JP6091163B2 - GLP-1 secretion promoter - Google Patents

Description

  The present invention relates to a GLP-1 (Glucagon-like peptide-1) secretion promoter.

  In recent years, lifestyle-related diseases such as diabetes, dyslipidemia, and hypertension and obesity have become major problems. In lifestyle-related diseases, lifestyle factors such as dietary habits are considered to contribute to the onset in addition to genetic factors. Obesity is one of the causes of the occurrence of excessive calorie intake relative to calorie consumption. Life style improvement is thought to be effective in preventing and improving these lifestyle-related diseases and obesity, but materials useful for the onset of lifestyle-related diseases and obesity by adjusting the physiological system, especially on a daily basis There are growing expectations for materials that can be used as food and drink that can be inoculated.

  GLP-1 is a hormone produced from a common gene and precursor with glucagon, which is an endocrine hormone. While glucagon is produced by α cells in the islets, GLP-1 is produced by endocrine cells (L cells) of the gastrointestinal mucosal epithelium, and is produced through processing different from that of glucagon from its precursor. GLP-1 is a hormone with an incretin (Intestine Secretion Insulin) action that plays an important role in glucose metabolism. It is secreted into the blood by ingestion of nutrients and acts on the pancreatic β-cell to secrete insulin. Promotes and lowers blood sugar levels. GLP-1 also suppresses glucagon secretion from pancreatic alpha cells, thereby reducing glucose release from the liver and lowering blood glucose levels. Other actions of GLP-1 are known to promote proliferation of pancreatic β cells, suppress gastric excretion and gastric acid secretion, and suppress appetite and food intake (Non-patent Document 1). Therefore, enhancing the effect of GLP-1 is useful for improving lifestyle-related diseases such as obesity and diabetes. In recent years, development of diabetes treatment methods using GLP-1 replacement therapy and GLP-1 receptor (GLP-1R) agonists has also been promoted.

  GLP-1 is also known to have an effect on the central nervous system. GLP-1's appetite and feeding-suppressing effects are thought to be via GLP-1R present in the central nervous system (Non-patent Document 1).

  Furthermore, GLP-1 is considered useful for controlling blood glucose levels in diabetic patients. When GLP-1 suppresses pancreatic glucagon secretion, glucose release from the liver decreases and blood glucose decreases. It has been reported that this action does not antagonize glucagon secretion due to hypoglycemia and does not depend on insulin concentration. It has also been reported that administration of GLP-1 decreased the amount of insulin required to make blood glucose constant in both type 1 diabetic patients and type 2 diabetic patients. Furthermore, GLP-1 can exert an effect on blood glucose level control in the long term by acting on the central nervous system and suppressing appetite. Therefore, GLP-1 may improve the symptoms of patients with diabetes and insulin resistance through these actions. Exenatide and Liraglutide, which are actually GLP-1 analog preparations, have been used as antidiabetic drugs and have been reported to have an effect of improving insulin resistance (Non-patent Document 2).

Furthermore, GLP-1 enhances myocardial contractile force by increasing cAMP in myocardial cells by signaling via GLP-1 receptors present in cardiomyocytes, endocardium, coronary vascular endothelial cells and smooth muscle. It has been reported that it promotes NO production and increases glucose uptake through GLUT1 to show an effect of improving cardiac function. GLP-1 has been reported to increase NO production from vascular endothelial cells and improve vasorelaxation by signaling via GLP-1R present on vascular endothelial cells (Non-patent Document 3). .
It has also been reported that administration of GLP-1 and exenatide (GLP-1 receptor agonist) analogs to Dahl salt-sensitive rats (4 weeks, subcutaneous administration) significantly reduces systolic blood pressure ( Non-patent document 4).
Therefore, enhancing the effect of GLP-1 is useful for improving lifestyle-related diseases such as hypertension.

  However, the active body of GLP-1 is a polypeptide, and when GLP-1 is orally ingested, it is easily digested and degraded by digestive enzymes in the digestive tract and has a very short half-life in vivo. Therefore, even if GLP-1 is administered from outside the body, it is very difficult to keep the blood concentration constant. Therefore, in order to increase the in vivo GLP-1 concentration over a long period of time, it is desirable to promote the secretion of endogenous GLP-1 rather than the administration of GLP-1 from outside the body.

