JP4464082B2 - Muscle cell sugar transport enhancing composition containing mugwort as an active ingredient - Google Patents

Description

【００４８】
上記の結果、ヨモギエキスが筋肉細胞へのグルコース取り込み量において、つまり、筋肉細胞糖輸送促進作用において優れていることがわかる。
【００４９】
【発明の効果】
本発明によって、ヨモギ又はその処理物の新規かつ有用な用途を提供することができる。より具体的には、本発明のヨモギ又はその処理物を含有する筋肉細胞糖輸送促進作用組成物は、糖尿病予防又は治療薬として有用であり、医薬、食品組成物又は食品として用いられる。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a muscle cell sugar transport promoting composition containing mugwort or a processed product thereof, or a food or food composition that promotes muscle cell sugar transport.
[0002]
[Prior art]
Artemisia is a perennial plant belonging to the family Asteraceae and is widely distributed from the coast to the high mountains. Mugwort is used for grass moths and has other names such as mochigusa and mogusa or cypress. There are many types of mugwort. There are about 30 species in Japan, and it is said that there are about 250 to 400 species all over the world. Depending on the type of mugwort, it is used as a coating for the purpose of preventing itching from insect bites, treating cuts or hemostasis, etc., used for beverages intended for the treatment of neuralgia, rheumatism, stomach diseases, etc. Or it is used for general foods such as mugwort. Recently, disaccharide-degrading enzyme inhibitory activity by Artemisia is also reported (Patent Document 1), and this action is useful for the treatment of diabetes, and seems to be specific to Artemisia. Patent Document 1 discloses a method of delaying the absorption of monosaccharides in the body by inhibiting the enzymes that decompose oligosaccharides and polysaccharides derived from orally ingested meals, thereby delaying the absorption of monosaccharides into the body. It is an invention aimed at preventing an increase in oxidative stress due to postprandial hyperglycemia and prevention of diabetic complications such as arteriosclerosis caused by postprandial hyperinsulinemia. Therefore, Patent Document 1 suppresses an increase in blood glucose level derived from the diet of a diabetic patient whose glucose tolerance has decreased due to insulin secretion failure, and is not an invention for lowering blood glucose level.
[0003]
In recent years, by using mugwort for cosmetics, cleaning compositions, oral compositions or foods, the cosmetics can be wound healing, rough skin prevention, rough skin improvement, improvement of skin itching, or body odor or bad breath. (Patent Document 2) is known to have such effects as roasting treatment or far-infrared roasting treatment of mugwort, food such as sprinkling or shampoo, rinse, toothpaste, bathing agent, deodorant agent, When used in cosmetics such as skin lotions, it is known to impart antibacterial activity, deodorant activity, antioxidant activity, amylase inhibitory activity, etc. to the food or cosmetic (Patent Document 3). However, the details of the action and effect of mugwort have not been clarified, and further action and effect of mugwort have been found, and development of a new and useful application of mugwort is expected.
[0004]
[Patent Document 1]
Japanese Patent Laying-Open No. 2003-26694 [Patent Document 2]
Japanese Patent Laid-Open No. 05-000962 [Patent Document 3]
Japanese Patent Application Laid-Open No. 07-033636
[Problems to be solved by the invention]
An object of this invention is to provide the novel and useful use of a mugwort or its processed material.
[0006]
[Means for Solving the Problems]
The present inventors have intensively studied to achieve the above object. The inventors of the present invention have succeeded in creating a method for evaluating the glucose uptake regulating action of cells (patent application scheduled on the same day as the present application). In order to clarify the relationship between various plants or their treated products and the glucose uptake regulating action of cells, the present inventors conducted intensive experiments using the above method, and as a result, mugwort or its treated products It has been found that it has a surprisingly excellent muscle cell sugar transport promoting action.
