Expression enhancers and functional foods for promoting mental health

Abstract

To provide a mental health-related gene expression promoter and a functional food for mental health enhancement that are expected to enhance mental health, especially to improve dementia.SOLUTION: Provided is an expression promotor, which is a mental health-related gene expression promoter, and is set to contain a dipeptide represented by Gly-Pro and / or Leu-Pro as a main component for inducing function. Further, it is also characterized that the mental health-related gene is a brain-derived neurotrophic factor gene. Further, the functional food for mental health promotion is set to contain a dipeptide represented by Gly-Pro and / or Leu-Pro as a main component for inducing function.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to an expression promoter and a functional food for promoting mental health. [Background technology]

[0002] Dementia is a major social problem, and as Japan is facing an aging society and its incidence is expected to continue to increase, addressing the issue is an urgent task.

[0003] Depending on the severity of the symptoms, dementia can cause confusion in daily life and problems with those around them, and since understanding and assistance from family and acquaintances is important, it can also place a burden on these people.

[0004] Therefore, medical institutions have traditionally administered drug treatments to alleviate as many of the problems in daily life caused by dementia as possible (see, for example, Non-Patent Document 1). [Prior art documents] [Non-patent literature]

[0005] [Non-Patent Document 1] Takeshi Tabira, "Treatment of Alzheimer's Disease: Current Status and Future", Journal of the Japan Geriatrics Society, Japan Geriatrics Society, 2012, Vol. 49, p. 402-418 Summary of the Invention [Problem to be solved by the invention]

[0006] Incidentally, preventing and improving dementia is extremely meaningful not only in terms of individual health issues, but also in terms of the country's medical finances.

[0007] In particular, if it is possible to prevent or improve dementia through daily eating habits, it will be possible to improve quality of life for the long term without relying on support from medical institutions, and it will be possible to reduce the personal and financial burden caused by the onset of dementia.

[0008] The present invention has been made in consideration of the above circumstances, and provides an expression promoter for mental health-related genes, which are expected to promote mental health, particularly to improve dementia, as well as a functional food for promoting mental health and an external skin product. [Means for solving the problem]

[0009] In order to solve the above-mentioned problems, the expression promoter of the present invention comprises: (1) Contains dipeptides as the main component for inducing function An agent for promoting expression of a mental health-related gene, comprising: The dipeptide contains at least Leu-Pro, and the mental health-related genes are a brain-derived neurotrophic factor gene and an arylalkylamine-N-acetyltransferase gene. It was decided.

[0011] In addition, in the functional food for promoting the function of the present invention, ( 2) Ji Contains peptides as the main components for inducing functions and promotes the expression of genes related to mental health Functional foods for promoting mental health wherein the dipeptide comprises at least Leu-Pro, and the mental health-related genes are a brain-derived neurotrophic factor gene and an arylalkylamine-N-acetyltransferase gene. It was decided.

[0012] In addition, in the skin care product according to the present invention, 3 )Above (1 ) The expression promoter described above is contained.

[0014] In addition, in the present invention, ( 4 ) In a functional food for promoting mental health, which aims to prevent or improve dementia by promoting the expression of brain-derived neurotrophic factor gene, and to improve sleep by promoting the expression of arylalkylamine-N-acetyltransferase gene, a dipeptide represented by Leu-Pro is used as the main ingredient for said prevention or improvement. Effect of the Invention

[0015] According to the expression promoter of the present invention, Contains dipeptides as the main component for inducing function An agent for promoting expression of a mental health-related gene, comprising: The dipeptide contains at least Leu-Pro, and the mental health-related genes are a brain-derived neurotrophic factor gene and an arylalkylamine-N-acetyltransferase gene. It is therefore possible to provide an agent for promoting the expression of mental health-related genes, which is expected to promote mental health, particularly improvement of dementia.

[0017] Furthermore, if the dipeptide contains at least Leu-Pro and the mental health-related genes are the brain-derived neurotrophic factor gene and the arylalkylamine-N-acetyltransferase gene, it is possible to provide an expression-promoting agent that is expected to improve mental health by improving sleep in addition to improving dementia.

[0018] In addition, according to the functional food for promoting mental health of the present invention, , J Contains peptides as the main components for inducing functions and a functional food for promoting mental health that promotes the expression of mental health-related genes, the dipeptide containing at least Leu-Pro, the mental health-related genes being a brain-derived neurotrophic factor gene and an arylalkylamine-N-acetyltransferase gene. As a result, it is possible to provide a functional food for promoting mental health that is expected to promote mental health, particularly to improve dementia. In addition, it is possible to provide a functional food that is expected to promote mental health by improving sleep in addition to improving dementia.

[0019] Furthermore, since the topical skin product of the present invention contains the above-mentioned expression promoter, it is possible to provide a topical skin product that is expected to transdermally promote mental health, in particular improve dementia.

