Food and drink composition for promoting brain-derived neurotrophic factor secretion

Abstract

To provide a food and drink composition which has an excellent effect of promoting secretion of brain-derived neurotrophic factor (BDNF) from small intestinal endocrine cells from safe food materials.SOLUTION: There is provided a food and drink composition for promoting BDNF secretion from small intestinal endocrine cells containing 4'-demethylnobiletin as an active ingredient. The food and drink composition of the present disclosure may have an effect of reducing stress or depression in daily life, and alleviating anxiety, an effect of increasing vitality, energy or motivation, and / or an effect of reducing stomach discomfort or constipation in daily life. Since 4'-demethylnobiletin can be obtained by conversion from nobiletin of a citrus peel component by a koji mold fermentation method, the food and drink composition of the present disclosure is highly safe and has no concerns about side effects.SELECTED DRAWING: Figure 2

Description

[Technical Field]

[0001] The present disclosure relates to a food and beverage composition that contains 4'-demethylnobiletin as an active ingredient and thereby has the effect of promoting the secretion of brain-derived neurotrophic factor (BDNF) from small intestinal endocrine cells, thereby reducing stress and depressed moods in daily life, promoting a positive mood, and alleviating stomach discomfort. [Background technology]

[0002] Brain-derived neurotrophic factor (BDNF) is important for neuronal development, growth, differentiation, survival, plasticity, and synaptic transmission. BDNF is also present in the intestine, such as in small intestinal endocrine cells and enteric neurons, and is involved in the survival and growth of serotonergic neurons (see, for example, Non-Patent Document 1). Furthermore, intestinal BDNF is involved in strengthening the intestinal circuit and stimulating intestinal peristalsis and propulsion, and its upregulation plays a role in visceral hypersensitivity accompanied by lower abdominal pain, abdominal bloating, gas, constipation, diarrhea, and other abdominal discomfort in inflammatory bowel disease and irritable bowel syndrome (see, for example, Non-Patent Document 1).

[0003] On the other hand, the gut and brain are closely related. As the term "gut-brain axis" suggests, for example, stress-induced changes in intestinal motility due to brain-to-intestinal signals can lead to constipation or diarrhea. Conversely, gut-to-brain signals can lead to anxiety or relaxation. Numerous afferent nerves are distributed throughout the intestinal tract, transmitting information about the state of the intestinal tract to the central nervous system. The sympathetic nervous system from the brain controls the entire intestine, from the small intestine to the large intestine, while the vagus nerve, which is part of the parasympathetic nervous system, controls the upper part of the small intestine, such as the duodenum (see, for example, Non-Patent Document 2). One type of signaling pathway from the gut to the brain is serotonin neurons, which stimulate the vagus nerve in the small intestine, affecting serotonin in the brain and exerting anxiolytic effects (see, for example, Non-Patent Document 3). Small intestinal BDNF exerts its anxiolytic effect by promoting the survival and differentiation of serotonin neurons. Thus, the gut-brain axis is interrelated with stress and anxiety, and the role of BDNF in the anxiolytic effect mediated by the vagus nerve from the small intestine is crucial. However, although there have been reports of caffeic acid esters enhancing BDNF secretion in colonic epithelial cells (see, for example, Patent Document 1), little is known about the BDNF secretion-promoting effect from the small intestine. [Prior art documents] [Non-patent literature]

[0004] [Non-Patent Document 1] Al-Qudah M, et al., Neurogastroenterol Motil ,2015 ;27(8) :1162-74. [Non-patent document 2] "Autonomic nervous system and gut hormones in the regulation of small intestinal function" Research project / area number 01570415 (KAKEN: Grant-in-Aid for Scientific Research Database (National Institute of Informatics)) (URL: https: / / kaken.nii.ac.jp / ja / grant / KAKENHI-PROJECT-01570415 / ) [Non-patent document 3] McVey Neufeld KA et al., Sci Rep. 2019, 3;9 (1):14290 [Patent documents]

[0005] [Patent Document 1] JP 2018-145100 [Patent Document 2] Patent No. 5667561 specification Summary of the Invention [Problem to be solved by the invention]

[0006] However, although there have been reports of caffeic acid esters increasing BDNF secretion using colonic epithelial cells (see, for example, Patent Document 1), there are few reports of their promoting effect on BDNF secretion from the small intestine.

