JP2020169149A - Brain detox promoter - Google Patents

Abstract

To provide a brain detox promoter that has high safety and can be continuously administered.SOLUTION: A brain detox promoter has caffeoylquinic acid or a salt thereof as an active ingredient.SELECTED DRAWING: None

Description

The present invention relates to a brain detox promoter that excretes waste products from the brain.

Cerebral nervous system cells consume 20-25% of the total energy consumed by the body, and in the process, a large amount of biotransformers, that is, water-soluble substances such as proteins and lactic acid and lipophilic substances such as lipids are excreted as waste products. (Non-Patent Document 1, Non-Patent Document 2).
Peripheral waste removal is done through the lymphatic system, but it was thought that the brain had no lymphatic system. For this reason, it has been thought that the removal of waste products in the brain is processed by the brain cells on their own. However, in recent years, a brain waste removal system called a Glymphatic system has been discovered (Non-Patent Documents 1 and 2). Cerebrospinal fluid (CSF) flows through the periarterial space, which is the cavity surrounding the artery. The outer wall of the periarterial space is made up of astrocyte foot processes, and CSF flows from the periarterial space into the astrocytes through aquaporin 4 (AQP4), which is a water channel expressed in the astrocyte foot process. .. After that, CSF exudes from astrocytes, moves in the brain by convection, collects waste products, enters the perivenous cavity, is excreted outside the brain, and is metabolized (Non-Patent Documents 1 and 2). The transport of CSF by this waste removal system is significantly reduced in mice lacking AQP4 (Non-Patent Document 3), and the expression of AQP4 surrounding the perivascular cavity is reduced in mice in which waste products are accumulated (Non-Patent Document 3). Patent Document 4) has been reported.

It has also been found that the excretion of waste products in the brain is activated during sleep, and the amount of waste products in the brain is higher during sleep than during awakening (Non-Patent Documents 1 and 2). For example, it has been reported that lactic acid in brain tissue (Non-Patent Document 5), which is used as a marker of neural activity, is produced in the tissue and then the surplus is excreted by the waste product excretion system of the brain. It has been reported that the amount of lactic acid (Non-Patent Document 6), especially during sleep, increases and there is diurnal variation as compared with the time of awakening (Non-Patent Document 7).

The excretion of such waste products is important for maintaining the homeostasis of the brain and keeping its function healthy, but it is considered that such excretion function decreases with aging. For example, it has been reported that sleep apnea waste products are reduced in aging and Alzheimer's disease model mice, and as a result, unnecessary waste products are accumulated in the brain (Non-Patent Documents 4 and 6). Therefore, a material that improves and promotes the excretion of waste products in the brain, that is, a brain detox promoter, is useful for improving the deterioration of brain function associated with aging.

On the other hand, chlorogenic acids typified by cafe oil quinic acid have been found in coffee beans and the like in plants, and have so far been effective in suppressing an increase in blood glucose level (Patent Document 1), enhancing sensory stimulation (Patent Document 2), and blood. It has been reported that peripheral waste products are excreted by improving fluidity (Patent Document 3). It has also been reported that di-O-caffeic oil quinic acid, in which two caffeic acids are ester-bonded, has a neuroprotective effect (Patent Document 4).

However, it is not known that caffe oil quinic acid has a brain detoxifying effect.

Japanese Unexamined Patent Publication No. 2003-34636 Japanese Unexamined Patent Publication No. 2006-104071 Japanese Unexamined Patent Publication No. 2004-168949 International Publication No. 2007/0916113

Nedergaard M et al. Nikkei Science 2016.7: 72-77. Jessen NA et al. Neurochem Res. 2015.40: 2583-2599. Iliff JJ et al. Sci Transl Med. 2012.4: 147 ra111. Xu Z et al. Mol Neurodegener. 2015.10: 58. Uehara T et al. Pharmacol Biochem Behav. 2008.90: 273-281 Roh JH et al. Sci Transl Med. 2012.4: 150ra122. Lundgaard I et al. J Cereb Blood Flow Metab. 2017.37: 2112-2124.

The present invention relates to providing a highly safe and continuously ingestible brain detox promoter.

As a result of various studies on highly safe ingredients that can be taken or ingested for a long period of time, the present inventors reduced the amount of lactic acid in the interstitial fluid near the hippocampus during sleep, and the caffe oil quinic acid decreased Since it increases the expression level of AQP4 around the cerebral blood vessels of the hippocampus, it has been found to be useful for promoting the glyptic system, that is, promoting brain detox.

