KR20170019501A - Composition for anti-diabete comprising extract of hull and sprout parts from germinated rough rice as an effective component - Google Patents
Composition for anti-diabete comprising extract of hull and sprout parts from germinated rough rice as an effective component Download PDFInfo
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- KR20170019501A KR20170019501A KR1020150109877A KR20150109877A KR20170019501A KR 20170019501 A KR20170019501 A KR 20170019501A KR 1020150109877 A KR1020150109877 A KR 1020150109877A KR 20150109877 A KR20150109877 A KR 20150109877A KR 20170019501 A KR20170019501 A KR 20170019501A
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- South Korea
- Prior art keywords
- rice
- diabetic
- germinated
- extract
- present
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
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Abstract
Description
The present invention relates to a composition for anti-diabetic comprising germinated rice hull extract as an active ingredient.
Currently, Korea is experiencing rapid changes in the pattern of disease due to the rapid growth of Westernized dietary habits and nutrients, and chronic degenerative diseases such as arteriosclerosis, hypertension, cancer, obesity and diabetes are major causes of death .
In particular, the incidence of diabetes mellitus and its complications is increasing rapidly. The incidence of diabetes was less than 1% of the population in the 1970s. Since the 1990s, 17.2 people per 100,000 population have died from diabetes, and it is estimated that the incidence of diabetes will continue to increase in the future. Diabetes mellitus is a chronic metabolic disorder in which hyperglycemia and its metabolic disturbance persist for a long period of time. It is a chronic metabolic disorder in which insulin-dependent diabetes mellitus and insulin secretory ability, which are caused by an absolute deficiency of insulin due to dysfunction of the pancreas Langerhan's island β- Non-insulin dependent diabetes mellitus.
Diabetes mellitus is a typical chronic disease, and it is a chronic disease that causes microvascular complications such as retinas, kidneys and nerves, and macrovascular complications such as stroke, angina, myocardial infarction and peripheral vascular disease due to various metabolic disorders including glucose. Recently, the development of diabetes mellitus has led to an increase in the life expectancy of patients with diabetes mellitus and a rapid decrease in mortality due to acute metabolic complications. However, due to the increased incidence of diabetic chronic complications, diabetic complications are more severe than diabetes mellitus itself It is pointed out as a problem.
Diabetes mellitus is medication, exercise and diet, and insulin medicines and various blood glucose drugs are used depending on the patient's symptoms. However, diabetes is a complex disease characterized by overgrowth of glucose in the liver, insulin resistance, and decreased glucose tolerance in muscle and adipocytes. Therefore, specific treatment alone can not prevent the occurrence of various side effects. Because drug therapy uses insulin and chemicals, drug therapy is a constant problem for side effects and patient resistance due to the use of drugs. Therefore, recently, diabetes can be eaten and diabetes can be diarrhea, It is necessary to study for treatment.
Accordingly, the inventors of the present invention confirmed that the ginger rice husk extract had excellent effects in the treatment of diabetic and diabetic complications, and completed the present invention.
Accordingly, an object of the present invention is (a) (b) drying the germinated rice; (c) separating the dried germinated rice into a rice husk fraction and a brown rice fraction using a rice germ, and then selecting a rice hull fraction; And (d) solvent extraction of the selected rice husk fraction; And a method for producing germinated rice hull extract.
Another object of the present invention is to provide a pharmaceutical composition for preventing or treating diabetic or diabetic complications comprising the germinated rice hull extract prepared by the above invention as an active ingredient.
It is a further object of the present invention to provide a functional health food for preventing or ameliorating diabetic or diabetic complications comprising the germinated rice hull extract prepared as described above as an active ingredient.
In order to achieve the above object, the present invention provides a method for producing rice seedlings comprising: (a) germinating rice; (b) drying the germinated rice; (c) separating the dried germinated rice into a rice husk fraction and a brown rice fraction using a rice germ, and then selecting a rice hull fraction; And (d) solvent extraction of the selected rice husk fraction; And a method for producing germinated rice hull extract.
In one embodiment of the present invention, the germination in the step (a) may be germinated at a temperature of 35 to 40 ° C for 1 to 6 days while maintaining a humidity of 80 to 90%.
In one embodiment of the present invention, the solvent extraction in step (d) may be carried out with a solvent selected from the group consisting of water, methanol, ethanol, hexane, butanol, ethyl acetate, chloroform and a mixed solvent thereof.