[0007] The present disclosure aims to solve the above problems and provide a food and beverage composition that is made from safe food ingredients and has an excellent effect of promoting BDNF secretion from small intestinal endocrine cells. [Means for solving the problem]

[0008] Nobiletin, a polymethoxyflavonoid, is a flavonoid unique to citrus fruits, and in recent years has become known for its various physiological effects, including cancer prevention, anti-aging, and anti-arteriosclerosis. The present inventors have clarified that by using citrus peels that contain a large amount of nobiletin and fermenting them with a specific type of koji mold, the main component nobiletin is converted to 4'-demethylnobiletin (see formula (I) below). The present inventors have also found that 4'-demethylnobiletin has an excellent memory-improving effect (see Patent Document 2).

[0009] [ka]

[0010] The present inventors further investigated the functionality of 4'-demethylnobiletin and found that it has an excellent effect of promoting the secretion of BDNF from small intestinal endocrine cells. Based on these findings, the present inventors have completed the present disclosure.

[0011] That is, the present disclosure relates to a food or drink composition for promoting BDNF secretion from small intestinal endocrine cells, which contains 4'-demethylnobiletin as an active ingredient.

[0012] Furthermore, it is desirable that the food and beverage compositions of the present disclosure have the effect of reducing stress or depression in daily life, easing anxiety, and / or increasing vitality, energy, or motivation.

[0013] Furthermore, the food and beverage composition of the present disclosure desirably has the effect of alleviating abdominal discomfort selected from abdominal bloating, rumbling, and gas generation and / or constipation occurring in daily life. [Effects of the Invention]

[0014] The present disclosure makes it possible to provide an excellent food and drink composition for promoting BDNF secretion from small intestinal endocrine cells by containing 4'-demethylnobiletin as an active ingredient.

[0015] Because 4'-demethylnobiletin is a food-derived component contained in a koji mold fermentation product of a citrus peel component, the food and beverage compositions of the present disclosure are highly safe and there is no need to worry about side effects. [Brief explanation of the drawings]

[0016] [Figure 1] FIG. 1 is a graph showing the promoting effect of adding a composition containing 4′-demethylnobiletin (4′-DeNob) on the amount of BDNF secretion from the small intestinal endocrine cell line STC-1 cells. [Figure 2] FIG. 1 is a graph showing the promoting effect of adding 4′-demethylnobiletin (4′-DeNob) on the amount of BDNF secretion from the small intestinal endocrine cell line STC-1 cells. DETAILED DESCRIPTION OF THE INVENTION

[0017] Hereinafter, embodiments of the present disclosure will be described in detail. The present embodiment relates to a food and drink composition for promoting BDNF secretion from small intestinal endocrine cells, which contains 4'-demethylnobiletin as an active ingredient.

[0018] [4'-demethylnobiletin] Although 4'-demethylnobiletin (see formula (I) above) is not commercially available, it is possible to use a synthetic product, or a pure 4'-demethylnobiletin (isolate) or 4'-demethylnobiletin-containing composition obtained by koji mold fermentation using citrus fruits containing nobiletin, particularly the peel, by the previously reported method of Patent Document 2. However, the method of Patent Document 2, which utilizes the bioconversion of nobiletin by koji mold fermentation, is preferable because it is simpler and less expensive.

[0019] 4'-Demethylnobiletin is also one of the metabolites produced after nobiletin is absorbed in the body. Citrus peel is used as an ingredient in sweets such as marmalade and candied fruits, and mandarin oranges (Citrus reticulata), which have a high nobiletin content, have a long history of being eaten as tangerine, and 4'-demethylnobiletin and compositions containing it are extremely safe.

