JP2008019199A - Insulin resistance-improving agent obtained from lyophyllum shimeji - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a composition for preventing or improving the type 2 diabetes, obesity or insulin resistance by ingesting crushed products of a fruit body or a mycelium of Lyophyllum shimeji that has abundant dietary experiences and exhibits adiponectin production-promoting actions. <P>SOLUTION: The composition exhibiting adiponectin production-promoting activities comprises crushed products or extracts of a fruit body or a mycelium of Lyophyllum shimeji, or extracts obtained therefrom using a solvent. The insulin resistance-improving agent, foods and drinks and fodder exhibiting insulin resistance-improving actions comprise the composition. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to a composition having adiponectin production promoting activity, an insulin resistance improving agent containing the composition, a food and drink having an insulin resistance improving action, and a feed.

  Modern people are likely to become obese due to satiety, changes in dietary habits (high-fat diet), decreased physical labor associated with changes in social life, decreased exercise habits, overeating and overdrinking caused by stress As a result, type 2 diabetes and metabolic syndrome (hyperlipidemia, hypertension, arteriosclerotic disease, hyperinsulinemia, hypertriglyceridemia, hyper-LDL, abnormal glucose tolerance, etc.) are likely to occur. .

  Adipocytes produce and secrete adipocytokines (adiponectin, leptin, PAI-1, TNF-α, angiotensinogen, etc.), which are various endocrine factors, and are important for sugar and lipid metabolism and maintenance of arterial wall homeostasis It has become clear that it plays a role. Among them, adiponectin is a “good adipocytokine” produced specifically for adipose tissue identified from human adipocyte tissue, and its blood concentration is high if adipocytes are in a precursor state, but obesity and type 2 diabetes, In an ischemic disease, adipocytes differentiate and enlarge and decrease. At this time, the concentration of “bad adipocytokine” that causes insulin resistance increases, and the risk of insulin resistance increases. Experiments using humans and animals have confirmed that a low adiponectin state caused by high calorie intake and fat accumulation increases insulin resistance and causes arteriosclerosis.

  On the other hand, it has been experimentally shown that administration of adiponectin by injection and raising the blood concentration can reduce the blood glucose level of diabetic model mice and suppress the formation of vascular lesions that lead to arteriosclerosis (Non-patent Document 1). To 3).

  Although a method of directly administering adiponectin is useful, it is considered to be very important for prevention and treatment of lifestyle-related diseases over a long period of time to improve or promote production failure of adiponectin in the body. In an oral administration test using a diabetic model mouse, isobutylmethylxanthine (non-patent document 4), which is a cAMP degrading enzyme inhibitor, and thiazolidine derivative (see patent document 1, non-patent document 5), which is a therapeutic agent for type 2 diabetes, It has been confirmed that the concentration of adiponectin in the blood is increased.

  In addition, it has recently been found that ingredients that can be taken orally as food also have an adiponectin production promoting action. For example, rose or grape plant fruit extract (Patent Document 2), flavonones of citrus fruits (Patent Document 3), soy isoflavones (Non-Patent Document 6), rice bran, rahan fruit, shimeji, chrysanthemum, rye, birch And sterols derived from moon peach (Patent Document 4), curcumin belonging to the genus Turmeric (Patent Document 5), gingerol (Patent Document 6) contained in ginger and the like.