That is, the present invention relates to the following 1) to 6).
1) Café oil A brain detox promoter containing quinic acid or a salt thereof as an active ingredient.
2) Café oil A food for promoting brain detox containing quinic acid or a salt thereof as an active ingredient.
3) Café oil A glyptic system accelerator containing quinic acid or a salt thereof as an active ingredient.
4) Café oil A food for promoting the grintic system containing quinic acid or a salt thereof as an active ingredient.
5) Café oil An AQP4 expression promoter containing quinic acid or a salt thereof as an active ingredient.
6) Café oil A food for promoting AQP4 expression containing quinic acid or a salt thereof as an active ingredient.

According to the present invention, pharmaceuticals and foods that promote brain detoxification and are useful for maintaining or improving brain function are provided.

The figure which shows the change of the amount of lactic acid in the interstitial fluid near the hippocampus by cafe oil quinic acid. The figure which shows the change of the expression level of AQP4 around the cerebral blood vessel of the hippocampus by café oil quinic acid.

The "Cafeoylquinic acid" of the present invention is 3-cafe oil quinic acid (3-CQA), 4-cafe oil quinic acid (4-CQA) and 5-cafe oil quinic acid (5-CQA). It is a general term for, and one or more of these can be used, but it is preferable to contain at least 5-cafe oil quinic acid.

The salt of caffe oil quinicic acid of the present invention includes pharmaceutically acceptable salts such as alkali metal salts such as sodium and potassium, alkaline earth metal salts such as magnesium and calcium, monoethanolamine, diethanolamine and triethanolamine. Examples thereof include organic amine salts such as arginine, lysine, histidine, and basic amino acid salts such as ornithine.

The caffe oil quinic acid of the present invention or a salt thereof can be obtained from an extract of a plant containing the same, a concentrate thereof or a purified product thereof, but not only the isolated caffe oil quinic acid or a salt thereof. , Café oil quinic acid or its salt-rich extract of the plant, its concentrate or its refined product can also be used. The method and conditions for extracting, concentrating, and purifying cafe oil quinic acid or a salt thereof are not particularly limited, and known methods and conditions can be adopted. Of these, extraction with an ascorbic acid aqueous solution, a citric acid aqueous solution or hot water is preferable.

Plant extracts containing caffeine quinic acid or salts thereof include, for example, sunflower seeds, immature apple fruits, coffee beans, simon leaves, Pinaceae bulbs, Pinaceae seed husks, potatoes, citrus fruits, sugar cane, etc. Extracted from wheat, southern leaves, gobo, carrot, cabbage, lettuce, arch choke, tomato, moroheiya, eggplant skin, pear, plum, peach, apricot, cherry, pinaceae fruit, fukitanpopo, vines, etc. Can be mentioned. Among them, coffee bean extract is preferable from the viewpoint of cafe oil quinic acid content, and roasted coffee beans may be used, but lightly roasted coffee beans, slightly roasted coffee beans, and raw coffee beans are preferable. The type of coffee tree may be any of Arabica, Robusta, Coffea liberica and Arabsta.

When coffee bean extract is used as the caffeine oil quinic acid or its salt of the present invention, it is preferable that caffeine is removed, and the mass ratio of caffeine to caffeine oil quinic acid or its salt [caffeine / caffeine oil quinic acid]. Alternatively, the salt thereof (hereinafter, caffeine oil quinic acid equivalent amount)] is preferably 0.1 or less, more preferably 0.06 or less, and further preferably 0.04 or less from the viewpoint of flavor. The lower limit of the ratio of caffeine / caffeine oil quinic acid or a salt thereof is not particularly limited and may be 0.
The coffee bean extract has a mass ratio of the sum of potassium (K) and sodium (Na) to caffe oil quinic acid or a salt thereof [(K + Na) / caffe oil quinic acid or a salt thereof] from the viewpoint of flavor. , 0.4 or less, more preferably 0.3 or less, further 0.2 or less, and particularly preferably 0.1 or less. The lower limit of the mass ratio [(K + Na) / cafe oil quinic acid or a salt thereof] is not particularly limited and may be 0, but from the viewpoint of production efficiency, 0.0002 and further 0.002 are used. preferable.

