Composition containing plant fat-soluble component

Abstract

Provided is a composition that is useful for preventing or reducing obesity.　A fat-soluble component is extracted from a plant by using a solvent, and the solvent is removed from the fat-soluble component to thereby produce a composition that enhances energy metabolism.

Description

Composition containing plant fat-soluble components

[0001] The present invention relates to a composition containing a fat-soluble component derived from a plant and having an effect of increasing energy metabolism.

[0002] In the Designer Foods Pyramid, a compilation of foods useful for cancer prevention created by the National Cancer Institute in the United States in the 1990s, umbelliferous vegetables such as carrots, celery, and parsnips are ranked highly as foods with high preventive effects (Non-Patent Document 1). Carrots, a representative umbelliferous vegetable, are cultivated and consumed around the world and have been reported to contribute to the prevention of cancer and cardiovascular diseases (Non-Patent Documents 2 and 3). β-Carotene is a functional component abundant in carrots and is thought to be responsible for the health benefits of carrot consumption. However, carrots also contain functional components such as polyacetylenes and phenols, which have been reported to also contribute to the functionality of carrots (Non-Patent Document 4).

[0003] Parsnips are a type of Umbelliferae vegetable similar in shape to carrots, and are widely cultivated around the world, including Asia and Europe, and various pharmacological effects have been reported (Non-Patent Document 5).

[0004] Obesity significantly increases the risk of developing lifestyle-related diseases such as diabetes and heart disease, and the increase in the number of obese patients has become a global social problem (Non-Patent Document 6). In 2019, the obesity rate in Japan was 33.0% for men and 22.3% for women, a rate that had remained almost flat over the previous 10 years (Non-Patent Document 7). Obesity increases the risk of developing lifestyle-related diseases such as diabetes, hypertension, and dyslipidemia, and can also increase the risk of serious diseases such as arteriosclerosis, myocardial infarction, and stroke. Therefore, there is a high demand for foods and other products that are useful for preventing or reducing obesity in order to promote health.

[0005] Toshihiko Osawa, Journal of the Japanese Dietetic Society, Vol. 20, No. 1, pp. 11-16 (2009)Zurbau A, Au-Yeung F, Blanco Mejia S, Khan TA, Vuksan V, Jovanovski E, Leiter LA, Kendall CWC, Jenkins DJA, Sievenpiper JL., J Am Heart Assoc. 9(19), e017728 (2020)Xu H, Jiang H, Yang W, Song F, Yan S, Wang C, Fu W, Li H, Lyu C, Gan Y, Lu Z., Br J Nutr., 122(5), 488-498(2019)Ahmad T, Cawood M, Iqbal Q, Arino A, Batool A, Tariq RMS, Azam M, Akhtar S., Foods, 8(9), 424(2019)Kenari HM, Kordafshari G, Moghimi M, Eghbalian F, TaherKhani D., J Pharmacopuncture, 24(1), 14-23 (2021)GBD 2019 Risk Factors Collaborators., Lancet., 396(10258), 1223-1249 (2020) Ministry of Health, Labor and Welfare 2019 National Health and Nutrition Survey Report Problem to be solved by the invention

[0006] As mentioned above, the health-promoting effects of consuming Umbelliferae vegetables are known, but there have been few studies on the components commonly contained in these plants that exert their health functions, and many points remain to be clarified.

[0007] An object of the present invention is to provide a composition useful for preventing or reducing obesity, particularly by using a widely consumed plant such as carrot, a plant of the Umbelliferae family.

[0008] The present invention provides the following: [1] A composition for improving the energy metabolism of a subject, comprising a fat-soluble component of a plant. [2] The composition according to [1], wherein the plant is at least one plant selected from the group consisting of Apiaceae, Araliaceae, Asteraceae, and Solanaceae. [3] The composition according to [2], wherein the plant is at least one plant selected from the group consisting of parsnip, carrot, celery, celeriac, Japanese parsley, coriander, rock laurel, dill, chervil, staghorn, caraway, Centella asiatica, samphire, Japanese honeysuckle, fennel, honeysuckle, lovage, sweet sisley, Pimpinella maior, Angelica keiskei, Saussurea Root, Angelica acutiloba, Panax ginseng, American holly, American ginseng, Siberian ginseng, Aralia udo, tomato, and eggplant. [4] The composition according to any of [1] to [3], wherein the fat-soluble component is a component extracted from a plant. [5] The composition according to any one of [1] to [4], wherein the fat-soluble component comprises a compound having a polyacetylene structure. [6] The composition according to [5], wherein the compound having a polyacetylene structure comprises falcarindiol, falcarinol, or an analog thereof. [7] The composition according to any one of [1] to [6], wherein the subject is a human. [8] The composition according to any one of [1] to [7], wherein the composition is an oral composition. [9] The composition according to [8], wherein the composition is a food composition.

[10] A composition for improving energy metabolism in a subject, comprising falcarindiol or falcarinol.

[11] A method for producing a composition for improving energy metabolism, comprising the steps of extracting a fat-soluble component from a plant using a solvent and removing the solvent from the fat-soluble component.