On the other hand, although the mechanism of action has not been clarified, as a food having adiponectin production promoting activity, extract of roots of garlic mushroom and chixetsunin ginseng (Patent Document 7), alcohol extract of leafhopper stem, leaf, stem ( Patent Literature 8), Kaileunositol Extract (Patent Literature 9), Ishiren or Blunted Stone Lotus Extract (Patent Literature 10), Lactic Acid Bacteria (Patent Literature 11), Cyclametous Polysaccharide (Patent Literature 12), Kawaratake Known polysaccharides (Patent Document 13), Mannentake polysaccharides (Patent Document 14), Hatake shimeji extract (Patent Document 15), Maitake mycelium (Non-patent Document 7), etc. Alternatively, it has not been known at all that the mycelium has an adiponectin production promoting activity and an insulin resistance improving action.
Ichiro Shimomura et al., Experimental Medicine, Vol. 20, No. 12, 1762-1767 (2002) A. H. Berg et al., Nature Medicine, 7, 947-953 (2001) Y. Okamoto, Circulation, 106, 2767-2770 (2002) A. K. G. Loeffler, Horm. Metab. Res. , 32, 548-554 (2000) N. Maeda et al. , Diabetes, 50, 2094-2099 (2001) Nagasawa A, Fukui K et al., Horm Metab Res., 34, 635-9 (2002) Keiko K, Hisao A, Hiroaki N, Biol. Pharm. Bull., 17, 1106-1110 (1994) US Pat. No. 6,153,432 JP 2000-186043 A JP-A-11-171766 JP 2005-68132 A JP 2005-60308 A JP 2006-45210 A JP-A-2005-47814 JP 2002-154978 A JP 2001-261554 A JP 2000-128797 A Japanese Patent Laid-Open No. 10-7777 JP-A-9-67267 JP-A-60-45532 JP 60-184025 A JP 2003-34647 A

  Drugs that increase blood adiponectin concentration as described above to lower blood glucose levels are already known, but all have problems in terms of safety and side effects. That is, isobutylmethylxanthine is not approved as a pharmaceutical product, and thiazolidine derivatives are highly hepatotoxic. Therefore, their use must be under the strict control of doctors and cannot be taken easily. On the other hand, as described above, some foods or their components are known to have adiponectin production promoting activity and insulin resistance improving action, but the action is not sufficient and not satisfactory.

  Under such circumstances, there is abundant dietary experience, and by taking a crushed or extract of food having adiponectin production promoting activity, blood sugar level is lowered, and type 2 diabetes, obesity or insulin resistance is prevented or It is expected to improve.

  The present invention has been made in view of the above circumstances, and is excellent in the effect of lowering blood glucose level by adiponectin production promoting activity, improving insulin resistance, and further preventing or improving the occurrence of obesity and insulin resistance. It aims at providing the composition, the insulin resistance improving agent containing the composition, the food-drinks and feed which have an insulin resistance improvement effect.

  The present inventors have intensively studied a composition derived from edible mushrooms having adiponectin production promoting activity, and found that the fruit body or mycelium of hon-shimeji mushroom has high activity, and have completed the present invention.

  That is, a first aspect of the present invention is a gist of a composition having adiponectin production promoting activity, which is obtained from the fruit body or mycelium of Honshimeji.

  The second aspect of the present invention is a method for producing a composition having adiponectin production promoting activity, characterized in that an extract is obtained from a fruit body or mycelium of hon-shimeji mushroom using a solvent. Preferably, the solvent is one solvent selected from the group consisting of methanol, ethanol, hexane, and carbon dioxide, or a solvent in which two or more are mixed.

  The third aspect of the present invention is to provide an insulin resistance improving agent characterized by comprising the above-mentioned composition having adiponectin production promoting activity as an active ingredient.

  A fourth aspect of the present invention is a food or drink having an insulin resistance improving action containing the composition, and a fifth aspect of the invention is a feed containing the composition.

  According to the present invention, by using the fruit body or mycelium of hon-shimeji mushroom with rich dietary experience as a pharmaceutical composition or a food composition, it is possible to prevent the progression of diabetes or related diseases, or to improve these diseases.

  Hereinafter, the present invention will be described in detail.

  The shimeji mushroom (Lyophyllum shimeji) in the present invention is a mycorrhizal fungus belonging to the genus Asteraceae, and is also known as Daiko shimeji. It is known as an excellent edible fungus that has one of the strongest flavors of mushrooms, as it is said to be “scented matsutake, taste shimeji”. In autumn, these trees grow in mycorrhiza and live in pine forests and red pine forests, and the fruiting bodies are single to clustered on the ground. Since it is a mycorrhizal fungus, it was rare because it could not be cultivated so far, but recently it has succeeded in forming fruit bodies under cultivation.

  Regarding the functionality of the components contained in hon-shimeji, the solvent extract of fruiting bodies is known to induce differentiation of MC3T3E1 cells, which are mouse preosteoblasts, but has an adiponectin production promoting activity and an insulin resistance improving effect. That was completely unknown.