[0020] The method for producing 4'-demethylnobiletin and a composition containing it, which are described in Patent Document 2, will be described below.

[0021] [Fermentation ingredients] The raw material for koji fermentation is the 'fruit' of citrus fruits (the entire fruit including the peel, juice, pulp, seeds, etc.), which contains the polymethoxyflavonoid nobiletin. However, it is particularly desirable to use the 'peel' from the standpoint of nobiletin content and effective utilization of waste materials. Furthermore, any variety or lineage of citrus fruit (for example, ponkan, shikuwasha, tangerine, tachibana, etc.) can be used as long as it contains nobiletin. The fermentation raw material may contain other parts of citrus plants (for example, leaves, buds, stems, flowers, etc.), but it is desirable that the fermentation raw material does not contain these parts in terms of the nobiletin content.

[0022] The above citrus fruits are preferably harvested and collected fresh, or washed, but dried, frozen, or long-term stored fruits can also be used. Citrus fruits may be used in their original form, but it is preferable to chop, crush or grind them. This process includes a wide range of actions, such as roughly chopping the citrus fruits into several pieces, shredding into small pieces, crushing, grinding, powdering, etc. Preferably, this process can be carried out by chopping the citrus fruits into roughly one to several centimeters in size.

[0023] Furthermore, it is also possible to use an extract (extract, dried product) obtained by extracting nobiletin in advance from these fermentation raw materials, or nobiletin isolated as a pure product. It is preferable to heat-treat these fermentation raw materials to sterilize any unwanted bacteria in the raw materials before carrying out the koji mold fermentation described below.

[0024] [Koji mold fermentation] Examples of koji molds that can be used to ferment the fermentation raw materials include Aspergillus kawachii, Aspergillus awamori, Aspergillus niger, Aspergillus oryzae, Aspergillus sojae, Aspergillus saitoi, Aspergillus usamii, and Rhizopus filamentous fungi (also known as Rhizopus), and mixtures of these may also be used. Among the koji molds, Aspergillus kawachii, Aspergillus awamori, Aspergillus oryzae, and Aspergillus niger are preferably used to obtain a high content of 4'-demethylnobiletin. Two or more of these koji molds can also be used in combination.

[0025] The method of inoculating the koji mold into the fermentation raw material can be to sprinkle koji mold spores directly onto the fermentation raw material to attach them to the fermentation raw material. Alternatively, the inoculum source can be a medium in which the koji mold has been pre-fermented by liquid culture, and this can be inoculated so that the spores are distributed throughout the fermentation raw material. When the koji mold is inoculated into the fermentation raw material, the microbial fermentation is preferably carried out under aerobic conditions, and therefore a suitable container is, for example, a cylindrical container with a wide bottom and a shallow depth. It is advisable to spread the fermentation raw materials evenly on the bottom of such a container so that the contact area with the air becomes large.

[0026] The fermentation temperature is not particularly limited as long as it is a suitable condition for the growth of the koji mold, and can be preferably 10 to 40°C, more preferably 20 to 40°C, and even more preferably 25 to 32°C. In addition, as a suitable condition for the growth of the koji mold, fermentation is preferably carried out in a dark place. Furthermore, it is preferable that the raw materials contain sufficient moisture. The fermentation period for microbial fermentation may be any period that allows a large amount of 4'-demethylnobiletin to be obtained, and is preferably 2 to 21 days, more preferably 3 to 14 days, and even more preferably 4 to 12 days. If the fermentation period is less than two days, the microbial fermentation by the koji mold hardly progresses, and sufficient 4'-demethylnobiletin cannot be obtained. Conversely, if the fermentation period exceeds 21 days, decomposition of the 4'-demethylnobiletin produced by microbial conversion progresses, and the desirable citrus-derived aroma is lost.

