KR100842054B1 - Composition containing extracts of Glycyrrhizin Radix Praepara or compounds isolated therefrom for the Blood Glucose-Lowering effect - Google Patents

Abstract

The present invention relates to a composition for lowering blood sugar comprising a roasted licorice extract or a compound isolated therefrom, and more particularly to a composition for lowering blood sugar comprising a roasted licorice extract, a glycyrrhizin or glycyrrhetinic acid compound isolated therefrom. Baked licorice extract and glycyrrhetinic acid compounds isolated therefrom increase insulin secretion by glucose stimulation in isolated island of Langerhans, insulin receptor substrate-2 (IRS2), pancreatic homeobox-1 Induced production of pancreas duodenum homeobox-1 (PDX-1) and glucokinase mRNA to enhance beta cell function and viability. Lowers blood sugar by acting as a secretory and improves pancreatic beta cell function and viability Have geulrisirijin is increases the glucose uptake by insulin stimulation in an isolated islets compositions of the present invention may be useful in the prevention and treatment of diabetes.

Baked licorice extract, glycyrrhizin, glycyrrhetinic acid, glucose, insulin, hypoglycemic, diabetes, PPAR-γ

Description

Composition containing extracts of Glycyrrhizin Radix Praepara or compounds isolated therefrom for the Blood Glucose-Lowering effect}

Figure 1a is a graph showing the results of oral glucose tolerance test (OGTT) when treated with licorice and baked licorice.

Figure 1b is a graph showing the lower part of the blood glucose and insulin curves when treated with licorice and baked licorice.

FIG. 2 is a graph showing triglyceride accumulation when licorice extract, baked licorice extract, glycyrrhizin and glycyrrhetinic acid were treated during differentiation from 3T3-L1 fibroblasts to 3T3-L1 adipocytes.

Figure 3 is a graph showing the degree of glucose absorption when 3T3-L1 adipocytes were treated with licorice extract, baked licorice extract, glycyrrhizin and glycyrrhetinic acid, respectively, with insulin.

4 is a graph showing the activity of PPAR-γ when HEK293 cells were treated with licorice extract, roasted licorice extract, glycyrrhizin and glycyrrhetinic acid.

5 is a graph showing insulin secretion when glucose is administered to the isolated island of Langerhans and treated with licorice extract, roasted licorice extract, glycyrrhizin and glycyrrhetinic acid.

Figure 6a is a graph showing the expression of IRS2, PDX-1, glucokinase when treated with licorice extract, baked licorice extract, glycyrrhizin, glycyrrhetinic acid on isolated Langerhans Island.

Figure 6b is a graph showing the viability of beta cells when treated with licorice extract, baked licorice extract, glycyrrhizin, glycyrrhetinic acid on isolated Langerhans Island.

The present invention relates to a composition for lowering blood sugar comprising a roasted licorice extract or a compound separated therefrom, and more particularly, a composition for lowering blood sugar comprising an extract of roasted licorice, a glycyrrhizin or glycyrrhetinic acid compound isolated therefrom It is about.

Diabetes is a non-communicable chronic disease. Insulin secreted by the pancreatic beta cells (beta-cell) is insufficient or does not function properly, and glucose is not used as an energy source in the body. It is a disease that is excreted. Diabetes mellitus is largely dependent on the cause of the disease and how to treat the symptoms. Insulin dependent diabetes mellitus (IDDM) and non-insulin dependent diabetes mellitus (NIDDM) Classified as

Type 1 diabetes is a state in which the function of the pancreatic beta cells is reduced due to genetic causes, viral infections, etc., almost no secretion of insulin, and suddenly occurs in the 10s to 20s.