[0007]
The present inventors have also found that the composition for promoting muscle cell sugar transport containing the mugwort of the present invention or a processed product thereof is useful for the prevention or treatment of diabetes. This diabetes prevention or treatment effect is based on the action of mugwort or its processed product on muscle cells acting on the living body, resulting in the action directly on the muscles to promote sugar transport and lowering the blood sugar level increased by diet Can also reduce the fasting blood glucose level. Therefore, the present inventors consider that the present invention is completely different from Patent Document 1. Therefore, the present invention is also a preventive or therapeutic agent for diabetes due to muscle cell sugar transport promoting action, characterized by containing mugwort or a processed product thereof. In addition, examples of tissues that promote glucose uptake in an insulin-dependent manner include fat and skeletal muscle, but when adipocyte sugar uptake is promoted, adipocytes enlarge and secrete adipocytokines that cause insulin resistance. It is not an essential solution for the treatment of diabetes because it leads to failure and enhancement. However, since skeletal muscle is reported to take up 85% of glucose absorbed in the body, it is known to be the most important organ for lowering blood glucose level. unknown. Therefore, it can be said that the method for promoting the sugar transport of muscle cells is the most effective method for the prevention and treatment of diabetes that is not related to dietary intake.
[0008]
The present inventors have further studied and have found that the above-mentioned mugwort is preferably Japanese mugwort or Chinese mugwort. The various findings described above are new findings by the present inventors.
After obtaining the above various findings, the present inventors have made further studies and completed the present invention.
[0009]
That is, the present invention
(1) A composition for promoting muscle cell sugar transport, comprising a mugwort or a processed product thereof as an active ingredient,
(2) A composition for promoting muscle cell sugar transport according to (1), which prevents or treats diabetes,
(3) The composition of (1), wherein the mugwort is a Japanese mugwort or a Chinese mugwort,
(4) A food composition for promoting muscle cell sugar transport, characterized by comprising mugwort or a processed product thereof,
(5) A food that promotes muscle cell sugar transport, comprising the food composition according to (4),
About.
[0010]
DETAILED DESCRIPTION OF THE INVENTION
The mugwort used in the present invention is not particularly limited to the production area, and may be Japanese mugwort or Chinese mugwort. It may be mugwort distributed in all countries. Examples of the artemisia include Artemisia, Artilleon, Siphonostegia, and the like.
[0011]
As a plant of Artemisia schmidtiana Maxim., Artemisia keiskeana Miq., Artemisia iwayomogi Kitam., Estragon (Artemisia dracunculus L.), Artemisia trifura unc. , Artemisia Montana (NAKAI) PAMP., Artemisia vulgaris L.var.vulgatissima BESS.}, Artemisia insularis Kitam., Artemisia koidzumii Nakai, Artemisia japonica Thun Artemisia congesta Kitam.), Arthrosia lavandulaefolia DC., Artemisia princeps PAMP., Artemisia vulgaris L.indica MAXIM, Artemisia apiacea Hance, Artemisia capillaris Temib. Artemisia capillaris Temib. , Carrot (Artemisia annua Linn.), Crumb Artemisia kurramensis, Artemisia dubia Wall. Ex DC., Artemisia arctica Less. Subsp. Sachalinensis Hulten, Artemisia laciniata Willd., China (Artemisia cina Berg.), Artemisia cina Berg. (Artemisia arctica Less. Subsp. Sachalinensis Hulten f. Villosa (Koidz.) Kitam.), Artemisia stelleriana Besser, Artemisia sinanensis Yabe, Artemisia selengensis Turcz. Artemisia argyi LEVL. Et VANT., Artemisia campestris Linn., Artemisia absinthium Linn., Artemisia indica Willd., Artemisia sieversiana Willd.ata Lemi, Artemisia sieversiana Willd. .), Artemisia japonica Thunb. Var. Littoricola (Kitam.) Kitam. ), Artemisia fukudo Makino, Artemisia monophylla Kitam., Artemisia feddei Leveil. Et Vaniot, Artemisia stolonifera (Maxim.) Komar., And Artemisia fate , Artemisia maritima Linn., Artemisia pedunculosa Miq., Artemisia rubripes Nakai, Artemisia momiyamae Kitam., Artemisia lactiflora Wall. Ex DCsia, gil Miq.).
[0012]
As plants of the genus Artemisia, for example, Azumagiku (Erigeron thunbergii A. Gray), Apoiazumagiku (Erigeron thunbergii A. Gray var. Angustifolius), Arechinogiku (Erigeron bonariensis Linn.), Ezomu no ogi (Erigeron acer Retz.), Erigeron pusillus Nutt., Euleron philadelphicus Linn., Erigeron canadensis Linn., Erigeron acer Linn. Var. Amplifus Kit .), Erigeron acer Linn. Var. Linearifolius (Koidz.) Kitam., Erigeron thunbergii A. Gray subsp. Glabratus (A. Gray) Hara, Erigeron miyabeanus Tatew. Et Kitam. ), Mugwort (Erigeron acer Linn. Var. Kamtschaticus (DC.) Herder) or willow Himejon (Erigeron pseudo-annuus Makino).