[12] A method for improving energy metabolism in a non-human mammal, comprising using the composition according to any one of [1] to

[10] .

[13] A method for improving energy metabolism in a human, comprising using the composition according to any one of [1] to

[10] .

[0009] According to the present invention, it is possible to provide a composition that uses a plant such as carrot as a raw material and is useful for preventing or reducing obesity.

[0010] 1 is a graph showing the change in cumulative food intake over time for the ND group, HF group, and HF+E group in Example 1. The values ​​indicate the mean value for each group, and the error bars indicate the standard error. An "*" in the graph indicates that p<0.05 was found in a Student's t-test comparing the HF group and the HF+E group. FIG. 1 is a graph showing the change in body weight for the ND group, HF group, and HF+E group in Example 1. The values ​​indicate the mean value for each group, and the error bars indicate the standard error. An "*" in the graph indicates that p<0.05 was found in a Student's t-test comparing the HF group and the HF+E group. FIG. 1 is a graph showing the activity levels of mice in the ND group, HF group, and HF+E group in Example 1. The values ​​indicate the mean value for each group, and the error bars indicate the standard error. In the graph, "ZT" stands for Zeitgeber time. The symbols "*" and "**" in the figure indicate that the Student's t-test comparing the HF group and the HF+E group showed p<0.05 and p<0.01, respectively. ２) in Example 1. The values ​​indicate the mean value for each group, and the error bars indicate the standard error. In the figure, "ZT" is Zeitgeber time. The "*" in the figure indicates that p<0.05 was found in the Student's t-test comparing the HF group and the HF+E group. This graph shows the rectal temperatures of mice in the ND group, HF group, and HF+E group in Example 1. The values ​​indicate the mean value for each group, and the error bars indicate the standard error. The "*" in the figure indicates that p<0.05 was found in the Student's t-test comparing the HF group and the HF+E group. This graph shows the time course of blood glucose levels in the ND group, HF group, and HF+E group in the glucose tolerance test in Example 1. The values ​​indicate the mean value for each group, and the error bars indicate the standard error. In the figure, "#" and "*" indicate p<0.1 and p<0.05, respectively, in the Student's t-test comparing the HF group and the HF+E group. This is a graph showing the time course of plasma insulin concentrations in the ND group, the HF group, and the HF+E group in the glucose tolerance test of Example 1. The values ​​indicate the mean values ​​for each group, and the error bars indicate the standard error. This is a graph showing the time course of blood glucose levels in the ND group, the HF group, and the HF+E group in the insulin tolerance test of Example 1. The values ​​indicate the mean values ​​for each group, and the error bars indicate the standard error. The vertical axis indicates relative values, with the value at 0 minutes set to 100. This is a graph showing iWAT weights in the ND group, the HF group, and the HF+E group in Example 1. The values ​​indicate the mean values ​​for each group, and the error bars indicate the standard error. This is a graph showing the time course of ... 1 shows micrographs of iWAT in the ND, HF, and HF+E groups in Example 1. FIG. 2 is a graph showing the average cell diameter of iWAT in the ND, HF, and HF+E groups in Example 1. The values ​​indicate the mean values ​​for each group, and the error bars indicate standard errors. An "*" in the figure indicates that p<0.05 was obtained in the Student's t-test comparing the HF and HF+E groups. FIG. 3 is a graph showing the changes in cumulative food intake over time in the HF and HF+F groups in Example 2. The values ​​indicate the mean values ​​for each group, and the error bars indicate standard errors. FIG. 4 is a graph showing the changes in body weight over time in the HF and HF+F groups in Example 2. The values ​​indicate the mean values ​​for each group, and the error bars indicate standard errors."*" in the figure indicates that p<0.05 was obtained in Student's t-test comparing the HF group and the HF+E group. Figure 1 is a graph showing the activity levels of mice in the HF group and the HF+F group in Example 2. The values ​​indicate the average values ​​for each group, and the error bars indicate the standard errors. In the figure, "ZT" stands for Zeitgeber time. "*" in the figure indicates that p<0.05 was obtained in Student's t-test comparing the HF group and the HF+F group. Oxygen consumption (VO2) of mice in the HF group and the HF+F group in Example 2. ２) in Example 2. The values ​​indicate the mean values ​​for each group, and the error bars indicate the standard error. The "*" and "**" in the figure indicate p<0.05 and p<0.01, respectively, in a Student's t-test comparing with the HF group. This graph shows the rectal temperatures of mice in the ND group, HF group, and HF+F group in Example 2. The values ​​indicate the mean values ​​for each group, and the error bars indicate the standard error. The "*" and "**" in the figure indicate p<0.05 and p<0.01, respectively, in a Student's t-test comparing with the HF group. This graph shows the time course of blood glucose levels in the HF group and the HF+F group in the glucose tolerance test in Example 2. The values ​​indicate the mean values ​​for each group, and the error bars indicate the standard error. The "#" and "*" in the figure indicate p<0.1 and p<0.05, respectively, in a Student's t-test comparing the HF group and the HF+F group. 1 is a graph showing the change in plasma insulin concentration over time in the HF group and the HF+F group in the glucose tolerance test of Example 2. The values ​​indicate the mean value for each group, and the error bars indicate the standard error. This is a graph showing the change in blood glucose level over time in the HF group and the HF+F group in the insulin tolerance test of Example 2. The vertical axis indicates the relative value, with the value at 0 minutes set to 100. The values ​​indicate the mean value for each group, and the error bars indicate the standard error. In the figure, "#", "*", and "**" indicate p<0.1, p<0.05, and p<0.01, respectively, in the Student's t-test comparing with the HF group. This is a graph showing iWAT, eWAT, and liver weight in the HF group and the HF+F group in Example 2. The values ​​indicate the mean value for each group, and the error bars indicate the standard error. In the figure, "#" and "*" indicate p<0.1 and p<0.05, respectively, in a Student's t-test comparing the HF group and the HF+F group. This graph shows the average cell diameter of iWAT and eWAT in the HF group and the HF+F group in Example 2. The numerical values ​​indicate the mean values ​​for each group, and the error bars indicate the standard error. In the figure, "#" and "**" indicate p<0.1 and p<0.01, respectively, in a Student's t-test comparing the HF group and the HF+F group. This graph shows microscopic photographs of the livers of the HF group and the HF+F group in Example 2. This graph shows the amount of triglyceride (TG) in the livers of the HF group and the HF+F group in Example 2. The numerical values ​​indicate the mean values ​​for each group, and the error bars indicate the standard error.The "#" in the figure indicates that p<0.1 in the Student's t-test comparing the HF group and the HF+F group.