[0027] Furthermore, in the koji mold fermentation, nobiletin is demethylated by an enzyme secreted from the koji mold, converting it to 4'-demethylnobiletin. Therefore, instead of performing koji mold fermentation, it is also possible to obtain 4'-demethylnobiletin by performing solution extraction from the koji mold or the fermented product obtained after fermentation to obtain an enzyme solution containing an enzyme that demethylates nobiletin, and then performing an enzymatic reaction with the raw material using the enzyme to obtain a reaction product. Specifically, the enzymatic reaction can be carried out by recovering a water-soluble matter from the fermented product after koji mold fermentation and using this as a crude enzyme solution.

[0028] By carrying out the above-mentioned koji mold fermentation, all of the nobiletin, which is a polymethoxyflavonoid contained in the citrus raw material, is converted to 4'-demethylnobiletin. Specifically, by fermenting the citrus raw material with koji mold, it is possible to obtain a koji mold fermentation product containing 4'-demethylnobiletin at a high content of approximately 0.5 to 1.5 mass% (specifically, approximately 1 mass%) per dry weight. Therefore, the koji mold fermentation product obtained here can be used as an active ingredient in the food and beverage composition of this embodiment either in the form in which it is obtained or after processing (e.g., by pulverizing, crushing, powdering, drying, etc.).

[0029] [Solution extraction] In view of purity, in the production of the food and beverage composition of this embodiment, it is desirable to obtain an extract by performing solution extraction from the fermented product obtained after the koji mold fermentation. The solution extraction step can be performed directly on the koji mold fermentation product, but is preferably performed on the koji mold fermentation product after further processing such as shredding, crushing, grinding, or powdering.

[0030] The solvent used in the solution extraction step may be water, a buffer solution, an organic solvent, or a water-containing solvent thereof. Examples of the organic solvent include lower aliphatic alcohols such as ethanol, methanol, isopropanol, and butanol, as well as acetone, ethyl acetate, and chloroform. Among these solvents, water, ethanol, or aqueous ethanol is particularly preferred in terms of extraction efficiency, ease of handling, and safety.

[0031] In particular, aqueous ethanol is preferred, and by performing extraction using aqueous ethanol with a final concentration of more preferably 55% or more, even more preferably 60% or more, and particularly preferably 80% or more (all v / v), the elution of polysaccharides as impurities can be suppressed and the extraction efficiency of 4'-demethylnobiletin can be improved, which is preferable. The extraction conditions are as follows: the raw material (preferably the crushed material) is added with 1 to 50 times, preferably 2 to 15 times (both by mass) the amount of the solvent; and the raw material is soaked or shaken at a temperature of 0°C to the boiling point of the solvent, preferably room temperature to a temperature below the boiling point of the solvent, for 5 minutes to 1 month, preferably 20 minutes to 1 week.

[0032] The obtained extract can be concentrated to dryness by freeze-drying or drying using an evaporator or the like. Furthermore, the solution extraction step can be performed multiple times using multiple different solvents. In particular, when the first extraction is performed with water or a low-concentration aqueous alcohol, the extraction efficiency of 4'-demethylnobiletin can be improved by subsequently performing an extraction using aqueous ethanol having the specific concentration or higher. The extract obtained as described above (the extract liquid or concentrated dry product) has an excellent effect of promoting BDNF secretion from small intestinal endocrine cells, and can therefore be used as is as an active ingredient in the food and beverage composition of this embodiment.

[0033] 〔purification〕 Furthermore, by subjecting these to a purification step, the 4'-demethylnobiletin content can be further increased. As a purification step, a high-content composition can be obtained by liquid-liquid separation extraction or column purification using silica gel, chemically modified silica gel, activated carbon, synthetic adsorption resin carrier, etc. An example of suitable purification conditions is shown below.

[0034] First, the extraction solvent (specifically, ethanol) is removed from the extract, and the resulting removed solution is applied to a column of porous synthetic adsorption resin (specifically, Diaion HP-20 [manufactured by Mitsubishi Chemical Corporation]) equilibrated with water. Then, after removing components eluted with water from the column, components eluted with 30 to 35% (v / v) ethanol are further removed. Next, components eluted with 44 to 46% (v / v) ethanol are collected from the column, thereby obtaining a composition with a high content of 4'-demethylnobiletin (specifically, a purity of 15% (w / w) or more).