[0013]
Examples of the plant belonging to the genus Akimugi include Siphonostegia laeta S. Moore and Siphonostegia chinensis Benth.
In the present invention, the mugwort is preferably Japanese mugwort or Chinese mugwort.
[0014]
The processed mugwort used in the present invention is obtained by treating the above mugwort. Examples of such a mugwort are the above-mentioned mugwort whole plant, roots, leaves or seeds made into fine powder, water or / and / or Extract obtained by immersing and extracting the above mugwort with an organic solvent (for example, alcohol such as methanol or ethanol, ether or ketone, etc.), and filtering the residue, an extract obtained by removing the solvent from the extract, Examples thereof include powders, or those obtained by dissolving, dispersing or diluting them with an appropriate solvent (for example, water or an organic solvent). In the present invention, the above-mentioned processed artemisia is preferably an extract of mugwort alcohol, and more preferably an ethanol extract. According to the present invention, when the mugwort extract is a mugwort alcoholic extract, the blending ratio of the alcohol and the mugwort is preferably about 10 g to 200 g of the mugwort with respect to 1 liter of alcohol. More preferably, it is ˜100 g.
[0015]
In the present invention, the above mugwort or its treated product may be used as it is as the composition for promoting muscle cell sugar transport of the present invention, and may further contain other physiologically active substances. Various additives such as excipients, pH adjusters, cooling agents, suspending agents, antifoaming agents, thickeners, solubilizers, disintegrating agents, binders, lubricants, antioxidants, You may use as said composition mixed with a coating agent, a coloring agent, a flavoring agent, surfactant, a plasticizer, or a fragrance | flavor.
[0016]
Examples of the excipient include sugar alcohols such as D-sorbitol, D-mannitol and xylitol, sugars such as glucose, sucrose, lactose and fructose, crystalline cellulose, carmellose sodium, calcium hydrogen phosphate, wheat starch, rice Examples thereof include starch, corn starch, potato starch, dextrin, β-cyclodextrin, light anhydrous silicic acid, titanium oxide, or magnesium aluminate metasilicate.
[0017]
Examples of the pH adjuster include citric acid, malic acid, sodium hydrogen phosphate, and dipotassium phosphate.
[0018]
Examples of the refreshing agent include l-menthol or mint water.
[0019]
Examples of the suspending agent include kaolin, carmellose sodium, xanthan gum, methylcellulose, and tragacanth.
[0020]
Examples of the antifoaming agent include dimethylpolysiloxane or silicon antifoaming agent.
[0021]
Examples of the thickener include xanthan gum, tragacanth, methylcellulose, and dextrin.
[0022]
Examples of the solubilizer include ethanol, sucrose fatty acid ester, and macrogol.
[0023]
Examples of the disintegrant include low-substituted hydroxypropylcellulose, carboxymethylcellulose calcium, croscarmellose sodium, hydroxypropyl starch, or partially pregelatinized starch.
[0024]
Examples of the binder include methylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, gelatin, gum arabic, ethylcellulose, polyvinyl alcohol, pullulan, pregelatinized starch, agar, tragacanth, sodium alginate, or propylene glycol alginate. Can be mentioned.
[0025]
Examples of the lubricant include stearic acid, magnesium stearate, calcium stearate, polyoxyl stearate, cetanol, talc, hydrogenated oil, sucrose fatty acid ester, dimethylpolysiloxane, beeswax, and white beeswax.
[0026]
Examples of the antioxidant include dibutylhydroxytoluene (BHT), propyl gallate, butylhydroxyanisole (BHA), tocopherol, and citric acid.
[0027]
Examples of the coating agent include hydroxypropylmethylcellulose, hydroxypropylcellulose, methylcellulose, ethylcellulose, hydroxypropylmethylcellulose phthalate, hydroxypropylmethylcellulose acetate succinate, carboxymethylethylcellulose, cellulose acetate phthalate, polyvinyl acetal diethylaminoacetate, aminoalkyl methacrylate. Copolymer, hydroxypropyl methylcellulose acetate succinate, methacrylic acid copolymer, polyvinyl acetate diethylaminoacetate or shellac.