[0011] 1. Composition for Improving Energy Metabolism A first embodiment of the present invention is a composition for improving energy metabolism in a subject. In one aspect of this embodiment, the composition is characterized by comprising a fat-soluble component of a plant.

[0012] The present inventors have discovered that an organic solvent extract of dried carrot powder has the effect of enhancing energy metabolism in mammals, leading to the completion of the present invention. Since the extract did not contain detectable concentrations of β-carotene, it was determined that the energy metabolism-enhancing effect was due to the action of fat-soluble components other than β-carotene. Furthermore, as a result of extensive research, the present inventors have found that, among the fat-soluble components contained in carrot extract, falcarindiol alone has an energy metabolism-enhancing effect similar to that of the above extract, suggesting that falcarindiol is one of the components in carrot extract that contribute to the enhancement of energy metabolism.

[0013] The composition of this embodiment is a composition that, when ingested by a subject, has the effect of enhancing the energy metabolism of the subject through the action of contributing components contained as fat-soluble components of the plant.

[0014] As used herein, the term "subject" refers to an individual who takes the composition of the present invention by oral administration or the like, and specifically includes humans or non-human mammals. Non-human mammals include, but are not limited to, laboratory animals such as mice, rats, and guinea pigs, livestock animals such as cows, horses, and sheep, and pet animals such as dogs and cats. As used herein, the subject is preferably a human.

[0015] In this specification, "improving energy metabolism" refers to achieving at least one of the following effects: increasing oxygen consumption, increasing normal body temperature, suppressing increases in blood glucose levels, accelerating the decrease in blood glucose levels, and decreasing body fat percentage. More specifically, it refers to achieving an effect of preventing / alleviating obesity or obesity syndrome.

[0016] As used herein, the term "obesity" refers to a state in which body weight is higher than normal or body fat is excessively accumulated. In humans, this refers to a state in which the body mass index (BMI), calculated by the following formula (I), is 25 or higher: BMI = weight (kg) / (height (m)) ２ ...(I) In humans, if a person has obesity and one or more of the following complications, specifically impaired glucose tolerance (such as type 2 diabetes and impaired glucose tolerance), dyslipidemia, hypertension, hyperuricemia and gout, coronary artery disease (myocardial infarction and angina pectoris), cerebral infarction (cerebral thrombosis and transient ischemic attack (TIA)), non-alcoholic fatty liver disease (NAFLD), menstrual disorders and infertility, obstructive sleep apnea syndrome (OSAS) and obesity-hypoventilation syndrome, musculoskeletal diseases (osteoarthritis (knee and hip) and spondylosis osteoarthritis), osteoarthritis of the fingers, or obesity-related kidney disease, or if the person is at high risk of developing these complications, the person is diagnosed with "obesity" and is a target for weight loss treatment.

[0017] As used herein, the term "plant" generally refers to plants that can be ingested by mammals such as humans through oral ingestion or other means without causing health hazards, such as plants known as vegetables, fruits, herbal medicines, etc. As used herein, the term "plant" preferably refers to plants belonging to the order Apiales, and more preferably to plants belonging to the families Apiaceae, Araliaceae, Asteraceae, and Solanaceae.The plant is more preferably parsnip (Pastinaca sativa), carrot (Daucus carota subsp. sativus), celery (Apium graveolens var. dulce), celeriac (Apium graveolens L. var. rapaceum), water dropwort (Oenanthe javanica), parsley (Petroselinum crispum), coriander (Coriandrum sativum), rock honeysuckle (Aegopodium podagraria), dill (Anethum graveolens), chervil (Anthriscus cerefolium), sedge (Anthriscus sylvestris Hoffm.), caraway (Carum carvi), centella asiatica, samphire (Crithmum maritimum), honeybee (Cryptotaenia canadensis), wild fennel (Ferula communis, fennel (Foeniculum vulgare), honeysuckle (Heracleum sphondylium), lovage (Levisticum officinale), sweet sisley (Myrrhis odorata), Pimpinella major, angelica tree (Angelica keiskei), Saposhnikovia divaricata, Angelica acutiloba, ginseng (Panax ginseng), American holly (Oplopanax horridus), American ginseng (Eleutherococcus senticosus), Siberian ginseng (Eleutherococcus senticosus), Aralia cordata, tomato (Solanum lycopersicum), and eggplant (Solanum melongena).