Type 2 diabetes is caused by family history, obesity, stress, eating errors, or drugs that antagonize insulin, etc., and appears well after the age of 40, also called adult diabetes. In fact, the majority of all diabetics are Type 2 diabetics. Type 2 diabetes can be defined as a disorder of heterologous metabolism due to abnormal insulin secretion of pancreatic beta cells and insulin resistance in peripheral cells such as liver, skeletal muscle, and adipocytes. Insulin resistance occurs mainly as a result of insulin resistance in human and laboratory animals and as a result of insulin resistance in hyperinsulinem (Kahn, SE et al. al ., Diabetologia 46: 3-19, 2003; Chiasson, JL et al ., Diabetes 53: S34-S38, 2004; Weir, GC et al ., Diabetes 53: S16-S21, 2004). In order to prevent or prolong diabetes progression, insulin is secreted sufficiently as a compensation for insulin resistance in peripheral cells, so anti-diabetic substances require insulin sensitivity in peripheral cells. Insulin secretion is required in pancreatic beta cells (Perseghin, G. et al., Diabetes) . Care 26: 2112-2118, 2003).

The scientific name of licorice is Glycyrrhiza uralensis Fisch, belonging to the Leguminosae family (Nakagawa, K. et. al ., Biol. Pharma . Bull 27: 1775-1778, 2004). Licorice has been used traditionally for a variety of treatments because of its unique efficacy since ancient Egyptian times. Licorice is known to be effective in preventing or ameliorating metabolic disorders such as diabetes, obesity, and hypertension in animal models (Nakagawa, K. et al., Biol . Pharma . Bull 27: 1775-1778, 2004; Mae , T. et al ., J. Nutri . 133: 3369-3377, 2003). Glycyrrhizin, the main ingredient in licorice and has been used in traditional Japanese herbal medicine for almost 4000 years, is a flavoring and sweetening agent (Nakagawa, K. et. al ., Biol . Pharma . Bull 27: 1775-1778, 2004). Takii et al. Have shown that glycyrazine has a clear inhibitory effect on postprandial blood glucose levels in normal and diabetic mice (Takii, H. et. al ., Biol . Pharm . Bull 24: 484-487, 2001). Other studies have also shown that licorice ethanol extract improves glucose homeostasis by activating the peroxisome proliferation-activated receptor-γ (PPAR-γ) in animal models (Nakagawa, K. et. al ., Biol . Pharma . Bull 27: 1775-1778, 2004; Kuroda, M. et al ., Bioorg . Med . Chem . Lett 13: 4267-4272, 2003; Mae, T. et al ., J. Nutri 133: 3369-3377, 2003). The activating mixture, however, was not glycyrrhizin but prenyflavonoids such as glycycoumarin, glycyrin, dehydroglyasperin C and dehydroglyasperin D. Thiazolidinedione-based drugs such as pioglitazone and rosiglitazone, potent PPAR-γ agonists, have been demonstrated to treat type 2 diabetes (Hammarstedt, A. et. al ., Prostaglandins Leukot. Essent . Fatty Acids 73: 65-75, 2005). Many studies of these drugs indicate that PPAR-γ agonists have various effects on metabolic disorders and other diseases such as inflammation and cancer (Jiang, C. et. al ., Nature ( Lond .) 391: 82-86, 1998; Berstein, LM et al ., Cancer Lett . 224: 203-212, 2005).

Roasted licorice (Glycyrrhizin Radix Praeparata), although constitutively different from licorice, is unknown about the hypoglycemic effect of baked licorice. Roasted licorice decreases glycyrrhizin, whereas glycyrrhetinic acid is significantly increased, and isoliquiritigenin is also slightly increased (Sung, MW et al ., Electrophoresis 25: 3434-3440, 2004). Metabolites of glycyrrhizin are glycyrrhetinic acid, 3-ketoglycyrrhetinic acid or 3-epiglycyrrhetinic acid ( Planta ) Med ., 48, 32-42, 1983; Seno H et al ., J. Trad . Med . 9, 1-13, 1992).

Therefore, the present inventors compared the characteristics of hypoglycemic action before and after baking licorice, baked licorice extract and glycyrrhetinic acid compounds isolated therefrom have better hypoglycemic action than licorice extract and increase insulin secretion, pancreatic beta Increasing the expression of IRS2, PDX-1 and glucokinase related to cell function, enhancing pancreatic beta cell viability, and glycyrrhizine compounds isolated from roasted licorice extract increased glucose uptake by insulin stimulation in isolated islets Confirming the completeness of the present invention was completed.