[0028]
Examples of the colorant include turmeric extract, riboflavin, titanium oxide, or carotene solution.
[0029]
Examples of the flavoring agent include citric acid, adipic acid, ascorbic acid, and menthol.
[0030]
Examples of the surfactant include polyoxyethylene hydrogenated castor oil, glyceryl monostearate, sorbitan monostearate, sorbitan monolaurate, polyoxyethylene polyoxypropylene, polysorbates, sodium lauryl sulfate, macrogol or sucrose. Examples include fatty acid esters.
[0031]
Examples of the plasticizer include triethyl citrate, polyethylene glycol, triacetin, and cetanol.
[0032]
As said fragrance | flavor, synthetic fragrance | flavors, such as natural fragrance | flavors, such as an animal fragrance | flavor or a vegetable fragrance | flavor, or an isolated fragrance | flavor, a pure synthetic fragrance | flavor, etc. are mentioned, for example.
[0033]
The dosage form is appropriately selected according to the administration form or usage form, and is a known dosage form, for example, a solid dosage form such as a powder, granule, tablet, capsule, suppository or ointment, for example, a solution or suspension. It can be processed into liquid dosage forms such as agents, gels, sols and the like. The administration form is generally oral administration, but is not limited thereto.
[0034]
In the present invention, a composition containing mugwort or a processed product thereof may be used for food, or may be circulated on the market as a food additive alone. For example, the composition containing mugwort or a processed product thereof is used as a food production raw material by a known means such as adding to a food, its food material or its food intermediate material.
[0035]
Examples of the food include confectionery (for example, snacks including potato chips, baked confectionery such as biscuits or cookies, chocolate, gum, candy, etc.), desserts (for example, pudding, jelly, yogurt or ice cream). In addition to taste foods such as noodles (for example, buckwheat, udon, ramen or pasta), food equivalent to staple foods such as cereal foods (for example corn flakes or oatmeal), seasoned foods (for example soup, curry or stew) Processed agricultural products (eg jams), milk oil foods (eg spreads or cheese), health foods (eg protein or fiber), calorie-adjusted foods, non-alcoholic beverages (eg soybean roasted tea drinks, grain teas, coffee drinks) , Tea drinks, green tea drinks, barley tea drinks, matcha drinks , Vegetable juice drinks, orange juice, grapefruit juice, soft drinks, etc.) or alcoholic drinks (eg beer, wine, sake, sparkling liquor, plum wine, whiskey, brandy, shochu, vodka, rum, gin, liqueurs or cocktails etc. ) And the like.
[0036]
Furthermore, you may mix | blend a carbohydrate, protein, minerals, vitamins, etc. with the said muscle cell sugar transport promotion action composition, food composition, or foodstuff suitably.
[0037]
Examples of the carbohydrate include polysaccharides such as starch or corn starch, and other saccharides such as dextrin, sucrose, glucose or fructose.
[0038]
Examples of the protein include a combination of animal protein and vegetable protein, and more specifically milk protein, soybean protein, egg protein, and the like.
[0039]
Examples of the minerals include calcium, magnesium, iron, sodium, potassium, zinc, copper, chromium, selenium, manganese, and molybdenum.
[0040]
Examples of the vitamins include vitamin A, vitamin B ₁ , vitamin B ₂ , vitamin B ₆ , vitamin B ₁₂ , vitamin C, vitamin D, vitamin E, niacin, pantothenic acid, and folic acid.
[0041]
Examples of the amino acid include glutamine, leucine, isoleucine, valine, tryptophan, phenylalanine, lysine, threonine, methionine, histidine, glycine, alanine, serine, aspartic acid, glutamic acid, asparagine, arginine, cystine, cysteine, tyrosine, proline or And hydroxyproline.
[0042]
When a person or animal ingests the composition, preparation, or food of the present invention, sugar is promoted to muscle cells, and diabetes can be prevented or treated.
