Composition for improving mental state, production method for composition for improving mental state, and use of fruit of eggplant for improving mental state

Abstract

To provide a novel composition having the effect of improving a mental state.SOLUTION: The present invention relates to a composition for improving a mental state, comprising, as an active ingredient, a water-soluble component of the fruit of eggplant (Solanum melongena), and to a production method for an eggplant-derived composition for improving a mental state, the method comprising squeezing an eggplant fruit to obtain a juice, or adding water to an eggplant fruit, and squeezing the water-added fruit.SELECTED DRAWING: Figure 12

Description

[Technical Field]

[0001] The present invention relates to a composition for improving psychological state, a method for producing a composition for improving psychological state, and the use of eggplant fruit for improving psychological state. [Background technology]

[0002] According to a report published on World Health Day, cardiovascular disease accounts for approximately 17 million deaths annually, accounting for approximately one-third of all deaths worldwide (Non-Patent Document 1). Hypertension accounts for 9.4 million deaths worldwide each year, with at least 45% attributable to heart disease and 51% attributable to stroke. Hypertension also contributes to kidney failure, premature death, and disability (Non-Patent Document 1). Therefore, the prevention and management of hypertension is a major public health challenge worldwide. Several studies have shown that lifestyle modifications, including dietary changes, exercise, and weight loss, contribute to the primary prevention of hypertension and significantly reduce blood pressure in people with hypertension (Non-Patent Documents 2-4). Functional foods with antihypertensive effects are also expected to prevent and manage hypertension (Non-Patent Document 5). In Japan, functional foods for people with higher-than-normal blood pressure are commercially available as government-approved "foods for specified health uses" or "foods with nutritional function claims," ​​which are labeled at the discretion of the food manufacturer.

[0003] Eggplant (Solanum melongena) is a popular vegetable consumed daily worldwide and is an agriculturally and economically important cultivated crop. Because eggplant is low in energy, carbohydrates, and protein and rich in dietary fiber and minerals (Non-Patent Document 6), it is recommended for reducing energy intake and body weight (BW) to prevent type 2 diabetes (Non-Patent Documents 7-9). Clinical trials investigating the efficacy of eggplant have been conducted in the past, focusing on its cholesterol-lowering effects in hypercholesterolemic subjects (Non-Patent Document 10) and its efficacy in reducing fat mass in overweight women (Non-Patent Document 11).

[0004] Acetylcholine is a well-known neurotransmitter present not only in mammals but also in almost all living organisms, including those used as food ingredients (Non-Patent Document 12). Acetylcholine has been reported to be present in food ingredients such as eggplant, bamboo shoots (Phyllostachys bambusoides), and shiitake mushrooms (Lentinus eddoes) (Non-Patent Documents 12, 13). The present inventors have reported the isolation of acetylcholine and lactoylcholine from a lactic acid-fermented food that exhibits antihypertensive effects in spontaneously hypertensive rats (SHRs) and the possibility that these choline esters are the causative agents of the antihypertensive effect (Non-Patent Documents 14, 15). Furthermore, we recently demonstrated the antihypertensive effect of oral administration of acetylcholine-rich eggplant powder in SHRs, suggesting that the acetylcholine in eggplant suppresses sympathetic nervous activity, resulting in the antihypertensive effect (Non-Patent Document 16). The cholinergic drug betanechol stimulates the parasympathetic nervous system via muscarinic acetylcholine receptors and reduces blood pressure (Non-Patent Document 17). Therefore, it is presumed that orally administered acetylcholine in eggplant enhances parasympathetic nervous activity and suppresses sympathetic nervous activity through its antagonistic action, thereby lowering blood pressure. Stress and psychological state (PS) are closely related to sympathetic nervous activity (Non-Patent Documents 18, 19). Psychological factors are also related to blood pressure and may lead to hypertension (Non-Patent Document 20). Therefore, eggplant intake may improve stress and psychological state in addition to blood pressure.

[0005] The present inventors have studied the antihypertensive and vasodilatory components contained in fermented osmanthus (a product of lactic acid fermentation of buckwheat plants) and have provided an extract composition containing quaternary alkylammonium compounds based on multiple choline esters, including at least acetylcholine and propionylcholine. They have also demonstrated that purified acetylcholine, propionylcholine, butyrylcholine, and lactoylcholine exhibit antihypertensive effects when administered orally to SHRs in a single dose (Patent Documents 1 and 2). Furthermore, the present inventors have demonstrated that freeze-dried powders of edible plants such as eggplant and bamboo shoots, as well as ethanol or hydroethanol extracts of edible plants, contain active ingredients with antihypertensive effects, such as acetylcholine, and that these can be used for oral administration (Patent Document 3).

[0006] On the other hand, there are reports that a composition for suppressing hypertension containing the active ingredients of vegetable juices such as tomato, carrot, and spinach, and the active ingredient of germinated buckwheat juice (Patent Document 4), and a composition containing a water-soluble, sugar-free tomato extract can be used as an antihypertensive drug (Patent Document 5).However, these compositions all require multiple raw materials, require the removal of sugar from the extract, and are not easy to prepare. [Prior art documents] [Patent documents]

[0007] [Patent Document 1] International Publication No. 2015 / 147251 [Patent Document 2] Japanese Patent Application Laid-Open No. 2015-189745 [Patent Document 3] International Publication No. 2018 / 070545 [Patent Document 4] Japanese Patent Application Laid-Open No. 2008-214221 [Patent Document 5] Special Publication No. 2015-515493 [Non-patent literature]

[0008] [Non-Patent Document 1] 世界卫生组织。《高血压全球简报:无声杀手,全球公共卫生危机》。2013年。可在线获取:https: / / www.who.int / cardiovascular_diseases / publications / global_brief_hypertension / en / (于2018年3月29日访问)。 [Non-Patent Document 2] 乔班尼安,A.V.;巴克里斯,G.L.;布莱克,H.R.;库什曼,W.C.;格林,L.A.;伊佐,J.L. Jr;琼斯,D.W.;马特森,B.J.;奥帕里尔,S.;赖特,J.T.,Jr;等。国家高血压教育计划协调委员会。《预防、检测、评估和治疗高血压联合国家委员会第七次报告》。《美国医学会杂志》2003年,289卷,2560 - 2571页。 [Non-Patent Document 3] Go, A.S.; Bauman, M.A.; Coleman, King, S.M.; Fonarow, G.C.; Lawrence, W.; Williams, K.A.; Sanchez, E. An effective approach to high blood pressure control: A science advisory from the American Heart Association, the American College of Cardiology, and the Centers for Disease Control and Prevention. J. Am. Coll. Cardiol. 2014, 63, 1230-1238. [Non-Patent Document 4] Williams, B.; Poulter, N.R.; Brown, M.J.; Davis, M.; McInnes, G.T.; Potter, J.F.; Sever, P.S.; McG, Thom, S. British Hypertension Society. Guidelines for management of hypertension: Report of the fourth working party of the British Hypertension Society, 2004 - BHS IV. J. Hum. Hypertens. 2004, 18, 139-185. [Non-Patent Document 5] Mohamed, S. Functional foods against metabolic syndrome (obesity, diabetes, hypertension and dyslipidemia) and cardiovascular disease. Trends Food Sci. Tech. 2014, 35, 114-128. [Non-Patent Document 6] 美国农业部农业研究局(USDA ARS)。《美国国家营养数据库标准参考版第28版》(https: / / ndb.nal.usda.gov / ndb / )。在线获取:https: / / ndb.nal.usda.gov / ndb / foods / show / 2962?fgcd=&manu=&lfacet=&format=&count=&max=50&offset=&sort=default&order=asc&qlookup=eggplant&ds=&qt=&qp=&qa=&qn=&q=&ing= / (于2018年3月14日访问)。 [Non - Patent Document 7] 美国国立卫生研究院(NIH)下属的国立糖尿病、消化和肾脏疾病研究所(NIDDK)。《2015年及2016年营养研究报告》。预防2型糖尿病。在线获取:https: / / www.niddk.nih.gov / health - information / diabetes / overview / preventing - type - 2 - diabetes / (于2018年3月29日访问)。 [Non - Patent Document 8] 美国糖尿病协会(ADA)。食用色彩丰富的食物有益健康。在线获取:http: / / www.diabetesforecast.org / 2011 / aug / eating - colorful - food - has - health - benefits.html (于2018年3月29日访问)。

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[0009] The inventors focused on the idea that if a composition that can be prepared more easily using fewer raw materials and has a more effective psychological state improving effect could be obtained, it would be possible to mass-produce it at low cost as a health food such as a supplement or a pharmaceutical, and they searched for new materials that have the effect of improving psychological state.