As shown in Example 1 below, café oil quinic acid has an effect of reducing the amount of lactic acid in the interstitial fluid near the hippocampus during sleep in mice. In the brain, lactic acid is an energy substrate produced by astrocytes in response to neuronal activity and is very important for neuronal activity and function maintenance (Cell Metabo, 14: 724-738, 2011). For this reason, lactic acid in brain tissue is used as a marker of nerve activity (Non-Patent Document 5), and since an energy substrate is required at the time of awakening when the brain (nerve) works, the concentration in brain tissue is high, and the brain interstitial fluid It has been reported that the medium concentration increases (Non-Patent Document 6). On the other hand, it has been reported that lactic acid that is not used and becomes surplus after being produced in brain tissue is excreted by the waste product discharge system of the brain (Non-Patent Document 6), and is particularly awake during sleep. It has been reported that there is a diurnal variation in which the amount of excretion increases and the concentration in the cerebral interstitial fluid decreases as compared with the occasion (Non-Patent Document 7). Therefore, measuring the amount of lactic acid in the interstitial fluid of the brain and observing the diurnal variation is also an index for judging whether the cerebral waste product discharge is normal, and in mice with decreased cerebral waste product discharge function, It has been reported that the amount of lactic acid in the interstitial fluid of the brain during sleep is increased, and as a result, unnecessary waste products are accumulated in the brain (Non-Patent Document 6).

Further, as shown in Example 2 below, caffe oil quinic acid has an action of increasing the expression level of AQP4 around the cerebral blood vessels of the hippocampus in mice. AQP4 is expressed in the astrocyte foot process that constitutes the outer wall of the perivascular space, and is very important for the transport of CSF by the waste removal system (glymptic system) (Non-Patent Documents 1, 2, and 3). ). In the above-mentioned Non-Patent Document 4, it is reported that the expression of AQP4 surrounding the blood vessel is decreased in the mouse in which the waste product is accumulated. Is it possible to normally discharge the waste product in the brain by observing the expression of AQP4 around the cerebral blood vessel? That is, it is an index for judging whether the glymphatic system functions normally.

Therefore, caffe oil quinic acid or a salt thereof, which has an action of lowering the amount of lactic acid in the interstitial fluid of the brain during sleep and an action of increasing the expression of AQP4 around the cerebral blood vessels, is a brain detox promoter, a glyptic system promoter, It can be an AQP4 expression promoter (hereinafter referred to as "brain detox promoter, etc."), can be used to promote brain detox, promote the glyptic system, promote AQP4 expression, and can be used in the brain. It can be used to produce detox accelerators and the like.
Here, "use" can be administration or ingestion to a human or non-human animal, and may be therapeutic or non-therapeutic use. In addition, "non-therapeutic" is a concept that does not include medical practice, that is, a concept that does not include a method of surgery, treatment, or diagnosis of a human being, more specifically, a doctor or a person who has been instructed by a doctor to treat a human being. It is a concept that does not include a method of performing surgery, treatment or diagnosis.

In the present invention, "promoting brain detoxification" means promoting the excretion of various biotransforms and waste products (for example, proteins, lipids, lactic acid, etc.) accumulated in the brain from the brain and suppressing the accumulation in the brain. Means.

In addition, "promotion of the grintic system" means promoting the grintic system, which is a mechanism for discharging waste products from the brain through the perivascular space, and suppressing the accumulation of waste products in the brain.

Further, "promotion of AQP4 expression" includes inducing or promoting transcription of the AQP4 gene into AQP4 mRNA and inducing or promoting translation of AQP4 mRNA into AQP4 protein, preferably expressing around the cerebrovascular. To promote. Here, AQP4 is one of the aquaporin (AQP) families with extremely high water selectivity, and is considered to be a major AQP involved in the transport of water in the brain.

Further, in the present invention, the "brain function" particularly refers to a higher brain function, and specifically, various functions performed in the brain such as language, action, perception, cognition, memory, attention, judgment, and emotion. means.
In addition, "improvement" means improvement of disease, symptom or condition, prevention or delay of deterioration of disease, symptom or condition, or reversal, prevention or delay of progression of disease or symptom.

The brain detox promoter and the like of the present invention may itself be a drug, a quasi drug, a supplement or a food for promoting brain detox, or may be added to the drug, a quasi drug, or a food. It may be a material or preparation used in the above.
The foods are based on the concept of promoting brain detox, promoting the grintic system, or promoting the expression of aquaporin 4, and if necessary, foods labeled to that effect, foods with functional claims, foods for the sick, foods for specified health use, and supplements. Is included. Since these foods are foods for which functional labeling is permitted, they can be distinguished from general foods.

