Long-term memory capacity improves with the use of components

Abstract

The problem that this invention aims to solve is to provide a novel composition for improving long-term memory ability. [Solution] The inventors of this application have diligently studied and discovered a composition for improving long-term memory ability, which contains at least one of sulforaphane, glucoraphanin, sulforaphene, and glucoraphenine as a contributing component. By administering or ingesting this composition, it is possible to improve long-term memory ability, prevent the decline of long-term memory ability, and improve long-term memory ability.

Description

Technical Field

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[0001] The present invention relates to a composition for improving long-term memory ability.

Background Art

[0002] In Japan, with the progress of an aging society, an increase in dementia is predicted, and its prevention is an urgent social issue. Therefore, research on the onset mechanism of dementia and its treatment methods is actively underway. There are many components that have been suggested to be effective against dementia, and sulforaphane is one of them. Patent Document 1 discloses that sulforaphane has an effect of suppressing the aggregation of tau protein and suggests that it contributes to the treatment or prevention of neurodegenerative diseases such as Alzheimer's disease.

[0003] Also, in memory impairment models caused by inflammation or drugs, it has been reported that sulforaphane improves the impaired spatial memory ability. Non-Patent Document 1 discloses that intraperitoneal administration of sulforaphane suppresses the decrease in spatial memory ability induced by intraperitoneal administration of LPS. Non-Patent Document 2 discloses that oral administration of sulforaphane suppresses the decrease in spatial memory ability caused by intraperitoneal administration of scopolamine.

[0004] However, the effects of sulforaphane and its analogs on memory ability in a healthy state, particularly on long-term memory ability, have not been clarified.

Prior Art Documents

Patent Documents

[0005]

Patent Document 1

Non-Patent Documents

[0006]

Non-Patent Document 1

[0007] The problem that this invention aims to solve is to provide a novel composition for improving long-term memory ability. [Means for solving the problem]

[0008] Based on the above, the inventors of this application have diligently studied and discovered a composition for improving long-term memory ability, a composition for preventing the decline of long-term memory ability, or a composition for improving long-term memory ability, which contains at least one of sulforaphane, glucoraphanin, sulforaphene, and glucoraphenine as a contributing component. In other words, by administering or ingesting a composition containing at least one of sulforaphane, glucoraphanin, sulforaphene, and glucoraphenine as a contributing component, it is possible to improve long-term memory ability. From this viewpoint, the present invention is defined as follows.

[0009] The contributing component of the composition for improving long-term memory according to the present invention is at least one of sulforaphane, glucoraphanin, sulforaphene, and glucoraphenin. The long-term memory is retained for 24 hours or more. Furthermore, the period during which the effect of improving long-term memory persists during the administration or intake of the composition is at least 10 months. The long-term memory is declarative memory, preferably episodic memory.

[0010] The contributing component of the composition for preventing the decline of long-term memory according to the present invention is at least one of sulforaphane, glucoraphanin, sulforaphene, and glucoraphenin. The duration for which long-term memory is retained is 24 hours or more. Furthermore, the effect of preventing the decline of long-term memory persists for at least 10 months during the period of administration or ingestion of the composition. The long-term memory is declarative memory, preferably episodic memory.

[0011] The contributing component of the composition for improving long-term memory according to the present invention is at least one of sulforaphane, glucoraphanin, sulforaphene, and glucoraphenin. The effect of improving long-term memory persists for at least 10 months during the administration or intake period of the composition. The long-term memory is declarative memory, preferably episodic memory. [Effects of the Invention]

[0012] The present invention provides novel compositions for improving long-term memory capacity, preventing the decline of long-term memory capacity, and enhancing long-term memory capacity. The contributing components of the compositions, sulforaphane, glucoraphanin, sulforaphene, and glucoraphenin, are all materials that can be used as food ingredients, and the side effects of the compositions of the present invention are lower and safer than those of conventional pharmaceuticals containing non-natural compounds. [Brief explanation of the drawing]

[0013] [Figure 1] Time (in seconds) to enter the darkroom during training trials and measurement trials. [Figure 2] The difference in time (seconds) before entering the darkroom between the training trial and the measurement trial. [Figure 3] Ratio of time taken to enter the darkroom during training trials versus measurement trials [Modes for carrying out the invention]

[0014] <Composition according to the present invention> The composition according to the present invention is a composition for improving long-term memory ability, a composition for preventing the decline of long-term memory ability, and a composition for improving long-term memory ability, and contains at least one of sulforaphane, glucoraphanin, sulforaphene, and glucoraphenine as a contributing component.

