Anti-stress food composition

Abstract

To provide a new food composition having an anti-stress effect.SOLUTION: The food composition includes green tea extract containing epigallocatechin gallate and citrus extract containing flavanone glycoside.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present invention relates to a food composition comprising a green tea extract, such as catechin, and a citrus extract. [Background technology]

[0002] EGCG (Epigallocatechin-O-gallate), a major catechin contained in green tea, has been reported to have anticancer effects (Non-Patent Document 1), and a phase II clinical trial is being conducted in patients with chronic lymphocytic leukemia, a type of blood cancer (Non-Patent Document 2). It is known that EGCG exerts its anticancer effects by binding to the target molecule 67-kDa Laminin Receptor (67LR) on the cell membrane, but the lethal effect of EGCG on leukemia cells and multiple myeloma cells is limited (Non-Patent Document 2), and there is a strong demand for enhancing the effect of EGCG in order to use it as an anticancer drug.

[0003] Patent Document 1 discloses that citrus extracts or flavanone glycosides enhance the anti-cancer effects of catechins, and that a composition containing a green tea extract such as catechins and a citrus extract or a flavanone glycoside has various effects such as anti-cancer effects, anti-muscle atrophy effects, and anti-obesity effects. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] WO2015 / 199169 [Non-patent literature]

[0005] [Non-Patent Document 1] Khan N, Afaq F, Saleem M, et al. Targeting multiple signaling pathways by green tea polyphenol (-)-epigallocatechin-3-gallate. Cancer. res., 2006;66:2500-2505. [Non-Patent Document 2] Shanafelt TD, Call TG, and Zent CS, et al. Phase I trial of daily oral Polyphenon E in patients with asymptomatic Rai stage 0 to II chronic lymphocytic leukemia. J. Clin. Oncol., 2009;27:3808-3814. Summary of the Invention [Problem to be solved by the invention]

[0006] According to Patent Document 1, it has been suggested that citrus extracts or flavanone glycosides enhance the anti-cancer, anti-muscle atrophy, anti-obesity, anti-inflammatory, cholesterol-lowering, thrombus or cerebral infarction prevention, and immune-enhancing effects of green tea extracts such as catechins. However, it was completely unclear whether a composition containing a citrus extract and a green tea extract has an anti-stress effect. Therefore, the present invention aims to identify a novel effect of a composition containing a citrus extract and a green tea extract and to provide a novel food composition having an anti-stress effect. [Means for solving the problem]

[0007] In order to achieve the above-mentioned object, the present inventors conducted extensive research and discovered that a composition containing a citrus fruit extract and a green tea extract has an excellent anti-stress effect, leading to the completion of the present invention.

[0008] The present invention encompasses the following: (1) An anti-stress food composition comprising a green tea extract containing epigallocatechin gallate and a citrus extract containing flavanone glycosides. (2) The anti-stress food composition according to (1), which is a beverage. (3) The ratio (B / A) of epigallocatechin gallate (A) contained in the green tea extract to flavanone glycoside (B) contained in the citrus extract is 0.2. (4) The anti-stress food composition according to (3), wherein the ratio (B / A) is 0.4≦B / A≦0.8. (5) The anti-stress food composition according to (3), wherein the ratio (C / A) is 0.25≦C / A≦0.34. (6) The anti-stress food composition according to (1), wherein the flavanone glycoside is a glycosyl hesperidin.

[0009] Furthermore, the present invention relates to an anti-stress agent comprising a green tea extract containing epigallocatechin gallate and a citrus extract containing a flavanone glycoside.

[0010] Furthermore, the present invention is a method for improving or preventing symptoms caused by stress (excluding medical procedures for humans), which comprises having a subject ingest a composition comprising a green tea extract containing epigallocatechin gallate and a citrus extract containing flavanone glycosides.

[0011] In the present invention, the green tea extract may include at least one catechin selected from the group consisting of epicatechin, epigallocatechin, epicatechin gallate, gallocatechin gallate, epigallocatechin gallate, and methylated catechin.

[0012] ​In the present invention, the citrus extract may include flavanone glycosides, eriodictyol, and naringenin. The flavanone glycoside may include glycosylated hesperidin.