  Here, as a substance that promotes secretion of GLP-1 from research in a culture system, palmitic acid, oleic acid, meat hydrolyzate (MH), gastrin releasing peptide (GRP), carbachol, forskolin, ionomycin, myristic acetate Acid phorbol (PMA), essential amino acid (EAA), leucine, isoleucine, skim milk, casein, leptin, muscarinic receptor M1, M2, kiraya or its extract, lysophosphatidylinositol or its salt have been reported so far (Non-patent documents 5 to 9, Patent documents 1 and 2).

On the other hand, Tsukinuki-psycho is a plant belonging to the family Aceraceae, and it is known that the saponin component contained in the extracted component is partly the same as that of Mishima-saiko.
Sikakai is a leguminous plant that contains a lot of saponin in its pods, leaves, and skins, and it can be used as a hair wash and is known to be effective in preventing white hair. . The extract of Sikakai reduces TNFα and IL-1β to prevent cognitive decline and age-related memory impairment (Patent Document 3), parasite prevention (Non-Patent Document 10), in vitro suppression of TBARS production (oxidative stress) Suppression), α-amylase, maltase, sucrase, and lipase activity inhibition (Non-patent Document 11) are reported to be effective.
However, it is not known about the relationship between the chinook or sikakai and the promotion of GLP-1 secretion.

JP 2012-131742 A International Publication No. 2012/086406 Japanese Patent No. 4842818

Eur J Pharmacol, 2002, 440 (2-3): 269-279 History of Medicine, 2009, 231 (7): 755-758 History of Medicine, 2012, 241 (7): 507-516 Cardiovascular Diabetology 2010, 9:32 Endocrinology, 2001, 142 (10): 4522-4528 Journal of Endocrinology, 2006, 191,159-170 Nutrition, 2009, 25 (3): 340-349 Endocrinology, 2003, 144 (7): 3244-3250 Diabetes, 2006, 52 (2): 252-259 Biomedicine 31 (3), pp.329-333 2011 Journal of Natural Remedies 10 (2), pp.123-135

  The present invention relates to providing pharmaceuticals, quasi-drugs, foods, feeds, and materials that can be blended in them, which have an excellent GLP-1 secretion promoting action and are highly safe.

  As a result of searching for an effective component in promoting GLP-1 secretion, the present inventors have a GLP-1 secretion promoting action on the Japanese cypress or deer silkworm, which suppresses glucagon secretion, suppresses appetite, prevents or improves obesity, It was found useful as a pharmaceutical, quasi-drug, food, feed, etc. that can exert effects such as prevention or improvement of postprandial hyperglycemia, prevention or improvement of diabetes, blood pressure lowering, and enhancement of blood vessel protection.

That is, the present invention relates to the following (1) to (9).
(1) A GLP-1 secretion promoter comprising as an active ingredient a plant selected from Japanese cypress and deer, or an extract thereof.
(2) A glucagon secretion inhibitor comprising as an active ingredient a plant selected from cypress and sikakai, or an extract thereof.
(3) An appetite suppressant containing, as an active ingredient, a plant selected from Japanese cypress and deer, or an extract thereof.
(4) An obesity preventive or ameliorating agent comprising as an active ingredient a plant selected from Japanese cypress and deer, or an extract thereof.
(5) A preventive or ameliorating agent for postprandial hyperglycemia comprising, as an active ingredient, a plant selected from Japanese cypress and deer, or an extract thereof.
(6) A preventive or ameliorating agent for diabetes comprising, as an active ingredient, a plant selected from Japanese cypress and deer, or an extract thereof.
(7) An antihypertensive agent comprising, as an active ingredient, a plant selected from Japanese cypress and deer, or an extract thereof.
(8) A vascular protection enhancer comprising, as an active ingredient, a plant selected from Japanese cypress and deer, or an extract thereof.
(9) A non-therapeutic GLP-1 secretion promoting method, a non-therapeutic glucagon secretion inhibiting method, a non-therapeutic appetite suppressing method, a non-therapeutic method, which takes a plant selected from Japanese cypress and deer silkworm or an extract thereof as an active ingredient A method for preventing or improving obesity, a method for preventing or improving non-therapeutic diabetes, a method for reducing non-therapeutic blood pressure, or a method for enhancing non-therapeutic vascular protection.

  Since the present invention has an excellent GLP-1 secretion promoting action and is highly safe even when ingested for a long period of time, it suppresses glucagon secretion, suppresses appetite, prevents or improves obesity, prevents or improves postprandial hyperglycemia It is useful as a pharmaceutical, a quasi-drug, a cosmetic and a food that can exert an effect of preventing or ameliorating diabetes, lowering blood pressure, and enhancing blood vessel protection, or a material or preparation for blending them.

