Composition comprising triacetylresveratrol as active ingredient for adenosine a2a receptor activation

Abstract

To provide a composition comprising triacetylresveratrol as an active ingredient for adenosine A2A receptor activation.SOLUTION: The present invention provides a composition comprising triacetylresveratrol as an active ingredient for adenosine A2A receptor activation. The present invention also provides a food with function claims, a supplement, or a food for specified health uses that comprises the composition for the purpose of improving sleep quality.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a composition containing triacetylresveratrol as an active ingredient having an adenosine A2A receptor activating effect. [Background technology]

[0002] Adenosine A2A receptors are G protein-coupled receptors distributed throughout the body and are known to be deeply involved in sleep regulation in the sleep center of the brain. Activating this adenosine A2A receptor can induce deep non-REM sleep and improve sleep quality. For example, it is known that CGS21680, an adenosine A2A receptor agonist, increases non-REM sleep when administered to animals (see, for example, Non-Patent Documents 1 and 2). As a natural ingredient that activates the adenosine A2A receptor, sake yeast has been reported to increase non-REM sleep in humans and improve sleep quality through activation of the adenosine A2A receptor (see, for example, Patent Document 1, Non-Patent Documents 3 and 4).

[0003] Triacetylresveratrol is known to have a whitening effect when applied to the skin (see, for example, Patent Document 2), and to have a protective effect against radiation due to its strong antioxidant properties when taken orally (see, for example, Non-Patent Document 5). [Prior art documents] [Patent documents]

[0004] [Patent Document 1] JP 2013-82641 A [Patent Document 2] Special Publication No. 2016-506925 [Non-patent literature]

[0005] [Non-Patent Document 1] Satoh S, et al. Proceedings of the National Academy of Sciences of the United States of America. 1996 Jun 11;93(12):5980-4. DOI:10.1073 / pnas.93.12.5980. [Non-Patent Document 2] Korkutata M, et al. Neuropharmacology. 2019 Jan;144:122-132. DOI:10.1016 / j.neuropharm.2018.10.022. [Non-Patent Document 3] Nakamura Y, et al. Journal of sleep research. 2016 Dec;25(6):746-753. DOI:10.1111 / jsr.12434. [Non-Patent Document 4] Monoi N, et al. Journal of sleep research. 2016 Feb;25(1):116-23. DOI:10.1111 / jsr.12336. [Non-Patent Document 5] Koide K, et al. ACS Medicinal Chemistry Letters. 2011 Jan 25;2(4):270-274. DOI: 10.1021 / ml100159p. Summary of the Invention [Problem to be solved by the invention]

[0006] The object of the present invention is to provide a substance that activates the adenosine A2A receptor, and a functional food, supplement, or food for specified health uses that uses the substance and is intended to improve sleep quality. [Means for solving the problem]

[0007] As a result of extensive research conducted by the inventors in order to achieve the above-mentioned object, they discovered that triacetylresveratrol activates adenosine A2A receptors, thereby improving the quality of sleep, and thus completed the present invention. Therefore, the present invention is a composition containing triacetylresveratrol as an active ingredient that activates adenosine A2A receptors. It is also used in functional foods, supplements, and foods for specified health uses that aim to improve sleep quality. Effect of the Invention

[0008] The composition of the present invention containing the triacetylresveratrol as an active ingredient for activating the adenosine A2A receptor has not been reported to have any notable adverse events when triacetylresveratrol was ingested in animal tests, and is therefore considered to be safe when used in the amounts described herein. The present invention can increase non-REM sleep and improve sleep quality. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0009] The present invention will be described in detail below. The triacetylresveratrol of the present invention is represented by chemical formula 1 and can be produced by reacting resveratrol contained in grape skins, seeds, etc. with acetic anhydride in the presence of pyridine, for example, to acetylate the three hydroxyl groups. When triacetylresveratrol is orally ingested, it is absorbed in the intestinal tract and part of it is metabolized to resveratrol, but the remainder circulates throughout the body via the blood.

[0010] [ka]

[0011] <How to obtain triacetyl resveratrol> As described above, triacetylresveratrol can be obtained by acetylating the three hydroxy groups of resveratrol. Resveratrol is found in grape skins and seeds, and can be extracted using methods such as solvent extraction using ethanol, methanol, ethyl acetate, acetone, etc., followed by hydrolysis and purification using column chromatography, etc. Triacetylresveratrol is commercially available, and commercially available triacetylresveratrol can also be used in the present invention.