[0013] In a preferred embodiment of the present invention, the green tea extract is gallocatechin gallate, epigallocatechin gallate or methylated catechin and the citrus extract is eriodictyol. Effect of the Invention

[0014] The food composition of the present invention has an anti-stress effect due to the green tea extract containing epigallocatechin gallate and the citrus extract containing flavanone glycosides, and therefore the food composition of the present invention can improve and prevent various symptoms caused by stress. [Brief description of the drawings]

[0015] [Figure 1] FIG. 1 is a characteristic diagram showing the results of measuring the weight of the thymus collected from mice after an administration test. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0016] The present invention will be described in detail below. The food composition according to the present invention is a composition comprising a green tea extract containing epigallocatechin gallate and a citrus extract containing flavanone glycosides, and exhibits an excellent anti-stress effect.

[0017] The anti-stress effect means an effect of reducing damage to the body caused by the continuous secretion of adrenal cortical hormones (anti-stress hormones) due to the continuation of a stressful state and the enhancement of oxidative stress in the body. The anti-stress effect can improve various conditions caused by stress. For example, the anti-stress effect can reduce or alleviate mental and / or physical fatigue, reduce depression, reduce anxiety, improve sleep quality, improve immunity, reduce or eliminate anxiety, reduce or alleviate impatience, etc. In addition, causes of stress include, for example, work, study, changes in the living environment (changing jobs, retiring, moving, accidents, theft, etc.), changes in human relationships (marriage, childbirth, divorce, death of a family member, etc.), and economic situations (reduction in income, debt, etc.).

[0018] Furthermore, if these stresses are not relieved and become chronic, they may lead to not only mental disorders but also physical disorders. For example, stress-induced bronchial asthma, hyperarousal syndrome, essential hypertension, coronary artery disease (angina pectoris and myocardial infarction), gastric and duodenal ulcers, irritable bowel syndrome, ulcerative colitis, psychogenic vomiting, simple obesity, diabetes, muscle contraction headache, spasmodic torticollis, writer's cramp, chronic urticaria, atopic dermatitis, alopecia areata, chronic rheumatoid arthritis, lower back pain, nocturnal enuresis, psychogenic impotence, eye strain, essential blepharospasm, Meniere's disease, temporomandibular joint disorder, etc. can be mentioned. Therefore, the food composition according to the present invention can have a preventive or improving effect against these diseases.

[0019] Since the food composition of the present invention has the above-mentioned anti-stress effect, it can be used as a functional food or an ingredient of a functional food that is labeled with an indication related to the anti-stress effect. For example, the functional claims of this food with functional claims can include "relieves temporary mental stress and fatigue caused by desk work", "reduces temporary stress caused by psychologically taxing clerical work", "relieves stress associated with temporary work", "makes temporarily depressed mood more positive (makes you feel positive, lively, motivated)", "relieves anxiety, depression, and mental stress", "reduces stress felt in daily life and reduces mental and physical fatigue", "relieves psychological stress and improves sleep quality (depth of sleep)", "relieves stress in situations causing temporary mental stress and improves sleep quality (depth of sleep, refreshing awakening)", "prevents weakening of the immune system caused by thymus disorders due to stress", "relieves stress due to restraints or restrictions on movement, reduces stress and relieves fatigue", "prevents and recovers from PTSD", "relieves anxiety and restlessness", "relieves stress and stabilizes the mind", "relieves irritability", "relieves anxiety caused by stress", and "relieves psychological stress and keeps the body healthy".

[0020] In the food composition according to the present invention, the composition ratio of the green tea extract and the citrus extract can be arbitrarily set. For example, the ratio (B / A) of the epigallocatechin gallate (A) contained in the green tea extract to the flavanone glycoside (B) contained in the citrus extract is 0.2.

[0021] (1) Green tea extract ​The green tea extract is an extract made from tea plants, which are evergreen trees of the Theaceae family, and contains at least epigallocatechin gallate. Examples of green tea plants include tea plants such as Camellia taliensis and Camellia sinensis. For example, the tea plant (Camellia sinensis (L.) Kuntze) and Assam tea (Camellia sinensis (L.) Kuntze var. assamica (JW Mast.) Kitam.), hybrids of Camellia sinensis and Camellia taliensis, 'Yabukita', 'Benifuki', 'Benifuji', 'Benimomare', 'Yaeho', 'Surugawase', 'Yutakamidori', 'Kanayamamidori', 'Okumusashi', 'Seishin Daipan', 'Seishin Oolong', 'Ooba Oolong', 'Safflower', 'Benihikari', 'Yamakai', 'Yamamidori', 'Karabeni', 'Koshun', 'Soufu', 'Fukumidori', 'Minekaori', 'Benihikari', 'Minamikaori', 'Izumi', 'Fushun', 'Tamamidori', 'Yamakai', 'Kuritawase', 'Shunmei', 'Sayamamidori', 'Asagiri', 'Hokumei', 'Tadanishiki', 'Asahi', 'Sayamakaori', 'Meiryo', 'Yamatomidori', 'Asatsuyu', 'Toyoka', 'Natsumidori', 'Ujihikari', 'Ooiwase', 'Gokou', 'Inzasshi' Tea varieties such as "131", "Makinoharawase", "Takachiho", "Komakage", "Samidori", "Komakage", "Hatsumomiji", "Ryofu", "Minamisayaka", "Saemidori", "Okuyutaka", "Fujimidori", "Sunrouge" and "Okumidori" are used, and "Yabukita", "Benifuki", "Kanayamamidori", "Okumusashi", "Soufu", "Fushun", "Tadanishiki" and "Sunrouge" are more preferred. Examples of tea leaves from these tea plants include sencha, gyokuro, bancha, kukicha, budcha, genmaicha, powdered tea, matcha, kamagarecha, tengcha, baozhongcha, oolong tea, black tea and the like.

