite PRO multifunctional microplate reader TECAN, Switzerland at 37°C for fluorescence readings.

Wells were read from the bottom with an excitation wavelength of nm and an emission wavelength of — nm nm bandwidth at 5-min intervals with 15 s of shaking after measurement to aid protein aggregation.

In order to evaluate the self-assembled morphology of the Aβ peptides, TEM JEMF, JEOL Company operating at kV was used. For negative staining, fibrils were allowed to form for an appropriate amount of time in Aβ aggregation buffer, and the formed fibrils were immediately placed on formvar-coated copper grids Ted Pella.

The samples were dried overnight before measurements were taken by TEM. The aggregation of Aβ42 under GCG and EGCG treatment was tested as described above. The blots were washed three times with TBS-T and visualized with a SuperSignal West Femto maximum-sensitivity substrate kit Pierce.

All procedures for animal experiments followed the guidelines approved by the Animal Care Committee of Chiba University. Tg mice, which express human amyloid precursor protein with Swedish mutation, were purchased from Taconic Laboratories [ 18 ]. PS2Tg double mutant mice were generated by crossbreeding Tg mice and transgenic mice carrying human mutant PS2 NI for five or six generations [ 19 ].

In vivo analyzes were performed using in vitro fertilization and embryonic transfer techniques. Genotyping of the PS2Tg allele was performed using genomic PCR with genomic DNA biopsied from the tail tips of mice at 3—4 weeks of age. Male mice were separated from female mice at 3 weeks of age, and the housed cages were divided into groups based on average body weight at one week before administration.

The animals were orally fed HTP-GTE dissolved in drinking water twice a week from 16 weeks to 26 weeks of age. Mouse brains were isolated under sterile conditions on ice after anesthesia and perfusion. Frozen brain tissue 0. After centrifugation 55, × g, 4°C, 30 min , the resultant supernatant was pooled as a soluble fraction.

The pellet was suspended in 6 M guanidine-HCl and centrifuged at 55, × g, 4°C, 30 min. Then, the supernatant was collected as an insoluble fraction [ 11 , 21 ]. Aβ40 and Aβ42 in the soluble fraction were detected in brain homogenates prepared with lysis buffer at a dilution.

Protein levels of homogenate samples were normalized by DC protein assay Bio-rad, CA, USA prior to dilution. The Y maze apparatus Muromachi Kikai was made from gray polyvinyl chloride, consisting of three open arms 40 × 2 cm connected by 2 × 2 cm passages, with walls of 12 cm height.

The mice were placed on the one of three arms and allowed to freely explore on the apparatus for 5 min [ 22 ]. Total arm entry and alteration behavior were counted. Novel object recognition test was performed as previously reported [ 20 ].

Mice were habituated to the apparatus with 10 min of free exploration on 3 consecutive days. For training, two distinct objects A and B were placed in the field, and mice were allowed to freely explore them for 10 min.

The long-term memory test was performed on day 7. Object B was changed for a novel object C. Exploration was confined as sniffing or touching the object with a nose.

The preference index [ 23 ] was determined by the difference in the amount of time spent exploring the novel object and the familiar object. Each experiment was performed in triplicate and analyzed with SPSS Statistics standard ver.

The catechin contents of HTP-GTE are listed in Table 1 and depicted with GTE in Figure 1. In the catechin components, HTP-GTE had a lower proportion of EGCG but a higher rate of GCG compared to GTE Figure 1 a.

The HPLC catechin composition data of GTE and HTP-GTE by HPLC are presented in Figure S1. To investigate whether these composition differences of catechin could affect the neuroprotective effect of green tea, we examined the viability of neurons against Aβ-induced neurotoxicity.

Moreover, GCG and EGCG, the possible major active compound of HTP-GTE and GTE, also effectively decreased Aβ toxicity Figure 1 c. These results indicate that GCG reduced the neurotoxicity of Aβ and that HTP-GTE also showed a neuroprotective effect against Aβ in vitro.

The protective effects of GTE and HTP-GTE against Aβ-induced neurotoxicity in vitro. a The catechin content of HTP-GTE. Data are presented as the means ± S.

of three independent experiments. Because GCG attenuated the cellular neurotoxicity of Aβ, we tested whether GCG could inhibit Aβ aggregation itself. Using a thioflavin T ThT fluorescent assay, we evaluated the kinetics and inhibition rate of Aβ aggregation.