It is an object of the present invention to provide a composition for lowering blood glucose, which comprises a roasted licorice extract, glycyrrhizin or glycyrrhetinic acid compound isolated therefrom as an active ingredient.

In order to achieve the above object, the present invention provides a composition for lowering blood sugar, which has a roasted licorice extract as an active ingredient.

In another aspect, the present invention provides a composition for lowering blood sugar, comprising a glycyrrhizin or glycyrrhetinic acid compound isolated from the roasted licorice extract as an active ingredient.

In addition, the present invention provides a health food for preventing diabetes comprising the above-mentioned roasted licorice extract, glycyrrhizin or glycyrrhetinic acid compound isolated from the roasted licorice extract.

Hereinafter, the present invention will be described in more detail.

The present invention provides a composition for lowering blood sugar, which comprises an extract of Glycyrrhizin Radix Praeparata.

The present inventors evenly sliced licorice and licorice purchased in Gyeongdong market (Seoul, Korea), sprinkled evenly and sprinkled with water, and the baked licorice baked until the licorice becomes yellowish violet on fire when wet. Re-editing the library, Dong Pharmaceutical Co., Ltd., Yeogang Publishing Co., Seoul, 61-64, 1993) were carefully ground and extracted with alcohol or distilled water at 70 ° C. for 12 hours. The alcohol is preferably C ₁ to C ₄ lower alcohols, more preferably ethanol, the alcohol concentration is preferably 0 to 100%, more preferably 70%.

The extraction method may be any extraction method usually performed, preferably, hot water extraction at 40 ~ 120 ℃, or when using ethanol as the extraction solvent, it is left to extract for 1 day to 5 days at room temperature It is preferable to extract for 1 hour to 24 hours, more preferably for 12 hours at 70 ℃ temperature conditions. The extract obtained by the above method may be used as a baked licorice extract through filtration, purification, concentration using a filter paper or the like.

The powder produced by concentrating the extract was used by dissolving in 1 mg / ml of sterile dimethylsulfoxide (DMSO; Sigma Co., St. Louis, USA).

Baked licorice extract obtained by the above method improved insulin secretion by glucose stimulation of Px diabetic mice (see Experimental Example 1) as much as positive control group exendin-4 (exendin-4) (see FIG. 1). Exendin-4, used as a positive control, was recently approved by the US Food and Drug Administration as an insulin secretant. In pancreatic beta cells, exendin-4, like peptide-1, acts continuously like glucagon, enhancing the transcription, biosynthesis and secretion of insulin genes by glucose stimulation. This inhibits glucagon secretion and reduces gastric motility and emptying, resulting in satiety (Kieffer, TJ et. al ., Endocr . Rev. 20: 876-913, 1999; Drucker, DJ et al ., Gastroenterology 122: 531-544, 2002). Glucagon or exendin-4, such as peptide-1 in beta cells, together with insulin secretion activity enhances DNA synthesis, expression of PDX-1, differentiation from in vitro pancreatic cells to insulin producing cells. Baked licorice extract may therefore be used as an insulin secretant.

Increased glucose uptake by insulin stimulation is associated with activation of peroxisome proliferation-activated receptor-γ (PPAR-γ) with increased triglyceride accumulation in adipocytes (Perseghin, G. et. al ., Diabetes Care 26: 2112-2118, 2003) Baked licorice extract improves glucose uptake by insulin stimulation by activating PPAR-γ while improving adipocyte differentiation and triglyceride accumulation (see FIG. 2). 4). Rosiglitazone, a commercially widely used PPAR-γ agonist, was used as a positive control. Licorice (Glycyrrhizae Radix) extract and roasted licorice extract are known to differentiate fibroblasts 3T3-L1 into adipocytes and triglycerides. Glycyrrhizin and glycyrrhetinic acid, the main components of licorice and roasted licorice extract, did not improve differentiation and triglyceride accumulation. Thus, licorice extract and roasted licorice extract can be said to contain other PPAR-γ agonists in addition to glycyrrhizin and glycyrrhetinic acid.