[0012] <How to use triacetyl resveratrol> Triacetylresveratrol can be incorporated into, for example, functional foods, supplements, and foods for specified health uses. Examples of foods that may be designated as functional foods or foods for specified health uses include noodles, rice, bread, Western confectioneries, Japanese confectioneries, gum, juice, and alcoholic beverages. The oral dose of the composition of the present invention containing triacetylresveratrol as an active ingredient for activating the adenosine A2A receptor is usually 1 mg to 1000 mg / day in terms of the daily intake of triacetylresveratrol by humans. EXAMPLES

[0013] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples. <Establishment of an adenosine A2A receptor activity evaluation system> The following reporter assay was constructed to evaluate adenosine A2A receptor activity. When adenosine A2A receptors are activated, they interact with intracellular Gs proteins and activate adenylate cyclase, thereby producing cAMP. Activation of adenosine A2A receptors can be evaluated by detecting cAMP signals. The cAMP signal can be detected by measuring the amount of luminescence from firefly luciferase and Renilla luciferase as follows. (1) A plasmid encoding firefly luciferase (product name: pGL4.29, manufactured by Promega Corporation) downstream of CRE (cAMP-response element) and a Renilla luciferase expression vector (product name: pF9A CMV hRluc-neo Flexi® Vector, manufactured by Promega Corporation; Barnase sequence was removed) were introduced into HEK293 cells. A transfection reagent (product name: FuGENE (registered trademark) HD ​​Transfection Reagent, manufactured by Promega Corporation) was used for gene introduction. (2) 5 × 10 cells obtained in (1) were added to a 96-well plate in DMEM medium. 4 Cells were seeded per well. (3) After 23 hours, ZM241385 dissolved in DMSO was added to the samples at the concentrations shown in Samples 1 to 4 below. (4) One hour after (3) above, the medium from (2) above was removed and replaced with DMEM medium containing 10% FBS, and NECA dissolved in DMSO was added to the concentrations shown in Samples 1 to 4 below. (5) Five hours after the medium change in (4) above, the medium was removed, and the luminescence intensities of firefly luciferase and Renilla luciferase were measured using the Dual-Glo (registered trademark) Luciferase Assay System (Promega Corporation). (6) The luminescence intensity of Renilla luciferase was used as a standard, and the luminescence intensity of firefly was compared to this to calculate the ratio. (7) The ratio obtained in (6) above was converted so that the ratio when nothing was added (sample 1) was 1, and the relative amount of light emission was calculated.

[0014] *NECA (5'-N-Ethylcarboxamidoadenosine) is a general adenosine receptor agonist that exhibits high affinity for the adenosine A2A receptor. *ZM241385 is a selective antagonist of the adenosine A2A receptor.

[0015] Sample 1 contained neither NECA nor ZM241385. In sample 2, NECA was added to the medium to a concentration of 100 nM, and ZM241385 was not added. In sample 3, NECA was not added, and ZM241385 was added to the medium to a concentration of 10 μM. In sample 4, NECA was added to the medium to a concentration of 100 nM, and ZM241385 was added to the medium to a concentration of 10 μM.

[0016] As a result, the relative light emission amount of sample 1 was 1.00, the relative light emission amount of sample 2 was 12.17, the relative light emission amount of sample 3 was 1.03, and the relative light emission amount of sample 4 was 1.14. NECA, an agonist of the adenosine A2A receptor, activated the cAMP signal, and ZM241385, an antagonist selective for the adenosine A2A receptor, inhibited the activation of the cAMP signal, demonstrating that the activation of the adenosine A2A receptor can be evaluated using this evaluation system.

[0017] <Adenosine A2A receptor activity evaluation of triacetylresveratrol> The reporter assay was performed in the same manner as above, except that the NECA concentration in the medium was changed from 100 nM to 10 μM in the triacetylresveratrol medium. Sample 5 contained neither triacetylresveratrol nor ZM241385 added. In sample 6, triacetylresveratrol was added to the medium to a concentration of 10 μM, and ZM241385 was not added. In sample 7, triacetylresveratrol was added to the medium to a concentration of 10 μM, and ZM241385 was added to the medium to a concentration of 10 μM.

[0018] As a result, the relative light emission intensity of sample 5 was 1.00, that of sample 6 was 2.42, and that of sample 7 was 1.23, confirming that triacetylresveratrol activates the adenosine A2A receptor.

[0019] [Example 1 Beverage] A beverage was produced by mixing 30 g of fructose glucose liquid sugar, 0.5 g of emulsifier, 1 g of a composition containing 1% by mass of triacetylresveratrol, an appropriate amount of flavoring, and 60 g of purified water in a mixer in a conventional manner.

Claims

1. A composition containing triacetylresveratrol as an active ingredient for activating adenosine A2A receptors.

2. A functional food, supplement, or food for specified health uses intended to improve the quality of sleep, using a composition containing the triacetylresveratrol described in claim 1 as an active ingredient for activating adenosine A2A receptors.

Images