JP2013060380A - Composition for improving brain function, having black vinegar-derived ingredient as active ingredient - Google Patents

Abstract

PROBLEM TO BE SOLVED: To ascertain whether or not an ingredient derived from black vinegar has a brain function improving action, and to provide a composition for improving a brain function, having the black vinegar-derived ingredient as an active ingredient.SOLUTION: The invention provides the composition for improving a brain function, having the black vinegar-derived ingredient as an active ingredient. More specifically, the composition for improving a brain function having an ingredient specific to black vinegar which eliminates acetic acid from the black vinegar or unrefined black vinegar powder is provided.

Description

  The present invention relates to a composition for improving brain function comprising a black vinegar-derived component as an active ingredient. More specifically, the present invention relates to a composition for improving brain function comprising a black vinegar-specific component obtained by removing acetic acid from black vinegar or black vinegar moromi powder as an active ingredient.

The estimated number of people with dementia in 2010 is said to be 2 million. Although research on iPS cells has progressed and therapeutic methods using regenerative medicine are expected, the path to clinical application to humans is unclear because of the risk of canceration. Therefore, primary prevention of dementia onset or secondary prevention that slows its progression after onset is important.
Here, it has been pointed out that the brain that has developed dementia is in a higher oxidation state than the normal brain. Resveratrol contained in grape skin has been reported to have an antioxidant effect and improve cognitive impairment (Non-patent Document 1). This report suggests that resveratrol's cognitive function-improving action is not only an anti-oxidative action, but also a cognitive function-improving action through induction of insulin-like growth factor-1 (IGF-1) expression.
On the other hand, black vinegar is also known to have a high antioxidant effect. Black vinegar is a rice black vinegar that originated in Fukuyama Town, Kagoshima Prefecture, and is regulated by the JAS Law. Put steamed rice, rice bran, and water in a potter's pot, until saccharification, alcoholic fermentation, and acetic acid fermentation. It is a vinegar with a unique deep taste that is obtained by proceeding with one jar and further aging. In addition, black vinegar mash powder is produced as a by-product during the fermentation process of black vinegar. This black vinegar mash powder is a water-insoluble substance and contains dietary fiber, β-glucan and peptides. It is also attracting attention as a material.
Black vinegar has been used exclusively as a seasoning in the past, but in recent years it has become clear that black vinegar has the effect of lowering blood pressure and smoothing blood, and there is evidence such as lipid metabolism improving action and blood sugar lowering action. It has been clarified that it has various biological function regulation functions. However, there has been no report so far on whether black vinegar or black vinegar-derived components such as black vinegar improves the brain function.
Here, there is a technology that a substance derived from acetic acid, which is the main component of black vinegar, has a certain brain function improving action (for example, Patent Document 1). This document describes a composition for improving brain function containing N-acyl sphinganine derived from acetic acid as an active ingredient.
As described above, although there are reports on components derived from acetic acid, the specific components of black vinegar other than acetic acid or the brain function-improving action of black vinegar mash is completely unknown.

JP 2007-70342 A

Harada N, Zhao J, Kurihara H, Nakagata N, Okajima K. Resveratrol im proves cognitive function in mice by increasing production of insulin-like growth fa ctor-I in the hippocampus.J Nutr Biochem. 2011 in press.

  An object of the present invention is to provide a composition for improving brain function, which is an ingredient derived from black vinegar, which has been confirmed to be safe as food, and contains an ingredient specific to black vinegar as an active ingredient.

The inventors of the present invention evaluated whether a component derived from black vinegar has an effect of improving brain function by using an aging accelerated mouse (SAM P8) in a water maze test. Surprisingly, acetic acid was removed from black vinegar. It was found for the first time that the ingredients and black vinegar moromi powder have a cognitive function lowering inhibitory effect, and the present invention has been completed.
That is, the present invention has the following configuration.
(1) A composition for improving brain function comprising a black vinegar-derived component as an active ingredient.
(2) The composition for improving brain function according to (1), wherein the black vinegar-based component is a component obtained by removing acetic acid from black vinegar or black vinegar mash.
(3) The composition for improving brain function according to (1) or (2), wherein the improvement of brain function is improvement of Alzheimer's disease.
(4) A food or drink containing the composition for improving brain function according to any one of (1) to (3) (excluding black vinegar and black vinegar mash).