[0035] Furthermore, the 4'-demethylnobiletin-rich composition obtained as described above can be further subjected to ODS column chromatography (specifically, 45% [v / v] methanol elution), thin layer chromatography (TLC) (specifically, hexane / ethanol [7:3]), or ODS-HPLC (specifically, 37% [v / v] acetonitrile-water mixed solvent), and the target peak can be collected to isolate pure 4'-demethylnobiletin. The 4'-demethylnobiletin obtained as described above is a monodemethyl form of nobiletin in which the 4'-position has been demethylated. 4'-demethylnobiletin becomes more polar due to demethylation, and has superior solubility in alcohol and water compared to nobiletin.

[0036] [Medicines and functional foods and beverages] The present embodiment relates to a food and drink composition for promoting BDNF secretion from small intestinal endocrine cells, which contains 4'-demethylnobiletin as an active ingredient. The "food and drink composition" in this embodiment includes functional foods, functional drinks, and general food and drink.

[0037] In this embodiment, 4'-demethylnobiletin can be used as an active ingredient in a food or beverage composition for promoting BDNF secretion by mixing it with various raw materials as each composition obtained in the above process (such as a 'composition directly containing the fermentation product,' 'solution extract,' or 'purified product') or as an 'isolate.'

[0038] The effective intake amount of 4'-demethylnobiletin in this embodiment is 1 mg or more, preferably 5 mg or more, per day for an adult weighing 60 kg, and by orally taking this amount, it is possible to obtain the excellent effect of promoting the secretion of BDNF from small intestinal endocrine cells, the effect of reducing stress or depression in daily life and easing anxiety, the effect of increasing vitality, energy, or motivation, and / or the effect of reducing abdominal discomfort or constipation selected from abdominal bloating, rumbling, and gas generation in daily life.

[0039] The content of 4'-demethylnobiletin in the food and beverage composition according to this embodiment may be any content that ensures the above-mentioned necessary intake amount, and specifically, it can be contained so that it is 0.001% by mass or more, preferably 0.01% by mass or more, and more preferably 0.1% by mass or more. The upper limit can be 20% by mass or less.

[0040] Therefore, it is expected that the above-mentioned effects can be obtained by ingesting the food and beverage composition of this embodiment in a form and by an ingestion method (frequency and amount) that ensures the necessary amount. However, it is desirable to appropriately determine the intake amount depending on the subject's age, weight, symptoms, ingestion schedule, composition form, etc.

[0041] With regard to the food and beverage composition according to this embodiment, 4'-demethylnobiletin or a composition containing same can be mixed with various food ingredients and additives to form, for example, biscuits, snacks, gum, tablets, chewable tablets, soft drinks, drinks, soups, jellies, candies, and the like. The food and beverage composition according to this embodiment may contain, in addition to 4'-demethylnobiletin or a composition containing same, various carriers, additives, other medicinal ingredients, and the like, as long as the effects of the present disclosure are achieved. [Example]

[0042] The present disclosure will be described below with reference to examples, but the scope of the present disclosure is not limited to these examples.

[0043] Example 1 Preparation of a 4'-demethylnobiletin-containing composition According to the method described in Patent Document 2, a composition containing 4'-demethylnobiletin, a nobiletin conversion product, was prepared by fermenting Ponkan orange peel with koji mold.

[0044] Specifically, 10 kg of Ponkan peel was chopped into small pieces and sterilized by steaming. The resulting Ponkan peel was inoculated with Aspergillus awamori (manufactured by Bioc Co., Ltd.) so that it was distributed throughout the peel. Fermentation (Koji mold fermentation) was then carried out aerobically in a thermostatic chamber at 30°C for 5 days to obtain a Koji mold fermentation product. 60 L of water was added to 5 kg of the resulting Koji mold fermentation product, and hot water extraction was carried out at 100°C for 1 hour to obtain an extract.