Another method of improving glucose tolerance is insulin receptor substrate-2 (IRS2) and pancreas duodenum homeobox-1 in isolated Langerhans, which are involved in the survival and function of pancreatic beta cells. 1: PDX-1) and glucokinase mRNA levels are increased. Induction of IRS2 expression is known to be caused by the activation of Min6 cells and the cAMP response element-binding protein (CREB) in the island of Langerhans (Hennige, AM et. al ., J. Clin. Invest. 112: 1521-1532, 2003; Jhala, US et al ., Genes Dev . 17: 1575-1580, 2003; Park, S. et al . J. Biol . Chem . 281: 1159-1168, 2006). For example, exendin-4 from lizards enhances IRS2 induction through CREB phosphorylation. They also showed that IRS2 induction activates the Insulin-like Growth Factor-1 (INSF-1) / insulin signal cascade that increases expression of PDX-1 and glucokinase. Many studies show that the expression level of PDX-1 in the island of Langerhans is consistent with the proliferation of beta cells leading to improved increases (Hennige, AM et. al ., J. Clin . Invest . 112: 1521-1532, 2003; Park, S. et al . J. Biol . Chem . 281: 1159-1168, 2006; Choi, SB et al . Endocrinology . 146: 4786-4794, 2005). On the island of Langerhans, glucokinase acts as a glucose sensor that causes glucose to produce adenosine triphosphate (ATP) and close the KATP channel, effectively secreting insulin when serum glucose is elevated. Thus, the induction of IRS2, PDX-1, and glucokinase expression enhances the ability to regulate beta cell growth and insulin secretion by glucose stimulation.

Baked licorice extract was found to increase the function and viability of beta cells by inducing the expression of IRS2, PDX-1 and glucokinase (see Figure 6) to enhance the hypoglycemic action. However, licorice extract did not induce IRS2, PDX-1 and glucokinase expression, which may be associated with an increase in glycyrrhetinic acid during licorice baking.

Baked licorice extract as described above has a hypoglycemic function. Therefore, the roasted licorice extract of the present invention can be usefully used as a composition for lowering blood sugar.

In another aspect, the present invention provides a composition for lowering blood sugar, comprising a glycyrrhizin or glycyrrhetinic acid compound isolated from the roasted licorice extract as an active ingredient.

The inventors performed high performance liquid chromatography (HPLC) analysis on licorice extract and roasted licorice extract to separate glycyrrhizin and glycyrrhetinic acid.

The main components of licorice extract and roasted licorice extract are glycyrrhizin and glycyrrhetinic acid. HPLC analysis showed that glycyrrhizine was more abundant in licorice extract than roasted licorice extract and glycyrrhetinic acid was richer in licorice extract than licorice extract (Table 1 Reference). This means that while licorice is baked, glycyrrhizin decreases and glycyrrhetinic acid increases.

The glycyrrhetinic acid isolated by HPLC from the roasted licorice extract was not separated into 18 alpha-glyciretinic acid and 18 beta-glycitinic acid. Glycyretinic acid is difficult to separate by HPLC analysis and has isomers of 18 alpha-glyciretinic acid and 18beta-glyciretinic acid, which have similar biological activities (Sabbioni, C. et. al ., J. Chromatogr A, 1081: 65-71 , 2005; Squires, PE et al ., Cell Calcium 27: 287-296, 2000). Therefore, in the present invention, a natural glycyrrhetinic acid compound isolated from roasted licorice was used.

The glycyrrhizin or glycyrrhetinic acid compound of the present invention showed significant glucose uptake by insulin stimulation (see FIG. 3) and the glycyrrhetinic acid compound acted as an insulin secretion agent in isolated Langerhans (see FIG. 5). Since the mRNA levels of IRS2, PDX-1 and glucokinase related to survival and function were increased (see FIG. 6), it can be seen that the glycyrrhizin or glycyrrhetinic acid compounds of the present invention have a hypoglycemic function. Therefore, glycyrrhizin or glycyrrhetinic acid compound isolated from the roasted licorice extract can be usefully used in the composition for lowering blood sugar.