[0021] Furthermore, according to the present invention, in a functional food for promoting mental health aimed at preventing or improving dementia by promoting the expression of the brain-derived neurotrophic factor gene, and improving sleep by promoting the expression of the arylalkylamine-N-acetyltransferase gene, a dipeptide represented by Leu-Pro is used as the main ingredient for said prevention or improvement, and therefore an expression promoter can be provided that is expected to promote mental health by improving sleep as well as improving dementia, making it possible to promote mental health through daily dietary habits. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0022] The present invention relates to an expression promoter for mental health-related genes, and in particular provides an expression promoter for mental health-related genes that is expected to promote mental health, in particular to improve dementia.

[0023] Here, mental health refers to mental health and mental hygiene, and in this specification is a concept that includes matters relating to dementia and sleep.

[0024] Furthermore, a feature of the expression promoter according to this embodiment is that it contains a dipeptide represented by Gly-Pro and / or Leu-Pro as a main component for inducing function.

[0025] Gly-Pro is a dipeptide (glycylproline) formed by the peptide bond between glycine and proline, and is a compound represented by the following structural formula (i). [ka]

[0026] Leu-Pro is a dipeptide (leucylproline) formed by the peptide bond between leucine and proline, and is a compound represented by the following structural formula (ii). [ka]

[0027] As will be explained later with reference to experimental results, these dipeptides have the effect of promoting the expression of mental health-related genes, making it possible to provide an agent for promoting the expression of mental health-related genes that is expected to improve mental health, in particular dementia.

[0028] The mental health-related gene may also be a brain-derived neurotrophic factor gene.

[0029] Promoting the expression of the brain-derived neurotrophic factor (BDNF) gene is expected to affect the brain function control mechanism via intestinal activation, enhance the growth and maintenance of the nervous system, and further alleviate and suppress dementia through the brain function control mechanism.

[0030] It is also expected to contribute to improving mental health in terms of improving memory, increasing energy (preventing or improving depression), and suppressing appetite (preventing overeating and obesity).

[0031] The dipeptide may also contain at least Leu-Pro, and the mental health-related genes may be a brain-derived neurotrophic factor gene and an arylalkylamine-N-acetyltransferase (AANAT) gene.

[0032] With this configuration, in addition to the effect resulting from the increased expression of the brain-derived neurotrophic factor gene described above, a sleep-improving effect resulting from the increased expression of the arylalkylamine-N-acetyltransferase gene can be expected.

[0033] In other words, melatonin is known as a substance that has the effect of switching between wakefulness and sleep and inducing natural sleep, and arylalkylamine-N-acetyltransferase is the rate-limiting enzyme in melatonin biosynthesis. Since promoting the expression of the arylalkylamine-N-acetyltransferase gene can increase the amount of melatonin, using it at the appropriate time can improve sleep, such as making it easier to fall asleep.

[0034] The present specification also provides functional foods for promoting mental health, which contain a dipeptide represented by Gly-Pro and / or Leu-Pro as a main component for inducing function.

[0035] In other words, the functional food for promoting mental health in this embodiment contains dipeptides represented by Gly-Pro and / or Leu-Pro, and is expected to improve dementia and sleep due to the above-mentioned effects derived from these dipeptides.

[0036] In addition, "containing as a main ingredient for inducing a function" means "containing as an active ingredient" in the context of medicines. In other words, in the case of health functional foods, it means containing the above dipeptide as an ingredient for exerting a function or efficacy, although the expressions may differ, such as functional ingredients in functional foods, nutritional ingredients in nutrient functional foods, and ingredients involved in foods for specified health uses. In addition, functional foods for promoting mental health also include beverages.

[0037] This specification also provides a skin care product containing the expression promoter. Here, the skin care product refers to toiletries and the like that are applied to the skin or hair by coating or spraying, and includes quasi-drugs, cosmetics, and the like.

[0038] For example, cosmetics include not only basic cosmetics (skin care cosmetics) and finishing cosmetics (makeup cosmetics), but also hand soap, shampoo, body soap, etc. Furthermore, quasi-drugs include, for example, hair dyes, permanent wave agents, bath agents, mouth fresheners, hair growth agents, hair removers, etc.

[0039] Such topical skin products allow the dipeptide to be taken in transdermally, and can provide topical skin products that are expected to promote mental health, particularly dementia, transdermally. In other words, the products can be in the form of quasi-drugs, cosmetics, or other products that allow the dipeptide to be absorbed transdermally.

[0040] This specification also provides a method for using the dipeptide as a major ingredient in functional foods for improving mental health.

[0041] Specifically, in a first aspect, the present invention provides a method for using a dipeptide represented by Gly-Pro and / or Leu-Pro as a main ingredient for preventing or improving dementia in a functional food for promoting mental health, the purpose of which is to prevent or improve dementia by promoting the expression of brain-derived neurotrophic factor genes.