Regarding inhibitory effects on Aβ aggregation, GCG exhibited greater efficacy than the same concentration of EGCG Figure 2 a,b.

Similarly, the combinations with higher proportions of GCG showed stronger inhibitory effects Figure 2 a,b. Furthermore, we examined the inhibitory effects of GCG and EGCG on Aβ aggregation through an in vitro assay.

We found that GCG showed greater inhibitory capacity than EGCG against Aβ aggregation as assessed by TEM Figure 2 c and a dot blot assay Figure 2 d. These results could explain why HTP-GTE represses Aβ-induced neurotoxicity effectively.

a Time-dependent curves of Aβ aggregates in 90 min. Positive fluorescence signal in relative fluorescence units , indicating thioflavin T dye bound to Aβ aggregates, under treatment with GCG, EGCG, and a combination of the two.

b The relative inhibition rates of Aβ aggregates under treatment with GCG, EGCG, and a combination of the two. c TEM images of Aβ aggregates under 20 μM application of GCG or EGCG for 1. d The total 6E10 and Aβ A11 aggregates were dot blotted under 20 μM application of EGC or EGCG for 1.

At present, the amyloid cascade is hypothesized to be the cause of cognitive decline [ 24 ]. Therefore, we investigated whether HTP-GTE feeding could affect this cascade. PS2Tg mice showed elevated concentrations of Aβ40 and Aβ42 in both the soluble and insoluble fractions compared with wild-type mice Figure 3.

The Aβ in the insoluble fraction increases in an age-dependent manner in neurons [ 25 ], and the Aβ in this fraction is more toxic than that in the soluble fraction, since the former is not secreted [ 26 ]. Considering insoluble Aβ forms oligomers and aggregates, it suggests that HTP-GTE feeding suppresses Aβ aggregation in AD brain.

Because dietary administration of HTP-GTE lowered the Aβ40 and Aβ42 levels in the insoluble fraction, we proceeded to consider the effects on cognitive function. The amount of Aβ in the 6-month-old PS2Tg brain after 8 weeks of treatment with HTP-GTE.

Data are represented as the means ± S. To assess the effect of dietary HTP-GTE on spatial learning and short-term memory decline, we subjected mice to a Y-maze test after an 8-week experimental diet period.

Next, we subjected mice to novel object recognition and memory retention test to evaluate the effect on long-term memory decline. PS2Tg showed decreased number of total touch to the objects and preference index, suggesting decreased attention and long-term memory, respectively.

Considering there is no difference of total entry in Y maze test among each group Figures 4 a and 5 a , HTP-GTE has no effects on obvious motor function. These results of behavioral analysis indicate that HTP-GTE feeding can prevent short-term and long-term cognitive decline in PS2Tg Effects of HTP-GTE consumption on spatial learning and memory in 6-month-old PS2Tg Total entry counts a and alteration rates b were investigated.

Effects of HTP-GTE treatment on long-term memory in 6-month-old PS2Tg Total touch counts a and preference index ratios b were recorded. Previous studies regarding the effects of green tea on neurotoxicity and cognitive function showed that supplementation with green tea or GTE could normalize cognitive activity, improve working memory and reaction time, and protect against cognitive impairment [ 5 , 27 , 28 ].

However, these studies presented the effect of crude green tea, which allows general inferences but does not sufficiently convey the effects of the individual catechins that compose the tea.

To assess the positive effects of green tea on cognitive function, it is necessary to determine whether various catechin components of green tea can function as protective agents against cognitive decline.

Our previous study showed that HTP-GTE and its bioactive catechins exhibited reactive oxygen species scavenging activity in human brain microvascular endothelial cells treated with Aβ42; the extract also showed anti-amyloidogenic effects on fibril formation and destabilization [ 29 ].

In addition, GCG from HTP-GTE can be released in digestive fluid, absorbed by the small intestine, and metabolized in the liver, resulting in transport across the blood-brain barrier, with the highest permeability rates at the lowest concentration [ 17 ].

In this study, HTP-GTE and its active catechin, GCG, protected neurons against Aβ-induced neurotoxicity Figure 1 b,c. These neuroprotective effects of HTP-GTE might be derived from the inhibitory effect of GCG on Aβ aggregation Figure 2.

This could be derived from the effects of EGCG on Aβ conformations, which determines oligomer toxicity [ 30 ]. Previous reports indicated that EGCG could exert anti-amyloidogenic effects by binding to the Aβ structure, modifying nontoxic oligomers and stabilizers of amyloidogenic proteins, preventing amorphous aggregates associated with fibril formation [ 31 , 32 ].