In one embodiment of the present invention, the solvent extraction in the step (d) may further include a step of column purification using C18 resin.
The present invention also provides a pharmaceutical composition for preventing or treating diabetic or diabetic complications comprising germinated rice hull extract prepared by the above method as an active ingredient.
In one embodiment of the present invention, the germinated rice husk extract may regulate blood glucose level by introducing glucose into the adipocytes.
In one embodiment of the present invention, the diabetic complication may be diabetic retinopathy, diabetic cataract, diabetic nephropathy, diabetic neuropathy, diabetic vascular complication.
Furthermore, the present invention provides a functional health food for preventing or ameliorating diabetic or diabetic complications comprising germinated rice hull extract prepared by the above method as an active ingredient.
The germinated rice hull extract according to the present invention has an effect of controlling the glucose level in the blood by introducing glucose into the adipocytes and thus can be effectively used for the prevention or treatment of diabetes or diabetic complications. In addition, the germinated rice hull extract of the present invention is a natural substance and is stable in the body and can be used as a material for functional health food.
FIG. 1 shows the results of measurement of the glucose uptake activity of 3T3-L1 adipocytes from germinated rice extracts according to germination, site, and extraction solvent.
FIG. 2 shows the glucose uptake activity of 3T3-L1 adipocytes in germinated rice hull extract according to the solvent fraction.
FIG. 3 shows the glucose uptake activity of 3T3-L1 adipocytes in germinated rice hull extract according to column purification.
(C57BLKS / J-db / m + mice), positive control group, and
(C57BLKS / J-db / m + mice), positive control group, and C550 mg / kg group. The results are shown in FIG. 5. FIG. 5 shows the effect of the germination rice extract of the present invention on glucose tolerance of a diabetic animal model / kg group, C: 100 mg / kg group, □: control group (
6 is a graph showing the expression level of glucose transporter 4 (GLUT-4) transcription factor after treatment with germinated rice hull extract of the present invention (A: control, B:
FIG. 7 is a graph showing the expression levels of the activated insulin receptor substrate 1 (pIRS-1) transcription factor using the immunofluorescence method (A: control, B:
FIG. 8 shows the results of confirming the release amount of insulin-related transcription factors after treatment of germinated rice hull extract of the present invention.
FIG. 9 is a process diagram showing a process for producing germinated rice hull extract of the present invention.
The present invention relates to a novel use of a germinated rice hull extract, and is characterized by providing a composition for preventing or treating diabetes and diabetic complications comprising germinated rice hull extract as an active ingredient.
Rice (Oryza sativa L.) is one of the world's three major crops, and more than half of the world's population uses rice as rice. Rice is a major source of carbohydrates worldwide and is not a source of diverse nutrients, but it is a key crop in terms of the proportion of nutrients that depend on rice, especially in countries such as Asia where rice is a stock. Rice seeds are activated and germinated when inactivated DNA genetic information and various enzymes and nutrients in seeds and endosperm are improved in external environment condition. Generally, as germination proceeds, various components are increased or produced and various It has been reported that physiological activity tends to increase. In particular, germinated brown rice has been reported to increase physiologically active ingredients such as γ-oryzanol, arabinoxylane, γ-aminobutyric acid and vitamin E, and to activate enzymes during germination, facilitating absorption of nutrients into the body.
It is known that there is an antidiabetic effect on the existing brown rice. However, there is no disclosure about the measurement of various changes occurring in rice husks and rice bran during the germination of whole rice germ, and the antidiabetic effect in germinated rice hull extract.
Therefore, the present invention firstly confirms the fact that diabetic and diabetic complications can be prevented or treated by confirming that the germinated rice hull extract has an effect of lowering blood glucose and controlling blood glucose level by introducing glucose into adipocytes Respectively.
Accordingly, the present invention can provide a composition capable of preventing or treating diabetic and diabetic complications including germinated rice hull extract as an active ingredient.
The germinated rice hull extract according to the present invention can be obtained by extracting and isolating from nature using an extraction and separation method known in the art, and the 'extract' defined in the present invention can be obtained by germination For example, crude extracts of germinated rice hulls, polar solvent-soluble extracts, or non-polar solvent-soluble extracts.