It is the figure which measured the GLP-1 secretion of NCI-H716 by the extract of a hornbill or a deer silkworm.

  In the present specification, “GLP-1 secretion promotion” refers to promoting GLP-1 secretion in vivo caused by ingesting a meal, particularly a meal rich in carbohydrates or lipids. Alternatively, the increase in blood GLP-1 concentration associated with GLP-1 secretion in vivo mainly after meal is maintained, the increased GLP-1 concentration is maintained, or the decrease in the increased GLP-1 concentration is suppressed. To do.

In the present specification, “suppression of glucagon secretion” refers to suppression of the effect of increasing blood glucose via glucagon secretion. The suppression includes not only suppression of glucagon secretion by direct action of GLP-1 on pancreatic α cells, but also paracrine α cell suppression via insulin from β cells and somatostatin from δ cells.
“Appetite suppression” refers to a decrease in appetite or food intake and the accompanying suppression of weight gain. The suppression is mainly effected via the hypothalamic feeding center of the central nervous system of GLP-1.
“Enhanced vascular protection” refers to the action of improving arteriosclerosis promoting factors such as sugar / lipid metabolism, blood pressure and body weight, and anti-arteriosclerosis by acting on vascular endothelial cells, macrophages and vascular smooth muscle cells. Refers to the effect. The latter includes increased production of nitric oxide in vascular endothelial cells and suppression of PAI-1 and VCAM-1 expression.

As used herein, “prevention” refers to preventing or delaying the onset of a disease or symptom in an individual, or reducing the risk of developing an individual's disease or symptom. “Improvement” refers to improvement of a disease, symptom or condition, prevention or delay of worsening of the disease, symptom or condition, or reversal, prevention or delay of progression of the disease or symptom.
“After meal” means the time until the carbohydrates in the ingested meal are generally absorbed. Immediately after taking the meal (0 minutes) to 6 hours later, preferably 5 hours later, more preferably 4 hours. Time until later, more preferably after 3 hours (Diabete Care, 2001, 24 (4): 775-778).

  As used herein, “non-therapeutic” is a concept that does not include medical practice, that is, does not include methods for surgery, treatment or diagnosis of humans.

  In the present specification, “Tsunuki psycho” refers to Bupleurum rotundifolium belonging to the genus Mycophoridae. Sikakai refers to Acacia concinna of the leguminous Acacia genus.

Such plants can use any arbitrary part, for example, whole grass, leaves, stems, buds, flowers, buds, roots, rhizomes, temporary corms, corms, tubers, seeds, etc., or combinations thereof. It is preferable to use the root bark for the eelwood and the root for the deer silkworm.
The part may be subjected to the extraction process as it is, or may be subjected to the extraction process after being pulverized, cut or dried to obtain an extract. The extract is derived from natural ingredients and has high safety.

  As the above extract, commercially available ones may be used, or various solvent extracts obtained by a conventional method, or diluted solutions thereof, concentrated solutions thereof, dried powders thereof, pastes or activated carbon treatments thereof. There may be. As an example, the extract is obtained by extracting the plant at room temperature (for example, 4 to 50 ° C.) or under heating (room temperature to solvent boiling point), or using an extraction device such as a Soxhlet extractor. Can be obtained.

Specific examples of the extraction means for obtaining the extract include solid-liquid extraction, liquid-liquid extraction, immersion, decoction, leaching, reflux extraction, ultrasonic extraction, microwave extraction, and stirring. In order to shorten the extraction time, solid-liquid extraction with stirring is desirable. Examples of suitable conditions for this solid-liquid extraction include stirring at 10 to 100 ° C. and 100 to 400 rpm / min for 1 to 30 minutes. As a suitable example of immersion, the immersion for 1 hour-14 days is mentioned at 10-50 degreeC. Moreover, when shortening extraction time, solid-liquid extraction with stirring is desirable.
In order to prevent oxidation of the extract, a means for extraction under a so-called non-oxidizing atmosphere while removing dissolved oxygen by bubbling degassing or inert gas such as nitrogen gas may be used in combination.