[0018] As used herein, the term "fat-soluble component" refers to a component that has a higher solubility in organic solvents (e.g., methanol, ethanol, ethyl acetate, etc.) with an SP value of less than 15.0 compared to its solubility in water (SP value 23.4). The fat-soluble component of a plant contained in the composition of this embodiment may be contained in the form of a dried powder, crushed, ground, pulverized, sheared, or squeezed juice of the plant itself, or may be added as a plant extract or a specific purified compound. Preferably, the fat-soluble component is added as a plant extract or purified compound. More preferably, it is added as a plant extract.

[0019] As used herein, the term "extract" refers to a substance obtained by extracting a part or the whole of a plant, either as is or in the form of a dried powder, crushed, ground, pulverized, sheared, squeezed juice, or the like, with a solvent or the like. Examples of solvents for extraction include water, lower monohydric alcohols (e.g., methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol), liquid polyhydric alcohols (e.g., glycerin, propylene glycol, 1,3-butylene glycol), lower esters (e.g., ethyl acetate), hydrocarbons (e.g., benzene, hexane, pentane), ketones (e.g., acetone, methyl ethyl ketone), ethers (e.g., diethyl ether, tetrahydrofuran, dipropyl ether), acetonitrile, and combinations thereof. In particular, the use of solvents other than water that are suitable for extracting fat-soluble components, particularly solvents with an SP value of less than 15.0, 13.0, or 10.0, is preferred. The extraction method may involve, for example, crushing the plant in a solvent, adding an excess amount of solvent, and then shaking the mixture to extract, or adding a dried powder of the plant to a solvent and leaving it to stand for several minutes to 10 days to extract the plant, followed by centrifugation or filtration to obtain an extract. The extract obtained may be used as is, or the solvent may be removed by distillation, fractionation, and / or purification.

[0020] In this embodiment, the fat-soluble component preferably includes a compound having a polyacetylene structure (polyyne structure). In particular, it preferably includes falcarindiol, falcarinol, or known analogs thereof. As used herein, "analog" refers to a compound that has the same carbon skeleton as the original compound (here, falcarindiol or falcarinol) but has been modified to an extent that does not significantly affect physiological activity (e.g., by substituting a hydrogen molecule with a halogen group). As used herein, the term "falcarindiol or falcarinol" is not intended to exclude compounds equivalent to these compounds, but rather encompasses "falcarindiol, falcarinol, or known analogs thereof."

[0021] Falcarindiol and falcarinol are compounds represented by the following formulas (II) and (III).

[0022] Compounds with a falcarindiol-type acetylene structure are known to be abundant in plants of the Umbelliferae family, such as carrots, and have been reported to have anticancer effects (HE Jin, et al., Cell Death & Disease, 3, e376 (2002)) and glucose metabolism-promoting effects (A Atanasov, et al., Plos One, 8(4), e61755 (2013)). However, their specific energy metabolism-enhancing effects, which could lead to obesity suppression, have not been reported.

[0023] Falcarindiol or falcarinol may be added in a purified state to the composition of this embodiment, but may also be included as a plant component in the form of a plant itself (crushed, ground, pulverized, sheared, squeezed, etc.) or a plant extract. In particular, the composition of this embodiment is preferably included in the form of a plant itself or a plant extract. Of these, the form of a plant extract is preferred.

[0024] In another aspect of this embodiment, the composition contains falcarindiol or falcarinol, preferably falcarindiol, as a contributing component. The falcarindiol or falcarinol referred to here is not limited to those purified from plants, but also includes those produced by chemical synthesis or the like.

[0025] The composition of this embodiment may take various forms, including, but not limited to, supplements, tablets, coated tablets, granules, powders, solutions, emulsions, capsules, injections or liquids, dry syrups, syrups, and patches. In one aspect, the composition of this embodiment may be for oral intake (orally administered). In another aspect, the composition of this embodiment may be for enteral administration, tube administration, or gastrostomy administration, etc. The composition for gastrostomy administration may be a liquid or liquid diet or nutritional composition.

[0026] In one aspect, the composition of the present embodiment may contain other ingredients typically contained in compositions for oral ingestion, enteral administration, tube administration, or gastrostomy administration, such as excipients, disintegrants, binders, lubricants, colorants, flavorings, suspending agents, solubilizers, coating agents, adjuvants, preservatives, fragrances, vitamins, pH adjusters, emulsifiers, thickeners, isotonicity agents, antioxidants, chelating agents, sweeteners, flavors, etc., but the additional ingredients are not limited thereto. In one aspect, the composition of the present embodiment may be a food composition or a feed composition. In one aspect, the composition of the present embodiment may be a pharmaceutical composition, a drug, or a quasi-drug.