[0010] Therefore, an object of the present invention is to provide a novel composition that has a psychological state improving effect. [Means for solving the problem]

[0011] The main invention of the present invention for solving the above problems is a composition for improving psychological state, which contains a water-soluble component of eggplant (Solanum melongena) fruit as an active ingredient.

[0012] Other problems and solutions disclosed in this application will be made clear in the section on preferred embodiments of the invention and the drawings. [Effects of the Invention]

[0013] According to the present invention, a new composition having an effect of improving psychological state can be provided. [Brief explanation of the drawings]

[0014] [Figure 1] 1 is a flowchart showing subject selection in a placebo-controlled, randomized, double-blind, parallel-group comparative study to verify the effects of continued ingestion of eggplant powder on improving blood pressure, stress, and psychological state. [Figure 2] FIG. 1 shows a test schedule. [Figure 3] FIG. 1 shows the blood pressure improving effect of continuous intake of eggplant powder, and is a graph showing the change in diastolic blood pressure at the time of visit for all subjects (high-normal blood pressure subjects and stage 1 hypertension subjects). [Figure 4] FIG. 1 shows the blood pressure improving effect of continuous intake of eggplant powder, and is a graph showing the amount of change in diastolic blood pressure at the time of visit to the clinic in subjects with high-normal blood pressure. [Figure 5] FIG. 1 shows the blood pressure improving effect of continuous intake of eggplant powder, and shows the actual measured values ​​of systolic blood pressure at the time of visit for all subjects (high-normal blood pressure subjects and stage 1 hypertension subjects). [Figure 6] FIG. 1 shows the blood pressure improving effect of continuous intake of eggplant powder, and is a graph showing the actual measured values ​​of systolic blood pressure at the time of visit to the clinic for patients with stage 1 hypertension. [Figure 7] FIG. 1 shows the blood pressure improving effect of continuous intake of eggplant powder, and is a graph showing the actual measured values ​​of diastolic blood pressure at the time of visit to the clinic for patients with stage 1 hypertension. [Figure 8] This figure shows the blood pressure improving effect of continuous intake of eggplant powder, and shows the amount of change in home and morning blood pressure for all subjects (subjects with high-normal blood pressure and subjects with stage 1 hypertension). [Figure 9] FIG. 1 shows the blood pressure improving effect of continuous intake of eggplant powder, and is a graph showing the amount of change in home and morning blood pressure in subjects with high-normal blood pressure. [Figure 10] FIG. 1 shows the blood pressure improving effect of continuous intake of eggplant powder, and is a graph showing the amount of change in diastolic blood pressure at home and while sleeping in subjects with high-normal blood pressure. [Figure 11] FIG. 10 is a graph showing the effect of continuous intake of eggplant powder on improving psychological state, showing the amount of change in the level of psychological state in patients with stage 1 hypertension. [Figure 12] FIG. 10 shows the effect of continuous intake of eggplant powder on improving psychological state, and is a graph showing the amount of change in vitality and vitality in patients with stage 1 hypertension. [Figure 13] FIG. 1 shows the psychological state improving effect of continuous intake of eggplant powder, and is a graph showing the actual measured values ​​of confusion and bewilderment for all subjects (high-normal blood pressure subjects and stage 1 hypertension subjects). [Figure 14] FIG. 10 shows the psychological state improving effect of continuous intake of eggplant powder, and is a graph showing the actual measured values ​​of depression and dejection in subjects with high-normal blood pressure. [Figure 15] FIG. 10 shows the psychological state improving effect of continuous intake of eggplant powder, and is a graph showing actual measured values ​​of confusion and bewilderment in subjects with high-normal blood pressure. [Figure 16] FIG. 10 shows the psychological state improving effect of continuous intake of eggplant powder, and is a graph showing the actual measured values ​​of anger-hostility in subjects with high-normal blood pressure. [Figure 17] FIG. 1 shows the psychological state improving effect of continuous intake of eggplant powder, and is a graph showing the actual measured values ​​of TMD (Total Mood Disturbance) scores in subjects with high-normal blood pressure. [Figure 18] Part of Table S1. [Figure 19] Part of Table S1. [Figure 20] Part of Table S2. [Figure 21] Part of Table S2. [Figure 22] Part of Table S2. [Figure 23] Part of Table S3. [Figure 24] Part of Table S3. [Figure 25] Part of Table S3. [Figure 26] Part of Table S3. [Figure 27] Part of Table S4. [Figure 28] Part of Table S4. [Figure 29] Part of Table S4. [Figure 30] Table S5. [Figure 31] This is part of Table S6. [Figure 32] This is part of Table S6. DETAILED DESCRIPTION OF THE INVENTION

[0015] The present invention will be described below by listing the contents of the embodiments. For example, the present invention has the following configuration. [Item 1] A composition for improving psychological state, comprising ingredients derived from eggplant (Solanum melongena) fruit. [Item 2] Item 1. A composition for improving psychological state according to item 1, comprising a water-soluble component of eggplant (Solanum melongena) fruit as an active ingredient. [Item 3] Item 1. A composition for improving psychological state according to item 1, comprising a water-soluble component of eggplant (Solanum melongena) fruit. [Item 4] 4. The composition for improving psychological state according to any one of items 1 to 3, which is to be orally taken at a dose such that the amount of choline ester in the water-soluble component is 0.5 μg / kg body weight or more and 50 mg / kg body weight or less. [Item 5] 5. The composition for improving psychological state according to any one of items 1 to 4, wherein the choline ester content is 5 μg to 50 mg, and the composition is for oral intake. [Item 6] 6. The composition for improving psychological state according to item 4 or 5, wherein the choline ester is any one selected from acetylcholine, butylcholine, and propionylcholine. [Item 7] 7. The composition for improving psychological state according to any one of items 1 to 6, which is a dry powder. [Item 8] 8. The composition for improving psychological state according to any one of items 1 to 7, which is a food composition. [Item 9] A method for producing a composition for improving psychological state that contains an eggplant-derived component, the method comprising squeezing eggplant (Solanum melongena) fruit to obtain a juice. [Item 10] A method for producing a composition for improving psychological state that contains an eggplant-derived component, the method comprising adding water to eggplant (Solanum melongena) fruit and squeezing the fruit to which the water has been added to obtain a juice. [Item 11] Item 11. A method for producing a composition for improving psychological state according to Item 10, comprising crushing the fruit before or after adding the water to the fruit. [Item 12] 12. A method for producing the composition for improving psychological state according to any one of items 9 to 11, comprising heating the fruit. [Item 13] 13. A method for producing a composition for improving psychological state according to any one of items 9 to 12, comprising drying the squeezed juice into a powder. [Item 14] A composition for improving psychological state, produced by the production method according to any one of items 9 to 13. [Item 15] Use of eggplant (Solanum melongena) fruit for improving psychological state. [Item 16] Item 16. Use according to item 15, by oral ingestion of the eggplant fruit. [Item 17] A composition for improving psychological state, comprising as an active ingredient a water-soluble component of a food product made from agricultural products with a high content of choline ester.

[0016] The composition for improving psychological state according to one embodiment and the method for producing the composition for improving psychological state will be described below.

[0017] 1. Composition for improving psychological state A composition for improving psychological state according to one embodiment includes a water-soluble component of eggplant fruit as an active ingredient. Also, a composition for improving psychological state according to another embodiment may consist of a water-soluble component of eggplant fruit.

[0018] Here, the water-soluble components of eggplant fruit refer to the water-soluble components obtained by squeezing eggplant fruit, but also refer to the water-soluble components contained in the squeezed juice obtained by adding water to eggplant fruit and squeezing the juice. For example, even if the squeezed juice inevitably contains water-insoluble components or even if some of the water-soluble components inevitably remain as residue during juicing, the components contained in the squeezed juice are considered to be water-soluble components.