  As the solvent for extraction, either a polar solvent or a nonpolar solvent can be used. Specific examples of the solvent include water; alcohols such as methanol, ethanol, propanol and butanol; polyhydric alcohols such as propylene glycol and butylene glycol; ketones such as acetone and methyl ethyl ketone; methyl acetate and ethyl acetate Esters; linear and cyclic ethers such as tetrahydrofuran and diethyl ether; polyethers such as polyethylene glycol; hydrocarbons such as squalane, hexane, cyclohexane and petroleum ether; aromatic hydrocarbons such as toluene; dichloromethane and chloroform And halogenated hydrocarbons such as dichloroethane; and supercritical carbon dioxide; pyridines; organic solvents such as oils and fats, other oils such as wax; and mixtures thereof. Preferable examples include water, alcohols, alcohol-water mixtures and hydrocarbons, with alcohol-water mixtures and hydrocarbons being more preferred. As the alcohol, an alcohol having 1 to 5 carbon atoms is preferable, and ethanol is more preferable. Hexane is preferred as the hydrocarbon.

  When an alcohol-water mixture is used as a solvent for extraction, the blending ratio (volume ratio) of alcohols and water is preferably 0.001 to 100: 99.999-0, preferably 5 to 95. : 95-5 is more preferable, and 20-80: 80-20 is still more preferable. In the case of an ethanol aqueous solution, the ethanol concentration is preferably 40% by volume or more, more preferably 45% by volume or more. Moreover, Preferably it is 40-100 volume%, More preferably, it is 70-95 volume%.

  The amount of the solvent used is preferably 1 mL or more, more preferably 5 mL or more, preferably 100 mL or less, more preferably 50 mL or less, with respect to 1 g of each plant (in terms of dry mass). Moreover, Preferably it is 1-100 mL, More preferably, it is 8-50 mL. The extraction time is preferably 1 minute or longer, more preferably 10 minutes or longer, preferably 30 days or shorter, more preferably 10 days or shorter. Moreover, it is preferably 1 minute to 30 days, more preferably 10 minutes to 10 days. The extraction temperature at this time is preferably 0 ° C. or higher, more preferably 10 ° C. or higher, further preferably 20 ° C. or higher, preferably the solvent boiling point or lower, more preferably 100 ° C. or lower, still more preferably 90 ° C. or lower. Moreover, Preferably it is 0 degreeC-solvent boiling point, More preferably, it is 10-100 degreeC, More preferably, it is 20-90 degreeC.

  The extract thus obtained may be used as it is as an extract or fraction, or may be used as a diluted solution diluted with an appropriate solvent, or may be a concentrated extract or a dry powder, or prepared as a paste. But you can. Also, freeze-dry and dilute with a solvent usually used for extraction, such as water, ethanol, propylene glycol, butylene glycol, water / ethanol mixture, water / propylene glycol mixture, water / butylene glycol mixture, etc. It can also be used. It can also be used by encapsulating in vesicles such as liposomes or microcapsules.

  The extract may be a crude product as long as it conforms to food and pharmaceutical acceptable standards and exhibits the effects of the present invention, and the obtained crude product is further purified by a known separation and purification method. These purity may be increased by appropriately combining them. Examples of the purification means include organic solvent precipitation, centrifugation, ultrafiltration membrane, high performance liquid chromatograph, column chromatograph and the like.

  The woodpecker as an active ingredient of the present invention contains an oleanane type triterpenoid saponin represented by the following chemical formula.

  Sikakai as an active ingredient of the present invention contains an oleanane type triterpenoid saponin represented by the following chemical formula.

  The extract preferably contains a large amount of the saponin. The saponin is generally obtained by fractionating a crude saponin containing no non-saponin component from an extract extracted with a lower alcohol and purifying the crude saponin. For example, the method described in “Natural Organic Compound Experimental Method Extraction and Separation of Physiologically Active Substances, 1978, Kodansha, Nozomi Natori et al., Chapter 23 Separation of Triterpenoid Saponins” and the like can be used.

  For the extraction, ethanol or methanol, or a mixed solution of these lower alcohols and water can be used. In the case of particularly high oil content such as seeds and fruits, the oil can be removed by degreasing or pressing with an appropriate solvent. In the case of leaves, since chlorophyll is present, it can be used after extraction with cyclohexane or carbon tetrachloride to remove chlorophyll. When saponins are stable to heat, they can be extracted by heating directly with water.

  The obtained extract is concentrated under reduced pressure, the solvent is distilled off, suspended in water, and extracted with water-saturated butanol, so that most of the saponin can be transferred to the butanol phase.