Since gallate compounds such as GCG disturbed Aβ42 fibril formation and destabilized the preformed Aβ42 fibrils more effectively than non-gallate compounds, and since GCG has the same number of OH groups as EGCG [ 33 ], it is thought that GCG may inhibit Aβ aggregation by reducing oxidative stress levels with the same efficiency as EGCG [ 34 , 35 ].

The specific machinery by which Aβ is produced before secretion has not yet been uncovered because of the difficulty of intracellular Aβ detection. Intracellular Aβ can be divided into two fractions defined by solubility.

The soluble fraction is secreted from the cell into the extracellular space as soluble Aβ during metabolic processing. Soluble Aβ is thought to be produced in the endocytotic route, Golgi complex, or trans-Golgi pathway [ 36 — 38 ].

The intracellular accumulation of Aβ in the insoluble fraction has been found to increase in an age-dependent manner in neuronal N2TN cells, and Aβ in the insoluble pool is not secreted [ 25 ]. In the brain, Aβ exists in the insoluble, glycolipid-enriched fraction [ 40 ], and increased accumulation of Aβ in the insoluble fraction may be implicated in the age-dependent progression of cognitive impairment over time [ 41 ].

In our results, GCG interrupted the accumulation of Aβ40 and Aβ42 in the insoluble fraction but not in the soluble fraction Figure 3.

Although GCG could not repress all Aβ pools, these results may imply that GCG effectively reduced neurotoxicity by inhibiting the accumulation of highly toxic non-secreted Aβ in AD progression.

Prior cohort studies found that green tea consumption was related to a decreased risk of MCI and incident dementia [ 9 , 10 , 27 , 42 ]. Because HTP-GTE showed preventive effects on Aβ aggregation and accumulation, we expected positive effects of HTP-GTE against cognitive decline.

Many studies have focused on EGCG as an active component of green tea, and indeed, EGCG administration has shown positive effects against Aβ accumulation [ 11 — 13 ] and long-term memory decline [ 14 , 15 ].

In this study, we performed behavioral tests to confirm the effects of 10 weeks of HTP-GTE consumption on cognitive decline. Notably, HTP-GTE appeared to efficiently affect spatial learning as well as short-term and long-term memory decline without any change in locomotor activity Figure S2.

GCG and its metabolites in HTP-GTE can be delivered to the brain by oral intake of the extract Table S1 [ 17 ], and the concentration of GCG in the blood remains high for an extended period Figure S3. These results indicate that HTP-GTE could act as a useful natural functional agent for the prevention of degenerative cognitive decline.

In conclusion, HTP-GTE appears to positively prevent cognitive decline in AD model mice by inhibiting Aβ aggregation and accumulation and preventing it from permeating into the brain. Dietary consumption of this GTE may help to prevent age-related cognitive decline.

We thank Mr. Yusuke Ozawa and Mr. Toshihiko Toda for the preparation of the experimental mice. We also thank Dr. Cheayeon Song and Dr. Hyungsu Kim for helpful advice on TEM imaging and in vitro Aβ aggregation assays.

performed all biochemical assays and wrote the manuscript. and N. performed the behavior test. designed the study, wrote the manuscript, edited the article, and coordinated and directed the project.

All relevant data are within the paper and its Supporting Information files. supplemental data for this article can be accessed here. Lin CH , Lin E , Lane HY Genetic biomarkers on age-related cognitive decline.

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A combination of green tea extract and l-theanine improves memory and attention in subjects with mild cognitive impairment: a double-blind placebo-controlled study.

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Green tea epigallocatechingallate EGCG modulates amyloid precursor protein cleavage and reduces cerebral amyloidosis in Alzheimer transgenic mice. J Neurosci. Rezai-Zadeh K , Arendash GW , Hou H , et al. Green tea epigallocatechingallate EGCG reduces beta-amyloid mediated cognitive impairment and modulates tau pathology in Alzheimer transgenic mice.

Brain Res. Epigallocatechin gallate reduces amyloid beta-induced neurotoxicity via inhibiting endoplasmic reticulum stress-mediated apoptosis. The idea underpinning fMRI is that increases in blood flow in certain areas of the brain correspond to neural activity.

The researchers found that drinking a soft drink laced with green tea extract appeared to increase blood flow to a part of the brain called the dorsolateral prefrontal cortex DLPFC.