[0015] <Long-Term Memory Ability> Long-term memory ability is a cognitive function related to memory, specifically the ability to retain memories for extended periods. While it is generally said that long-term memories can be retained for several hours to several years, the examples described below confirmed that they could be retained for more than 24 hours. Long-term memory is classified into declarative memory and non-declarative memory. Declarative memory, also called declarative memory, includes episodic memory and semantic memory. Declarative memory is thought to be handled by the hippocampus in the brain. In the examples described below, tests were conducted using a long-term memory assessment system to confirm the effect on avoidance learning ability in response to aversive stimuli, i.e., on long-term memory classified as episodic memory.

[0016] Here, "improvement of long-term memory ability" refers to a state in which long-term memory ability is enhanced from a normal state. Specifically, this can be confirmed by administering or ingesting the composition according to the present invention to an individual with normal long-term memory ability, compared to the case where a control composition without contributing components is administered or ingested. "Prevention of decline in long-term memory ability" refers to a state in which the decline in long-term memory ability is suppressed. Specifically, this can be confirmed by administering or ingesting the composition according to the present invention to an individual who currently exhibits a decline in long-term memory ability, or an individual who is expected to experience a decline in long-term memory ability in the future, compared to the case where a control composition without contributing components is administered or ingested, the degree of decline in long-term memory ability observed after a certain period of ingestion is lower; in other words, the decline in long-term memory ability is suppressed.

[0017] In addition, "improvement of long-term memory ability" means that the decline in long-term memory ability is suppressed and the state is equal to or higher than the normal state. Specifically, when the composition according to the present invention is administered or ingested to an individual with a decline in long-term memory ability, the long-term memory ability of the individual can be confirmed to be in a state equal to or higher than that of an individual with normal long-term memory ability who has been administered or ingested a control composition containing no contributing components.

[0018] <Sulforaphane and glucoraphanin> Glucoraphanin is a kind of glucosinolate and is a precursor of sulforaphane. It is hydrolyzed by the enzyme myrosinase to become sulforaphane. Also, even when mammals such as humans ingest glucoraphanin, it is converted to sulforaphane by the enzymes of intestinal bacteria and absorbed from the intestinal tract. Glucoraphanin is known to be abundantly contained in cruciferous plants. In the present invention, glucoraphanin may be contained in a purified state in a drug, food composition or food and drink product, or may be contained in one or more states selected from cruciferous plants, their extracts or their fractions, and their pulverized products. The structural formula of glucoraphanin is shown in the following (1), and the structural formula of sulforaphane is shown in the following (2).

[0019]

Chemical formula

[0020] From the viewpoint of improving the efficiency of metabolism in the body, the composition according to the present invention can further preferably contain myrosinase. The enzyme activity of myrosinase with respect to the amount of glucoraphanin (myrosinase activity (UNIT) / glucoraphanin (mg)) may have a lower limit of 0.0001 (UNIT / mg) or more, preferably 0.001 (UNIT / mg) or more, and an upper limit of 0.022 (UNIT / mg) or less, preferably 0.01 (UNIT / mg) or less.

[0021] Furthermore, myrosinase may be chemically synthesized or natural, and is not particularly limited, but natural is preferred, and plant-derived is more preferred. Examples of such plants include Brassicaceae plants, and more specifically, mustard, radish, wasabi, etc. Myrosinase may be contained in the preparation or food in a purified state, or it may be contained in one or more states selected from Brassicaceae plants, their extracts or fractions thereof, and their pulverized products.