[0019] The eggplant used in this embodiment is not particularly limited. Commonly eaten eggplants are preferred, and examples that can be used include varieties such as Tosataka, Shintaro, Ryuma, Senshu Mizunasu, Battennasu, Koryo Salad Nasu (also known as Bijin), Higomurasaki, Onaga Nasu, Chikuyo, and Senryo.

[0020] In this embodiment, examples of choline esters that can be contained in the composition for improving psychological state include acetylcholine, butyrylcholine, and propionylcholine, and the composition may contain one or more of these.

[0021] In this embodiment, when used in humans, the composition for improving psychological state is orally ingested at a dose such that the amount of acetylcholine in the water-soluble component is 0.5 μg / kg body weight to 50 mg / kg body weight, preferably 2 μg / kg body weight to 20 mg / kg body weight, particularly preferably 5 μg / kg body weight to 1 mg / kg body weight, and even more preferably 8 μg / kg body weight to 100 μg / kg body weight. Oral ingestion at such a dose can more effectively achieve the psychological state improving effect.

[0022] In this embodiment, the composition for improving psychological state is for oral ingestion and may have a choline ester content of 5 μg to 50 mg. Furthermore, the choline ester content in the composition for improving psychological state is preferably 500 μg to 20 mg, more preferably 1 μg to 10 mg. Oral ingestion of such a dose can more effectively improve psychological state.

[0023] In this embodiment, in one aspect, the composition for improving psychological state may be, for example, a dry powder such as a freeze-dried powder or a hot-air dried powder.

[0024] The composition for improving psychological state of this embodiment can be used as a food composition such as various functional health foods or a pharmaceutical composition.

[0025] In the case of food, it may be used in combination with an appropriate food additive. In addition to such food compositions, it can also be provided in a form that can be ingested daily, such as by blending it with green tea, black tea, oolong tea, multigrain tea, health drinks, sports drinks, etc. as a beverage, or by blending it with biscuits, bread, candy, chocolate, macaroons, etc. as a food. It can also be used as a so-called supplement in an appropriate dosage form according to the formulation of pharmaceuticals described below.

[0026] When used as a pharmaceutical, it can be combined with appropriate pharmaceutical additives and used in various dosage forms according to conventional compounding techniques, such as solid preparations such as powders, granules, capsules, pills, and tablets, and liquid preparations for oral administration such as solutions, suspensions, and emulsions.

[0027] When the composition for improving psychological state according to this embodiment is used as a food, it can be used not only as a general food or drink, but also as a food for specified health uses or a food with functional claims that exerts specific functions to promote health.

[0028] Specific forms in this case include supplements consisting of capsules, tablets, powders, granules, etc. containing the psychological state improving composition of this embodiment as an active ingredient; bakery foods such as bread, cakes, cookies, macarons, etc.; seasonings such as sauces, soups, dressings, mayonnaise, etc.; dairy products such as milk, yogurt, cream, etc.; confectioneries such as chocolate, candy, etc.; and various beverages such as green tea, black tea, oolong tea, barley tea, multigrain tea, fruit juice, vegetable drinks, dairy drinks, soft drinks, and carbonated drinks.

[0029] When the psychological state improving composition according to this embodiment is used as an active ingredient in a pharmaceutical composition, the dosage will vary depending on the ratio of each ingredient, as well as on various factors such as the patient's age, weight, sex, symptoms, and administration method. The dosage can also be increased or decreased as appropriate depending on the degree of symptom improvement. The dosage can be administered once or several times a day.

[0030] When the psychological state improving composition according to the present embodiment is used as a food, the intake amount can be selected in accordance with the case of oral administration of the above-mentioned medicine. However, unlike medicine, the dosage and frequency of administration are not particularly limited in the case of food and drink, and therefore, as long as no particularly serious symptoms occur, the intake amount may be selected without limitation, taking into consideration the purpose of maintaining health, as well as the taste and preference.

[0031] The composition for improving psychological state according to this embodiment can be used, for example, not only as a composition for improving psychological state, but also for subjects with hypertension and healthy subjects (not with hypertension) who have high blood pressure.

[0032] Various additives can be added to the psychological state improving composition according to this embodiment, as needed. Various additives can be used, and are not particularly limited. Examples include sugars such as lactose hydrate, sucrose, glucose, reduced maltose, mannitol, and sorbitol; starches and derivatives thereof such as corn starch, potato starch, partially pregelatinized starch, dextrin, and pullulan; celluloses such as crystalline cellulose and microcrystalline cellulose; derivatives such as carboxymethylcellulose; macrogol; and mixtures of one or more of magnesium aluminometasilicate. Among these, dextrin is more preferred. One type of additive may be used alone, or two or more types may be used in combination. These additives are preferably contained in an amount of 1 to 1,000 parts by weight, more preferably 10 to 300 parts by weight, per 100 parts by weight of the composition of the present invention.

[0033] The choline ester, which is the active ingredient of the composition for improving psychological state according to this embodiment, is not limited to the eggplant mentioned above, and can be derived from any of animals, plants, and microorganisms. In particular, it is preferable to use one derived from an organism that humans have eaten, and it is preferable to use one derived from an edible plant. In other words, the composition for improving psychological state according to this embodiment is not limited to being derived from eggplant fruit, and can contain, as an active ingredient, a water-soluble component of a food made from agricultural products with a high content of choline ester.

[0034] Edible plants other than eggplant are not particularly limited as long as they contain choline esters. Examples of edible plants include cucumbers, tomatoes, paprika, bell peppers, asparagus, yam, cabbage, lettuce, carrots, apples, shishito peppers, Japanese pears, grapes, radish sprouts, broccoli, alfalfa, pea sprouts, buckwheat, and bamboo shoots. Among these, agricultural products with a high choline ester content are preferred, and from the viewpoint of acetylcholine content, bamboo shoots and bamboo shoots of the Poaceae family, subfamily Bambusoideae, family Bambusoideae are preferred, and the tips of bamboo shoots are preferred.

[0035] 2. Method for producing a composition for improving psychological state In one aspect, the composition for improving psychological state according to the present embodiment can be obtained by the following manufacturing method.

[0036] The method for producing the composition for improving psychological state according to this embodiment includes squeezing eggplant fruit to obtain juice, or adding water to eggplant fruit and squeezing the fruit to which water has been added. When producing the composition from a raw material other than eggplant fruit, the composition for improving psychological state can also be obtained by the same method.

[0037] The water to be added to the eggplant fruit is not particularly limited, and may be water at a temperature ranging from 5°C to 40°C. It is preferable to add water at room temperature. The amount of water added is preferably 50 to 200 parts by weight, more preferably 75 to 150 parts by weight, and particularly preferably 100 parts by weight, per 100 parts by weight of the eggplant fruit as the raw material. If the amount of water is too small, the extraction of the water-soluble active ingredients may be insufficient. If the amount of water is too large, the processing volume may become large, making it difficult to process into a dry powder, for example.

[0038] The eggplant fruit is preferably crushed before or after adding water, and crushing before adding water is particularly preferable from the viewpoint of ease of crushing. Crushing the eggplant fruit facilitates the extraction of water-soluble components. Crushing can be carried out in various forms, for example, into strips, diced blocks, or a paste, but crushing into a paste is preferred to make it easier to extract the juice. For crushing, for example, a juicer, mixer, mill, crusher, etc. can be used.

[0039] The water used in the method for producing a psychological state improving composition according to this embodiment can be water commonly used in food processing, such as mineral water, distilled water, deionized water, ion-exchanged water, electrolyzed water, tap water, well water, or industrial water used for food. There are no particular limitations on the pH, but to stably maintain acetylcholine, the pH should be between 9.0 and 3.0, preferably between 8.0 and 4.0, and more preferably between 6.5 and 4.5. Water whose pH has been adjusted using a pH adjuster such as citric acid or ascorbic acid can be used.

[0040] Ethanol may also be added to reduce bacterial contamination during the juicing process. Increasing the ethanol concentration helps reduce microbial contamination, but it also reduces the solubility of the water extract and reduces the extraction efficiency of water-soluble components. Therefore, the ethanol concentration is preferably 9.9% or less, more preferably 6% or less, and even more preferably 4% or less.