[0027] Examples of the food compositions include, but are not limited to, beverages (juice, black tea, green tea, coffee, carbonated drinks, sports drinks, soft drinks, etc.), confectioneries (gum, caramel, candy, chocolate, cookies, biscuits, snacks, jelly, gummies, candy tablets, etc.), noodles (soba, udon, ramen, etc.), dairy products (milk, ice cream, yogurt, etc.), seasonings (miso, soy sauce, dressing, etc.), soups, and other general foods and processed foods, health foods (tablets, capsules, etc.), and nutritional supplements (supplements, energy drinks, etc.).

[0028] These food compositions can contain various ingredients depending on the type thereof, and food additives such as glucose, fructose, sucrose, maltose, raffinose, sorbitol, stevioside, corn syrup, lactose, citric acid, tartaric acid, malic acid, succinic acid, lactic acid, L-ascorbic acid, dl-α-tocopherol, sodium erythorbate, glycerin, propylene glycol, glycerin fatty acid esters, polyglycerin fatty acid esters, sucrose fatty acid esters, sorbitan fatty acid esters, propylene glycol fatty acid esters, gum arabic, carrageenan, casein, gelatin, pectin, agar, B vitamins, nicotinamide, calcium pantothenate, amino acids, calcium salts, colorings, flavorings, and preservatives can be used as desired.

[0029] In this specification, "contributing component" refers to a substance that affects the physiological functions of the body. The contributing component in pharmaceuticals and quasi-drugs is the so-called "active ingredient." The contributing component in foods for specified health uses and foods with functional claims is the so-called "contributing component" and "functionally contributing component."

[0030] The composition of this embodiment may contain the fat-soluble component of the plant such that the amount of falcarindiol and / or falcarinol administered to a subject is 0.1 mg / kg body weight or more, 0.2 mg / kg body weight or more, 0.5 mg / kg body weight or more, 1 mg / kg body weight or more, 2 mg / kg body weight or more, 5 mg / kg body weight or more, 10 mg / kg body weight or more, 20 mg / kg body weight or more, 50 mg / kg body weight or more, 100 mg / kg body weight or more, 200 mg / kg body weight or more, or 500 mg / kg body weight or more. The composition of this embodiment may contain the fat-soluble component of the plant such that the amount of falcarindiol and / or falcarinol administered to a subject is 1000 mg / kg body weight or less, 500 mg / kg or less, 200 mg / kg body weight or less, 100 mg / kg body weight or less, 50 mg / kg body weight or less, or 10 mg / kg body weight or less. In another aspect, the composition of this embodiment may contain the fat-soluble component of a plant such that the concentration of falcarindiol and / or falcarinol in the composition is 0.001% by weight or more, 0.005% by weight or more, 0.01% by weight or more, 0.02% by weight or more, 0.05% by weight or more, 0.1% by weight or more, 0.2% by weight or more, 0.3% by weight or more, 0.4% by weight or more, 0.5% by weight or more, 1.0% by weight or more, or 2.0% by weight or more. The composition of this embodiment may contain the fat-soluble component of a plant such that the concentration of falcarindiol and / or falcarinol in the composition is 2.0% by weight or less, 1.0% by weight or less, 0.5% by weight or less, 0.3% by weight or less, 0.2% by weight or less, or 0.1% by weight or less.

[0031] The intake amount of the composition of this embodiment, when the subject is a human, may vary depending on the subject's age, sex, symptoms, and administration method. However, it may be an amount of falcarindiol and / or falcarinol typically ingested by an adult (body weight approximately 60 kg) per day of 1 mg or more, 5 mg or more, 10 mg or more, 20 mg or more, for example, 30 mg or more. Note that "30 mg or more per day" may vary depending on the form of the composition, but refers to the recommended daily intake amount indicated, or the amount contained in one bottle of a beverage that is typically consumed in one sitting. The daily amount may be achieved by single administration or multiple administrations (ingestions). Administration or ingestion may be before, after, or between meals. The duration of administration or ingestion is not particularly limited, but in some embodiments, the composition of the present invention may be ingested over a long period of time or continuously. Long-term or continuous ingestion refers to ingestion for, for example, one month or more, two months or more, three months or more, four months or more, five months or more, or, for example, six months or more. In some embodiments, the composition of the present invention may be packaged in a form suitable for long-term or continuous ingestion. Furthermore, a person skilled in the art can appropriately determine the intake or administration amount of the composition of the present invention.

[0032] In a specific embodiment, the food composition of the present invention can be designated as a functional food or a food for specified health uses based on the above-mentioned functionality and beneficial effects on the living body.