As the suitable solvent for extracting the extract from the germinated rice hulls, any organic solvent which is pharmaceutically acceptable may be used, and water or an organic solvent may be used. Examples thereof include, but not limited to, purified water, An alcohol having 1 to 4 carbon atoms, acetone, ether, benzene, and the like, including methanol, ethanol, propanol, isopropanol, butanol, Various solvents such as chloroform, ethyl acetate, methylene chloride, hexane and cyclohexane may be used alone or in combination. More preferably, water or ethanol (alcohol) can be used.
As the extraction method, any one of the methods such as hot water extraction method, cold extraction method, reflux cooling extraction method, solvent extraction method, steam distillation method, ultrasonic extraction method, elution method and compression method can be selected and used. In addition, the desired extract may be further subjected to a conventional fractionation process or may be purified using a conventional purification method. The method for producing the germinated rice husk extract of the present invention is not limited, and any known method may be used.
For example, the germinated rice husk extract contained in the composition of the present invention may be prepared in powder form by an additional process such as vacuum distillation, freeze drying, or spray drying, . Further, the primary extract can be further purified by using various chromatographies such as silica gel column chromatography, thin layer chromatography, high performance liquid chromatography and the like, You can get it.
Therefore, the germinated rice hull extract of the present invention is a concept including all the extracts, fractions and tablets obtained in each step of extraction, fractionation or purification, their diluted solutions, concentrates or dried products.
The method of preparing the germinated rice hull extract according to one embodiment of the present invention will be described in more detail as follows.
In the present invention, a typical rice variety is used. In the germination, the rice is washed with water at 20 DEG C for 3 days and then germinated in a germination machine (WGC 450 Dahan Inc, Korea). Germinate at germination temperature of 35 ~ 40 ℃ and humidity of 80 ~ 90%, water is changed once a day, germinated by watering for 10 minutes three times a day. The germination period is 1 to 6 days, and the germinated rice can be dried in a hot air dryer at 50 to 60 ° C for 2 days.
The dried germinated rice was divided into hull & sprout and brown rice by using a micro mill, and then the seeds were separated by using a crusher (Micro hammer cutter mill type-3, Culatti AG, Zurich, Switzerland) To 80 mesh and then stored at -20 ° C. Water and ethanol extracts can be used to extract useful components contained in the sample.
The composition of the present invention comprising the germinated rice hull extract prepared by the above method as an active ingredient may be a pharmaceutical composition or a food composition.
The pharmaceutical composition of the present invention can be prepared by using pharmaceutically acceptable and physiologically acceptable adjuvants in addition to the above-mentioned active ingredients. Examples of the adjuvants include excipients, disintegrants, sweeteners, binders, coating agents, swelling agents, lubricants, A lubricant or a flavoring agent can be used.
The pharmaceutical composition may be formulated into a pharmaceutical composition containing at least one pharmaceutically acceptable carrier in addition to the above-described active ingredients for administration.
The pharmaceutical composition of the present invention can be prepared by using pharmaceutically acceptable and physiologically acceptable adjuvants in addition to the above-mentioned active ingredients. Examples of the adjuvants include excipients, disintegrants, sweeteners, binders, coating agents, swelling agents, lubricants, A lubricant or a flavoring agent can be used.
The pharmaceutical composition may be formulated into a pharmaceutical composition containing at least one pharmaceutically acceptable carrier in addition to the above-described active ingredients for administration.
The pharmaceutical composition may be in the form of granules, powders, tablets, coated tablets, capsules, suppositories, liquids, syrups, juices, suspensions, emulsions, drops or injectable solutions. For example, for formulation into tablets or capsules, the active ingredient may be combined with an oral, non-toxic pharmaceutically acceptable inert carrier such as ethanol, glycerol, water, and the like. Also, if desired or necessary, suitable binders, lubricants, disintegrants and coloring agents may also be included as a mixture. Suitable binders include, but are not limited to, natural sugars such as starch, gelatin, glucose or beta-lactose, natural and synthetic gums such as corn sweeteners, acacia, tracker candles or sodium oleate, sodium stearate, magnesium stearate, sodium Benzoate, sodium acetate, sodium chloride, and the like. Disintegrants include, but are not limited to, starch, methyl cellulose, agar, bentonite, xanthan gum and the like. Acceptable pharmaceutical carriers for compositions that are formulated into a liquid solution include sterile water and sterile water suitable for the living body such as saline, sterile water, Ringer's solution, buffered saline, albumin injection solution, dextrose solution, maltodextrin solution, glycerol, One or more of these components may be mixed and used. If necessary, other conventional additives such as an antioxidant, a buffer, and a bacteriostatic agent may be added. In addition, diluents, dispersants, surfactants, binders, and lubricants may be additionally added to formulate into injectable solutions, pills, capsules, granules or tablets such as aqueous solutions, suspensions, emulsions and the like. Further, it can be suitably formulated according to each disease or ingredient, using the method disclosed in Remington's Pharmaceutical Science, Mack Publishing Company, Easton PA as an appropriate method in the field.