  As a method of removing non-saponin components from the crude saponin fraction, a fractionation method in which a cholesterol complex is formed in an alcohol solution, a method in which the complex is dissolved in a small amount of methanol and injected into a large amount of ether or acetone to precipitate (nonpolar substance) And a method of filtering with a small amount of alumina (removal of phenolic substances and pigments). Thereafter, the desired saponin can be obtained by isolation and purification by recrystallization or reprecipitation. Furthermore, it can be isolated and purified by column chromatography, preparative TLC, and droplet countercurrent chromatography.

As will be described later in Examples, plants selected from cypress and sikakai or extracts thereof, preferably saponins contained therein, have an action of promoting GLP-1 secretion from gastrointestinal cells. Therefore, the plant or the extract thereof is useful for promoting GLP-1 secretion, and these can be expected to suppress glucagon secretion, suppress appetite, prevent or improve obesity, lower blood pressure, and enhance vascular protection (not described above). Patent Documents 1 to 4).
In addition, it has been reported that the rate of developing diabetes decreases by continuously suppressing postprandial blood glucose elevation (Foods Food Ingredients J. Jpn., 310 (12), 2005). Therefore, the plant or an extract thereof is useful for preventing and / or improving postprandial hyperglycemia, and further preventing and / or improving diseases such as diabetes and insulin resistance.

  Therefore, the plant or the extract thereof is GLP-1 secretion promoter, glucagon secretion inhibitor, appetite suppressant, obesity prevention or improvement agent, postprandial hyperglycemia prevention or improvement agent, diabetes prevention or improvement agent, blood pressure It can be used as a depressant, a vascular protection enhancer (hereinafter referred to as “GLP-1 secretion promoter, etc.”), and can further be used to produce these agents.

  The GLP-1 secretion promoter or the like per se, when ingested or administered to animals including humans, promotes GLP-1 secretion, suppresses glucagon secretion, suppresses appetite, prevents or improves obesity, prevents or improves postprandial hyperglycemia It may be a medicine or quasi-drug, food or feed for humans or animals that exhibits the effects of preventing or improving diabetes, lowering blood pressure, and strengthening blood vessel protection, or the drug or quasi-drug. In addition, it may be a material or a preparation used by mixing with food or feed.

  The food also includes GLP-1 secretion promotion, glucagon secretion suppression, appetite suppression, obesity prevention or improvement, postprandial hyperglycemia prevention or improvement, diabetes prevention or improvement, blood pressure, etc. Foods, functional foods, foods for the sick, and foods for specified health use, which are based on the concept of descent and strengthening blood vessel protection, are displayed as necessary. Since these foods are foods whose function is permitted, they can be distinguished from general foods.

  The dosage forms of the above-mentioned pharmaceuticals (including quasi-drugs) containing the above-mentioned plants or extracts thereof include tablets, capsules, granules, powders, syrups, intravenous injections, intramuscular injections, suppositories, and inhalation. Preparations, transdermal absorption agents, eye drops, nasal drops, poultices, poultices, ointments, lotions, creams, oral preparations (dentifrices, liquid dentifrices, mouthwashes, gum massage creams, oral ointments, gargles) Tablets, troches, throat lozenges, etc.). The administration form may be either oral administration (internal use) or parenteral administration (external use, injection).

  In addition, in order to prepare pharmaceutical preparations of such various dosage forms, the above-mentioned plant or an extract thereof is used alone, or other pharmaceutically acceptable excipients, binders, extenders, disintegrations. It can be prepared by appropriately combining agents, surfactants, lubricants, dispersants, buffers, preservatives, flavoring agents, fragrances, coating agents, carriers, diluents, medicinal ingredients other than the present invention. Of these dosage forms, the preferred form is oral administration, and oral liquid preparations can be prepared by conventional methods with the addition of flavoring agents, buffers, stabilizers and the like.

  The content of the plant or extract thereof in the preparation for oral administration is generally preferably 0.0001% by mass or more, more preferably 0.001% by mass or more, preferably 20% by mass or less as a solid content concentration. More preferably, it is 10 mass% or less. Moreover, Preferably it is 0.01-10 mass%, More preferably, it is 0.05-5 mass%.