  With the composition for improving brain function comprising the black vinegar-derived component of the present invention as an active ingredient, the onset of dementia can be prevented and the progression after the onset can be delayed.

2 is a diagram showing an animal experiment schedule in Example 1. FIG. It is a figure which shows the schematic diagram of the pool used for the Morris water maze test of Example 1 and 2. FIG. The pool was set up at the corner of the room. Two screens were set up behind the experimenter to prevent the outside from entering the field of view. The platform is made of transparent acrylic resin and cannot be recognized from the surface of the water when thrown under the surface of the water. The figure on the left is from above and the figure on the right is from the side. The dotted line shown in the left figure is shown for easy understanding of the area, and there is actually no mark on the bottom of the pool. FIG. 3 is a diagram showing an animal experiment schedule of Example 2. It is a figure which shows a probe test result (Example 1). The left figure shows the staying time of each feeding group, and the right figure shows the number of passages. (Average value + SD (n = 5), indicating that there is a significant difference between different characters (p <0.05)) (Example 2) which is a figure which shows the evacuation time measurement result to the platform used as a goal after releasing a mouse | mouth on the water surface in a water maze training period (15 days). (R1 only n = 16, other n = 9. Characters that differ between groups on each day are significantly different (p <0.05).) It is a figure which shows a probe test result (Example 2). The left figure shows the staying time of each feeding group, and the right figure shows the number of passages. (Average value + SD (n = 5). Shows that there is a significant difference between different characters. Residence time: p <0.01, Number of passes: P8-Moromi p <0.05; P8-R1, P8-Black vinegar P <0.01)

As described above, the black vinegar used in the present invention is rice black vinegar defined by the JAS method. In the present invention, any black vinegar as defined above may be used. It is a vinegar with a unique deep taste obtained by adding steamed rice, rice bran, water to a porcelain bowl, saccharification, alcoholic fermentation, and acetic acid fermentation in one bowl and further aging .
The black vinegar moromi powder used in the present invention is a by-product produced when black vinegar is made using koji. The water-soluble fraction becomes black vinegar, and the water-insoluble fraction is squeezed, dried and powdered, resulting in black vinegar mash. It contains dietary fiber, β-glucan and peptide as its components.
The black vinegar-derived component of the present invention may be any component as long as it is derived from black vinegar and exhibits the effects of the present invention. In addition to black vinegar itself, a component obtained by removing the acetic acid component from black vinegar, black vinegar Moromi powder is mentioned.
In addition, in the test to be described later, each test was performed on the component obtained by removing acetic acid from black vinegar in order to clarify the difference from the action by the acetic acid component that is the main component of black vinegar. As a result, it was found that the component obtained by removing acetic acid from black vinegar, and that mash mash of black vinegar has a brain function improving effect, so the brain function improving effect is a component other than acetic acid among the components derived from black vinegar. It can be said that.

  The brain function improving action referred to in the present invention means an action for preventing / suppressing a decrease in brain function, and includes those caused by aging in addition to those caused by dementia.

The composition for improving brain function of the present invention may be black vinegar itself, the remaining component itself obtained by removing the acetic acid component from black vinegar, or the black vinegar mash powder itself, which affects the action of the present invention. It may be a mixture with other components that do not give any.
Further, the form may be a liquid or a dried solid. The solid may be a solid or a powder. In the case of solids, it is dissolved or dispersed in a suitable liquid, or mixed with a suitable powder carrier or adsorbed thereto, and in some cases, further emulsifiers, dispersants, suspending agents, spreading Additives, penetrants, wetting agents, stabilizers and the like can be used as preparations such as emulsions, oils, wettable powders, powders, tablets, capsules, and liquids. When used as a preparation, the amount of the extract to be used varies depending on the form of the preparation, and there is no problem with safety, so there is no particular upper limit.

  Examples of the administration target of the composition for improving brain function of the present invention include humans and animals other than humans. Examples of animals other than humans include dogs, pets including cats, mice, small animals such as rabbits, elephants, and giraffes. Any large animal can be targeted.