[0022] The extraction solvent is not particularly limited, but water, an organic solvent, or a mixture thereof is used.

[0023] Examples of organic solvents include lower alcohols having 1 to 4 carbon atoms, such as methanol, ethanol, propanol, isopropanol, n-butanol, isobutanol, sec-butanol, and tert-butanol; polar organic solvents such as ketones, such as dimethyl ketone, methyl ethyl ketone, acetone, and methyl isobutyl ketone; and non-polar organic solvents, such as methyl acetate, ethyl acetate, butyl acetate, and diethyl ether. Furthermore, a mixture of these polar organic solvents and non-polar organic solvents in appropriate combination can also be used. Preferred are hot water, ethanol, and hydrous ethanol. The alcohol concentration of the hydrous alcohol is 30 v / v% to 90 v / v%, preferably 40 v / v% to 70 v / v%. In the case of hot water, the temperature is 40 to 100°C, preferably 60 to 100°C.

[0024] The extraction method for obtaining the green tea extract may include known methods such as extraction by immersion, heat extraction, continuous extraction, and supercritical extraction. The green tea extract may then be concentrated by a known method. The obtained green tea extract or concentrate may be further purified by a known method. Examples of the purification method include ultrafiltration, adsorption resin treatment, molecular chromatography, partition chromatography, and liquid-liquid extraction.

[0025] Drying methods include, but are not limited to, spray drying, freeze drying, etc. The green tea extract may contain polyphenols and catechins other than epigallocatechin gallate. The green tea extract preferably contains catechin, epicatechin, epigallocatechin, catechin gallate, epicatechin gallate, gallocatechin gallate, methylated catechin, etc.

[0026] The methylated catechins in the present invention are mainly epigallocatechin-3-O-(3-O-methyl) gallate (hereinafter referred to as EGCG3″Me), epicatechin-3-O-(3-O-methyl) gallate (hereinafter referred to as ECG3″Me), epicatechin-3-O-(4-O-methyl) gallate (hereinafter referred to as ECG4″Me), and epigallocatechin-3-O-(4-O-methyl) gallate (hereinafter referred to as EGCG4″Me). Preferably, the catechin-3-O-(3-O-methyl)gallate (hereinafter referred to as GCG3"Me), catechin-3-O-(3-O-methyl)gallate (hereinafter referred to as CG3"Me), catechin-3-O-(4-O-methyl)gallate (hereinafter referred to as CG4"Me), or gallocatechin-3-O-(4-O-methyl)gallate (hereinafter referred to as GCG4"Me), and their isomers.

[0027] The content of the green tea extract in the composition varies depending on the formulation or administration form of the composition, but can be appropriately set in consideration of the content of the citrus extract described below. In addition, in the present invention, a catechin other than the catechin contained in the green tea extract can be contained in the composition. For example, synthetic catechin can be included. Synthetic catechin can be obtained by a known method (Chem. Asian J. 2010, 5, 2231-2248. DOI: 10.1002 / asia.201000372).

[0028] The green tea extract may be commercially available, such as Polyphenon (registered trademark) manufactured by Mitsui Norin Co., Ltd.

[0029] (2) Citrus extract The citrus extract is an extract from citrus fruits and contains at least eriocitrin or flavanone glycosides. Examples of citrus fruits include the following:

[0030] Examples of the Citrus genus include orange, grapefruit, yuzu, bitter orange, kabosu, sudachi, yukou, yukou, shekwasha, lemon, lime, natsumikan, hassaku, iyokan, pomelo, mandarin orange, unshu mikan, ponkan, tachibana, Kishu mikan, Valencia orange, navel orange, blood orange, Jaffa orange, bergamot, and chinotto.