[0022] <Sulforaphene and Glucorafenine> Glucorafenine is a type of glucosinolate and a precursor of sulforaphene. It is hydrolyzed by the enzyme myrosinase to produce sulforaphene. When mammals such as humans ingest glucoraphenine, it is converted to sulforaphene by enzymes of intestinal bacteria and absorbed from the intestinal tract. Glucorafenine is known to be abundant in cruciferous plants, especially radishes, radish leaves, and seeds. In the present invention, glucoraphenine may be contained in a purified state in a drug, food composition, or food and beverage, or it may be contained in one or more states selected from cruciferous plants, their extracts or fractions thereof, and their pulverized products. The structural formula of glucoraphenine is shown below (3), and the structural formula of sulforaphene is shown below (4).

[0023] [ka]

[0024] Because glucoraphenin is structurally similar to glucoraphanin, it is expected to have similar effects and behaviors. For example, glucoraphenin is an indicator of the activation of the transcription factor Nrf2 (NF-E2-related-factor 2). It has been reported to contribute to the activity of the second-phase enzyme (Barillari et al., J Agric Food Chem. 55(14), 5505-11, 2007). Furthermore, Nrf2 is known to be activated in response to stress, such as oxidative stress (Itoh et al., Genes Dev. 13(1), 76-86, 1999), and has been reported to increase the gene expression of antioxidant enzymes (Ishii et al., J Biol Chem. 275(21), 16023-9, 2000), increase the gene expression of detoxification metabolic enzymes (Itoh et al., Biochem Biophys Res Commun. 236(2), 313-22, 1997), and reduce the gene expression of cytokines that cause inflammation (Kobayashi et al., Nat Commun. 7, 11624, 2016 and Itoh et al., Mol Cell Biol. 24(1), 36-45, 2004). These effects are common to those of glucoraphanin. Furthermore, there are reports that activation of Nrf2 in the cognitive domain suppresses oxidative stress and inflammation in the brains of Alzheimer's disease model mice, leading to improved cognitive function (Uruno et al., Mol Cell Biol. 40(6), e00467-19, 2020). From the above, it can be inferred that glucoraphenin has similar effects on cognitive function as glucoraphanin and sulforaphane.

[0025] The composition according to the present invention may further suitably contain myrosinase from the viewpoint of improving the efficiency of metabolism in the body. The enzymatic activity of myrosinase relative to the amount of glucoraphenine (myrosinase activity (UNIT) / glucoraphenine (mg)) may have a lower limit of 0.0001 (UNIT / mg) or more, preferably 0.001 (UNIT / mg) or more, and an upper limit of 0.022 (UNIT / mg) or less, preferably 0.01 (UNIT / mg) or less.

[0026] Furthermore, myrosinase may be chemically synthesized or natural, and is not particularly limited, but natural is preferred, and plant-derived is more preferred. Examples of such plants include Brassicaceae plants, and more specifically, mustard, radish, wasabi, etc. Myrosinase may be contained in the preparation or food in a purified state, or it may be contained in one or more states selected from Brassicaceae plants, their extracts or fractions thereof, and their pulverized products.

[0027] <Brassicaceae Plants> Brassicaceae plants are not particularly limited, but examples include broccoli, kale, cabbage, cauliflower, mustard greens, rapeseed, mustard greens, radish, radish leaves, Japanese mustard greens, Japanese mustard greens, Chinese cabbage, Brussels sprouts, Petit Vert, snow radish, and plants produced by appropriately crossbreeding these. The part of the plant can be the growing body (buds, leaves, stems, roots, or flowers, etc.), sprouts (germinating bodies), or seeds, and is not particularly limited. Of these, broccoli, which belongs to the genus Brassica in the family Brassicaceae, is preferred. Furthermore, broccoli sprouts or seeds are particularly preferred due to their high content of sulforaphane and glucoraphanin.