[0041] In the method for producing a psychological state improving composition according to this embodiment, eggplant fruit may be heated. Heating inactivates acetylcholinesterase, allowing for efficient extraction of acetylcholine. Furthermore, the eggplant fruit tissue is softened, destroying the cell walls and facilitating extraction of water-soluble components and crushing the eggplant fruit.

[0042] The heating method is not particularly limited, and for example, heating can be carried out for 2 to 60 minutes at a temperature ranging from 30° C. to 120° C. The heating temperature is preferably from 80° C. to 100° C.

[0043] Examples of methods for heating eggplant fruit include heating in a microwave oven, on a hot plate or in a pan, immersing in boiling water, exposing eggplant to steam, etc. Among these, immersing in boiling water and exposing eggplant to steam are preferred.

[0044] Furthermore, the eggplant fruit may be heated before or after the addition of water, during heating with water, before crushing, after crushing, or during crushing. However, crushing the heated eggplant and then heating the crushed eggplant quickly is preferable for inactivating the acetylcholinesterase.

[0045] The method for extracting juice from crushed eggplant is not particularly limited as long as it can separate the juice from the residue. For example, the juice can be extracted using a strainer bag and a wine extractor, or by using a juice extractor. A centrifuge or screw press can also be used.

[0046] The obtained squeezed juice can be dried to produce a dried product in the form of a lump or powder. The drying method is not particularly limited, but it is preferable to dry the dried product until the moisture content is 0% by mass or more and 10% by mass or less. For example, drying can be performed by heat drying such as hot air drying, drum drying, freeze drying, spray drying, etc.

[0047] The dried product can be pulverized into a dry powder. The pulverization method is not particularly limited, but it is preferable that the product can be pulverized to a size of about 5 to 100 mesh. For example, it can be pulverized using a mill.

[0048] The composition produced by the method for producing a composition for improving psychological state according to the present embodiment tends to contain less dietary fiber and more carbohydrates. The ratio of dietary fiber to carbohydrates in the composition of the present invention is, for example, 1:2 to 1:100, preferably 1:5 to 1:40, and particularly preferably 1:10 to 1:20.

[0049] Continuous ingestion of the composition for improving psychological state containing eggplant-derived choline ester according to this embodiment significantly improves the blood pressure and psychological state of stressed individuals with high-normal blood pressure and stage I hypertension, as demonstrated, for example, in a placebo-controlled, randomized, double-blind, parallel-group comparative study as described in the Examples below.

[0050] For example, with regard to blood pressure improvement, continuous ingestion of the psychological state improving composition according to this embodiment significantly improves the blood pressure at presentation (diastolic / post-stress diastolic) and the blood pressure at home (systolic upon waking / diastolic / diastolic upon going to bed) in patients with high-normal blood pressure, and significantly improves the blood pressure at presentation (systolic / diastolic) in patients with stage I hypertension. Overall, the blood pressure at presentation (systolic / diastolic) and the blood pressure at home (systolic / diastolic upon waking) are significantly improved.

[0051] Regarding improvement of psychological state, by continuously taking the composition for improving psychological state according to this embodiment, negative psychological states such as "depression-dejection," "confusion-bewilderment," "anger-hostility," and "TMD score" are significantly improved in high-normal blood pressure individuals, and positive psychological states such as "friendship" and "liveliness-vigor" are significantly improved in stage I hypertension individuals. Overall, "confusion-bewilderment" is significantly improved.

[0052] As will be described later, there are no safety issues with continuous intake of the composition for improving psychological state according to this embodiment, and no side effects or problematic adverse events were observed during the 12-week intake period.

[0053] As described above, the composition for improving psychological state and the method for producing the composition for improving psychological state according to this embodiment can provide a new composition having a psychological state improving effect.

[0054] Since the composition for improving psychological state according to the present embodiment is intended for oral ingestion, the effect of improving psychological state can also be obtained by consuming eggplant fruit itself. In this case, as described above, for example, by consuming eggplant fruit at a dose that allows for the intake of a choline ester content of 5 μg to 50 mg, the effect of improving psychological state and other effects, such as the effect of improving blood pressure, can be obtained. The effect can be obtained whether the eggplant is eaten raw or cooked, or even if it is processed into a pickled food.

[0055] 3. Working Example The present invention will be described in more detail below with reference to examples and comparative examples, but the present invention is not limited to these examples. In the examples and comparative examples, "parts" and "%" are by mass unless otherwise specified.

[0056] This study aims to investigate the long-term effects of eggplant on improving blood pressure, stress, and psychological state in stressed human subjects with high-normal blood pressure and / or stage 1 hypertension through a randomized, double-blind, placebo-controlled, parallel-group comparative study.

[0057] Blood pressure is classified in the 2014 Hypertension Treatment Guidelines (edited by the Hypertension Treatment Guidelines Committee of the Japanese Society of Hypertension, April 2014, published by the Japanese Society of Hypertension, ISBN: 978-4-89775-322-5) and is defined as follows: High-normal blood pressure: 130mmHg≦ systolic blood pressure ≦139mmHg and / or 85mmHg≦ diastolic blood pressure ≦89mmHg; Grade I hypertension: 140mmHg≦ systolic blood pressure ≦159mmHg and / or 90mmHg≦ diastolic blood pressure ≦99mmHg

[0058] Materials and Methods Subjects A screening test was conducted on 189 people, and 100 Japanese men and women aged 35 to 65 who had high-normal blood pressure or stage 1 hypertension and were feeling stressed participated in this study. However, subjects who met the following conditions were excluded from the study. Those receiving medical treatment, medication, or instructions from a doctor for high blood pressure, schizophrenia, depressive disorder, manic disorder, arrhythmia, or bradycardia. BMI of 30 kg / m 2 The above persons Perimenopausal women who report obvious physical changes Those who may have allergic reactions to medicines or food, especially eggplant, which may cause secondary hypertension, serious cerebrovascular disease, cardiac dysfunction, liver damage, kidney damage, or gastrointestinal disorders. - Those suffering from an infectious disease that must be reported to the authorities -Persons who have had major surgery on the digestive system. -Those with abnormally high or low blood pressure or abnormal blood data -Those with severe anemia Those who regularly take medication, functional foods, or supplements due to blood pressure or stress Alcoholism or eating disorders Women who donated 400 mL of blood within the past 16 weeks Men who donated 400 mL of blood within the past 12 weeks Men and women who donated 200 mL of blood within the past four weeks -Those who are currently participating in another clinical trial or have participated in a clinical trial within the past four weeks Pregnant or breastfeeding women Women who are likely to become pregnant during this study -Those with any other illnesses or health concerns that may cause problems in this test

[0059] Subjects who met the eligibility criteria were randomly assigned to either the eggplant (capsules containing eggplant powder) group or the placebo (capsules containing dextrin) group, stratified by gender, age, and initial systolic and diastolic blood pressure. The demographics of the subjects in each group are shown in Table 1. The test meal was assigned by computer-assisted blocking at a third-party data center (Hokkaido Information Technology Research Institute, Media Education Center, Ebetsu City, Hokkaido). Clinical research collaborators were blinded to the allocation information throughout the study. The key was broken after the data analysis was completed.

[0060] [Table 1]

[0061] 3.1.2. Power analysis of sample size Based on the results of an 8-week preclinical trial (https: / / upload.umin.ac.jp / cgi-open-bin / ctr_e / ctr_view.cgi?recptno=R00003294, registration number UMIN000028785, registration date August 13, 2017), a sample size of 80 subjects (40 subjects per group) was calculated with a statistical power of 80% and a significance level of 5% to detect an effect size of 0.63. Assuming that 20% of subjects would drop out midway, the number of subjects was set at 100 (50 subjects per group).

[0062] 3.1.3. Preparation of eggplant dried powder capsules Test compositions were prepared according to the following method.

[0063] Eggplant powder was prepared from eggplant juice containing excipients for drying and powdering. The test food was defined as the daily intake of eggplant-derived choline ester (acetylcholine). The daily intake of acetylcholine was 2.3 mg (equivalent to 22 g of fresh eggplant used in this study).