[0031] In addition to the above-mentioned citrus fruits, trifoliate oranges, kumquats, etc. can also be used.

[0032] The extraction solvent used to extract citrus fruits is water or an organic solvent, or a mixture thereof, as described above. Examples of the organic solvent include lower alcohols having 1 to 4 carbon atoms, such as methanol, ethanol, propanol, isopropanol, n-butanol, isobutanol, sec-butanol, and tert-butanol; polar organic solvents such as ketones, such as dimethyl ketone, methyl ethyl ketone, acetone, and methyl isobutyl ketone; and non-polar organic solvents, such as methyl acetate, ethyl acetate, butyl acetate, and diethyl ether. Water or ethanol is preferable. Furthermore, a mixture of these polar organic solvents and non-polar organic solvents can be used in combination.

[0033] The extraction method for obtaining the citrus extract may include known methods such as extraction by immersion, heat extraction, continuous extraction, and supercritical extraction. The extract may then be concentrated by a known method. The obtained citrus extract or concentrate may be further purified by a known method. Examples of the purification method include ultrafiltration, adsorption resin treatment, molecular chromatography, partition chromatography, and liquid-liquid extraction.

[0034] The citrus extract contains at least eriocitrin or flavanone glycoside. Examples of flavanone glycosides include, but are not limited to, hesperidin, naringin, poncirin, and sakuranin. The citrus extract may contain flavanones such as butin, eriodictyol, hesperetin, homoeriodictyol, isosakuranetin, naringenin, pinocembrin, sakuranetin, and sterubin in addition to eriocitrin and flavanone glycosides.

[0035] In addition, the composition may contain a flavanone or its glycoside other than the flavanone or flavanone glycoside contained in the citrus extract. Examples of the glycosyltransferase include synthetic flavanones and glycosyltransferase compounds in which sugar is bound to a flavanone, such as glycosyltransferase hesperidin. Examples of the glycosyltransferase include synthetic eriodictyol, synthetic naringenin, and synthetic hesperetin, and these may be used alone or in combination. Synthetic eriodictyol, synthetic naringenin, and synthetic hesperetin may be obtained by known methods (European J Org Chem., 2012(3): 449-462. doi:10.1002 / ejoc.201101228). As the glycosyltransferase hesperidin, for example, glycosyltransferase hesperidin sold by Hayashibara Co., Ltd. or Glico Nutrition Foods Co., Ltd. may be used.

[0036] (3) Composition The composition according to the present invention contains a green tea extract and a citrus extract in any composition ratio, but in particular, the ratio (B / A) of epigallocatechin gallate (A) contained in the green tea extract to flavanone glycoside (B) contained in the citrus extract is 0.2.

[0037] ​In addition to the above-mentioned components, the composition may contain carriers acceptable for use in food and other known or well-known additives. Examples of the additives include excipients, binders, lubricants, disintegrants, colorants, flavorings, emulsifiers, surfactants, solubilizers, suspending agents, isotonicity agents, buffers, preservatives, antioxidants, stabilizers, absorption promoters, etc., which are generally used in medicines or foods, and these may be used in appropriate combinations as desired.

[0038] The composition may be in any form of liquid, solid, powder, or gel, and the dosage form of the composition may be an oral dosage form, such as tablets, powders, capsules (hard capsules, soft capsules), granules, pills, liquids, syrups, etc. These preparations can be prepared according to conventional methods. When the composition is in the form of a solution, the preferred carrier is an aqueous medium such as water.

[0039] When the composition is in a solid form, excipients such as crystalline cellulose, magnesium stearate, calcium stearate, etc., and leavening agents such as corn starch, alginic acid, etc. can be used as additives.

[0040] In addition, compounds necessary for forming into a powder, solid, or liquid preparation include erythritol, maltitol, hydroxypropyl cellulose, kaolin, talc, and the like.

[0041] In addition to the above-mentioned anti-stress effect, the composition has at least one effect selected from the group consisting of an anti-cancer effect, an anti-muscle atrophy effect, an anti-obesity effect, an anti-inflammatory effect, a cholesterol-lowering effect, a thrombosis or cerebral infarction prevention effect, and an immune enhancing effect.