[0028] <Broccoli Sprout Extract> When extracting at least one of sulforaphane and glucoraphanin from broccoli sprouts, the extraction can be performed at any number of days after germination, as long as the sprouts are not yet grown into mature plants where the content per unit weight decreases significantly. However, it is preferable to use sprouts that are 1 to 10 days after germination, more preferably 1 to 3 days after germination. Furthermore, it is preferable to use broccoli sprouts in which the content of at least one of sulforaphane and glucoraphanin is preferably 50 to 350 mg / 100g (wet weight), more preferably 150 to 330 mg / 100g (wet weight), and even more preferably 250 to 300 mg / 100g (wet weight).

[0029] <Obtaining Contributing Components> At least one of sulforaphane, glucoraphanin, sulforaphene, and glucoraphenin can be obtained from Brassicaceae plants, including broccoli sprouts, by well-known methods. In addition, isolated and purified sulforaphane, glucoraphanin, sulforaphene, and glucoraphenin are commercially available and can also be used. Examples of commercially available products include, but are not limited to, sulforaphane (Funakoshi Co., Ltd.) and L-Sulforaphene (Cayman Chemical Company).

[0030] <Extraction of Glucorafanin and Glucorafenin> For example, glucoraphanin and glucorafenin can be obtained by extracting part or all of a plant, either as is or after drying and grinding, with a solvent. Examples of solvents include water, lower monohydric alcohols (methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, etc.), liquid polyhydric alcohols (glycerin, propylene glycol, 1,3-butylene glycol, etc.), lower esters (ethyl acetate, etc.), hydrocarbons (benzene, hexane, pentane, etc.), ketones (acetone, methyl ethyl ketone, etc.), ethers (diethyl ether, tetrahydrofuran, dipropyl ether, etc.), acetonitrile, etc., and one or more of these can be used.

[0031] Considering that the compositions of the present invention are administered or ingested orally, water, ethanol, or aqueous ethanol are particularly preferred as extraction solvents. Examples of preferred extraction methods include, for example, extraction with hot water (90-100°C) for 10-50 minutes, or extraction with 0-100% by volume of aqueous ethanol at room temperature or heated for 1-10 days, after which the extract may be further fractionated and purified. In addition, glucoraphanin and glucoraphenin may be extracted by supercritical fluid extraction.

[0032] <Method for obtaining sulforaphane from glucoraphanin> The method for obtaining sulforaphane from glucoraphanin is not limited to reacting glucoraphanin with myrosinase. For example, one method involves crushing, grinding, pulverizing, shearing, or juicing cruciferous plants containing glucoraphanin without heating to react the glucoraphanin with endogenous myrosinase and metabolize it into sulforaphane, or by adding myrosinase to glucoraphanin to metabolize it into sulforaphane. Sulforaphane can be obtained from raw materials containing sulforaphane metabolized from glucoraphanin by these methods, using the same method as for glucoraphanin (for example, the extraction method mentioned above).

[0033] <Method for obtaining sulforaphene from glucoraphenin> The method for obtaining sulforaphene from glucoraphenin is the same as the method for obtaining sulforaphane from glucoraphanin described above.

[0034] <Measurement of Concentrations of Glucorafanin and Glucorafenin> The concentration of glucoraphanin in the composition of the present invention can be measured by methods well known to those skilled in the art. For example, high-performance liquid chromatography (HPLC) can be used, and a specific method can be followed, such as the method of Fahey et al. (Fahey et al., Proc. Natl. Acad. Sci. USA, 94, 10367-10372, 1997). The concentration of glucorafenin can be measured by the same method as for glucoraphanin.

[0035] <Measurement of Sulforaphane and Sulforafen Concentrations> The concentrations of sulforaphane and sulforafen in the composition can be measured by methods well known to those skilled in the art. For example, high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS) can be used. Specific methods include those described by Han et al. or Baenas et al. (Han et al., Int. J. Mol. Sci., 12, 1854-1861, 2011; Baenas et al., food Res. Int., 100(Pt1), 497-503, 2017).