[0033] The usefulness and functionality of the composition of the present invention may be indicated by the following labels when commercialized, but the labels are not limited to these. Examples include "functionality for improving energy metabolism," "functionality for improving basal metabolism," "functionality for suppressing a decline in energy metabolism," "functionality for suppressing a decline in basal metabolism," "functionality for reducing the risk of obesity," "functionality for improving glucose metabolism," "functionality for suppressing fat accumulation," "functionality for reducing fat," "functionality for facilitating fat consumption," and similar labels. These labels can be attached to container packaging means by known methods, or can be displayed or distributed by displaying the above explanation in product advertisements, price lists, or transaction documents, or by providing information containing these contents via electromagnetic means (such as the Internet).

[0034] 2. Method for Producing a Composition for Improving Energy Metabolism A second embodiment of the present invention is a method for producing a composition for improving energy metabolism. The method of this embodiment is characterized by comprising the steps of extracting fat-soluble components from a plant using a solvent and removing the solvent from the fat-soluble components.

[0035] 2-1 Step of Extracting Fat-Soluble Components from Plants The method of this embodiment includes a step of extracting fat-soluble components from plants using a solvent. The plants used in this embodiment generally refer to plants that can be ingested by mammals such as humans through oral ingestion or other methods without causing health hazards, and include, for example, plants known as vegetables, fruits, herbal medicines, etc. In this specification, the plants are preferably plants belonging to the Umbellidales order, and more preferably plants belonging to the Apiaceae family, Araliaceae family, Asteraceae family, or Solanaceae family. More preferably, the plant is at least one selected from parsnip, carrot, celery, celeriac, water dropwort, parsley, coriander, rock mitsuba, dill, chervil, staghorn, caraway, Centella asiatica, samphire, mitsuba, giant holly, fennel, honeysuckle, lovage, sweet cissery, Pimpinella maior, Angelica keiskei, Saussurea chinensis, Japanese angelica, Panax ginseng, American holly, American ginseng, Eleuthero, Aralia burdock, tomato, and eggplant.

[0036] In this embodiment, extraction refers to contacting a plant with a solvent. The state of the plant used here is not particularly limited, and can be, for example, a dry powder, crushed, ground, pulverized, sheared, or squeezed juice. Solvents other than water, particularly solvents with an SP value of less than 15.0, less than 13.0, or less than 10.0, are suitable for use as the extraction solvent. For example, extraction can be performed by adding a dry plant powder or the like to a solvent, leaving it to stand for several minutes to 10 days, and then filtering the mixture to obtain an extract. The resulting extract may be used as is, or may be further fractionated and / or purified.

[0037] 2-2 Step of Removing Solvent from Fat-Soluble Component The method of this embodiment includes a step of removing the solvent from the fat-soluble component. The solvent can be removed from the target fat-soluble component by evaporating it using a known method such as heating or reducing pressure. The fat-soluble component after removing the solvent is combined with other components such as excipients and used to produce a composition. Unless otherwise specified, the "composition" in this embodiment has the same meaning as the composition described in the section "1. Composition for Improving Energy Metabolism."

[0038] 3. Method for Improving Energy Metabolism A third embodiment of the present invention is a method for improving energy metabolism in a subject. The method of this embodiment comprises using the composition described in the section "1. Composition for Improving Energy Metabolism."

[0039] In the method of this embodiment, the subject is a human or a non-human mammal. In the method of this embodiment, a composition containing a fat-soluble component of a plant is administered to the human or non-human mammal by oral ingestion or the like, thereby improving the energy metabolism of the subject and contributing to the prevention and / or reduction of obesity.

[0040] In one aspect, the method of the present embodiment is a method for activating muscarinic acetylcholine receptors in non-human mammals, including, but not limited to, laboratory animals such as mice, rats, and guinea pigs, livestock animals such as cows, horses, and sheep, and pet animals such as dogs and cats.

[0041] In the method of the present invention, the components, preparation method, administration form, mechanism of action, administration target, etc. of the composition used are as described in the section "1. Composition for improving energy metabolism" unless otherwise contradicted.

[0042] Example 1: Study of the effect of parsnip extract on maintaining metabolic efficiency in mice fed a high-fat diet. Freeze-dried commercially available parsnips were cut into approximately 1 cm cubes, freeze-dried, and then ground into powder using a flour mill. 30 g of the freeze-dried product was placed in a 100 mL extraction cell of a high-speed solvent extractor (Dionex ASE 350, Thermo Fisher Scientific) and extracted twice with ethyl acetate to extract the fat-soluble components. The solvent was then removed to obtain a parsnip extract (yellowish-brown oil). C57BL / 6J mice (male, 6 weeks old) were divided into a normal diet group (ND group), a high-fat diet group (HF group), and a high-fat diet + carrot extract (HF+E group). The ND group received a normal solid sample (MF solid material for laboratory animals, manufactured by Oriental Yeast Co., Ltd.), the HF group received an ultra-high-fat diet with a fat content of 60 kcal (D12492, manufactured by Research Diets), and the HF+E group received the same diet as the HF group plus 0.5 wt% parsnip extract. The mice were fed ad libitum. Each group consisted of 10 mice. After the start of feeding, the amount of food intake and body weight of each mouse were measured over time. Activity was measured at 16-17 weeks after the start of feeding, and oxygen consumption (VO2) was measured at 18-20 weeks. ２ ), and rectal temperature was measured at 20 weeks. The activity level, oxygen consumption, and rectal temperature of the mice were measured using a mouse activity measurement device (ACTIMO-100S, Shin Factory), an Oxymax equal flow system (Columbus Instruments), and a thermocouple temperature sensor (RET-3, Physitemp), respectively. The mice were dissected on day 171, and inguinal white adipose tissue (iWAT) was removed. Each tissue was stained with hematoxylin and eosin (HE staining) and observed under a microscope. The average cell diameter was calculated for cells within one microscopic field.