[0042] According to this method of use, a functional food for promoting mental health that is expected to improve dementia can be provided, and mental health can be promoted through daily dietary habits.

[0043] In addition, as a second aspect, the present invention also provides a method for using a dipeptide represented by Leu-Pro as a main ingredient for preventing or improving dementia by promoting the expression of brain-derived neurotrophic factor gene and for improving sleep by promoting the expression of arylalkylamine-N-acetyltransferase gene in a functional food for promoting mental health, the method comprising the steps of:

[0044] Furthermore, this method of use can provide an expression promoter that is expected to improve mental health by improving sleep as well as improving dementia, making it possible to promote mental health through daily dietary habits.

[0045] The expression promoter and functional food for promoting mental health according to this embodiment will be further described below, along with the test results of the tests carried out to confirm the action of the dipeptide added to these preparations and foods.

[0046] [1. Anti-dementia evaluation test using brain-derived neurotrophic factor gene expression as an indicator] In this study, we used two types of dipeptides (Gly-Pro and Leu-Pro) to examine the changes in brain-derived neurotrophic factor gene expression.

[0047] First, human colon cancer-derived cells (Caco-2) were cultured. Caco-2 cells were precultured in Dulbecco's Modified Eagle Medium (DMEM) (high glucose) (containing 1% penicillin-streptomycin and 10% fetal bovine serum (FBS)) in a φ10 cm dish until they became confluent.

[0048] After washing with phosphate-buffered saline (PBS), the cells were resuspended in medium and then plated in a 24-well plate at 1.0 × 10 5The cells were seeded at a concentration of 1000 cells / well and cultured overnight in a CO2 incubator (37°C, 5% CO2).

[0049] Next, the medium of the cells cultured overnight was replaced with serum-free DMEM medium (containing 1% penicillin-streptomycin) containing one of the dipeptides, and the cells were cultured for 24 hours in a CO2 incubator. The dipeptides were added to the medium at a final concentration of 400 μg / mL.

[0050] Next, the gene expression levels were compared by real-time PCR. Specifically, Caco-2 cells were harvested after culturing with the addition of dipeptides, and total RNA was extracted using a PureLink RNA Mini kit (Invitrogen).

[0051] Next, cDNA was synthesized from the extracted total RNA using ReverTra Ace qPCR RT Master Mix with gDNA Remover (TOYOBO).

[0052] Next, real-time PCR was performed using the synthesized cDNA as a template with an AriaMX real-time PCR device (Agilent Technologies).

[0053] For the real-time PCR reaction, THUNDERBIRD SYBR qPCR Mix (TOYOBO) was used. 5'-GTCAAGTTGGGAGCCTGAAATAGTG-3' (SEQ ID NO: 1) and 5'-AGGATGCTGGTCCAAGTGGTG-3' (SEQ ID NO: 2) were used as primers for the brain-derived neurotrophic factor gene, and 5'-GCACCGTCAAGGCTGAGAAC-3' (SEQ ID NO: 3) and 5'-ATGGTGGTGAAGACGCCAGT-3' (SEQ ID NO: 4) were used as primers for the internal standard GAPDH. The real-time PCR reaction conditions were 40 cycles of a two-step PCR reaction consisting of initial denaturation at 95°C for 3 minutes, denaturation at 95°C for 3 seconds, and annealing / extension at 60°C for 30 seconds. The results are shown in Table 1. [Table 1]

[0054] Table 1 shows the change in expression of the brain-derived neurotrophic factor gene in Caco-2 cells after addition of the dipeptide (n=3, mean ± SD., *p<0.05, **p<0.01). As can be seen from Table 1, it was confirmed that the expression of the brain-derived neurotrophic factor gene significantly increased by about 1.5 times when Gly-Pro was added and by about 1.2 times when Leu-Pro was added, compared to the control (water).

[0055] These results suggest that Gly-Pro and Leu-Pro may alleviate and suppress dementia by enhancing the production of brain-derived neurotrophic factor, which in turn promotes the activation of nerve cells, thereby regulating brain function through intestinal activation.

[0056] In other words, it has been shown that the expression promoter and functional food for promoting mental health according to this embodiment are expected to alleviate and suppress dementia by containing the dipeptide represented by Gly-Pro and / or Leu-Pro.

[0057] 2. Sleep evaluation test using the expression of melatonin biosynthesis-related enzyme genes as an index In this study, we used Leu-Pro as the dipeptide and investigated the changes in expression of the arylalkylamine-N-acetyltransferase gene.