  The composition having adiponectin production promoting activity of the present invention is obtained from a fruit body or mycelium of hon-shimeji mushroom, and specifically, a crushed or dried crushed material obtained by pulverizing the fruit body or mycelium of hon-shimeji, It consists of an extract extracted from the fruit body or mycelium of Honshimeji using various solvents, and a product obtained by concentrating and drying the extract.

  In order to crush the fruit body or mycelium of Honshimeji to obtain a crushed material, it is preferable to dry them beforehand. Drying conditions are not particularly limited, and known methods can be used. For example, methods such as room temperature drying, heat drying, freeze drying, reduced pressure drying, vacuum drying and the like can be used, preferably economical heat drying at 30 to 100 ° C., and more preferably heat drying at 50 to 80 ° C. Examples of the dryer include, but are not limited to, mechanical devices such as a drum dryer, a fluidized bed dryer, a shelf dryer, a vibration dryer, and a rotary dryer.

  Next, the dried product is crushed, and a known crushing method can be employed. Examples of the crusher include, but are not particularly limited to, a dry millstone crusher, a roller mill, a cutter mill, a ball mill, a jet mill, and a hammer mill.

  The fruit body or mycelium crushed material of hon-shimeji mushroom obtained as described above becomes a composition having the adiponectin production promoting activity of the present invention as it is or by adding other components as necessary.

  Examples of the extraction solvent used when obtaining an extract from the fruit body or mycelium of Honshimeji include water, carbon dioxide, lower monohydric alcohol (methyl alcohol, ethyl alcohol, 1-propanol, 2-propanol, 1- Butanol, 2-butanol, etc.), liquid polyhydric alcohols (glycerin, propylene glycol, 1,3-butylene glycol, etc.), lower esters (such as ethyl acetate), hydrocarbons (benzene, hexane, pentane, etc.), ketones (acetone) , Methyl ethyl ketone, etc.), ethers (diethyl ether, tetrahydrofuran, dipropyl ether, etc.), acetonitrile, and the like, and a solvent in which one of these solvents or a mixture of two or more thereof can be used. Methanol, ethanol, hexane and carbon dioxide are preferred.

  The extraction temperature is not particularly limited as long as the extraction solvent is in a liquid state and the fruit body or mycelium of hon-shimeji mushrooms is not spoiled during the extraction, but is preferably 40 ° C. or less, more preferably 10 ° C. It is as follows. The extraction time is preferably 5 hours or longer, more preferably 1 week or longer, and most preferably 20 days or longer.

  After the extraction, the mixture of the crushed material and the solvent may be solid-liquid separated by a known method, and only the extract may be recovered. Examples of the solid-liquid separation method include, but are not particularly limited to, centrifugal separation, filter press, and suction filtration. Furthermore, the extract can be concentrated and dried as necessary.

  The fruit body or mycelium extract of hon-shimeji mushroom obtained as described above becomes a composition having the adiponectin production promoting activity of the present invention as it is or by adding other components as necessary.

  Other components that can be included in the composition having adiponectin production promoting activity of the present invention can be mixed as long as they do not reduce the adiponectin production promoting activity in the present invention, and are conventionally used, for example. It can be mixed with additives such as pharmaceutically acceptable surfactants, solvents, thickeners, stabilizers, preservatives, antioxidants, flavorings and the like.

  Composition forms include, but are not limited to, tablets, liquids, capsules, soft capsules, pastes or troches, gums, or drinkable solutions or emulsions, dry oral supplements, wet oral supplements, etc. is not. Moreover, these forms can be produced by a conventionally known method.

  Next, the insulin resistance improving agent of the present invention comprises the above-described composition having the activity of promoting adiponectin production of the present invention as an active ingredient. The content of the active ingredient may vary depending on the age, weight, etc. of the subject to be ingested, but may be set according to the form of the improving agent to be 0.1 to 1000 mg / kg per day for an adult. Is preferably 1 to 500 mg / kg, most preferably 5 to 200 mg / kg.