[0045] The obtained extract was applied to a Diaion HP20 (porous synthetic adsorption resin column) that had been equilibrated with water in advance, and after removing non-adsorbed components with 3 L of water, the components eluted with 2 L of 35% (v / v) ethanol were further removed. Next, the components eluted with 2 L of 45% (v / v) ethanol were collected, and the collected matter was concentrated to dryness using a rotary evaporator to obtain a 4'-demethylnobiletin-containing composition (4'-demethylnobiletin content 19.1%).

[0046] Example 2: Preparation of 4'-demethylnobiletin isolate 2 g of the 4'-demethylnobiletin-containing composition obtained in Example 1 was dissolved in 20% (v / v) methanol and subjected to ODS column chromatography (a column having an inner diameter of 20 mm and a length of 30 cm was packed with 30 g of Wako Gel 50C18). Components eluted with 40% (v / v) methanol were removed, and components eluted with 60% (v / v) methanol were collected.

[0047] The recovered components were then subjected to preparative TLC chromatography (silica gel 70PF) using a developing solvent of hexane / ethanol 7:3. 254 A Wako plate (film thickness 0.75 mm, manufactured by Wako Pure Chemical Industries) was used, and the fractions containing 4'-demethylnobiletin were collected while checking using a UV lamp.

[0048] The obtained fraction was then applied to a preparative HPLC column (TSK GEL ODS, manufactured by Tosoh Corporation, 4.6 mm×25 cm), and 20 mg of pure 4′-demethylnobiletin was obtained using a mobile phase of 37% (v / v) acetonitrile.

[0049] Example 3: Examination of the effect of 4'-demethylnobiletin on BDNF secretion Using the 4'-demethylnobiletin isolate obtained in Example 2, the effect of adding 4'-demethylnobiletin on BDNF production in small intestinal endocrine cells was evaluated at the cellular level.

[0050] STC-1 cells (a mouse cell line) were used as small intestinal endocrine cells. The cells were cultured in DMEM medium containing 10% fetal bovine serum in an incubator at 37°C under 5% CO2, and subcultured every 2–3 days using 0.25% trypsin containing 0.1% EDTA.

[0051] STC-1 cells were seeded in 24-well plates (1 × 10 5 After 24 hours, a 4'-demethylnobiletin-containing composition (product of Example 1) or an isolated product (product of Example 2) was added. As a comparative control, DMSO or nobiletin (both manufactured by Wako Pure Chemical Industries, Ltd.) was added.

[0052] 24 hours after the addition of 4'-demethylnobiletin, the medium was removed and 0.2 ml of lysate buffer ("Complete Lysis-M", Roche) was added to prepare a cell lysate. The cell lysate was centrifuged (2500 rpm, 10 minutes), and the supernatant was stored at -80°C for 3 days, after which the amount of BDNF was measured using an ELISA kit ("Mature BDNF kit", Funakoshi).

[0053] Figure 1 shows the results of an investigation into the BDNF secretion-promoting effect of a 4'-demethylnobiletin (4'-DeNob)-containing composition on small intestinal endocrine cells. In Figure 1, "Control" indicates the DMSO-added group, while "4'-DeNob Composition 25 μg / ml" and "4'-DeNob Composition 50 μg / ml" indicate test groups in which the 4'-DeNob-containing composition prepared in Example 1 was added to the medium at concentrations of 25 μg / ml and 50 μg / ml, respectively. The vertical axis indicates the amount of BDNF (unit: pg / ml), mean ± SD (n = 3), and ** indicates a significant difference from the control (Dunnett's method, significance level 5%). Figure 1 demonstrates that the 4'-DeNob-containing composition (25 μg / ml, 50 μg / ml)-added groups promoted BDNF secretion in a concentration-dependent manner.