In one embodiment of the present invention, the germinated rice hull extract of the present invention may be contained in an amount of 0.1 to 10% by weight based on the total weight of the composition.
The composition of the present invention may also be a food composition. In addition to containing germinated rice hull extract as an active ingredient, such a food composition may contain various flavors or natural carbohydrates as an additional component such as a conventional food composition .
Examples of the above-mentioned natural carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose and the like; And polysaccharides, for example, conventional sugars such as dextrin, cyclodextrin and the like, and sugar alcohols such as xylitol, sorbitol and erythritol. The above-described flavors can be advantageously used as natural flavorings (tau martin), stevia extracts (e.g., rebaudioside A, glycyrrhizin, etc.) and synthetic flavors (saccharin, aspartame, etc.).
The food composition of the present invention can be formulated in the same manner as the above pharmaceutical composition and used as a functional food or added to various foods. Foods to which the composition of the present invention can be added include, for example, beverages, meat, chocolates, foods, confectionery, pizza, ram noodles, other noodles, gums, candy, ice cream, alcoholic beverages, vitamin complexes, .
In addition, the food composition may contain various additives such as various nutrients, vitamins, minerals (electrolytes), synthetic flavors and flavors such as natural flavors, colorants and heavies (cheese, chocolate, etc.), pectic acid, Alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated drinks, and the like. In addition, the food composition of the present invention may contain natural fruit juice and pulp for the production of fruit juice drinks and vegetable drinks.
Since the gangrene rice husk extract as an active ingredient of the present invention is a natural substance with little toxicity and side effects, it can be safely used for prolonged use for the prevention or treatment of diabetes and diabetic complications.
The present invention also provides a health functional food for controlling blood glucose, which comprises germinated rice hull extract as an active ingredient.
The health functional food of the present invention can be manufactured and processed in the form of tablets, capsules, powders, granules, liquids, and rings for the purpose of controlling blood glucose.
In the present invention, the term "health functional food" refers to foods manufactured and processed using raw materials or ingredients having useful functions in accordance with Law No. 6727 on Health Functional Foods, Or to obtain a beneficial effect in health use such as physiological action.
The health functional foods of the present invention may contain conventional food additives and, unless otherwise specified, whether or not they are suitable as food additives are classified according to the General Rules for Food Additives approved by the Food and Drug Administration, Standards and standards.
Examples of the items listed in the above-mentioned 'food additives' include chemical compounds such as ketones, glycine, calcium citrate, nicotinic acid, and cinnamic acid; Natural additives such as persimmon extract, licorice extract, crystalline cellulose, high color pigment and guar gum; L-glutamic acid sodium preparations, noodle-added alkalis, preservative preparations, tar coloring preparations and the like.
For example, the health functional food in the form of tablets may be prepared by granulating a mixture obtained by mixing the germinated rice husk extract, which is an effective ingredient of the present invention, with an excipient, a binder, a disintegrant and other additives in a usual manner, Compression molding, or direct compression molding of the mixture. In addition, the health functional food of the tablet form may contain a mating agent or the like if necessary.
The hard capsule of the capsule type health functional food can be prepared by filling a normal hard capsule with a mixture of the ginger rice hull extract of the present invention as an excipient and an additive such as an excipient and the soft capsule is a germinated rice hull extract An excipient and the like may be filled in a capsule base such as gelatin. The soft capsule may contain a plasticizer such as glycerin or sorbitol, a coloring agent, a preservative and the like, if necessary.
The ring-shaped health functional food can be prepared by molding a mixture of the ginger rice husk extract, which is an effective ingredient of the present invention, with excipients, binders, disintegrants, etc., by a conventionally known method and, if necessary, The surface can be coated with a material such as starch, talc or the like.
The granular health functional food may be prepared by granulating a mixture of germinated rice hull extract, which is an effective ingredient of the present invention, with an excipient, a binder, a disintegrant, etc., by a conventionally known method and, if necessary, And the like.