  Examples of various additives contained in the insulin resistance improving agent of the present invention include surfactants, excipients, colorants, preservatives, coating aids, and combinations thereof. These additives are not particularly limited as long as they are additives in normal pharmaceutical production, and more specific examples include lactose, dextrin, sucrose, mannitol, corn starch, sorbitol, crystalline cellulose, polyvinylpyrrolidone, dextrin, and methylcellulose. , Carboxymethylcellulose salt, stearic acid and its salts, additives such as talc, and combinations thereof. Furthermore, spices, sweeteners and the like may be added. Furthermore, you may add another chemical | medical agent, a food ground material, and a food extract as needed.

  The dosage form of the insulin resistance-improving agent of the present invention is not particularly limited, and is manufactured into an appropriate dosage form according to the Japanese Pharmacopoeia. Specifically, it is produced in dosage forms such as capsules, tablets, powders, sustained-release agents.

  The food-drinks which have the insulin resistance improvement effect | action of this invention contain the composition which has the adiponectin production promotion activity of above-described this invention. The content of the active ingredient may be set according to the form of each food and drink so that the daily intake is 0.1 to 1000 mg / kg, more preferably 1 to 500 mg / kg, and 5 to 200 mg. / Kg is most preferred.

  Examples of other materials that can be mixed in the food and drink having the insulin resistance improving action of the present invention include those that can be generally used as food materials. Examples include polysaccharides obtained from rice, wheat, corn, potato, kelp, proteins obtained from soybeans and dairy products, animal raw materials, glucose, lactose, fructose, sucrose, mannitol, xylitol, various oligosaccharides, etc. Saccharides, as well as combinations thereof, may be mentioned. Furthermore, spices, colorants, sweeteners, acidulants, edible oils, vitamins and other food crushed products, food extracts and the like may be added. These suitable materials and additives are used alone or in combination. Furthermore, you may process to a desired shape by adding water as needed.

  Specific examples of the food and drink of the present invention include confectionery (gum, candy, caramel, chocolate, cookie, snack confectionery, jelly, gummy, tablet confectionery, etc.), noodles (soba, udon, ramen, etc.), and dairy products (milk, Ice cream, yogurt, etc.), seasonings (miso, soy sauce, etc.), soups, beverages (juice, coffee, tea, tea, carbonated drinks, sports drinks, etc.) and general foods and health foods (tablets, capsules, etc.) ), Nutritional supplements (nutrition drinks, etc.), but are not limited to these. Moreover, you may add the extract of this invention to an instant foodstuff. For example, a product obtained by spray-drying or freeze-drying an extract together with powdered cellulose can be easily contained in a food or drink by making it into a powder, granule, tablet, or solution.

  The feed having an insulin resistance-improving action of the present invention contains the above-described composition having the adiponectin production promoting activity of the present invention, and can be applied to all domestic animals, poultry and pets. Examples of livestock and poultry to which the feed of the present invention can be applied include domestic animals such as cows, pigs, horses, goats, sheep and rabbits, and animals such as chickens, turkeys, ducks, and quails. The pet animals to which the present invention can be applied are animals and birds raised for personal hobbies such as dogs, cats, hamsters and small birds. This may be administered alone as a feed composition, or may be added directly to the feed, and the form of use is not particularly limited. When adding to feed, the addition method, addition time, etc. are not specifically limited.

  The content of the active ingredient contained in the feed of the present invention may be set according to the form of each feed so that the feed amount of the active ingredient per day is 0.1 to 1000 mg / kg. ˜500 mg / kg is preferred, and 5 to 200 mg / kg is most preferred.

  Other materials that can be mixed in the feed of the present invention include, for example, corn, milo, soybean, soybean meal, wheat, barley, rice, buckwheat, fish meal, skim milk powder, beet pulp pellets, bran pellets, grain screening pellets, alfalfa pellets , Tapioca pellets, corn cob meal, cotton hull pellets, sweet potato chips, homini feed, beer koji, hay cube, mini cube, alfalfa baled hay, sudan grass, rice straw, ryegrass straw, fescue straw, timothy hay, oat hay, Molasses, lupine, canola, rapeseed meal, cottonseed, corn gluten meal, corn gluten feed, soy hull pellets, whey powder, brewer's yeast, cholesterol, and other pharmaceutically acceptable vitamins And minerals, feed additives, veterinary drugs and the like, and are not particularly limited.