The method for administering the composition for improving brain function of the present invention to humans or animals other than humans for improving brain function is preferably oral administration, and may be formulated, or may be ingested as food, drink or feed. Is possible.
For oral administration, the amount of ingestion may be any amount that can improve brain function. For example, as black vinegar moromi powder, 5 to 100 mg / kg body weight per day, 8.3-83 mg / kg body weight is preferred (as a double concentrate).

  Examples of foods and beverages include chewing gum, candy, tablet confectionery, gummy jelly, chocolate, biscuits or snacks, frozen confectionery such as ice cream, sherbet or ice confectionery, beverages, pudding, jam, dairy products, seasonings, etc. A brain function improving effect is obtained by daily intake of these foods and drinks to which the inventive composition is added. Content of this invention composition in food / beverage should just be contained in the range which does not impair the taste, flavor, etc. as a favorite product of the said food / beverage, and changes with kinds and forms of food / beverage products, respectively. Moreover, it can administer by mixing with the feed normally given as a feed. As a result of investigating the drug interaction, the black vinegar of the present invention was found to have no effect on the expression of genes and proteins related to drug metabolism, so there are side effects even when other drugs are used in combination. And can be taken safely.

[Test Example 1] Production of feed (1) Preparation of black vinegar and black vinegar moromi powder (i) Black vinegar moromi powder Black vinegar moromi powder is a squeezing machine for fermented residue of black rice vinegar (black vinegar moromi) After squeezing with squeezed and separated into squeezed liquid and squeezed squeezed pear, the squeezed sachet was dried at 110 ° C. for 6.5 hours in a vacuum dryer and further sterilized at 148 ° C., 0.2 MPa for 4 to 5 seconds.
(Ii) Black vinegar 10 times concentrate (black vinegar extract)
1000 ml of black vinegar (Sakamoto Brewing Co., Ltd., Sakamoto Kurozu (product name)) is freeze-dried and powdered. Distilled water is added to this and freeze-dried again. This process is repeated 4 times to completely remove acetic acid from black vinegar. A solution obtained by dissolving the obtained powder in 100 ml of distilled water is used as a black vinegar 10-fold concentrated solution.
(2) Preparation of feed (i) CE2 meal As a basic feed, CREA Rodent Diet CE-2 manufactured by CLEA Japan (see CLEA Japan http://www.clea-japan.com/Feed/ce2.html) is CE2. It was food. The feed was pelletized by steaming, dried at 100 ° C., and sterilized by radiation (30 kGy).
Thereafter, the same processing was performed in (ii) and (iii). The nutritional components and calories of CE-2 (content in 100g of feed) are shown below.

Moisture (%) 9.3
Crude protein (%) 25.1
Crude fat (%) 4.8
Crude fiber (%) 4.2
Crude ash (%) 6.7
NFE (%) 50.0
Energy (kcal) 343.1
Hardness (kg / cm ² ) 27.1

(Ii) Black vinegar extract-added CE2 meal A black vinegar extract-added CE2 meal was obtained by adding 0.25% of black vinegar 10-fold concentrated solution to the basic feed CE2 meal 99.75%.
(Iii) Moromi-added CE2 meal The mash-added CE2 meal was obtained by adding 0.5% black vinegar moromi powder to 99.5% of the CE2 meal as the basic feed.

[Example 1] Effect of rice black vinegar moromi powder on cognitive function of SAM P8 mice Test method (1) Animal breeding
Five-week-old male aging-promoting mice SAM P8 (10 mice) and aging-resistant mice SAM R1 (5 mice) of the same strain as SAMP8 were purchased from Japan SLC. A preliminary water maze test was conducted for 5 days after grouping for one week. It was divided into two groups (5 each) so that individuals with abnormal swimming were not concentrated. Group 1 (R1 group) received CE2 meals, Group 2 (P8 group) received CE2 meals, and Group 3 (P8 moromi group) received 0.5% (w / w) moromi powder added CE2 meals. Production of CE2 meal and moromi powder added CE2 meal was entrusted to CLEA Japan.
14 weeks after the start of feeding (21 weeks of age), a 10-day water maze test was started, and a probe test was conducted on the 11th day. Each experimental meal was also given during the water maze test. The schedule is shown in FIG.
At 24 weeks of age, whole blood was collected by cardiac blood sampling under ether anesthesia and euthanized. After blood collection, the brain, liver, kidney, lung, descending aorta, testicle, spleen, heart, kidney peripheral fat and testicular fat were removed and weighed and then frozen in liquid nitrogen. Plasma was separated from the collected blood. Plasma lipid peroxide (TBARS) measurement (Wako Pure Chemical Industries) was performed by 3 animals in each group with sufficient blood collection. Tissue homogenates were prepared from brain, liver and kidney, and TBARS concentration and protein concentration were measured. Animals were raised in an environment with an air temperature of 20 ° C and 12 hours of light irradiation (8: 00-20: 00, incandescent fluorescent lamp).
This experiment was approved by the Animal Experiment Committee of Kagoshima University (A10029), then the Act on the Protection and Control of Animals (Animal Protection Act) (promulgated on June 22, 2005, June 1, 2006) (The same applies to Example 2).