Baked licorice extract of the present invention, glycyrrhizin or glycyrrhetinic acid compound isolated from the oral administration to mice, as a result of toxicity test, 50% lethal dose (LD ₅₀ ) by oral administration toxicity test is at least 1,000 mg / kg It was judged that the above was a safe substance.

Therefore, the roasted licorice extract of the present invention, glycyrrhizin or glycyrrhetinic acid compound isolated therefrom exhibits an effective blood sugar lowering function and can be usefully used in a blood sugar lowering composition. The blood sugar lowering composition of the present invention can be usefully used for the treatment and prevention of diabetes mellitus, and the diabetes includes type 1 diabetes or type 2 diabetes.

Baked licorice extract of the present invention, glycyrrhizin or glycyrrhetinic acid compound isolated therefrom may further contain one or more active ingredients exhibiting the same or similar functions. For administration, it may be prepared further comprising one or more pharmaceutically acceptable carriers. Pharmaceutically acceptable carriers may be used in combination with saline, sterile water, Ringer's solution, buffered saline, dextrose solution, maltodextrin solution, glycerol, ethanol and one or more of these components, as necessary, including antioxidants, buffers, Other conventional additives such as bacteriostatic agents can be added. In addition, diluents, dispersants, surfactants, binders and lubricants may be additionally added to formulate injectable formulations, pills, capsules, granules or tablets such as aqueous solutions, suspensions, emulsions and the like. Furthermore, it may be preferably formulated according to each disease or component by a suitable method in the art or using a method disclosed in Remington's Pharmaceutical Science (Mack Publishing Company, Easton PA, 18th, 1990).

The compositions of the present invention may be administered parenterally (eg, intravenously, subcutaneously, intraperitoneally or topically) or orally, depending on the desired method, and the dosage may be based on the weight, age, sex, health status, The range varies depending on the diet, the time of administration, the method of administration, the rate of excretion and the severity of the disease. Baked licorice extract according to the present invention, the daily dosage of the glycyrrhizin or glycyrrhetinic acid compound isolated therefrom is 10 to 2,000 mg / kg, preferably 50 to 500 mg / kg, administered once to several times a day More preferably.

In addition, the baked licorice extract of the present invention, it provides a health food for preventing diabetes comprising a glycyrrhizin or glycyrrhetinic acid compound isolated therefrom as an active ingredient.

When the roasted licorice extract of the present invention, the glycyrrhizin or glycyrrhetinic acid compound isolated therefrom, is used as a food additive, the extract can be added as it is or used with other food or food ingredients, and can be suitably used according to conventional methods. Can be. The amount of the active ingredient is generally used in the preparation of food or beverages. The roasted licorice extract of the present invention, the glycyrrhizin or glycyrrhetinic acid compound isolated therefrom are 0.01 to 10 parts by weight, preferably 0.05 to 1 weight based on the raw materials. It is added in negative amounts. However, in the case of long-term intake for health and hygiene or health control purposes, the amount may be below the above range, and the active ingredient may be used in an amount above the above range because there is no problem in terms of safety.

There is no particular limitation on the kind of food. Examples of the food to which the substance can be added include dairy products including meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums, ice cream, various soups, drinks, tea, drinks, Alcoholic beverages and vitamin complexes, etc., includes all of the health food in the conventional sense.

The health beverage composition of the present invention may contain various flavors, natural carbohydrates, and the like as additional components, as in general beverages. The above-mentioned natural carbohydrates are glucose, monosaccharides such as fructose, disaccharides such as maltose and sucrose, and polysaccharides such as dextrin and cyclodextrin, sugar alcohols such as xylitol, sorbitol and erythritol. As the sweetening agent, natural sweetening agents such as tautin and stevia extract, synthetic sweetening agents such as saccharin and aspartame, and the like can be used. The ratio of the natural carbohydrate is generally about 0.01 to 0.04 g, preferably about 0.02 to 0.03 g, per 100 ml of the roasted licorice extract of the present invention, the glycyrrhizin or glycyrrhetinic acid compound isolated therefrom.