  Hereinafter, the present invention will be described in more detail with reference to examples.

Example 1 [Preparation of Honshimeji Extract]
The fruit body or mycelium of Honshimeji was dried with hot air at 80 ° C. and crushed with a blender with a rotary blade to obtain a powder. To 1 g of this powder, 10 mL of ethanol was added and stirred at 4 ° C. for 12 hours for extraction treatment. Moreover, it replaced with ethanol and performed the same extraction process using each solvent of water, methanol, and hexane. Each of these extracts was centrifuged (3000 rpm, 10 minutes) to recover the supernatant, and the supernatant was concentrated under reduced pressure to obtain a composition having adiponectin production promoting activity of the present invention.

[Measurement of adiponectin production promoting activity]
In each well of a 24-well titer plate, 0.5 mL of DMEM medium containing 10% FBS (GIBCO, glucose 4.5 mg / mL) and preadipocyte cell line 3T3-L1 cells (Human Science Promotion Foundation) 2.5 Add ⁴ × 10 ⁴ and incubate until confluent. To each well having cells attached to the bottom, DNEM medium containing 10% FBS (containing glucose 4.5 mg / mL) and 7.5 μL of specimen were added and cultured for 6 days. As a positive control, a mixed solution of an insulin solution (final concentration 3.3 μg / mL), a dexamethasone solution (final concentration 0.33 μM) and an isobutylmethylxanthine solution (final concentration 0.167 mM) was used. Each negative solvent was used as a negative control.

  After culturing for 6 days, the supernatant of each well was collected, and the amount of adiponectin in the supernatant was quantified by ELISA. For ELISA measurement, Quantikine Mouse Adiponectin / Acrp30 Immunoassay (manufactured by R & D Systems) was used and operated according to the attached instructions.

  The results are shown in Table 1, and it was confirmed that, among the extracts of the fruit body and mycelium of Honshimeji, the methanol and ethanol extract fractions of the fruit body have a high adiponectin production promoting activity.

Example 2 [Diabetes prevention test in type 2 diabetes model mouse]
Purchased a 4-week-old male spontaneously diabetic mouse KK-Ay from CLEA Japan, Inc. with a temperature of 22 ± 1 ° C and a humidity of 55 ± 5% while allowing free intake of normal feed (Nippon Agricultural Products, Lab MR Stock) Preliminary breeding was conducted for another week in the breeding room. At 5 weeks of age, a test diet was prepared by mixing 5% by weight of a hon-shimeji fruit body dry powder with a high-fat-containing diet (manufactured by Nippon Nosan Kogyo Co., Ltd., MR-DBT). In addition, the control group freely ingested a high fat-containing feed not mixed with Honshimeji fruit body dry powder. In all groups, water was ad libitum. The blood glucose level at all times was measured before the start of the test and every week after the start of the test. The blood glucose level was measured from a mouse tail and measured with a blood glucose level measuring electrode (manufactured by Nipro Corporation).

  The results are shown in FIG. 1, and it was confirmed that in the test group to which the hon-shimeji fruiting body was administered compared to the subject group, the increase in blood glucose level was constantly suppressed and there was an effect of preventing the onset of diabetes.

It is a figure which shows the raise inhibitory effect of a constant blood glucose level by this invention.

Claims (6)

A composition having adiponectin production promoting activity, which is obtained from a fruit body or mycelium of Honshimeji. The method for producing a composition having adiponectin production promoting activity according to claim 1, wherein an extract is obtained from a fruit body or mycelium of Honshimeji using a solvent. The method for producing a composition having adiponectin production promoting activity according to claim 1, wherein the solvent is a solvent selected from the group consisting of methanol, ethanol, hexane, and carbon dioxide, or a mixture of two or more. An insulin resistance-improving agent comprising the composition according to claim 1. A food or drink having an insulin resistance-improving effect, comprising the composition according to claim 1. A feed having an insulin resistance improving action, comprising the composition according to claim 1.