Examples of the administration form of the above-mentioned pharmaceutical products (including non-pharmaceutical products) include oral administration with tablets, capsules, granules, powders, syrups, etc., or parenteral administration with injections, suppositories, inhalants, etc. Be done. In addition, preparations of such various dosage forms are prepared by using the quinic acid of the present invention or a salt thereof alone or by other pharmaceutically acceptable excipients, binders, bulking agents, disintegrants, surfactants. An activator, a lubricant, a dispersant, a buffer, a preservative, a flavoring agent, a fragrance, a coating agent, a carrier, a diluent, a medicinal ingredient other than 5-cafe oil quinic acid of the present invention or a salt thereof, etc. are appropriately combined. Can be prepared. Of these dosage forms, the preferred form is oral administration.

The forms of the above foods include soft drinks, tea-based beverages, coffee beverages, fruit juice beverages, carbonated beverages, jelly, wafers, biscuits, bread, noodles, sausages and other foods and drinks, nutritional foods, and other foods. Examples of the nutritional supplement composition in the same form (tablets, capsules, syrup, etc.) as the above-mentioned orally administered preparation.

Various forms of foods are prepared by using the cafe oil quinicic acid of the present invention or a salt thereof alone, or by other food materials, solvents, softeners, oils, emulsifiers, preservatives, acidulants, sweeteners, bitterness agents, aromas. It can be prepared by appropriately combining active ingredients other than family, stabilizers, colorants, antioxidants, moisturizers, thickeners, caffe oil quinicic acid or salts thereof.
The content of the cafe oil quinic acid of the present invention or a salt thereof in the above-mentioned pharmaceutical products (including quasi-drugs) and foods can be appropriately determined depending on the mode of use thereof.
For example, in the case of foods or orally administered preparations and solids such as tablets, granules, pills, powders and gummy agents, 0.01% by mass or more is preferable, and 0.1% by mass or more in terms of the amount of caffe oil quinic acid. Is more preferable, and 1% by mass or more is further preferable. Further, 90% by mass or less is preferable. In the case of foods or orally administered preparations and liquids such as liquids, syrups, suspensions, emulsions, elixirs and jellies, 0.001% by mass or more is preferable in terms of the amount of caffe oil quinic acid, and 0.003% by mass. % Or more is more preferable, and 0.01% by mass or more is further preferable. Further, it is preferably less than 90% by mass, more preferably 10% by mass or less, and further preferably 1% by mass or less. Further, it is preferably 0.001 to 90% by mass, more preferably 0.003 to 10% by mass, and further preferably 0.01 to 1% by mass.

The dose or intake of the above-mentioned drugs (including quasi-drugs) and foods can be determined as appropriate, but usually, for an adult (60 kg), the amount equivalent to caffeoylquinic acid is preferably 30 mg per day. As mentioned above, it is more preferably 100 mg or more, preferably 1000 mg or less, and more preferably 300 mg or less. In the present invention, it is preferable to administer or ingest such an amount at a time.

The above-mentioned preparation is administered or ingested according to an arbitrary plan, and the administration or ingestion period is not particularly limited, but it is preferable to administer or ingest repeatedly and continuously, and it is more preferable to administer or ingest continuously for 7 days or more. , It is more preferable to administer or ingest continuously for 28 days or more.

The administration or ingestion target is not particularly limited as long as it is a human or non-human animal that requires or desires prevention or improvement of brain dysfunction, promotion of brain detoxification, or promotion of glymphatic system, but administration or ingestion in humans is It is valid.

Regarding the above-described embodiment, the following aspects are disclosed in the present invention.
<1> Café oil A brain detox promoter containing quinic acid or a salt thereof as an active ingredient.
<2> Café oil A food for promoting brain detox containing quinic acid or a salt thereof as an active ingredient.
<3> Café oil A glyptic system accelerator containing quinic acid or a salt thereof as an active ingredient.
<4> Food for promoting glyptic system containing caffe oil quinic acid or a salt thereof as an active ingredient <5> AQP4 expression promoter containing caffe oil quinic acid or a salt thereof as an active ingredient.
<6> Café oil A food for promoting AQP4 expression containing quinic acid or a salt thereof as an active ingredient.