[0036] <Form of Composition> The composition of the present invention can be administered as a drug or ingested as a food composition or food / beverage. Specifically, it may be a drug, food composition or food / beverage for human or animal use, or it may be a material or preparation used in combination with said drug, food composition or food / beverage. The said food composition or food / beverage includes food compositions, food / beverages, functional foods, foods for specified health uses, foods for sick people, and supplements that are based on the concept of improving, preventing or improving long-term memory ability, and that are indicated to that effect as necessary. Examples of how to indicate this include, but are not limited to, "improving long-term memory ability," "improving long-term memory," "enhancing long-term memory ability," "strengthening long-term memory ability," "maintaining long-term memory ability," "preventing decline in long-term memory ability," "improving long-term memory ability," "restoring long-term memory ability," "for those concerned about decline in long-term memory ability," and "helps with long-term memory."

[0037] These markings can be affixed to containers and packaging in known ways, displayed or distributed in advertisements, price lists, or transaction documents related to the product, or information containing these markings can be provided by electromagnetic means (such as the Internet). Furthermore, the compositions according to the present invention may be used to delay the onset of dementia, Alzheimer's disease, or Parkinson's disease, alleviate their symptoms, reduce their severity, or reduce or halt their progression.

[0038] <Agent Formulation> The composition of the present invention can be administered orally in the form of tablets, coated tablets, capsules, granules, powders, solutions, syrups, emulsions, etc. Parenteral administration is not excluded, and may also be performed by local tissue administration, subcutaneous, intradermal, intramuscular, or intravenous injection, or intranasal administration by volatilizing the active ingredient. The formulation can be prepared using known excipients that are commonly used in pharmaceutical and other formulation technology fields, such as excipients, binders, disintegrants, lubricants, colorants, flavoring and odor-correcting agents, solubilizers, suspending agents, and coating agents. It may also be in the form of a pharmaceutical or quasi-drug.

[0039] <Food Composition> Examples of the food composition of the present invention as a form of consumption include, but are not limited to, general foods and processed foods such as beverages (juice, black tea, tea, coffee, carbonated drinks, sports drinks, soft drinks, etc.), confectionery (gum, caramel, candy, chocolate, cookies, biscuits, snacks, jelly, gummies, tablets, etc.), noodles (soba, udon, ramen, etc.), dairy products (milk, ice cream, yogurt, etc.), seasonings (miso, soy sauce, dressing, etc.), soups, health foods (tablets, capsules, etc.), and nutritional supplements (supplements, energy drinks, etc.).

[0040] These food compositions can contain various ingredients depending on their type, and for example, food additives such as glucose, fructose, sucrose, maltose, raffinose, sorbitol, stevioside, corn syrup, lactose, citric acid, tartaric acid, malic acid, succinic acid, lactic acid, L-ascorbic acid, dl-α-tocopherol, sodium erythorbate, glycerin, propylene glycol, glycerin fatty acid ester, polyglycerin fatty acid ester, sucrose fatty acid ester, sorbitan fatty acid ester, propylene glycol fatty acid ester, gum arabic, carrageenan, casein, gelatin, pectin, agar, B vitamins, nicotinamide, calcium pantothenate, amino acids, calcium salts, colorants, flavorings, and preservatives can be used as desired.

[0041] <Food and Beverages> Examples of the forms in which the composition of the present invention can be consumed as food or beverages include, for example, fresh foods (raw vegetables), beverages (juice, coffee, black tea, tea, carbonated drinks, sports drinks, green juice, etc.), confectionery (gum, candy, caramel, chocolate, cookies, snacks, jelly, gummies, tablets, etc.), noodles (soba, udon, ramen, etc.), dairy products (milk, ice cream, yogurt, etc.), seasonings (miso, soy sauce, etc.), soups, and other general foods, as well as health foods (tablets, capsules, etc.) and nutritional supplements (supplements, energy drinks, etc.).