(2) Morris water maze test A schematic of the pool used in this test is shown in FIG. The diameter of the circular pool was 1.2m, and it was installed at the corner of the room and covered the four sides of the pool with a screen. The goal platform was submerged in the upper right area, which was divided into 4 pools, so that it could not be recognized from the water surface. A cardboard as a landmark was placed beside the lower left pool on the opposite side of the platform, and the experimenter sat in the lower right of the pool. The water temperature was warmed to 25 ° C. Mice were placed in an area where the platform was not submerged, and the time to reach the platform was measured. The arrival time from the upper left, lower left, and lower right to the goal was measured three times a day.
In this study, the water maze test was started 14 weeks after the start of feeding (21 weeks of age). The training period was 10 days, and the probe test was conducted on the 11th day. That is, when the mouse was allowed to swim for 70 seconds under the condition where the platform was removed, the number of passes through the place where the platform was submerged and the staying time in the area were quantified to determine the cognitive ability.

(3) Statistical analysis SPSS version 17 software was used for statistical analysis. Multiple comparison was performed by Dunnett's method.

2. Test results (1) Body weight and tissue weight after ingestion of moromi powder Table 1 shows changes in body weight from the start of the experiment to the time of sacrifice. Compared to the R1 group, the P8 group had lower weight gain and feeding efficiency. The P8 Moromi group had more food intake than the P8 group, and the body weight gain and feeding efficiency were similar to those of the R1 group. Table 2 shows the organ weight (mg) per gram body weight at the time of sacrifice. Since the body weight is light in the P8 group, each tissue weight value is large.

(2) Lipid peroxide concentration In the examination of the oxidation state in serum and tissues, malondialdehyde (MDA) that reacts with thiobarbituric acid produced by lipid peroxidation was used as an index (Table 3). There was no significant difference in TBARS levels in plasma, liver and kidney, but the brain tended to be higher in the P8 mash group.

(3) Water maze test (3-1) During the training period of 10 days, there was no difference in the time to reach the goal between the groups.
(3-2) Probe test
The results of the probe test performed on the 11th day are shown in FIG. The graph on the left shows the time spent in the area where the platform was installed (stay time), and the diagram on the right shows the number of passes (number of passes) that passed over the platform.
The P8 moromi group had the same residence time and number of passages as the R1 group. Compared with the P8 group, the residence time and the number of passages increased significantly in the P8 Moromi group. There was no significant difference in swimming speed between groups.

[Example 2] Effect of moromi powder and black vinegar extract on cognitive impairment in aging-promoted mice Test method (1) Animal breeding
Ten-week-old male aging-promoting mice SAM P8 (27 mice) and aging-resistant mice SAM R1 (16 mice) were purchased from Japan SLC. A preliminary water maze test was conducted for 5 days after grouping for one week. It was divided into three groups so that individuals with abnormal swimming were not concentrated. R1CE2 group is SAM R1 (n = 16) with CE2 diet, P8 CE2 group is SAM P8 (n = 9) with CE2 diet, P8 Moromi group is SAM P8 (n = 9) with 0.5% (w / w) The moromi-added CE2 diet, the P8 black vinegar group gave SAM P8 (n = 9) a 0.25% (w / w) black vinegar extract-added CE2 diet. A water maze test was conducted after 23 days free drinking and drinking. The training period was 15 days, and the probe test was conducted on the 16th day. Each experimental meal was also given during the water maze test. The schedule is shown in FIG.
After the experiment was completed, whole blood was collected by cardiac blood sampling and euthanized. After blood collection, brain, liver, kidney, lung, testis, spleen, heart, kidney peripheral fat and testicular fat were removed and weighed and then frozen in liquid nitrogen. Plasma and serum were separated from the collected blood. Plasma was used for lipid peroxide (TBARS) measurement (Wako Pure Chemical Industries). A frozen brain tissue homogenate was prepared and lipid peroxide (TBARS) in the tissue was measured. Animals were raised in an environment with an air temperature of 20 ° C. and 12 hours of light irradiation (8: 00-20: 00, incandescent fluorescent light).