  Examples of the form of the food containing the plant or extract thereof include soft drinks, tea-based beverages, coffee beverages, fruit juice beverages, carbonated beverages, juices, jelly, wafers, biscuits, breads, noodles, sausages and other foods and beverages. In addition to various foods such as foods and nutritional foods, further, nutritional supplement compositions in the same form (tablets, capsules, syrups, etc.) as the above-mentioned oral administration preparations can be mentioned.

  Various types of foods can be obtained from the above plants or their extracts alone, or other food materials, solvents, softeners, oils, emulsifiers, preservatives, fragrances, stabilizers, coloring agents, antioxidants, moisturizing agents. It can be prepared by appropriately combining agents, thickeners, active ingredients other than the present invention and the like.

  The content of the plant or extract thereof in the food feed is generally preferably 0.0001% by mass or more, more preferably 0.001% by mass or more, preferably 10% by mass or less, as a solid content concentration. More preferably, it is 5 mass% or less. Moreover, Preferably it is 0.01-10 mass%, More preferably, it is 0.05-5 mass%.

  Examples of the feed include feed for small animals used for rabbits, rats, mice, etc., feed for pet foods used for dogs, cats, and the like, and can be prepared in the same form as the above foods.

  The intake of the GLP-1 secretion promoter of the present invention may vary according to the subject's species, weight, sex, age, condition or other factors. The dose, route, interval of administration, and the amount and interval of intake can be appropriately determined by those skilled in the art, but are generally preferable as an above-mentioned plant or extract thereof (in terms of dry matter) per day for adults. Is 20 μg / 60 kg body weight or more, more preferably 200 μg / 60 kg body weight or more, more preferably 2 mg / 60 kg body weight or more, preferably 1000 mg / 60 kg body weight or less, more preferably 500 mg / 60 kg body weight or less, more preferably 200 mg / 60 kg body weight or less. It is. Moreover, it is preferably 20 μg to 2000 mg / 60 kg body weight, more preferably 200 μg to 1000 mg / 60 kg body weight, still more preferably 2 to 5000 mg / 60 kg body weight.

  The subject of administration or ingestion is not particularly limited as long as it is a person who needs or desires it regardless of whether it is a sick person or a healthy person, but is preferably an exercise deficient person or a middle-aged person. The GLP-1 secretion promoter of the present invention is not limited to patients with diabetes or insulin resistance, but also subjects who do not suffer from diabetes or insulin resistance, such as high postprandial hyperglycemia but abnormal fasting blood glucose. The present invention can be applied to a subject who does not need to lower fasting blood glucose but does not need to lower postprandial hyperglycemia. Alternatively, the present invention can be applied not only to obese patients but also to those who are easily fattened, those who desire appropriate weight maintenance, and the like. It can also be applied to hypertensive patients, or subjects who want to prevent hypertension or reduce the risk of the onset. Furthermore, the present invention can be applied to a subject who needs enhanced blood vessel protection or a subject who desires enhanced blood vessel protection.