[0042] Depending on the type, various ingredients can be blended, for example, glucose, fructose, sucrose, maltose, sorbitol, corn starch, dextrin, stevioside, corn syrup, lactose, citric acid, tartaric acid, malic acid, succinic acid, lactic acid, L-ascorbic acid Food additives such as nicotine, dl-α-tocopherol, sodium erythorbate, glycerin, propylene glycol, glycerin fatty acid ester, polyglycerin fatty acid ester, sucrose fatty acid ester, sorbitan fatty acid ester, propylene glycol fatty acid ester, cellulose, gum arabic, carrageenan, casein, gelatin, pectin, agar, B vitamins, nicotinamide, calcium pantothenate, amino acids, calcium salts, colorants, flavorings, and preservatives may be used as desired.

[0043] <Contributing Components> Contributing components are substances whose effect is on the physiological functions of the body. In Foods for Specified Health Uses and Foods with Function Claims, the contributing components are the so-called "active ingredients" and "functional active ingredients." In the case of pharmaceuticals and quasi-drugs, they are the so-called "active ingredients."

[0044] <Content of Contributing Components> When the composition of the present invention is used as an agent, it is not particularly limited, but it is preferable that it contains at least one of sulforaphane, glucoraphanin, sulforaphene, and glucoraphenin in a total of 0.03% by mass or more, more preferably 0.5% by mass or more, and particularly preferably 5% by mass or more.

[0045] Furthermore, when the composition of the present invention is used as a food composition, it is not particularly limited, but it is preferable that it contains at least one of sulforaphane, glucoraphanin, sulforaphene, and glucoraphenin in a total of 0.01% by mass or more, more preferably 0.04% by mass or more, and particularly preferably 0.25% by mass or more.

[0046] <Dosage / Intake> The dosage or intake of the composition of the present invention will vary depending on the sex, symptoms, age, and method of administration when the recipient is a human. However, at least one of sulforaphane, glucoraphanin, sulforaphene, or glucoraphenin should be at least 24 mg per day for an adult (weighing about 60 kg), and at least 30 mg is preferable from the viewpoint of ensuring that the effect is fully exerted. This daily amount can be administered / intaken all at once or divided into several doses, and the timing may be before, after, or between meals. Furthermore, there is no particular limit to the duration of administration / intake, but it is preferable to take it continuously for 12 weeks or more. In addition, the period during which the effect on long-term memory ability is sustained by continuous administration or intake is at least 10 months. Note that the above-mentioned daily dosage / intake will vary depending on the form of the composition, but it refers to the indicated daily intake amount or, in the case of single-serving beverages, the amount contained in one bottle. [Examples]

[0047] <Experiment> Long-term memory ability was evaluated in an aging-accelerated model mouse in which cognitive function declines early, and in its control strain mouse.

[0048] <Test Animals> Male SAMP8 mice (Senescence Accelerated mouse Prone 8, SLC Japan Co., Ltd.) were used as the aging acceleration model mouse, and male SAMR mice (Senescence Accelerated mouse resistant 1, SLC Japan Co., Ltd.) were used as the control mouse.

[0049] <Test Food> A feed containing a high amount of glucoraphanin was used as the test food. Specifically, a mixture of regular feed (#MF powder, Oriental Yeast Co., Ltd.) and 2.2% (w / w) broccoli sprout (BS) extract (Ogawa Fragrance Co., Ltd.) and 1.0% (w / w) mustard powder (#Y38, Minoku Co., Ltd.) was added. The control food was regular feed (#MF powder, Oriental Yeast Co., Ltd.) without the above BS extract and mustard powder. The test animals were continuously fed either the test food or the control food ad libitum from 1 month to 12 months of age.