[0064] Eggplants from Kochi Prefecture were used as raw materials. Fresh eggplants were washed and shredded immediately after harvest, and heated to prevent spoilage. They were then pressed to remove solids, yielding eggplant juice. Dextrin was added to the juice, which was then freeze-dried. Each gram of eggplant powder contained 1.92 mg of eggplant-derived choline ester (acetylcholine), for a yield of 4.08%. The eggplant powder was filled into 300 mg capsules. Placebo capsules were filled with dextrin only.

[0065] The capsules in the eggplant and placebo groups were prepared according to a strict quality-controlled protocol and were identical in appearance. Nutritional composition analysis of the capsules from each group was performed by the Japan Food Research Laboratories. See Table 2 for the analysis results. Acetylcholine was analyzed at Shinshu University using LC-MS / MS. In this study, subjects consumed 1200 mg of eggplant powder per day (four 300 mg capsules containing 25% dextrin-containing eggplant powder). This is equivalent to eating approximately 22 g of fresh eggplant per day.

[0066] [Table 2]

[0067] Testing This study was conducted at the Hokkaido Information University Center for Health Information Sciences. For 12 weeks, subjects took either four eggplant powder capsules (2.3 mg of acetylcholine) or four placebo capsules daily. Two capsules were taken in the morning (after meals) and in the evening (before bedtime). At baseline, Weeks 4, 8, 12, and 16 (four weeks after the final intake), medical examinations, vital signs, body composition measurements, urinalysis, hematological and biological tests, and questionnaires were completed. Throughout the study, subjects maintained their usual dietary and exercise habits and were instructed to avoid consuming supplements or processed foods such as eggplant or bamboo shoots. Subjects also kept a daily diary. Bamboo shoots are known to contain acetylcholine at levels similar to eggplant, and subjects were instructed not to consume any foods with high acetylcholine content other than the test food.

[0068] The primary outcome measure was blood pressure at the time of admission, consisting of systolic and diastolic blood pressure. Secondary outcome measures were home blood pressure (upon waking and at bedtime), stress assessment using a visual analogue scale (VAS), and psychological status assessment using the full version of the Profile of Mood States-2 Japanese Adult Mood Assessment Scale (POMS-2).

[0069] 3.1.5. Quantitative Determination of Antihypertensive Components in Eggplant Capsules Acetylcholine was quantified using a modified standard addition method described in International Publication No. 2018 / 070545. (2-Aminoethyl)trimethylammonium pivalamide (EN; internal standard, synthesized at Shinshu University) was added to the analytical sample, which was then dissolved in 100 mM phosphate buffer and processed on a weakly acidic cation exchange cartridge (Inertstep CBA 100 mg / 1 mL, GL Sciences Inc., Tokyo). The fraction containing acetylcholine was eluted with 1 M hydrochloric acid and collected in a volumetric flask. Once a constant volume was reached, the sample was divided into three portions, and different amounts of standard acetylcholine were added to create a dilution series.

[0070] Acetylcholine and EN contained in the samples were analyzed by LC-MS / MS under the following conditions. Separation was performed isocratically using a mobile phase (33% methanol containing 0.010% formic acid) on a YMC-Triart PFP column (4.6 mm x 250 mm, 5 μm, YMC Co., Ltd., Kyoto). Acetylcholine and EN were detected using positive multiple reaction monitoring (MRM) with the following MRM transitions: 146.15>87.10(acetylcholine) 187.30>128.15(EN)

[0071] The quantitative value of acetylcholine was corrected for the EN recovery rate. The quantitative values ​​of γ-aminobutyric acid (GABA) and chlorogenic acid (CA) were similarly detected using the following MRM transitions. 104.15>87.20(GABA) 355.10>163.20(CA)

[0072] 3.1.6. Assessment of clinic and home blood pressure Blood pressure was measured on the non-dominant upper arm by a physician or nurse using an automatic blood pressure monitor HEM-7080IC (Omron Healthcare Co., Ltd., Kyoto, Japan) after a minimum of 10 minutes of rest. Three consecutive measurements were performed, and the median value was obtained at each assessment point.

[0073] Subjects' home blood pressure was measured using an automated blood pressure monitor, HEM-7080IC, on the non-dominant upper arm. Subjects' blood pressure was measured daily for one week prior to visits 2-6, within one hour of waking (morning blood pressure) and before going to bed (night blood pressure). Three consecutive measurements were taken, and the median value was obtained each day. The mean blood pressure from the three days prior to each assessment point was evaluated.

[0074] 3.1.7. Physical examination, blood test, biochemistry test, urine test Blood samples were collected from subjects after a 12-hour fast and used for blood tests of white blood cells (WBC), red blood cells (RBC), hemoglobin (Hb), hematocrit (Hct), and platelet count (Plt). Biological tests included liver function (aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (γ-GTP), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) levels), kidney function (blood urea nitrogen (BUN), creatinine (CRE), and uric acid (UA) levels), lipid profile (total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) levels), and glycemic profile (fasting plasma glucose (FPG) and hemoglobin (Hb) Alc levels).

[0075] First-void urine was collected, and the sample was used for qualitative assessment of pH, glucose, protein, occult blood, urobilinogen, and ketones.

[0076] Blood and urine tests were performed at the Sapporo Clinical Laboratory (Hokkaido, Japan). Body composition (BW, body fat percentage (BFR), and BMI) was assessed using a DC-320 body composition analyzer (Tanita, Tokyo, Japan).

[0077] 3.1.8.Mood profile assessment using POMS-2 and stress assessment using VAS questionnaire A VAS questionnaire was used to assess the subjects' stress. The subjects were instructed to answer each question about their current physical and mental state by marking an "X" anywhere on a 100mm line representing the worst state (left end, 0mm) to the best state (right end, 100mm). The results of the questionnaire were evaluated based on the distance from the start of the left line to the "X," with a higher score indicating a greater improvement in stress.

[0078] The POMS-2 questionnaire was used to evaluate the effects of eggplant on psychological states. Subjects were instructed to complete the questionnaire before consuming the test food. Negative psychological states were defined as anger-hostility, confusion-embarrassment, depression-depression, fatigue-lethargic, and tension-anxiety, while positive psychological states were defined as vigor-vitality and friendliness.

[0079] All psychological states were assessed using the POMS-2 Adult Full Version (Success Bell Co., Ltd., Tokyo), which consists of 65 questions. Subjects answered questions about their activities over the past week using five options ranging from "not at all true" to "very true." The Total Mood Disorder (TMD), which comprehensively represents negative psychological states, was calculated by adding up the scores for anger-hostility, confusion-embarrassment, depression-depression, fatigue-apathy, and tension-anxiety, and then subtracting the scores for vigor-vitality and friendliness.

[0080] To evaluate the anti-stress effects of eggplant, subjects first ingested two capsules and then completed a 15-minute Uchida-Kraepelin Mental Performance Test (UKT) to induce mental stress. A VAS questionnaire was completed twice: before ingesting the test food and after completing the UKT.

[0081] FFQg All subjects completed a food frequency questionnaire (FFQg) (Kenpakusha Co., Ltd., Tokyo, Japan) during visits 2 to 6. The FFQg was used to estimate nutrient intake (energy, protein, fat, carbohydrates, dietary fiber, and salt) based on the subjects' usual diet. Subjects reported the quantity and frequency of weekly food intake for approximately 29 food groups and 10 cooking methods.

[0082] 3.1.10.Ethics This clinical study was conducted in accordance with the Declaration of Helsinki and the ethical guidelines for human clinical research (Ministry of Education, Culture, Sports, Science and Technology). Prior to participating in this study, subjects carefully read the consent form and provided written informed consent. The study protocol was approved by the Ethics Committee of Hokkaido Information University (Ebetsu, Hokkaido) (approved May 25, 2018, approval number 2018-06). This study has been registered at https: / / upload.umin.ac.jp / cgi-open-bin / ctr_e / ctr_view.cgi?recptno=R000037995 (registered July 10, registration number UMIN000033330).