[0042] The subjects to which the food composition of the present invention is ingested are not particularly limited, and include humans and non-human mammals, such as laboratory animals (mice, rats, guinea pigs, rabbits, etc.), livestock (cattle, horses, pigs, goats, etc.), and pets (pets such as dogs and cats).The composition of the present invention is expected to prevent or treat cancer, muscle atrophy (e.g., amyotrophic lateral sclerosis (ALS)), inflammatory diseases, thrombosis or cerebral infarction hyperlipidemia, and infectious diseases, or to improve lifestyle-related diseases and obesity.

[0043] Furthermore, the intake amount of the food composition according to the present invention is more preferably 0.1 to 30 mg, even more preferably 0.1 to 20 mg, even more preferably 0.1 to 10 mg, and most preferably 0.1 to 5 mg per kg of body weight per day in terms of epigallocatechin gallate.

[0044] (4)Food The food composition according to the present invention contains green tea extract and citrus extract. The form of food (particularly functional food) using this food composition includes, for example, supplements (powders, granules, soft capsules, hard capsules, tablets, chewable tablets, and rapid disintegration tablets), but also includes beverages (tea, carbonated drinks, lactic acid drinks, sports drinks, etc.), confectionery (gum, chocolate, cookies, candy, etc.), oil, oily foods (mayonnaise, dressing, butter, etc.), seasonings (ketchup, sauce, etc.), liquid diet, dairy products (milk, yogurt, cheese, etc.), bread, noodles (udon, soba, ramen, pasta, hiyamugi, rice vermicelli, etc.), etc. However, the form is not limited to these.

[0045] The subjects to which the food is to be ingested are not particularly limited, but include humans and non-human mammals such as laboratory animals (mice, rats, guinea pigs, rabbits, etc.), livestock (cows, horses, pigs, goats, etc.), and pets (pets such as dogs and cats).

[0046] The intake amount of the food of the present invention is more preferably 0.1 to 30 mg, even more preferably 0.1 to 20 mg, even more preferably 0.1 to 10 mg, and most preferably 0.1 to 5 mg per kg of body weight per day in terms of the amount of epigallocatechin gallate. EXAMPLES

[0047] The present invention will be described in more detail below with reference to examples, but the technical scope of the present invention is not limited to the following examples.

[0048] Example 1 In this example, the effect of a food composition containing green tea extract and citrus extract (functional food pairing) on ​​stress-induced thymus atrophy was investigated.

[0049] Five groups were prepared, each consisting of eight male C57BL / 6J mice (6 weeks old, weighing 25 g (Kyodo)). The five groups were: a healthy group without stress; a group given purified water from 5 days before stress (purified water group); a group given green tea extract from 5 days before stress (green tea extract group); a group given transglycosylated hesperidin as a citrus extract from 5 days before stress (transglycosylated hesperidin group); and a group given green tea extract and transglycosylated hesperidin from 5 days before stress (functional food pairing group). The dose of green tea extract was 30 mg / kg in terms of EGCG. The dose of transglycosylated hesperidin (α-hesperidin PA-T, Glyco Nutrition Foods) was 37.5 mg / kg.

[0050] The mice were subjected to stress by tail suspension for 10 days. After the end of the period, the spleen and thymus were collected from each mouse and their weights were measured. The results are shown in Figure 1 (relative values ​​are shown when the weight of the purified water group was set to 1). In Figure 1, groups that showed significant differences by the Tukey-Kramer's test are marked with different letters. As shown in Figure 1, the wet weight of the thymus was reduced when the mice were subjected to stress by tail suspension (purified water group), but it can be seen that the reduction in thymus weight could not be improved by administering green tea extract alone or transglycosylated hesperidin alone. In contrast, it was found that the functional food pairing group administered green tea extract and transglycosylated hesperidin improved the reduction in thymus weight caused by stress. From these results, it was revealed that the composition containing green tea extract and transglycosylated hesperidin exhibits excellent anti-stress effects.

Claims

1. The food composition is an anti-stress food composition that improves stress-induced thymus weight loss, comprising a green tea extract containing epigallocatechin gallate and a citrus extract containing flavanone glycosides, the flavanone glycosides including hesperidin, wherein the ratio (B / A) of epigallocatechin gallate (A) contained in the green tea extract to the flavanone glycosides (B) contained in the citrus extract is 0.2<B / A<1.

6.

2. 2. The food composition according to claim 1, which is a beverage.

3. 3. The food composition according to claim 1 or 2, characterized in that the ratio (B / A) is 0.4≦B / A≦0.

8.

4. An anti-stress food composition comprising a green tea extract containing epigallocatechin gallate and glycosyltransferase hesperidin, which improves stress-induced loss of thymus weight.

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