<7> Use of caffe oil quinic acid or a salt thereof for producing a brain detox accelerator.
<8> Use of cafe oil quinic acid or a salt thereof for producing foods for promoting brain detoxification.
<9> Use of caffe oil quinic acid or a salt thereof for producing a grintic system accelerator.
<10> Use of cafe oil quinic acid or a salt thereof for producing foods for promoting the grintic system.
<11> Use of cafe oil quinic acid or a salt thereof for producing an AQP4 expression promoter.
<12> Use of cafe oil quinic acid or a salt thereof for producing a food for promoting AQP4 expression.

<13> Café oil quinic acid or a salt thereof for use in promoting brain detoxification.
<14> Non-therapeutic use of caffe oil quinic acid or a salt thereof to promote brain detoxification.
<15> Café oil quinic acid or a salt thereof for use in promoting the glyptic system.
<16> Non-therapeutic use of caffe oil quinic acid or a salt thereof to promote the glyptic system.
<17> Café oil quinic acid or a salt thereof for use in promoting AQP4 expression.
<18> Non-therapeutic use of caffe oil quinic acid or a salt thereof to promote AQP4 expression.

<19> A method for promoting brain detoxification, in which cafe oil quinic acid or a salt thereof is administered or ingested in an effective amount to a subject who needs them.
<20> A method for promoting a glyptic system in which cafe oil quinic acid or a salt thereof is administered or ingested in an effective amount to a subject who needs them.
<21> A method for promoting the expression of aquaporin 4 in which cafe oil quinic acid or a salt thereof is administered or ingested in an effective amount to a subject who needs them.

<22><1>,<3>,<5>,<7>,<9> or <11> agent, <2>, <4>, <6>, <8>, <10> or < The content of the active ingredient in the food of 12> is 0.01 in terms of the amount of caffe oil quinicic acid in the case of foods or orally administered preparations and solids such as tablets, granules, pills, powders and gummy agents. By mass or more is preferable, 0.1% by mass or more is more preferable, and 1% by mass or more is further preferable. Further, 90% by mass or less is preferable. In the case of foods or orally administered preparations and liquids such as liquids, syrups, suspensions, emulsions, elixirs and jellies, 0.001% by mass or more is preferable in terms of the amount of caffe oil quinic acid, and 0.003% by mass. % Or more is more preferable, and 0.01% by mass or more is further preferable. Further, it is preferably less than 90% by mass, more preferably 10% by mass or less, and further preferably 1% by mass or less. Further, it is preferably 0.001 to 90% by mass, more preferably 0.003 to 10% by mass, and further preferably 0.01 to 1% by mass.
In <23><13> to <21>, the daily dose per adult is preferably 30 mg or more, more preferably 100 mg or more, and preferably 1000 mg or less, as caffe oil quinic acid. It is preferably 300 mg or less.

Example 1 Brain detox promoting action of cafe oil quinic acid (5-CQA) (1) Production example Preparation of animal feed Table 1 shows the feed composition in the test diet (powder feed) used in this test. The normal diet was prepared by replacing 61.5% potato starch, and the 5-CQA diet was prepared by replacing the amount of 5-CQA-equivalent potato starch to be mixed with 5-CQA (Cayman Chemical). The other components (casein, cellulose, minerals, vitamins) were the same amount in the normal diet and the 5-CQA diet. The corn oil, lard, casein, cellulose, AIN76 mineral mixture, AIN76 vitamin mixture, and potato starch used in the test meal were manufactured by Oriental Yeast Co., Ltd.

(2) Animals and breeding methods For the production of APP / PS2 double transgenic mice (APP / PS2WTg), which are Alzheimer's disease model mice, B6; SJL-background human amyloid precursor protein (APP) K670N and M671L APP-Tg mice (Taconic Biosciences) having a mutation (Sweden type mutation) throughout the body and PS2-Tg mice (Oriental yeast) having a N141 mutation of human presenin 2 (PS2) in the background of C57BL / 6J mice. used. Sperm collected from male APP-Tg mice (10 weeks or older) and oocytes of female PS2-Tg mice (4 weeks or older) were subjected to in vitro fertilization to produce APP / PS2WTg mice. A 10-week-old male APP / PS2WTg was used in the test, a 5-CQA diet containing 0.8% by mass of 5-CQA prepared in the production example was used in the experimental group, and a standard diet was used in the control group for 4 months. Ingested (each n = 4-5).