[0058] First, human neuroblastoma-derived SH-SY5Y cells were cultured. SH-SY5Y cells were precultured in a φ10 cm dish using Dulbecco's Modified Eagle Medium (DMEM) (high glucose) (containing 1% penicillin-streptomycin and 10% fetal bovine serum (FBS)) until they became confluent.

[0059] After washing with phosphate-buffered saline (PBS), the cells were resuspended in medium and then plated in a 24-well plate at 1.0 × 10 5 The cells were seeded at a concentration of 1000 cells / well and cultured overnight in a CO2 incubator (37°C, 5% CO2).

[0060] Next, the medium of the cells cultured overnight was replaced with serum-free DMEM medium (containing 1% penicillin-streptomycin) containing the dipeptide, and the cells were cultured for 24 hours in a CO2 incubator. The dipeptide was added to the medium at a final concentration of 400 μg / mL.

[0061] Next, we compared the gene expression levels by real-time PCR. Specifically, SH-SY5Y cells were harvested after culturing with the addition of dipeptides, and total RNA was extracted using a PureLink RNA Mini kit (Invitrogen).

[0062] Next, cDNA was synthesized from the extracted total RNA using ReverTra Ace qPCR RT Master Mix with gDNA Remover (TOYOBO).

[0063] Next, real-time PCR was performed using the synthesized cDNA as a template with an AriaMX real-time PCR device (Agilent Technologies).

[0064] For the real-time PCR reaction, THUNDERBIRD SYBR qPCR Mix (TOYOBO) was used. 5'-TCCTGTGGAGATACCTTCACCA-3' (SEQ ID NO: 5) and 5'-CACAGTTCAGAAGGCAAGAGGT-3' (SEQ ID NO: 6) were used as primers for the arylalkylamine-N-acetyltransferase gene, and 5'-GCACCGTCAAGGCTGAGAAC-3' (SEQ ID NO: 3) and 5'-ATGGTGGTGAAGACGCCAGT-3' (SEQ ID NO: 4) were used as primers for the internal standard GAPDH. The real-time PCR reaction conditions were 40 cycles of a two-step PCR reaction consisting of initial denaturation at 95°C for 3 minutes, denaturation at 95°C for 3 seconds, and annealing / extension at 60°C for 30 seconds. The results are shown in Table 2. [Table 2]

[0065] Table 2 shows the change in expression of the arylalkylamine-N-acetyltransferase gene in SH-SY5Y cells after the addition of dipeptides (n=3, mean ± SD., *p<0.05, **p<0.01). As can be seen from Table 2, it was confirmed that the expression of the arylalkylamine-N-acetyltransferase gene significantly increased by about 1.2 times when Leu-Pro was added compared to the control (water).

[0066] These results suggest that Leu-Pro is expected to increase melatonin levels and improve sleep by promoting the expression of the arylalkylamine-N-acetyltransferase gene, which is the rate-limiting enzyme in melatonin biosynthesis.

[0067] In other words, it has been shown that the expression promoter and functional food for promoting mental health according to this embodiment are expected to improve sleep by containing the dipeptide represented by Leu-Pro.

[0068] As described above, the expression promoter of this embodiment is an expression promoter of mental health-related genes that contains a dipeptide represented by Gly-Pro and / or Leu-Pro as the main component for inducing function, and therefore can provide an expression promoter of mental health-related genes that is expected to promote mental health, particularly improvement of dementia.

[0069] Furthermore, according to the functional food for promoting mental health of the present invention, since it contains a dipeptide represented by Gly-Pro and / or Leu-Pro as the main component for inducing function, it is possible to provide a functional food for promoting mental health that is expected to promote mental health, particularly improve dementia.

[0070] Finally, the above-mentioned embodiments are merely examples of the present invention, and the present invention is not limited to the above-mentioned embodiments. Therefore, even if the above-mentioned embodiments are different, various modifications can be made depending on the design, etc., as long as they do not deviate from the technical idea of ​​the present invention.

Claims

1. An expression promoter for a mental health-related gene, comprising a dipeptide as a main component for inducing a function, The expression promoter, characterized in that the dipeptide contains at least Leu-Pro, and the mental health-related genes are a brain-derived neurotrophic factor gene and an arylalkylamine-N-acetyltransferase gene.

2. A functional food for promoting mental health, which contains a dipeptide as a main component for inducing function and promotes the expression of mental health-related genes, A functional food for promoting mental health, characterized in that the dipeptide contains at least Leu-Pro, and the mental health-related genes are a brain-derived neurotrophic factor gene and an arylalkylamine-N-acetyltransferase gene.

3. A skin care product containing the expression promoter according to claim 1.

4. The present invention relates to a functional food for promoting mental health, the use of a dipeptide represented by Leu-Pro as a main ingredient for preventing or improving dementia by promoting the expression of a brain-derived neurotrophic factor gene, and for improving sleep by promoting the expression of an arylalkylamine-N-acetyltransferase gene.

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