[0054] Figure 2 shows the results of an investigation into the BDNF secretion-promoting effect of 4'-demethylnobiletin (4'-DeNob) isolate on small intestinal endocrine cells. In Figure 2, "control" indicates the DMSO-added group, "4'-DeNob 15 μM" and "4'-DeNob 30 μM" indicate test groups in which the 4'-DeNob isolate prepared in Example 2 was added to the medium at 15 μM and 30 μM (final concentrations), respectively, and "Nob 15 μM" and "Nob 30 μM" indicate test groups in which nobiletin was added to the medium at 15 μM and 30 μM (final concentrations), respectively. The vertical axis indicates the amount of BDNF (unit: pg / ml), mean ± SD (n = 3), and ** indicates a significant difference from the control (Dunnett's method, significance level 5%). FIG. 2 shows that in the 4'-demethylnobiletin (15 μM, 30 μM) added area, the amount of BDNF secretion was promoted in a concentration-dependent manner, but there was no change in the nobiletin (15 μM, 30 μM) added area.

[0055] The above results demonstrated that 4'-demethylnobiletin has a strong effect of promoting BDNF secretion from small intestinal endocrine cells, and that this effect is more pronounced than that of nobiletin. The effect of promoting BDNF secretion is known to bring about the effects of reducing stress or depression in daily life, alleviating anxiety, and increasing vitality, energy, or motivation. The effect of promoting BDNF secretion is also known to bring about the effects of reducing abdominal discomfort such as bloating, rumbling, and gas generation, or constipation in daily life. Therefore, 4'-demethylnobiletin or a composition containing it is expected to have not only the effect of promoting BDNF secretion from small intestinal endocrine cells, but also the effects of reducing stress or depression in daily life, alleviating anxiety, increasing vitality, energy, or motivation, and reducing abdominal discomfort or constipation in daily life.

[0056] Example 3: Beverage production example The ingredients were blended in the amounts shown below, and a 4'-demethylnobiletin-blended beverage (180 ml) was produced by a conventional method. 4'-demethylnobiletin-containing composition (Example 1) 0.026 g 5g apple juice concentrate 2 g lactose High fructose corn syrup 5g Acidulant (citric acid) 0.3 g Sweetener (sucralose) 0.01 g Preservative (sodium benzoate) 0.03 g Water Residual

[0057] The above has described in detail the embodiments and examples of the present disclosure with reference to the drawings, but the specific configurations are not limited to these, and design changes that do not deviate from the gist of the present disclosure are included in the present disclosure.

[0058] For example, in the above examples, the effect of promoting BDNF secretion from small intestinal endocrine cells by 4'-demethylnobiletin extracted and purified from Ponkan mandarin orange peel or a composition containing same was described, but the present disclosure is not limited to this, and food and beverage compositions for promoting BDNF secretion from small intestinal endocrine cells containing 4'-demethylnobiletin as an active ingredient, extracted from any citrus fruit containing nobiletin instead of Ponkan mandarin orange, can also be included in the present disclosure. [Industrial Applicability]

[0059] The present disclosure makes it possible to provide a food and beverage composition that has the effect of promoting the secretion of brain-derived neurotrophic factor (BDNF) from small intestinal endocrine cells by containing 4'-demethylnobiletin, a highly safe raw material, as an active ingredient.

[0060] Therefore, the present disclosure is expected to be used in functional foods and beverages that have the effect of reducing stress and depression in daily life, promoting a positive mood, and alleviating stomach discomfort. In modern society, people often experience stress and anxiety, and since everyone is prone to stress and anxiety in their social lives, food and beverage compositions for preventing and improving these conditions are particularly required to be highly safe products. In this context, the present disclosure, which is highly safe, is expected to be in great demand as a material for maintaining quality of life in modern society.

Claims

1. A food and drink composition for promoting brain-derived neurotrophic factor secretion from small intestinal endocrine cells, comprising 4'-demethylnobiletin as an active ingredient.

2. The food and beverage composition according to claim 1, which has the effect of reducing stress or depression in daily life, easing anxiety, and / or increasing vitality, energy, or motivation.

3. 3. The food and drink composition according to claim 1 or 2, which has the effect of alleviating stomach discomfort or constipation in daily life.

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