With respect to the above-described embodiment, the following aspects are disclosed in the present invention.
<1> A GLP-1 secretion promoter comprising as an active ingredient a plant selected from Japanese cypress and deer, or an extract thereof.
<2> A glucagon secretion inhibitor comprising as an active ingredient a plant selected from a hornbill and a deer, or an extract thereof.
<3> An appetite suppressant containing, as an active ingredient, a plant selected from Japanese cypress and deer, or an extract thereof.
<4> A preventive or ameliorating agent for obesity comprising, as an active ingredient, a plant selected from Japanese cypress and deer, or an extract thereof.
<5> A preventive or ameliorating agent for postprandial hyperglycemia comprising, as an active ingredient, a plant selected from Japanese cypress and deer, or an extract thereof.
<6> A preventive or ameliorating agent for diabetes comprising, as an active ingredient, a plant selected from Japanese cypress and deer, or an extract thereof.
<7> An antihypertensive agent comprising, as an active ingredient, a plant selected from tsukinuki psycho and sikakai, or an extract thereof.
<8> A vascular protection enhancer comprising, as an active ingredient, a plant selected from Tsukinuki-saiko and Sikakai, or an extract thereof.
<9> Use of a plant selected from Japanese cypress and deer, or an extract thereof, for producing a GLP-1 secretion promoter.
<10> Use of a plant selected from cypress and deer, or an extract thereof, for producing a glucagon secretion inhibitor.
<11> Use of a plant selected from Japanese cypress and deer, or an extract thereof, for producing an appetite suppressant.
<12> Use of a plant selected from cypress and deer, or an extract thereof, for producing an agent for preventing or improving obesity.
<13> Use of a plant selected from cypress and deer, or an extract thereof, for producing a preventive or ameliorating agent for postprandial hyperglycemia.
<14> Use of a plant selected from cypress and deer, or an extract thereof, for producing an agent for preventing or improving diabetes.
<15> Use of a plant selected from a cypress and a deer, or an extract thereof, for producing an antihypertensive agent.
<16> Use of a plant selected from Japanese cypress and deer, or an extract thereof, for producing a vascular protection enhancer.
<17> A plant selected from a cypress and a deer, or an extract thereof, for use in promoting GLP-1 secretion.
<18> A plant selected from a cypress and a deer, or an extract thereof, for use in suppressing glucagon secretion.
<19> A plant selected from tsukinuki-shiko and deer, or an extract thereof, for use in suppressing appetite.
<20> A plant selected from a hornbill and a deer, or an extract thereof, for use in the prevention or improvement of obesity.
<21> A plant selected from cypress and deer, or an extract thereof, for use in preventing or improving postprandial hyperglycemia.
<22> A plant selected from cypress and deer, or an extract thereof, for use in the prevention or improvement of diabetes.
<23> Plants selected from tsukinuki and deer, or extracts thereof, for use in lowering blood pressure.
<24> Plants selected from tsukinuki and deer, or extracts thereof, for use in enhancing blood vessel protection.
<25> A method for promoting GLP-1 secretion, comprising administering or ingesting a plant or an extract thereof selected from Japanese cypress and deer to humans or animals.
<26> A method for inhibiting glucagon secretion, comprising administering or ingesting a plant or an extract thereof selected from a hornbill and a deer to a human or an animal.
<27> A method for suppressing appetite, comprising administering or ingesting a plant or an extract thereof selected from Japanese cypress and deer to humans or animals.
<28> A method for preventing or ameliorating obesity, wherein a plant selected from Japanese cypress and deer, or an extract thereof is administered or ingested to a human or an animal.
<29> A method for preventing or improving postprandial hyperglycemia, comprising administering or ingesting a plant or an extract thereof selected from Japanese cypress and deer to humans or animals.
<30> A method for preventing or improving diabetes, comprising administering or ingesting to a human or an animal a plant selected from Japanese cypress and deer, or an extract thereof.
<31> A method for lowering blood pressure, comprising administering or ingesting a plant or an extract thereof selected from a hornbill and a deer to a human or an animal.
<32> A method for enhancing vascular protection, comprising administering or ingesting to a human or an animal a plant selected from a hornbill and a deer, or an extract thereof.
<33> The method according to <25> to <32>, which is a non-therapeutic method.
<34> Non-therapeutic use of a plant selected from a hornbill and a deer, or an extract thereof, for promoting GLP-1 secretion.
<35> Non-therapeutic use of a plant selected from a cypress and a deer, or an extract thereof, for suppressing glucagon secretion.
<36> Non-therapeutic use of a plant selected from a hornbill and a deer silkworm or an extract thereof for appetite suppression.
<37> Non-therapeutic use of a plant selected from a hornbill and a deer, or an extract thereof, for the prevention or improvement of obesity.
<38> Non-therapeutic use of a plant selected from Japanese cypress and deer, or an extract thereof, for prevention or improvement of postprandial hyperglycemia.
<39> Non-therapeutic use of a plant selected from a hornbill and a deer, or an extract thereof, for the prevention or improvement of diabetes.
<40> Non-therapeutic use of a plant selected from a hornbill and a deer, or an extract thereof, for lowering blood pressure.
<41> A non-therapeutic use of a plant selected from cypress and deer, or an extract thereof, for enhancing blood vessel protection.
<42> Use of a plant selected from Japanese cypress and deer, or an extract thereof, in a functional food for promoting GLP-1 secretion.
<43> Use of a plant selected from Japanese cypress and deer, or an extract thereof, in a functional food for suppressing glucagon secretion.
<44> Use of a plant selected from cypress and deer, or an extract thereof, in a functional food for suppressing appetite.
<45> Use of a plant selected from Japanese cypress and deer, or an extract thereof, in a functional food for the prevention or improvement of obesity.
<46> Use of a plant selected from Japanese cypress and deer, or an extract thereof, in a functional food for prevention or improvement of postprandial hyperglycemia.
<47> Use of a plant selected from Japanese cypress and deer, or an extract thereof, in a functional food for the prevention or improvement of diabetes.
<48> Use of a plant selected from Japanese cypress and deer, or an extract thereof, in a functional food for lowering blood pressure.
<49> Use of a plant selected from cypress and deer, or an extract thereof, in a functional food for enhancing blood vessel protection.
<50> GLP-1 secretion promotion, glucagon secretion suppression, appetite suppression, prevention or improvement of obesity, or prevention or improvement of postprandial hyperglycemia, blood pressure reduction, vascular protection enhancement or targeting humans, 25> to <32>.
<51> The plant according to <17> to <24> or an extract thereof for non-therapeutic use.