[0050] <Evaluation of Long-Term Memory Ability> To evaluate the long-term memory ability of mice, a step-through (ST) passive avoidance test was conducted. The passive avoidance test is a system for evaluating long-term memory, and the avoidance behavior that animals exhibit in response to aversive stimuli (e.g., electrical stimulation) that they have experienced once is used as an indicator of memory. The step-through test utilizes the fact that mice prefer dark places, and involves placing the mouse in the bright room of a device connected to a bright room and a dark room by a door, and using the time it takes to move to the dark room as an indicator of memory (Takuma, Kazuaki, et al. Folia Pharmacol. Jpn.). 130, 112~116, 2007; Mohammadi, International Journal of Peptide Research and Therapeutics. 26 (1), 357-367, 2019). The test was conducted using a device divided into two rooms, a bright room and a dark room, with electricity flowing through the bottom of the dark room. The specific procedure is as follows.

[0051] (1) Training Trial 1) A mouse was placed in a bright room with the door to the dark room closed. 2) After 60 seconds, the door to the dark room was opened. 3) After confirming that the mouse had entered the dark room, an electric shock of 1 mA for 2 seconds was administered as the door was closed. 4) After the electric shock, the mouse was left in the dark room for 30 seconds before being removed.

[0052] (2) Measurement Trial 5) 24 hours after the training trial, the mouse was placed in a bright room with the door to the dark room open. 6) The time it took for the mouse to enter the dark room was measured. If the mouse did not enter the dark room after 5 minutes, the 5 minutes was recorded and the trial was terminated.

[0053] After performing steps 1) through 6) above, long-term memory capacity was evaluated using the following three evaluation indicators. The first was latency during the measurement trial (time until entering the darkroom). A longer latency during the measurement trial suggested that the mouse remembered the aversive stimulus from the training trial for a longer period, and was judged to have high long-term memory capacity. The second was the difference in time until entering the darkroom between the training trial and the measurement trial. A larger difference in time until entering the darkroom between the training trial and the measurement trial suggested that the mouse remembered the aversive stimulus from the training trial for a longer period, and was judged to have high long-term memory capacity. The third was the ratio of time until entering the darkroom between the training trial and the measurement trial (measurement trial / training trial). A larger ratio of time until entering the darkroom between the training trial and the measurement trial suggested that the mouse remembered the aversive stimulus from the training trial for a longer period, and was judged to have high long-term memory capacity. Table 1 shows an explanation of each category.

[0054] [Table 1]

[0055] <Statistical Analysis> Within each group, an outlier test was performed using the Smirnov-Grubbs' test, and samples that were identified as outliers were excluded. Comparisons of the four groups were performed using ANOVA. Furthermore, as a post-hoc analysis, within each mouse strain, a comparison was performed between the group consuming the test food (hereinafter referred to as the "sulforaphane group") and the group consuming the control food (hereinafter referred to as the "control group") using Welch's t test corrected by the Holm method. The significance level was set at p<0.05. In Figures 1 to 3, * indicates statistical significance compared to the control group within the SAMR1 strain, and τ indicates statistical significance compared to the control group within the SAMP8 strain.

[0056] <Results> The evaluation results for long-term memory ability are shown below. <1. Time to enter the darkroom during training and measurement trials (latency)> For SAMR1 mice and SAMP8 mice that continued to ingest the test food or control food, the time to enter the darkroom during training and measurement trials is shown in Figure 1. In Figure 1, the mean values ​​for each group are shown as bar graphs, and the standard error is shown as error bars, for the results measured in Category 1 (N=10), Category 2 (N=9), Category 3 (N=9), and Category 4 (N=9). In both SAMR1 mice and SAMP8 mice, the latency during the measurement trial was significantly longer in the sulforaphane group compared to the control group (p<0.05). In the comparison between the control group (Category 1) and the sulforaphane group (Category 2) of SAMR1 mice, the mean value was longer in Category 2 than in Category 1, and a significant difference (p=0.041) was observed, confirming that the test food has the effect of improving long-term memory ability. Furthermore, a comparison between the control group (Category 3) and the SGS group (Category 4) of SAMP8 mice showed that the mean time was longer in Category 4 than in Category 3, with a significant difference (p=0.031), confirming that the test food has an effect in preventing the decline of long-term memory ability. In addition, the mean time was longer in the sulforaphane group (Category 4) of SAMP8 mice than in the control group (Category 1) of SAMR1 mice, confirming that the test food has an effect in improving long-term memory ability.