(3) Measurement of the amount of lactic acid in the interstitial fluid near the hippocampus The test was performed 4 months after ingesting the test meal. Guide cannula for microdialysis (Acom Co., Ltd.) on the hippocampus (A: -3.1, L: +2.5, V: -1.3 mm) using a brain localization device under isoflurane (Abbott Japan) anesthesia. Was inserted. After a recovery period of 4 days or more after surgery, a probe for microdialysis (PEP-4-3, semipermeable membrane 3 mm, Acom Co., Ltd.) was attached, and 0.15% Bovine serum Albumin (Sigma-Aldrich) was attached. ) Was added to the artificial cerebrospinal fluid (NaCl: 145 mM, KCl: 12.7 mM, CaCl ₂ : 1.2 mM, MgCl ₂ : 1.0 mM) at 10 μl / min, and the perfusion rate was adjusted 3 hours after the start of perfusion. The volume was changed to 1 μl / min, and bovine interstitial fluid was sampled at 1-hour intervals. The sample from 20:00 to 1:00 was defined as awakening, and the sample from 8:00 to 13:00 was defined as sleeping. Lactic acid in the hippocampal interstitial fluid was measured using a Lactate Colorometric / Fluorometric Assay kit (Bio Vision).

(4) Statistical analysis The analysis results are shown as mean value (Ave.) ± standard error (SE). Unpaired Student's t-test was used to compare the mean values of the control group and the 5-CQA group, and it was judged that there was a statistically significant difference when the P value was 0.05 or less.

(5) Results There was no change in the lactate level during awakening between the control group and the 5-CQA group. On the other hand, the lactate level during sleep was significantly lower in the 5-CQA group than in the control group, and it was clarified that 5-CQA promoted the brain detox function during sleep (Fig. 1). ).

Example 2 AQP4 expression increasing action around the cerebrovascular of caffeine oil quinic acid (5-CQA) (1) Measurement of AQP4 expression level around the cerebrovascular of the hippocampus The same animals as in Example 1 were used. 4 months after ingestion of the test meal, under deep anesthesia of isoflurane (Abbott Japan), PBS containing heparin (5 U / mL) and 4% paraformaldehyde phosphate buffer (PFA) under ice cooling at a rate of about 3 mL / min. A total of 15 mL was perfused. After perfusion, the entire brain was removed, immersed in 4% PFA, refrigerated and fixed. A paraffin block was prepared using a fixed brain. After preparing the paraffin block, a paraffin section having a thickness of 3 μm was prepared for the dorsal hippocampal region. Brain sections were deparaffinized and washed with alcohol, running water and TBS. Then, it was activated by Proteinase K and washed with TBS. Next, the mixture was immersed in a solution prepared by adding 1% hydrogen peroxide solution to methanol, and then washed with TBS. Blocking was performed with skim milk, and a primary antibody reaction was performed using an anti-AQP4 antibody (1: 500, Millipore). After the reaction, the cells were washed with TBS and a secondary antibody reaction was carried out using a biotin-labeled secondary antibody. After the reaction, the cells were washed with TBS and the sensitivity was amplified by the ABC method. After the reaction, it was washed with TBS and a color reaction was carried out with DAB. After nuclear staining with hematoxylin, the cells were washed with running water, dehydrated, permeated, and sealed to prepare slide samples. Observation was performed using an all-in-one microscope (BZX-710, KEYENCE), and the staining content area in the hippocampal region and the staining content area around the blood vessel were calculated using the attached analysis software (BZ-II application), and AQP4 expression around the blood vessel was expressed. The quantity ratio was calculated. The average stained area value of 6 sections per individual was taken as the value of that individual.

(2) Statistical analysis The analysis results are shown as mean value (Ave.) ± standard error (SE). Unpaired Student's t-test was used to compare the mean values of the control group and the 5-CQA group, and it was judged that there was a statistically significant difference when the P value was 0.05 or less.

(3) Results From the observation image (Fig. 2), it can be seen that the AQP4 expression around the cerebral blood vessels of the hippocampus is clearly increased in the 5-CQA group as compared with the control group, and it is significant from the calculation of the AQP4 expression rate. A significant increase was observed (Fig. 2).

Claims (6)

Café oil A brain detox promoter containing quinic acid or a salt thereof as an active ingredient. Café oil A food for promoting brain detox containing quinic acid or a salt thereof as an active ingredient. Café oil A glyptic system accelerator containing quinic acid or a salt thereof as an active ingredient. Café oil A food for promoting the grintic system containing quinic acid or a salt thereof as an active ingredient. Café oil An aquaporin 4 expression promoter containing quinic acid or a salt thereof as an active ingredient. Café oil A food for promoting the expression of aquaporin 4 containing quinic acid or a salt thereof as an active ingredient.