The health functional food containing the germinated rice hull extract of the present invention as an active ingredient is effective for controlling blood glucose because the blood glucose level can be controlled by introducing glucose into the adipocytes as shown in the following examples.
The health functional food may be a beverage, a meat, a chocolate, a food, a confectionery, a pizza, a ramen, a noodle, a gum, a candy, an ice cream, an alcoholic beverage, a vitamin complex and a health supplement food.
The present invention also provides a method of preventing or treating diabetic and diabetic complications comprising administering germinated rice hull extract to a mammal.
As used herein, the term " mammal " refers to a mammal that is the subject of treatment, observation, or experimentation, preferably a human.
As used herein, the term " therapeutically effective amount " refers to the amount of active ingredient or pharmaceutical composition that elicits a biological or medical response in a tissue system, animal or human, as contemplated by a researcher, veterinarian, The amount that induces the relief of the symptoms of the disease or disorder being treated. It will be apparent to those skilled in the art that the therapeutically effective dose and the number of administrations of the active ingredient of the present invention will vary depending on the desired effect. Thus, the optimal dosage to be administered can be readily determined by those skilled in the art and will vary with the nature of the disease, the severity of the disease, the amount of active and other ingredients contained in the composition, the type of formulation, and the age, The age, body weight, sex, diet, time of administration, route of administration and fraction of the composition, duration of treatment, concurrent medication, and the like. In the treatment method of the present invention, in the case of an adult, it is preferable to administer the germinated rice hull extract of the present invention at a dose of 1 mg / kg to 250 mg / kg once to several times a day.
The composition comprising the germinated rice hull extract of the present invention as an active ingredient in the treatment method of the present invention may be administered orally or rectally, intravenously, intraarterially, intraperitoneally, intramuscularly, intrasternally, transdermally, topically, ≪ / RTI > can be administered in a conventional manner.
Hereinafter, the present invention will be described in detail with reference to examples. However, these examples are intended to further illustrate the present invention, and the scope of the present invention is not limited to these examples.
< Example 1>
Experimental materials and germination method
In the present invention, a common rice variety, Oryza sativa L., was purchased from farmers and used. The germination was done by soaking the rice with water at 20 ° C for 3 days and germinating with germination (WGC 450 Dahan Inc, Korea). The germination temperature was maintained at 37 ℃ and the humidity was maintained at 85%. The water was exchanged once a day and germinated with water for 10 minutes three times a day. The germination period was 1-6 days, and ungerminated rice was used as a control. The germinated rice was dried in a 55 ° C hot air dryer for 2 days.
< Example 2>
Separation by parts and manufacturing method of extract
The dried germinated and germinated rice were separated into hull & sprout and brown rice using a hermit machine, followed by crushing with a micro hammer cutter mill type-3, Culatti AG, Zurich, Switzerland. And the mixture was pulverized to a size of 60 mesh and then stored at -20 ° C. Water and ethanol extracts were prepared to extract the useful components contained in the sample. Water extracts and ethanol extracts were added with 10 times of distilled water and 80% ethanol (v / v), respectively, and the mixture was stirred at room temperature for 24 hours. The extract was filtered under reduced pressure, concentrated, lyophilized, And used as a sample.
< Example 3>
Solvent fraction And Column refined fraction Manufacturing method
The rice husk fraction ethanol extracts of germinated rice were sequentially fractionated with hexane, chloroform, ethyl acetate, butanol and water, respectively. The extracts were then filtered and concentrated to obtain the solvent fractions . The hexane fraction of the ethanol extract was injected into a column filled with C18 resin activated with methanol, polar substances were removed with water and methanol, and then washed with hexane to prepare an active fraction.
< Example 4>
3 T3 - L1 Induction of adipocyte culture / differentiation and measurement of glucose uptake activity
Cells were cultured and maintained in DMEM (Dulbecco's modified Eagle's medium) supplemented with 10% bovine calf serum (BCS) (Bovine calf serum) and 1% penicillin / Streptomycin. The cells were used for the experiment under subculture at 37 ° C and 5% CO 2 every 2-3 days.
When 3T3-L1 adipose precursor cells are confluent in a concentration of 80 to 90%, the cells are separated by treatment with 0.25% trypsin-EDTA, and the cells are collected in a centrifuge, and a suspension solution is prepared from the 6-well plate for cell culture to confluent state After incubation, it was confirmed that it was saturated and then cultured for another 48 hours. When cells were post-confluent, differentiation medium was induced by treatment with IBMX (0.5 mM), dexamethasone (0.25 μM), insulin (5 μg / mL) and 10% FBS. After 2 days of induction of differentiation, the cells were cultured for 2 days with 10% FBS DMEM containing 5 μg / mL of insulin. After 4 and 6 days, the culture medium was replaced with 10% FBS DMEM to induce adipocyte differentiation.