(3) Morris water maze test The Morris water maze test was conducted in the same manner as in Example 1 except that the training period was 15 days.

(4) Statistical analysis It carried out similarly to Example 1.

2. Test Results (1) Body Weight and Tissue Weight Table 11 shows that the body weight of the SAM P8 mice was significantly lighter than that of the 11-week-old SAM R1 mice and SAM P8 mice whose body weights were shown at the start of the experiment and at the time of sacrifice. The body weight of 17 wk at the time of slaughter was also significantly different from 11 wk, but no significant difference was found among the P8 group, the P8 moromi group, and the P8 black vinegar group. There was no significant difference in weight gain, but the P8 Moromi group was higher than the other groups.
Table 5 shows the organ weight (mg) per gram body weight at the time of sacrifice. Since the body weight of the P8 mouse is lighter than that of the R1 mouse, the organ weight per body weight of each tissue is larger in each group of the P8 mouse than the R1 mouse. However, the testicular and peripheral kidney fat weight values are smaller in P8 mice than in R1 mice.

(2) Lipid peroxide concentration Plasma and brain lipid peroxide concentrations at the end of the experiment are shown in Table 6. In plasma, the P8 mice showed significantly higher values than the R1 mice, while the P8 black vinegar group and the moromi group showed significantly lower values than the P8 mice. In the brain, P8 mice showed significantly higher values than R1 mice, and P8 black vinegar showed significantly lower values than P8 mice.

(3) Water maze test (3-1) During a 15-day training period, the evacuation time from the release of the mouse to the surface of the water until reaching the goal platform was measured. Each mouse was tested 3 times, and the average value within the group was graphed and shown in FIG. Compared to the P8 group, the P8 Moromi group and the P8 black vinegar group tended to have a faster goal arrival time, and there were cases where a significant difference was observed after 12 days of training. There was no significant difference between the P8 group and the R1 group, but an early trend was observed in the R1 group.
(3-2) Probe test
The results of the probe test performed on the 16th day are shown in FIG. Residence time was significantly increased in the P8 black vinegar group compared to P8 mice. Regarding the number of passages, the P8 moromi group and the P8 black vinegar group significantly increased compared to the P8 mice.

[Discussion]
In Example 1, a decrease in cognitive function was observed in the senescence-accelerated mouse (SAM P8). In Example 2, the feeding period was extended, and the reproducibility of the effect of moromi powder and the cognitive ability of the black vinegar-added food were examined using mice that were aged older. An inhibitory effect on the decrease was observed. From the above, it has been clarified that the ingredients derived from koji-making rice black vinegar have an effect of improving brain function.

  The onset of dementia not only reduces the quality of life of the patient, but also creates great stress for the caring family. This disease, which is likely to occur at an older age, is a major problem in Japan and other developed countries, which will face an aging society in the future. At present, when there is no fundamental treatment method, the composition for improving brain function comprising the black vinegar-derived component of the present invention as an active ingredient can suppress the onset of dementia and slow the progression of the onset of dementia. it can.

Claims (4)

  A composition for improving brain function comprising a black vinegar-derived component as an active ingredient.   The composition for improving brain function according to claim 1, wherein the black vinegar-derived component is a component obtained by removing an acetic acid component from black vinegar or a black vinegar mash.   The composition for improving brain function according to claim 1 or 2, wherein the improvement of brain function is improvement of Alzheimer's disease. A food or drink containing the composition for improving brain function according to any one of claims 1 to 3 (except black vinegar and black vinegar mash).