[0043]
【Example】
(Example 1: Confirmation of sugar transport promoting action of skeletal muscle cells by mugwort)
(Preparation of L6 skeletal muscle cells)
L6 myoblasts were adjusted with α-MEM medium (containing 10% v / v fetal bovine serum) to a concentration of 2.5 × 10 ⁴ / mL, and applied to a 96-well tissue culture plate coated with collagen type I. After seeding 200 μL per well and culturing for 2 days in a 5% carbon dioxide incubator at 37 ° C. and becoming confluent, the medium was changed to α-MEM medium (containing 2% v / v fetal calf serum), 37 L6 skeletal muscle cells were prepared by culturing in a 5% carbon dioxide incubator at 5 ° C. for 5 days.
[0044]
(Production of mugwort extract)
2 g of chopped mugwort was placed in a 50 ml sample bottle, 30 ml of 99.5% ethanol was added, and the mixture was shaken at 5 ° C. for 48 hours for extraction. The extracted ethanol extract was filtered with paper no. Filtration at 2 and concentration by 7.5 with a vacuum concentrator yielded a mugwort ethanol extract.
[0045]
(Confirmation of glucose transport promoting action in L6 skeletal muscle cells)
Ethanol in mugwort ethanol extract prepared as in Example 1 above was removed with nitrogen gas, the residue was dissolved in an equal amount of dimethyl sulfoxide, and α-MEM medium (containing 2% v / v fetal calf serum) The mugwort extract-containing α-MEM medium was prepared by diluting 100 times. 100 μL of mugwort extract-containing α-MEM medium was added to a plate on which L6 skeletal muscle cells prepared as in Example 1 were cultured, incubated for 4 hours in a 5% carbon dioxide incubator at 37 ° C., and then PBS (− ) Twice, and 100 μL of KRPH buffer (pH 7.4) containing 1 mM 2-DG was added per well, incubated in a 5% carbon dioxide incubator at 37 ° C. for 30 minutes, and PBS (−) Washed twice. Then, add 25 μL of 0.1N NaOH per hole, put the plate in the freezer and freeze it, take the plate out of the freezer and return to room temperature, heat treatment in a hot water bath at 85 ° C. for 20 minutes, After standing to cool, 0.1N HCl was added at 25 μL per well, followed by 150 mM triethanolamine buffer (pH 8.1) added at 25 μL per well, and 2-DG in the sample was quantified as follows Then, by comparing with the 2-DG uptake amount of the control (α-MEM medium (containing 2% v / v fetal calf serum)), the sugar transport promoting action was examined.
[0046]
(Quantification of 2-deoxyglucose (2DG))
A sample containing 1 to 20 μg / mL of 2-DG was added to a 96-well tissue culture plate at 50 μL per well, and 150 μL of assay cocktail (ATP 1 μmol, hexokinase 0.54 units, NADP + 60 nmol, glucose-6-phosphate dehydrogenase 2 units, Resazurin sodium 3.8 nmol, diaphorase 0.15 units [50 mM triethanolamine buffer (pH 8.1), 50 mM KCl, 0.5 mM MgCl ₂ , 0.02% BSA]) were added and stirred with a microplate mixer. Quantification was carried out by measuring the fluorescence value (excitation wavelength: 530 nm, measurement wavelength: 590 nm) with a microplate reader after incubation in a 5% carbon dioxide incubator at 37 ° C. for 90 minutes.
[0047]
[Table 1]

[0048]
From the above results, it can be seen that mugwort extract is superior in the amount of glucose uptake into muscle cells, that is, in the muscle cell sugar transport promoting action.
[0049]
【The invention's effect】
According to the present invention, a novel and useful application of mugwort or a processed product thereof can be provided. More specifically, the composition for promoting muscle cell sugar transport containing the mugwort of the present invention or a processed product thereof is useful as a preventive or therapeutic agent for diabetes and is used as a pharmaceutical, a food composition or a food.

Claims (3)

Use of a mugwort selected from the group consisting of Artemisia princeps, Artemisia argyi, and Artemisia vulgaris or a processed product thereof for the manufacture of a composition for promoting sugar transport in muscle cells (prevention or treatment of diabetes) Except for the use of mugwort or processed product for The use according to claim 1, wherein the composition is a pharmaceutical composition . The use according to claim 1 or 2, wherein the mugwort or a processed product thereof is an ethanol extract of mugwort .