Two days after the bottom of the culture vessel was completely filled, induction differentiation material was added for 3 days. After 2 days, it was changed into a high glucose DMEM solution containing 10% FBS every 7 days, Glucose uptake experiments were performed. The differentiation-induced adipocytes were washed with PBS and incubated for 6 hours at 37 ° C in serum-free DMEM. Krebs Ringer Phosphate Hepes (KRPH) buffer (1.2 mM KH 2 PO 4 , 1.2 mM MgSO 4 , 1.3
In other words, KRPH buffer containing 2% BSA was treated with differentiation-induced adipocytes such as 1 μM insulin and 1 mM 2DG for 20 min at 37 ° C., followed by 200 μM phloretin Washed with cold PBS. Then, 3 mL of 10 mM Tris-HCl buffer (pH 8.0) was added to each well, and the cells were disrupted. Cell lysate was collected in a tube and then heat-treated at 80 ° C for 15 minutes. The supernatant was transferred to a new tube after centrifugation at 15,000 * g for 20 minutes at 4 ° C. The supernatant was resuspended in 1X sample diluent buffer (1: 4) (2G) Uptake Measurement Kit (COSMO BIO CO., LTD., TOKYO, JAPAN) using the solution in the kit, and then the test was performed at 420 nm and 25-30 ° C Absorbance was measured by kinetic reaction at intervals of 5 minutes for 30 minutes.
< Example 5>
Using a diabetic model mouse Anti-diabetic Efficacy evaluation method
6 weeks old male C57BLKS / J- db / db mice and C57BLKS / J- db / m + mice (Shizuoka Laboratory Animal Center; SLC, Shizuoka, Japan) After fasting blood glucose levels of all C57BLKS / J- db / db mice reached an average of 150 mg / dL after measurement, blood glucose levels were measured once every 3 weeks and group separation was performed at 10 weeks of age .
The animals were housed in a rabbits box (220 × 200 × 145 mm 3 ) for 2 to 3 animals. The animals were housed at a temperature of 22 ± 3 ° C, a relative humidity of 50 ± 20%, a ventilation frequency of 10 to 15 times / The period was adjusted to 12 hours / day (07: 00 ~ 19: 00) and the illumination was 150 ~ 300 Lux. The feed was fed free of animal feed (Teklad certified irradiated global 18% protein rodent diet, Harlan Laboratories, Inc., USA) and the sterilized purified water supplied by the Chungbuk National University Laboratory Animal Research Support Center Respectively. This test was approved by the Animal Experimental Ethics Committee of the Center for Experimental Animal Research, Chungbuk National University (Approval No. CBNUA-623-13-01).
After confirming that the blood glucose level of C57BLKS / J- db / db mice induced to type 2 diabetes reached 150 mg / dL on average, the mice were divided into 5 groups as follows. C5 was administered at a dose of 100 mg / kg, and C5 was administered at a dose of 100 mg / kg. The control group (
Blood glucose was measured 6 times in total at 0 week (before test substance), 1 week, 3 weeks, 5 weeks, 7 weeks and 9 weeks after the test. All animals were fasted for about 16 hours before the measurement of blood glucose, and after about 1 hour from the administration of the test substance, blood was collected from the tail vein and analyzed with a glucose meter (GlucoDr Plus TM AGM-3000, Allmedicus Co., Ltd. ., Anyang, Korea).
The mice were fasted for about 16 hours after 8 weeks of test substance administration. (1 g / kg, Sigma-Aldrich Inc., St. Louis, Mo., USA) was orally administered 1 hour after the administration of excipients, test substances and positive control substances. Blood was collected from the tail vein at 0, 30, 60, 90, and 120 minutes after glucose administration 0 (before administration) and measured using a blood glucose meter.
< Example 6>
Western Blot Analysis of expression levels of transcription factors
After subculture, 3T3-L1 fibroblasts were cultured until they were completely filled in a 75 cm 2 flask. After 2 days, the differentiation inducer was added and cultured for 7 days. After 2 days, high glucose DMEM medium supplemented with 10% FBS was changed and the experiment was conducted at the time of complete conversion to adipocytes.