The DLPFC is thought to be involved in cognitive tasks such as long-term memory, reasoning, and comprehension. However, it also showed that this did not affect performance in a working memory task that volunteers performed each time their brains were scanned.

However, reporting that soft drinks containing green tea may cause small changes in blood flow in the brain as was actually measured in the study , but do not seem to help in performing memory tasks, was perhaps seen as less headline-worthy. The study was carried out by researchers from Swiss and German Universities and was funded by the University of Basel and grants from Rivella Ltd, Rothrist, Switzerland.

The study was published in the peer-reviewed European Journal of Clinical Nutrition. Due to the funding coming from a drinks company whose products contain green tea extracts, there is the potential for a conflict of interest that would favour positive findings toward green tea to increase sales.

Much of the reporting into studies involving functional magnetic resonance imaging has fallen into a similar trap. While changes in blood flow may be indicative of certain types of neural activity, they cannot provide definitive proof that this is the case. Similarly, it is often not clear if, or how, these small changes in blood flow are related to actual behaviour or cognitive performance at various tasks.

This was a double blind, placebo controlled laboratory study that scanned the brains of men to examine the neural effects of drinking green tea extract or placebo on their brain activation and while performing a memory task.

The researchers state that green tea is being recognised as a beverage with potential benefits for human health and cognitive functions.

They cite a number of previous human studies, which they say, provide preliminary evidence that green tea intake may have a positive role in improving effects on cognitive functions. The men were first given test drinks, then asked to perform tasks known to use working memory. Their whole brains were scanned, but the researchers also focused in on a specific area of the brain they were interested in, called the dorsolateral prefrontal cortex DLPFC , a key area that mediates working memory processing.

The study used two types of commercially available drink provided by Rivella. Each man received all the drinks Variety C at ml and ml and Variety G at ml and ml sequentially across four separate sessions, but the sequence in which they were given the different drinks was different.

Shortly after being given the drink, the brain activity of the volunteers was scanned using functional magnetic resonance imaging fMRI , while the volunteers performed a working memory task. fMRI measures tiny blood flow changes in the brain that are related to its activity.

The analysis compared the effects of the different drinks variety C vs. G and amounts ml vs. Participants were told to abstain from any substance use for the duration of the study, and from the intake of alcohol, caffeine, green tea products and citrus juices for up to 24 hours before each study day.

Volunteers, who regularly use green tea or green tea products, or took any regular medication including over-the counter drugs, had ever used any illicit psychotropic substances, who consumed four to five units of alcohol daily or 20 units per week, or had any psychiatric, neurological or severe medical illness history were excluded.

The whole brain analysis showed no significant differences in brain activity measured by fMRI or task performance between the men consuming the two different drinks, or different amounts of the drinks. In fact, there was no difference in task performance even when they focused on the DLPFC area of the brain only.

However, there were some statistically significant findings reported for brain activity differences.

Green tea has fr hailed for many funnction benefits, including its effects against cancer, heart covnitive Smooth herbal coffee substitute type Tennis player nutrition diabetes. The research team — cogniitive Prof. Gree Beglinger and Prof. Stefan Borgwardt of the University Hospital of Basel in Switzerland — says their findings suggest that green tea could be promising in the treatment of cognitive impairments associated with neuropsychiatric disorders, such as dementia. Green tea, native to China and India, is produced from the leaves of the Camellia sinensis bush. Unlike other teas, green tea is made from unoxidized leaves. Teaa grams per day of cognifive green tea fxtract for Dairy-free weight control months were associated with Green tea extract for cognitive function improvements in the Mini-Mental State Fro Japanese version score of functioj elderly nursing home Polyphenols and arthritis with cognitive Smooth herbal coffee substitute. Wxtract study adds cogntive an ever-growing body of science supporting the potential benefits Gdeen green tea and its constituents, most notably EGCG epigallocatechin gallate. To date green tea has been linked to a reduced risk of Alzheimer's and certain cancers, improved cardiovascular and oral health, as well as benefits in weight management. Oolong tea is semi-fermented tea and is somewhere between green and black tea. The four primary polyphenols found in fresh tealeaves are epigallocatechin gallate EGCGepigallocatechin EGCepicatechin gallate ECGand epicatechin EC. The Japanese researchers recruited 12 elderly people with an average age of 88 to participate in their pilot study. All participants consumed the two grams per day of the green tea powder manufactured by Ito En Ltd for three months.