[0083] 3.1.11.Statistical analysis The Student's t-test was used to compare differences in subject data between the two groups for the primary endpoint, secondary endpoints, safety endpoints, and food frequency questionnaire. Differences in subject data were analyzed using multiple replicate analysis of variance between groups. Regarding subject attributes, Fisher's exact test was used for gender, the Mann-Whitney U test for intake rate, and the Student's t-test for other attributes. Subgroup analyses were performed by dividing subjects into those with presentation-based blood pressure of 130-139 mmHg (systolic blood pressure) or 85-89 mmHg (high-normal blood pressure) and those with 140-159 mmHg (systolic blood pressure) or 90-99 mmHg (stage 1 hypertension). All statistical analyses were performed using SPSS v25 (IBM Japan, Tokyo). Exploratory data analysis using measured values ​​was also performed in a similar manner. All results are expressed as the sample mean ± standard error. A p-value of 0.05 or less was considered statistically significant.

[0084] 3.2.Results 3.2.1. Subject attrition and characteristics Figure 2 shows the subject involvement and study schedule during the study period. Volunteers (n = 189) who provided informed consent were assessed to determine whether they met the eligibility criteria. After screening, 100 subjects were selected to participate in this study. All subjects were randomly assigned to one of two groups (placebo group, n = 50; eggplant group, n = 50). Four subjects (personal reasons, n = 4) withdrew before the study began, and nine subjects withdrew during the study due to adverse events or personal reasons (placebo group: adverse events such as pneumonia (n = 1), colonic diverticulitis (n = 1), dyslipidemia (n = 1), and urticaria (n = 1); eggplant group: adverse events such as injury (n = 2), mild liver dysfunction (n = 1), and renal impairment (n = 1), as well as personal reasons (n ​​= 1)). Ultimately, a total of 87 subjects, 42 in the eggplant group and 45 in the placebo group, completed the study. Excluding four subjects who withdrew for personal reasons before the start of the study, 96 subjects were included in the safety analysis. Ten subjects were excluded from the efficacy analysis. Reasons included abnormal values ​​(outside the reference range (n = 1), safety endpoints >120% compared to baseline (n = 1)), minor illness (allergies unrelated to the test food (n = 2)), compliance issues or failure to meet criteria (n = 3), lack of stress at the start of the study (n = 1), and missing data on the primary endpoint due to failure to measure blood pressure (n = 2). Efficacy analysis included 36 subjects in the eggplant group and 41 subjects in the placebo group. The gender ratio, mean age, height, BMI, systolic blood pressure at visit, diastolic blood pressure at visit, and intake rate for each group are shown in Table 1. No significant differences were observed in these indices between the two groups.

[0085] 3.2.2. Effect of eggplant on blood pressure at presentation Figures 3 to 7 show the change in blood pressure from week 0 at the time of visit (Figures 3 and 4) and the actual measured values ​​(Figures 5 to 7). Figure 3 shows the diastolic blood pressure of all subjects, Figure 4 shows the diastolic blood pressure of subjects with high-normal blood pressure, Figure 5 shows the systolic blood pressure of all subjects, Figure 6 shows the systolic blood pressure of subjects with stage I hypertension, and Figure 7 shows the diastolic blood pressure of subjects with stage I hypertension. Values ​​are shown as mean ± standard error. Statistical significance by Student's t-test: * p<0.05 and *** p<0.001 vs placebo group.

[0086] After 8 weeks of eggplant powder intake, diastolic blood pressure significantly improved in all subjects compared to the placebo group (p = 0.024) (Figure 3, Table S1; Figures 18 and 19). Subgroup analysis showed that after 8 weeks of eggplant powder intake, the rise in diastolic blood pressure in subjects with high normal blood pressure was significantly suppressed (placebo: n = 26; eggplant: n = 27) (Figure 4, Table S1; Figures 18 and 19). Exploratory data analysis showed that after 12 weeks of intake, the eggplant group showed significantly lower systolic blood pressure compared to the placebo group (p = 0.046) (Figure 5, Table S2; Figures 20-22). Systolic and diastolic blood pressures in subjects with stage 1 hypertension (placebo: n = 15; eggplant: n = 9) were significantly lower in the eggplant group than in the placebo group at week 12 (systolic blood pressure: p = 0.037, diastolic blood pressure: p = 0.041) (Figures 6 and 7, Table S2; Figures 20-22). Furthermore, significant time-food interactions for systolic blood pressure at visit for all subjects (change vs. measured value, p = 0.018), for subjects with stage 1 hypertension (change vs. measured value, p = 0.043), and for normotensive subjects (diastolic blood pressure at visit for normotensive subjects (change vs. measured value, p = 0.028) also supported the antihypertensive effect of eggplant powder intake (Table S1; Figures 18 and 19 and Table S2; Figures 20-22).

[0087] 3.2.3.Effectiveness of eggplant on home blood pressure Figures 8 to 10 show the change in home blood pressure from week 0. Figure 8 shows the systolic and diastolic blood pressures of all subjects upon waking, Figure 9 shows the systolic and diastolic blood pressures of high-normal blood pressure subjects upon waking, and Figure 10 shows the diastolic blood pressure of high-normal blood pressure subjects at bedtime. Values ​​are shown as mean ± standard error. Statistical significance by Student's t-test: * p<0.05 and *** p<0.01 vs placebo group.

[0088] After four weeks of eggplant powder intake, systolic blood pressure (Figure 8, p = 0.017) and diastolic blood pressure (Figure 8, p = 0.032) on waking were significantly reduced for all subjects compared to the placebo group. Subgroup analysis showed that subjects with high-normal blood pressure in the eggplant group had significantly lower systolic blood pressure (Figure 9, p = 0.041) and diastolic blood pressure (Figure 9, p = 0.008) on waking compared to the placebo group at week four, and significantly lower diastolic blood pressure at bedtime at weeks four and eight (Figure 10, p = 0.029). There were no significant differences in actual measurements between the placebo and eggplant groups.

[0089] 3.2.4. The effects of eggplant on stress and blood pressure The effects of eggplant on stress and psychological state were evaluated using a VAS test to measure stress levels and the POMS-2 test to measure psychological state (Table S3; Figures 23–26, Table S4; Figures 27–29). No differences in VAS scores were observed between the two groups either before or after UKT. Subgroup analysis of the POMS-2 test results showed that in subjects with stage 1 hypertension, the eggplant group had significantly better scores on "vigor / vitality" at week 4 and "friendliness" at week 8 than the placebo group. Exploratory data analysis showed significant improvements in "confusion / perplexity" at week 12 in all subjects, and in subjects with high-normal blood pressure in the eggplant group, significant improvements were seen in negative psychological states ("confusion / perplexity" and "depression / depressedness" at week 8, and "anger / hostility" and "TMD" at week 12) (Figures 11–17).

[0090] 3.2.5. Nutritional Assessment of Subjects During the Study The subjects' nutritional status was assessed using the FFQg (Table S5; Figure 30). The lipid and dietary fiber intakes of the eggplant group at week 12 were significantly lower than those of the placebo group (p = 0.009 and 0.035, respectively). However, there were no statistically significant differences in the intakes of energy, protein, carbohydrate, and salt between the eggplant and placebo groups.

[0091] 3.2.6. Safety assessment of eggplant To analyze the safety of eggplant powder intake, the subjects' body composition, complete blood count, liver function, kidney function, lipid profile, and blood glucose profile were evaluated (Table S6; Figures 31 and 32). Furthermore, urinary parameters were qualitatively evaluated (Table S6; Figures 31 and 32). All variations in values ​​were within the reference range. Adverse events were observed in each group, but all adverse events were inferred to be unrelated to the test food based on protocol criteria. Therefore, intake of eggplant powder, equivalent to 22 g / day of fresh eggplant and containing 2.3 mg of eggplant-derived choline ester (acetylcholine), resulted in no or minimal adverse events.

[0092] 3.3. Discussion A placebo-controlled, double-blind, parallel-group comparative study revealed that continuous intake of eggplant powder containing 2.3 mg of eggplant-derived choline ester (acetylcholine) per day improved blood pressure in subjects with high-normal blood pressure and stage 1 hypertension. Subgroup analysis confirmed the blood pressure-improving effect of eggplant powder intake in subjects with high-normal blood pressure. Furthermore, based on a thorough literature review, this study was confirmed to be the first clinical trial to provide evidence that eggplant improves blood pressure. Furthermore, this study showed that eggplant intake improves both positive and negative psychological states.