[0043] An oral glucose tolerance test was performed 18 weeks after the start of feeding. After fasting for 6 hours, the mice were orally administered a glucose solution at 1.5 g / kg body weight. Blood glucose levels and plasma insulin concentrations were measured over time, up to 120 minutes and 30 minutes after oral administration, respectively.

[0044] An insulin tolerance test was performed on mice 21 weeks after the start of feeding. After fasting for 6 hours, 1.0 U / kg of insulin solution was intraperitoneally administered to the mice. Blood glucose levels were measured over time up to 120 minutes after administration.

[0045] The results are shown in Figures 1 to 11. The values ​​in the graphs represent the mean values, and the error bars represent the standard error (SE). Figure 1 shows the cumulative food intake of mice in each group. An "*" in the figure indicates that p<0.05 was obtained in the Student's t-test comparing the HF group and the HF+E group. Figure 2 shows the weight change over time for mice in each group. An "*" in the figure indicates that p<0.05 was obtained in the Student's t-test comparing the HF group and the HF+E group. Compared to ND, the weight gain of the HF and HF+E groups was significantly higher. When comparing the HF and HF+E groups, the weight of the HF+E group remained slightly lower despite no difference in food intake.

[0046] Figure 3 shows the activity levels of mice in each group. In the figure, "*" and "**" indicate p<0.05 and p<0.01, respectively, in a Student's t-test comparing the HF group and the HF+E group. Activity levels tended to increase in the order of ND, HF, and HF+E groups, both during light and dark periods. Figure 4 shows the oxygen consumption levels of mice in each group. In the figure, "*" indicates p<0.05 in a Student's t-test comparing the HF group and the HF+E group. Figure 5 shows the rectal temperatures of mice in each group. In the Student's t-test comparing the HF group and the HF+E group, "*" indicates p<0.05. The results shown in Figures 3 to 5 indicate that the HF+E group had lower activity levels than the HF group, but higher oxygen consumption, rectal temperature, and energy metabolism.

[0047] Figure 6 shows the time course of blood glucose levels in mice of each group during an oral glucose tolerance test. The "#" and "*" in the figure indicate p<0.1 and p<0.05, respectively, in the Student's t-test comparing the HF group and the HF+E group. The blood glucose levels of the HF+E group 120 minutes after glucose loading were significantly lower than those of the HF group. These results suggest that ingestion of carrot extract can prevent impaired glucose tolerance induced by a high-fat diet. Figure 7 shows the time course of plasma insulin concentrations in mice of each group during an oral glucose tolerance test. Figure 8 shows the time course of blood glucose levels in mice of each group during an insulin tolerance test. The vertical axis shows relative values, with the value at 0 minutes set to 100. The insulin levels in the HF+E group during the oral glucose tolerance test were generally lower than those of the HF group. Furthermore, blood glucose levels during insulin loading were slightly lower in the HF+E group.

[0048] Figure 9 shows the weight of mouse iWAT in each group. The "*" in the figure indicates that p<0.05 was obtained by Student's t-test comparing the HF group and the HF+E group. The iWAT weights of the HF and HF+E groups were significantly higher than those of the ND group, but the iWAT weight of the HF+E group was significantly lower than that of the HF group. Figure 10 shows micrographs of iWAT in each group, and Figure 11 shows the average cell diameter in iWAT in each group. The "*" in the figure indicates that p<0.05 was obtained by Student's t-test comparing the HF group and the HF+E group. The results in Figures 10 and 11 indicate that hypertrophy of iWAT adipocytes was observed in the HF group, whereas hypertrophy of adipocytes was suppressed in the HF+E group.

[0049] Example 2: Study of the Effect of Falcarindiol on Maintaining Metabolic Efficiency in Mice Fed a High-Fat Diet Falcarindiol (85% purity) was obtained from the parsnip extract obtained by the method of Example 1 by preparative HPLC using an ODS column (Develosil® ODS-HG, 20.0 x 250 mm, 5 μm, Nomura Chemical Co., Ltd.) and gradient elution of acetonitrile and water. C57BL / 6J mice (male, 6 weeks old) were divided into a high-fat diet group (HF group) and a high-fat diet + falcarindiol group (HF+F group). The HF group was fed a 60 kcal% ultra-high-fat diet (D12492, Research Diets), while the HF+F group was fed the same diet as the HF group plus 0.04 wt% falcarindiol. Food intake was ad libitum. Each group consisted of n = 10, but one mouse in the HF group died after the start of feeding, so the results show n = 9. The food intake, body weight, and rectal temperature of each mouse were measured over time. The activity level and oxygen consumption (VO2) of the mice were measured 14 to 15 weeks after the start of feeding. ２ ) was measured.