In addition to the above-described roasted licorice extract of the present invention, glycyrrhizin or glycyrrhetinic acid compounds isolated therefrom are various nutrients, vitamins, electrolytes, flavoring agents, coloring agents, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloids Thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated drinks and the like. In addition, to the flesh for the production of natural fruit juices, fruit juice beverages and vegetable beverages can be added to the licorice extract, glycyrrhizin or glycyrrhetinic acid compounds isolated therefrom. These components can be used independently or in combination. The ratio of such additives is not critical, but is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the roasted licorice extract of the present invention, glycyrrhizin or glycyrrhetinic acid compound isolated therefrom.

Hereinafter, preferred examples, experimental examples, and formulation examples are provided to aid the understanding of the present invention. However, the following Examples, Experimental Examples and Formulation Examples are provided only to more easily understand the present invention, but the contents of the present invention are not limited by Examples, Experimental Examples, and Formulation Examples.

< Example  1> Baked licorice  Preparation of Extract

Glycyrrhizae Radix (Glycyrrhizae Radix) purchased at Gyeongdong Market (Seoul, South Korea) and evenly sliced licorice purchased and sprinkled with water, and when the surface is wet with enough water, baked licorice (Glycyrrhizin) until the licorice is yellowish on fire Radix Praeparata, Re-Edition of Synonym Data, Copper Pharmaceuticals Co., Yeogang Publishing Co., Seoul, 61-64, 1993) was carefully ground and extracted with 70% ethanol (EtOH) at 70 ° C for 12 hours. The extracts were each filtered with a 0.4 um filter and concentrated by vacuum deposition and lysophilization. The concentrated powder was used by dissolving in sterile dimethyl sulfoxide (DMSO; Sigma Co., St. Louis, MO) 1 mg / mL.

Experiment using the ethanol extract of the baked licorice according to the method of Experimental Example 1, because it was excellent in glucose tolerance was used in the following examples.

< Example  2> Licorice Extract Baked Licorice  Comparison of Main Components of Extracts

The present inventors performed HPLC analysis on the licorice extract and roasted licorice extract. Glycyrrhizin and glycyrrhetinic acid were diluted in acetic acid at a rate of 1 ml min-1, with a gradient of 10% acetic acid and acetonitrile (60:40, v: v). C18 separation tubes (4.6X150 mm, Waters, USA) were separated. The peak was found at 245 nm wavelength with a UV detector. The concentrations of glycyrrhizin and glycyrrhetinic acid were calculated using their standards purchased from Sigma and Wako Pure Chemical in Osaka, Japan.

HPLC analysis of the licorice extract confirmed that it was rich in glycyrrhizin (7.6 g / 100 g extraction) and low in glycyrrhetinic acid (1.0 g / 100 g extraction) (Table 1). While licorice was baked, glycyrrhizin was reduced to 49% and glycyrrhetinic acid was increased by 4.76 times. 100 g of roasted licorice contained 3.9 g of glycyrrhizin and 4.9 g of glycyrrhetinic acid (Table 1).

Licorice extract Baked Licorice  Of extract Glycyrrhizin Glycyrrhetinic acid  contain( mg / g) Licorice extract Roasted Licorice Extract Glycyrrhizin 76.3 ± 5.3 38.9 ± 4.1 Glycyrrhetinic acid 10.2 ± 1.7 48.6 ± 3.3

The above-mentioned isomers of glycyrrhetinic acid, 18 alpha-glyciretin acid and 18 beta-glycitinic acid, were not separated by HPLC analysis. These isomers have similar biological activity (Sabbioni, C. et al., J. Chromatogr A, 1081: 65-71,2005; Squires, PE et al ., Cell Calcium 27: 287-296, 2000) In the present invention, a mixture (1: 1) of 18 alpha-glyciretinic acid and 18beta-glyciletinic acid was used.

< Experimental Example  1> Baked Licorice  Determination of Hypoglycemic Effects of Extracts Raw vegetables ( in vivo ) Experiment

The inventors performed the following experiment to determine the glucose tolerance of the baked licorice extract.