[0057] <2. Difference in time to enter the darkroom between training and measurement trials> Figure 2 shows the difference in time to enter the darkroom between training and measurement trials for SAMR1 mice and SAMP8 mice that continued to ingest the test food or control food. In Figure 2, the mean values ​​for each group are shown as bar graphs, and the standard errors are shown as error bars, for the results measured in N=10 for category 1, N=9 for category 2, N=9 for category 3, and N=9 for category 4.

[0058] In both SAMR1 and SAMP8 mice, the time difference was significantly larger (p<0.05) in the sulforaphane group compared to the control group. In a comparison between the control group (category 1) and the sulforaphane group (category 2) of SAMR1 mice, the mean value was larger in category 2 than in category 1, showing a significant difference (p=0.024), confirming that the test food has an effect of improving long-term memory ability. In a comparison between the control group (category 3) and the sulforaphane group (category 4) of SAMP8 mice, the mean value was larger in category 4 than in category 3, showing a significant difference (p=0.038), confirming that the test food has an effect of preventing the decline of long-term memory ability. Furthermore, in the sulforaphane group (category 4) of SAMP8 mice, the mean value was higher than in the control group (category 1) of SAMR1 mice, confirming that the test food has an effect of improving long-term memory ability.

[0059] <3. Ratio of time to enter the darkroom between training trials and measurement trials> Figure 3 shows the ratio of time to enter the darkroom (measurement trial / training trial) between training trials and measurement trials for SAMR1 mice and SAMP8 mice that continued to ingest the test food or control food. In Figure 3, the mean values ​​for each group are shown as bar graphs, and the standard errors are shown as error bars, for the results measured in N=10 for category 1, N=9 for category 2, N=9 for category 3, and N=9 for category 4.

[0060] In SAMR1 mice, the ratio of time to enter the darkroom during training trials to time to measurement trials was significantly larger in the sulforaphane group (Category 2) compared to the control group (Category 1), confirming that the test food has an effect on improving long-term memory ability. On the other hand, in SAMP8 mice, the ratio of time to enter the darkroom during training trials to time to time to measurement trials was larger in the sulforaphane group (Category 4) compared to the control group (Category 3), suggesting that the test food has an effect on preventing the decline of long-term memory ability. Furthermore, the sulforaphane group (Category 4) of SAMP8 mice tended to be larger than the control group (Category 3) and was close to the value of the control group (Category 1) of SAMR1 mice, suggesting that the test food has an effect on improving long-term memory ability. <Numerical Data> Table 2 below shows the numerical data of the mean ± standard error of the above test results.

[0061] [Table 2] [Industrial applicability]

[0062] The field in which this invention is useful is the health food business.

Claims

1. A composition for preventing the decline of long-term memory ability, This long-term memory capacity is the memory capacity in a healthy state. This healthy state does not include states with memory impairment or cognitive impairment. The contributing component is at least one of sulforaphane and glucoraphanin.

2. The composition according to claim 1, wherein the time for which the long-term memory is retained is 24 hours or more.

3. The composition according to claim 1 or 2, wherein the period during which the effect of preventing the decline in long-term memory ability persists during the administration or intake of the composition is at least 10 months.

4. A composition according to any one of claims 1 to 3, wherein the long-term memory is declarative memory.

5. A composition for improving long-term memory ability, This long-term memory capacity is the memory capacity in a healthy state. This healthy state does not include states with memory impairment or cognitive impairment. The contributing component is at least one of sulforaphane and glucoraphanin.

6. The composition according to claim 5, wherein the time for which the long-term memory is retained is 24 hours or more.

7. The composition according to claim 5 or 6, wherein the period during which the long-term memory improvement effect persists during the administration or intake of the composition is at least 10 months.

8. A composition according to any one of claims 5 to 7, wherein the long-term memory is declarative memory.

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