[0050] An oral glucose tolerance test was performed 12 weeks after the start of feeding. On the 84th day after the start of feeding, the mice were fasted for 6 hours and then orally administered a glucose solution at 1.5 g / kg body weight. Blood glucose levels and plasma insulin concentrations were measured over time, up to 120 minutes and 30 minutes after oral administration, respectively.

[0051] An insulin tolerance test was performed on mice 13 weeks after the start of feeding. On the 91st day after the start of feeding, the mice were fasted for 6 hours and then intraperitoneally administered 1.0 U / kg of insulin solution. Blood glucose levels were measured over time up to 120 minutes after administration.

[0052] Mice were dissected at 17 weeks, and inguinal white adipose tissue (iWAT), epididymal white adipose tissue (eWAT), and liver were removed and weighed. Furthermore, each tissue was stained with HE and observed under a microscope. The average cell diameter was calculated for cells within one microscopic field. Furthermore, to measure the amount of triglycerides (TG) contained in the liver, liver tissue was homogenized with an extraction solvent (hexane:2-propanol = 3:2), the supernatant was dried, and then redissolved in 2-propanol containing 10% Triton® X-100. The amount of TG contained in the extract was measured using Triglyceride E-Test Wako (Fujifilm Wako Pure Chemical Industries, Ltd.).

[0053] The results are shown in Figures 12 to 23. The values ​​in the graphs show the average values, and the error bars show the standard error (SE). Figure 12 shows the cumulative amount of food intake for the mice in each group. Figure 13 shows the changes in body weight over time for the mice in each group. A comparison of the HF group and the HF+F group showed that, despite there being no difference in food intake, weight gain was significantly suppressed in the HF+F group.

[0054] Figure 14 shows the activity levels of mice in each group. The "*" in the figure indicates p<0.05 in the Student's t-test comparing the HF group and the HF+F group. Figure 15 shows the oxygen consumption levels of mice in each group. The "*" and "**" in the figure indicate p<0.05 and p<0.01 in the Student's t-test comparing the HF group and the HF+F group, respectively. Figure 16 shows the rectal temperature of mice in each group. The "*" and "**" indicate p<0.05 and p<0.01 in the Student's t-test comparing the HF group, respectively. As shown in Figure 14, there was almost no difference in activity levels between the HF group and the HF+F group. However, the results shown in Figures 15 and 16 indicate that the HF+F group had higher oxygen consumption, rectal temperature, and energy metabolism than the HF group.

[0055] Figure 17 shows the time course of blood glucose levels during an oral glucose tolerance test for mice in each group. In the figure, "#" and "*" indicate p<0.1 and p<0.05, respectively, in a Student's t-test comparing the HF group and the HF+F group. It was shown that the blood glucose levels of the HF+F group were lower than those of the HF group 30 minutes after glucose loading. Figure 18 shows the time course of plasma insulin concentrations during an oral glucose tolerance test for mice in each group. The plasma insulin levels of the HF+F group in the oral glucose tolerance test were lower than those of the HF group. Figure 19 shows the time course of blood glucose levels during an insulin tolerance test for mice in each group. In the figure, "#" and "*" indicate p<0.1 and p<0.05, respectively, in a Student's t-test comparing the HF group and the HF+F group. It was shown that the blood glucose levels of the HF+F group after insulin administration were generally lower than those of the HF group.

[0056] Figure 20 shows the weights of iWAT, eWAT, and livers of mice in each group. The "#" and "*" in the figure indicate p<0.01 and p<0.05, respectively, in a Student's t-test comparing the HF group and the HF+F group. Figure 21 shows the average cell diameter in iWAT and eWAT of each group. The "#" and "*" in the figure indicate p<0.1 and p<0.05, respectively, in a Student's t-test comparing the HF group and the HF+E group. The results in Figures 20 and 21 demonstrate that iWAT hypertrophy is suppressed in the HF+F group compared to the HF group. Figure 22 shows microscopic photographs of the livers of mice in each group, and Figure 23 shows the triglyceride (TG) levels in the livers of each group. The "#" in the figure indicates p<0.1, respectively, in a Student's t-test comparing the HF group and the HF+E group. The results in Figures 20, 22 and 23 show that liver hypertrophy and fatty liver due to TG accumulation were suppressed in the HF+F group compared to the HF group.

[0057] All publications, patents, and patent applications cited herein are hereby incorporated by reference in their entirety.

Claims

1. A composition for improving energy metabolism in a subject, comprising falcarindiol.

2. The composition described in claim 1, wherein the falcarindiol is a component extracted from a plant.

3. The composition of claim 1 , wherein the subject is a human.

4. The composition of claim 1, which is an orally ingestible composition.

5. The composition of claim 4, which is a food-grade composition.

6. Extracting fat-soluble components from plants using a solvent; and removing the solvent from the fat-soluble component A method for producing a composition for improving energy metabolism, comprising:

7. A method for improving energy metabolism in a non-human animal, comprising using the composition according to any one of claims 1 to 5.