[0093] In this study, eggplant powder intake improved the primary endpoint, diastolic blood pressure at presentation, in all subjects, with a particularly strong effect in subjects with high-normal blood pressure. Interestingly, the effect of eggplant intake on diastolic blood pressure was more pronounced in subjects with high-normal blood pressure (p<0.001) than in all subjects (p=0.024). Systolic blood pressure at presentation improved in all subjects and in subjects with stage 1 hypertension, and diastolic blood pressure at presentation also improved in subjects with stage 1 hypertension. These findings were revealed by exploratory data analysis. The fact that eggplant intake improved diastolic blood pressure in subjects with high-normal blood pressure and systolic and diastolic blood pressure in subjects with stage 1 hypertension suggests that eggplant may have different blood pressure-improving effects on different blood pressure categories.

[0094] Eggplant intake also showed improvements in the secondary endpoints of home systolic and diastolic blood pressure. Improvements were seen in systolic and diastolic blood pressure upon waking in all subjects and in subjects with high-normal blood pressure, and in diastolic blood pressure at bedtime in subjects with high-normal blood pressure, supporting the effect of eggplant intake in improving blood pressure at the time of visit.

[0095] Managing early morning blood pressure is important for preventing heart failure [White, WB Clinical assessment of early morning blood pressure in patients with hypertension. Prev. Cardiol. 2007, 10, 210-214.], [Wang, JG; Kario, K.; Chen, CH; Park, JB; Hoshide, S.; Huo, Y.; Lee, HY; Li, Y.; Mogi, M.; Munakata, M.; et al. Management of morning hypertension: A consensus statement of an Asian expert panel. J. Clin. Hypertens. 2018, 20, 39-44.].It has been reported that patients with anxiety disorders have higher morning and nighttime blood pressures than healthy individuals [Kayano, H.; Koba, S.; Matsui, T.; Fukuoka, H.; Toshida, T.; Sakai, T.; Akutsu, Y.; Tanno, K.; Geshi, E.; Kobayashi, Y. Anxiety disorder is associated with nocturnal and early morning hypertension with or without morning surge: Ambulatory blood pressure monitoring. Circ. J. 2012, 76, 1670-1677.], [Mellman, TA; Brown, DD; Jenifer, ES; Hipolito, MMS; Randall, OS. Posttraumatic stress disorder and nocturnal blood pressure dipping in young adult African-Americans. Psychosom. Med. 2019, 71, 627-630.], and sleep disturbance due to sympathetic nervous activity may be one of the contributing factors [Veith, RC; Lewis, N.; Linares, OA; Barnes, RF; Raskind, MA; Villacres, EC; Murburg, MM; Ashleigh, EA; Castillo, S.; Peskind, ER; et al. Sympathetic nervous system activity in major depression: Basal and desipramine-induced alterations in plasma norepinephrine kinetics. Arch. Gen. Psychiatry. 1994, 51, 411-422.] Therefore, it was speculated that eggplant intake suppressed sympathetic nervous activity during sleep, thereby improving morning blood pressure in stressed subjects.

[0096] Previously, we reported the antihypertensive effect of eggplant in SHRs. Daily oral administration of a low dose of eggplant powder (0.0821 mg / kg body weight) significantly suppressed increases in systolic and diastolic blood pressure in SHRs. The effective daily dose for an adult (60 kg) was calculated to be 13.1 mg using Kleiber's law [Kleiber, M. The Fire of Life: An Introduction to Animal Energetics; Wiley: New York, NY, USA, 1961.]. The efficacy of acetylcholine in eggplant may be lower in human hypertensives and stage 1 hypertensives than in SHRs with moderate to severe hypertension. In this study using SHRs, acetylcholine in eggplant acted on the M3-type muscarinic acetylcholine receptor (M3 mAChR) and reduced urinary catecholamine levels. This suggests that acetylcholine in eggplant inhibited sympathetic nervous activity via M3 mAChR in the digestive system, resulting in a decrease in blood pressure. M3 mAChR is present in epithelial cells of the stomach and intestine [Wess, J. Muscarinic acetylcholine receptor knockout mice: Novel phenotypes and clinical implications. Ann. Rev. Pharmacol. Toxicol. 2004, 44, 423-450.] Orally administered acetylcholine from eggplant acts on M3 mAChR to stimulate the parasympathetic nervous system, and when this stimulation reaches the medulla oblongata, sympathetic nervous activity automatically decreases through reciprocal innervation.

[0097] Impairment of autonomic nervous regulation is thought to be one of the causes of elevated blood pressure in SHRs. It has been reported that blood catecholamine levels in SHRs are higher than those in normotensive Wistar-Kyoto (WKY) rats, which is due to abnormally increased sympathetic nervous activity in SHRs [Tsunoda, M.; Takezawa, K.; Ina, Y.; Nagashima, K.; Ohomori, K.; Kobayashi, S.; Imai, K. New approach for measurement of sympathetic nervous abnormality in conscious, spontaneously hypertensive rats. Jpn. J. Pharmacol. 2000, 83, 39-45.] [Donohue, S.J.; Stitzel, RE; Head, R.J. Time course of changes in the norepinephrine content of tissues from spontaneously hypertensive and Wistar-Kyoto rats. J. Pharmacol. Exp. Ther. 1988, 245, 24-31.] It has been reported that the sensitivity of the baroreflex in SHR is lower than that in WKY rats [Kumagai, H.; Averill, DB; Ferrario, CM. Renal nerve activity in rats with spontaneous hypertension: Effect of converting enzyme inhibitor. Am. J. Physiol. 1992, 263, 109-115.]. This suggests that the neural regulation controlling blood pressure differs depending on the level of hypertension, and that acetylcholine in eggplant lowers blood pressure more effectively in stage 1 hypertensives than in high-normal blood pressure subjects. Regarding the primary endpoint of presentation blood pressure, eggplant intake improved only diastolic blood pressure in high-normal blood pressure subjects, but improved both systolic and diastolic blood pressure in stage 1 hypertensive subjects.The difference in blood pressure between the eggplant and placebo groups was 5.6 mmHg in diastolic blood pressure in subjects with high-normal blood pressure, and 7.6 mmHg in systolic blood pressure and 7.3 mmHg in diastolic blood pressure in subjects with stage 1 hypertension.

[0098] Stress and negative psychological states increase sympathetic nervous activity. Therefore, suppressing sympathetic nervous activity may lead to improvements in stress and negative psychological states. Therefore, in this study, we recruited stressed subjects and evaluated the effects of eggplant on improving stress and psychological states using the VAS and POMS-2 tests. A simple VAS test has been used in other studies to assess stress after oral drug administration [Diaper, A.; Papadopoulos, A.; Rich, AS; Dawson, GR; Dourish, CT; Nutt, DJ; Bailey, JE. The effect of a clinically effective and non-effective dose of lorazepam on 7.5% CO2-induced anxiety. Hum. Psychopharmacol. 2012, 27, 540-548.]Because psychological state is involved in the development and progression of hypertension [Andrew, MJ; Baker, RA; Kneebone, AC; Knight, JL Mood state as a predictor of neuropsychological deficits following cardiac surgery. J. Psychosom. Res. 2000, 48, 537-546], [Hassan, K.; Elimeleh, Y.; Shehadeh, M.; Fadi, H.; Rubinchik, I. The relationship between hydration status, male sexual dysfunction, and depression in hemodialysis patients. Ther. Clin. Risk Manag. 2018, 14, 523-529], we used the POMS-2 test to assess psychological state [Yu, BH; Dimsdale, JE; Mills, PJ Psychological states and lymphocyte beta-adrenergic receptor responsiveness. Neuropsychopharmacology 1999, 21, 147-152].

[0099] The results of the VAS and POMS-2 tests indicated that long-term intake of eggplant powder had no effect on stress but did improve psychological state. The anti-stress effects of eggplant should be evaluated objectively, rather than by subjective VAS assessment. The POMS-2 test showed that eggplant powder intake improved negative psychological states ("confusion-perplexity" in all subjects, "depression-depressed," "confusion-perplexity," "anger-hostility," and "TMD" in subjects with high-normal blood pressure) and positive psychological states ("friendliness" and "vigor-vitality" in subjects with stage 1 hypertension). The POMS-2 results also indicated that eggplant's effectiveness varied among subjects with different blood pressure levels. The trend toward improvement in psychological state from week 0 to week 4 suggests that subjects were adapting to the study. At week 8, a deterioration in psychological state was observed. Although this did not affect the overall study, this may be due to the earthquake that occurred 15 days prior to week 8 (September 6).