Production Example 1: Preparation of an extract of cypress cynosum And then filtered. The solvent was distilled off under reduced pressure and dried at 25 ° C. to obtain an extracted solid. To the obtained extracted solid, 500 mL of water and 500 mL of water-saturated n-butanol were added, shaken with a separatory funnel, allowed to stand, and separated into layers. Among these, the upper layer (n-butanol layer) was separated, and the solvent was distilled off under reduced pressure to obtain an extract containing saponin. To the obtained extract, 100 mL of acetone was added per 1 g of the solid content, and the mixture was stirred at 25 ° C. for 30 minutes and filtered. The solid matter remaining on the filter paper was dried to obtain 1.4 g of a Japanese quince extract.

Production Example 2: Preparation of sikakai extract In the same manner as described above, 100 g of sikakai (Acacia concinna, purchased from Monteagle Herbs) root shredded product was added and 1 L of 80 vol% ethanol was added at 25 ° C. Extraction was performed for 10 days, followed by filtration. The solvent was distilled off under reduced pressure and dried at 25 ° C. to obtain an extracted solid. Water (500 mL) and water-saturated n-butanol (500 mL) were added to the extracted solid obtained, and the mixture was shaken with a separatory funnel and allowed to stand to separate the layers. Among these, the upper layer (n-butanol layer) was separated, and the solvent was distilled off under reduced pressure to obtain an extract containing saponin. To the obtained extract, 100 mL of acetone was added per 1 g of the solid content, and the mixture was stirred at 25 ° C. for 30 minutes and filtered. The solid matter remaining on the filter paper was dried to obtain 4.8 g of a deer extract.

The extracts obtained in Production Examples 1 and 2 were diluted with 50% ethanol water so that the concentration of the extract was 1% (w / v), and used as test samples. As a control, 50% ethanol water was used.
NCI-H716 cells (human colon-derived cells; ATCC) were cultured at 37 ° C. in the presence of 5% CO ₂ . As the culture solution, RPMI1640 (containing 10% fetal bovine serum, high glucose; Invitrogen) was used. The cells were seeded on a 24-well plate coated with Matrigel (100 μL / well; BD) at 5 × 10 ⁵ cells / well (N = 12 for control, N = 8 for sample), and DMEM (10 % Fetal bovine serum-containing high glucose (Invitrogen) medium. Three days later, the medium was replaced with KRB · 0.2% BSA containing the extract obtained in Production Examples 1 and 2 at a concentration of 0.001%, cultured for 2 hours, and then the medium was collected. The medium was collected in a microcentrifuge tube to which diprotin-A (DPP4 inhibitor, Sigma) and aprotinin (serine protease inhibitor, Wako Pure Chemical Industries, Ltd.) were added. Stored at -80 ° C. GLP-1 in the medium was quantified by ELISA (LINCO Research) using GLUCAGON-LIKE PEPTIDE-1 (ACTIVE) ELISA KIT. The results are shown in Table 1 and FIG.

  From Table 1 and FIG. 1, the extracts derived from Japanese cypress and sikakai significantly promoted GLP-1 secretion at a concentration of 0.001% (* p <0.05, *** p <0.001).

Claims (6)

  A GLP-1 secretion promoter comprising tsukinuki psycho or an extract thereof as an active ingredient.   A glucagon secretion inhibitor comprising tsukinuki psycho or an extract thereof as an active ingredient.   An appetite suppressant comprising tsukinuki saiko or its extract as an active ingredient.   A prophylactic or ameliorating agent for obesity comprising tsukinuki psycho or an extract thereof as an active ingredient.   A preventive or ameliorating agent for postprandial hyperglycemia comprising tsukinuki psycho or an extract thereof as an active ingredient.   A prophylactic or ameliorating agent for diabetes comprising tsukinuki psycho or an extract thereof as an active ingredient.