Cells that were completely differentiated into adipocytes were treated with 3% bovine serum albumin (BSA) for 12 hours in serum-free DMEM medium and treated for 5 hours. After 5 h, insulin was treated with 1 and 50 μg / mL for 10 min. After treatment, the cells were washed with phosphate buffered saline (PBS) and lysed in 50 mM Tris pH 8.0, 150 mM NaCl, 0.02% sodium azide, 100 μg / mL PMSF, 1 μg / mL aprotinin, 1% Triton X -100) and centrifuged at 12,000 rpm to obtain supernatant. Protein quantitation was performed using the Bradford method, and 30 μg of protein was electrophoresed on 10% SDS-PAGE gel, and the separated proteins were transferred to a PVDF membrane at 80 V for 1 hour. And then blocked with 5% skim milk in TBS-Tween 20 for 1 hour at room temperature.
( S ) , GLUT4 (Santa Cruz Biotechnology , Inc.), PI3 kinase, AKT, pAKT (Ser473) , PPAR-gamma (Cell signaling technology. Beverly, MA), IRS-1, pIRS- , Anti-rabbit IgG (1: 2000), anti-goat (1: 2000) and anti-goat anti-mouse 3000) as a secondary antibody for 1 hour. After the reaction was completed, the cells were detected with ECL Kit (WEST-one TM , iNtRON Biotechnology).
< Experimental Example 1>
Evaluation of glucose uptake activity by germination, site and extraction solvent
As a result of evaluating the glucose uptake activity of 3T3-L1 adipocytes from ginseng extracts with and without germination, part and extraction solvent at a concentration of 500 μg / mL, only ethanol extract of rice hull fraction showed 40.97% to 157.53% Respectively. There was no significant difference between the extracts and the extraction solvent except for the germination - free ethanol extract. However, since the ethanol extract of the fraction containing the germinated ginger root and shoots showed the highest activity, it was used for further purification experiments (see FIG. 1).
< Experimental Example 2>
Evaluation of glucose uptake activity by solvent fraction
The ethanol extracts were sequentially fractionated and the glucose uptake activity of 3T3-L1 adipocytes in the fraction was evaluated at a concentration of 100 μg / mL. As a result, ethanol extracts were 153.86% at a concentration of 500 μg / mL (100.2 μg / mL), and that of hexane, chloroform, and butanol was 169.29, 145.41, and 145.41%, respectively, for all fractions except for the water layer (101.21%) at the concentration of 100 μg / mL for the solvent fraction (P < 0.05) (see Fig. 2). Among the ethanol extracts of the fraction containing the germinated hull root and shoots, which had the highest activity among the solvent fractions, the fractions of exanus were used as a sample in the subsequent purification experiments.
< Experimental Example 3>
C18 Evaluation of glucose uptake activity by column purification
After fractionation of the hexane fractions, the glucose uptake activity of 3T3-L1 adipocytes in the fractions was evaluated at a concentration of 10 μg / mL. As a result, the glucose uptake was significantly increased to 194.69% in the C5 fraction Was used as a sample in an in vivo antidiabetic efficacy evaluation experiment (see FIG. 3).
< Experimental Example 4>
Active Fraction Using Diabetic Model Mouse C5 ) Anti-diabetic Efficacy evaluation result
During the test period, the mean blood glucose level of the normal control group was varied from 70.2 to 85.0 mg / dL, and the blood glucose level of the positive control group was varied from 175.2 to 512.9 mg / dL, which was statistically significantly higher in the positive control group 4, p < 0.01). 50 mg of C5-treated group showed a mean change of 174.0 ~ 499.3 mg / dL. There was no statistically significant difference compared to the positive control group. The mean blood glucose level of C5 administered group of 100 mg / mL was 176.5 ( P <0.05: 7 weeks and 9 weeks) compared with the positive control group. The mean blood glucose level of the pioglitazone-treated group at 5 mg / kg was 181.1 to 182.7 mg / dL, which was statistically lowered from 1 to 9 weeks of administration compared with the positive control group ( p <0.05: 1 week, p <0.01: 3 weeks-9 weeks).