[0100] In this study, the dietary intervention involved taking eggplant powder capsules, and participants were prohibited from consuming foods rich in acetylcholine, such as eggplant and bamboo shoots. The capsules taken daily by subjects in the eggplant group contained 1.2g of eggplant powder and contained 4.39kcal of energy, while the placebo capsules, which did not contain eggplant powder, contained 4.35kcal of energy. Since there was no difference in nutritional value between the two, it was concluded that the improvements in blood pressure and psychological state were due to the eggplant powder. In addition to acetylcholine, eggplant also contains GABA [Horie, H.; Ando, ​​S.; Saito, T. The contents of γ-amino butyric acid in eggplant and its accumulation with heat treatment. J. Jpn. Soc. Food Sci. 2013, 60, 661-664.] and CA [Singh, AP; Luthria, D.; Wilson, T.; Vorsa, N.; Singh, V.; Banuelos, GS; Pasakdee, S. Polyphenols content and antioxidant capacity of eggplant pulp. Food Chem. 2009, 114, 955-961.], which have antihypertensive effects. According to Japan's functional food labeling system, the effective doses for antihypertensive effects of GABA and coffee-derived CA in adults are 12.3 mg and 271 mg per day, respectively. The amounts of GABA and CA ingested from the eggplant powder used in this study were 7.65 mg (62.2% of the effective dose) and 12.3 mg (4.54% of the effective dose) per day, respectively, both of which were less than the effective dose. The present inventors have reported that the main compound causing the hypotensive effect of eggplant in SHRs was not GABA or CA, but rather eggplant-derived choline ester (acetylcholine) (Non-Patent Document 16).

[0101] These results should be applied when considering the antihypertensive properties of eggplant in this clinical trial using subjects with high blood pressure. Because the amounts of GABA and CA contained in the eggplant powder used in this clinical trial were low, they alone would not be expected to have an antihypertensive effect. Furthermore, there have been no reports of a synergistic effect that enhances the antihypertensive effect when the two are present together. Therefore, it is reasonable to assume that the antihypertensive effect is due to acetylcholine. Therefore, it was concluded that the blood pressure-improving effects of GABA and CA in the eggplant powder used in this clinical trial were limited, and that acetylcholine is the primary antihypertensive component of eggplant powder. Research into the antihypertensive effects of oral acetylcholine is currently underway, and positive results are expected. This randomized controlled trial also confirmed the safety of continuous intake of eggplant powder, equivalent to 22 g of fresh eggplant per day.

[0102] In conclusion, continuous intake of eggplant powder significantly improved blood pressure and psychological state. Clinic and home blood pressure improved at weeks 4 and 8 in all subjects and in subjects with high-normal blood pressure. This transient improvement is likely due to environmental factors. Clinic and home blood pressure are known to vary with the seasons [Lewington, S.; Li, L.; Sherliker, P.; Guo, Y.; Millwood, L.; Bian, Z.; Whitlock, G.; Yang, L.; Collins, R.; Chen, J.; et al. Seasonal variation in blood pressure and its relationship with outdoor temperature in 10 diverse regions of China: The China Kadoorie Biobank. J. Hypertens. 2012, 30, 1383-1391.]. Blood pressure increases as temperatures decrease from summer to winter. This study was conducted from summer to early winter, with the mean temperature decreasing from 27.9°C to 9.6°C. This is equivalent to a 3.5mmHg increase in blood pressure.

[0103] The increase in blood pressure due to the temperature drop and the decrease in blood pressure due to eggplant powder ingestion are thought to be mediated by nervous system regulation. Because they compete with each other, the effects of eggplant may have weakened after the fourth or eighth week of the study. Blood pressure at the time of visit for all subjects and for subjects with stage 1 hypertension improved at week 12. This should be considered a manifestation of the effects of continued eggplant powder ingestion. The effects of eggplant powder are mild and gradually effective, distinct from those of antihypertensive drugs. Therefore, sustained eggplant intake is expected to improve blood pressure in subjects with high-normal blood pressure or stage 1 hypertension. Eggplant is considered a safe food. This study also confirmed the safety of eggplant powder, as well as its beneficial effects on blood pressure and psychological state. These novel effects support the usefulness of eggplant powder, which is rich in acetylcholine, as a safe approach to managing blood pressure and mental health.

[0104] Summary A placebo-controlled, double-blind, parallel-group comparative study confirmed that continuous intake of eggplant powder over a 12-week period improved blood pressure and psychological state without any side effects. Eggplant-derived choline ester (acetylcholine), contained 2.3 mg per 1.2 g of eggplant powder taken per day, can be said to be a new functional food factor. This study was also the first to demonstrate eggplant's antihypertensive and psychological state-improving effects. It is hoped that eggplant will be used as a safe method of managing blood pressure and mental health in the future.

[0105] As described above, the composition according to the present embodiment can provide a novel composition having excellent antihypertensive effects and psychological state-improving effects, which can be produced simply and inexpensively from the fruit of eggplant (Solanum melongena). Furthermore, when orally administered, the composition has a more pronounced antihypertensive effect than conventional compositions having a choline ester as an active ingredient, and can be used to produce a food with functional claims or a pharmaceutical for treating hypertension, etc.

[0106] Eggplant fruit, which is the raw material for the composition of this embodiment, is widely edible, and the composition of the present invention can be composed solely of eggplant-derived components, is highly safe, and can be taken continuously over a long period of time. Furthermore, the composition of the present invention can be used in foods, beverages, and pharmaceuticals in various forms, such as an aqueous extract of eggplant fruit, a concentrated extract obtained by concentrating the extract, a dried powder (e.g., freeze-dried powder, hot-air dried powder, spray-dried powder), or a suspension of the dried powder.

Claims

1. A composition for improving psychological state, comprising a component derived from eggplant (Solanum melongena) fruit.

2. 2. The composition for improving psychological state according to claim 1, comprising a water-soluble component of eggplant (Solanum melongena) fruit as an active ingredient.

3. 2. The composition for improving psychological state according to claim 1, which comprises a water-soluble component of eggplant (Solanum melongena) fruit.

4. A composition for improving psychological state according to any one of claims 1 to 3, for oral administration at a dose such that the amount of choline ester in the water-soluble component is 0.5 μg / kg body weight or more and 50 mg / kg body weight or less.

5. 5. The composition for improving psychological state according to claim 1, which contains 5 μg or more and 50 mg or less of choline ester and is for oral administration.

6. 6. The composition for improving psychological state according to claim 4 or 5, wherein the choline ester is any one selected from acetylcholine, butylcholine, and propionylcholine.

7. The composition for improving psychological state according to any one of claims 1 to 6, which is in the form of a dry powder.

8. The composition for improving psychological state according to any one of claims 1 to 7, which is a food composition.

9. A method for producing a composition for improving psychological state that contains an eggplant-derived component, the method comprising squeezing eggplant (Solanum melongena) fruit to obtain a juice.

10. A method for producing a composition for improving psychological state that contains an eggplant-derived component, the method comprising adding water to eggplant (Solanum melongena) fruit and squeezing the fruit to which the water has been added to obtain a juice.

11. The method for producing a composition for improving psychological state according to claim 10, comprising crushing the fruit before or after adding the water to the fruit.

12. A method for producing the composition for improving psychological state according to any one of claims 9 to 11, comprising heating the fruit.

13. A method for producing the composition for improving psychological state according to any one of claims 9 to 12, comprising drying the squeezed juice into powder.

14. A composition for improving psychological state, produced by the production method according to any one of claims 9 to 13.

15. Use of eggplant (Solanum melongena) fruit for improving psychological state.

16. 16. The use according to claim 15, by oral ingestion of the eggplant fruit.

17. A composition for improving psychological state, comprising as an active ingredient a water-soluble component of a food product made from agricultural products with a high content of choline ester.

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