In the glucose tolerance test on the 8th week of the test substance administration, the blood glucose levels at the 0 minute (before the administration), 30 minutes, 60 minutes, 90 minutes and 120 minutes of glucose administration in the normal control group were 70.3 mg / dL and 155.3 mg / DL, 119.3 mg / dL, and 102.2 mg / dL, respectively. The mean blood glucose levels of the positive control group were 547.2 mg / dL, 737.2 mg / dL, 712.5 mg / dL, 654.6 mg / dL and 636.0 mg / dL, respectively And the blood glucose level of the positive control group was statistically significantly higher at all time points (see FIG. 5, p < 0.01). The blood glucose levels of the C5-treated group of 50 mg / mL were 475.1 mg / dL, 757.1 mg / dL, 635.7 mg / dL and 615.6 mg / dL, The mean blood glucose level was 419.1 mg / dL, 628.3 mg / dL, 585.6 mg / dL, and 560.8 mg / dL and 527.4 mg / dL, respectively, at each time point and decreased slightly compared with the positive control group. Was not confirmed. The mean blood glucose level of the 5 mg / kg dose group was 256.1 mg / dL, 385.1 mg / dL, 368.1 mg / dL, 364.1 mg / dL and 349.1 mg / dL, Min and 120 min, respectively ( p <0.05).
< Experimental Example 5>
Western Blot Evaluation of expression levels of transcription factors through analysis
The reason for using 3T3-L1 fibroblasts for exploring insulin-sensitive substances is that 3T3-L1 cells are involved in the in vivo metabolic feedback loop and are not associated with complicated problems. They have insulin receptors and GLUT4 in the cytoplasm, , Insulin is bound to the insulin receptor present in the cell membrane of 3T3-L1 cells and this amplifies the process of IRS-1 → PI3 kinase → AKT, an insulin signaling system. As a result, the translocation of GLUT-4 into cell membranes increases, leading to an increase in glucose uptake.
Immunofluorescence and western blot were used to investigate the antidiabetic effect mechanism of the active fraction (GIP-HS_E_H_C5) extracted from germinated rice germ and the comparative substance (pioglitazone) by increasing the glucose uptake activity of 3T3-L1 adipocytes. In the immunofluorescence experiment, it was observed that the expression of GLUT-4 was increased in C5-treated cells (see FIG. 6), and the expression of pIRS-1 was also increased by the treatment of C5 Reference).
The expression of pIRS, PI3 kinase, pAKT and GLUT-4 in the C5-treated group was also increased in the western blot analysis of the major transcription factor compared with cells treated with 1 ng / mL insulin alone 8). This suggests that C5 increases the sensitivity of the insulin receptor. In addition, pioglitazone, which is used as a reference substance, is known to act as a PPAR-γ agonist as a typical anti-diabetic agent and to increase glucose uptake in adipocytes. The expression of PPAR-γ upon treatment with C5 increased the insulin-stimulated glucose uptake, suggesting that it improves the activity of PPAR-γ.
The present invention has been described with reference to the preferred embodiments. It will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention as defined by the appended claims. Therefore, the disclosed embodiments should be considered in an illustrative rather than a restrictive sense. The scope of the present invention is defined by the appended claims rather than by the foregoing description, and all differences within the scope of equivalents thereof should be construed as being included in the present invention.
Claims (8)
(b) drying the germinated rice;
(c) separating the dried germinated rice into a rice husk fraction and a brown rice fraction using a rice germ, and then selecting a rice hull fraction; And
(d) solvent extraction of the selected rice husk fraction; ≪ / RTI >
Wherein the germination in step (a) is germinated by maintaining a humidity of 80 to 90% at a temperature of 35 to 40 DEG C for 1 to 6 days.
Wherein the solvent extraction in step (d) is carried out with a solvent selected from the group consisting of water, methanol, ethanol, hexane, butanol, ethyl acetate, chloroform and a mixed solvent thereof.
Wherein the solvent extraction of step (d) further comprises column purification using C18 resin.
Wherein the germinated rice hull extract has a glucose level in the blood by introducing glucose into the adipocytes.
Wherein the diabetic complication is diabetic retinopathy, diabetic cataract, diabetic neuropathy, diabetic neuropathy, diabetic vascular complication.
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| KR101193085B1 (en) | 2010-03-10 | 2012-10-19 | 강원도 양구군 | Composition for treating diabetes or diabete-induced complication containing an extract from Taraxacum platycarpum Dahlst |
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| KR101193085B1 (en) | 2010-03-10 | 2012-10-19 | 강원도 양구군 | Composition for treating diabetes or diabete-induced complication containing an extract from Taraxacum platycarpum Dahlst |
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