Six-week-old C57BL6J male mice were purchased from Daehan Biolink (Seoul, Korea), and were bred in an animal room at 22 ± 3 ° C., 55 ± 10% humidity, and 12 L / 12D illumination. All surgical experimental procedures were performed under the guidelines of the Animal Care and Use Review Committe of Hoseo University, Korea. After breeding mice for two weeks, 55% pancreatic resection (Px mice) was confirmed by surgically removing the entire spleen portion of the pancreas and weighing the remaining portion and removed weight (Lee, CS et al. al . Diabetes 55: 269-272, 2006). Subsequently, the pancreas excised mice (partial pancreatectomized (Px) mice; hereinafter referred to as “Px mice”) exhibited type 2 diabetes. Produced diabetic Px mice were randomly divided into control group (fibrin treatment) and positive control group (exendin-4) treatment or experimental group (Licorice extract or baked licorice extract). The group was orally administered with licorice extract (1 mg / 1 kg), baked licorice extract (1 mg / 1 kg) or fibrin (1 mg / 1 kg) daily for 8 weeks. Positive control exendin-4 (150 pmol / 1 kg) was injected subcutaneously every 12 hours.

As a result, After confirming that the final body weight of Px mice administered fibrin, licorice extract, roasted licorice extract, or exendin-4 was not significantly different, fasting for three weeks (repeat fasting for 16 hours) and serum after meal and fasting Glucose and serum insulin concentrations were measured (Table 2).

Serum glucose and serum insulin levels were measured by glucose oxidase method (Glucose Analyzer II, Beckman, Fullerton, Calif.) And radioimmunoassay kit (Linco Research, St. Charles, MO), respectively.

After fasting for 16 hours, serum glucose levels were lowered without changes in serum insulin levels. Postprandial serum glucose concentrations were significantly decreased in the group treated with licorice extract or baked licorice extract as much as the group treated with exendin-4 than the control group treated with fibrin. However, after eating, serum insulin concentrations increased to the extent of the group receiving exendin-4 only upon administration of Baked Licorice extract.

Body weight and serum glucose and insulin after the experiment Control Licorice extract Baked Licorice  extract Exendin -4 Weight (g) 31.6 ± 3.8 30.2 ± 3.5 33.1 ± 3.7 30.0 ± 3.4 During fasting Serum glucose ( mM ) 8.4 ± 0.8 ^a 7.5 ± 0.9 ^b 6.7 ± 0.9 ^b 6.2 ± 0.9 ^{b *} After meal Serum glucose ( mM ) 20.6 ± 3.1 ^a 15.2 ± 2.8 ^b 14.2 ± 2.5 ^b 12.6 ± 1.9 ^{b *} During fasting Serum insulin ( nM ) 0.26 ± 0.04 0.27 ± 0.04 0.28 ± 0.05 0.29 ± 0.05 After meal Serum insulin ( nM ) 1.01 ± 0.13 ^a 1.03 ± 0.17 ^a 1.29 ± 0.25 ^b 1.38 ± 0.24 ^{b *}

¹ Mean ± standard deviation.

^* Is significantly different from other groups with P <0.05.

The ^{a, b} values by Tukey's test are P <0.05, Show a difference.

All results are expressed as mean ± standard deviation (SD). Statistical analysis was performed using SAS statistical analysis program. One-way analyses of variance (ANOVA) was used to determine the effects of licorice extract, roasted licorice extract, glycyrrhizin and glycyrrhetinic acid. Various comparisons of groups treated at various doses with the Tukey assay were performed. The significance test of all statistical treatments was α = 0.05. Statistical analysis in all the following Experimental Examples were as described above.

In addition, Px mice that were fasted for 3 weeks (repeated fasting for 16 hours) were orally administered 2 g of glucose per kg of body weight to perform an oral glucose tolerance test (OGTT). . Thereafter, after 0, 10, 20, 30, 45, 60, 90 and 120 minutes, blood was collected from the tail and blood glucose levels were measured (FIG. 1A), and the area of the lower portion of the curve was calculated (FIG. 1B). ^* Was significantly different from other groups with P <0.05, and ^{a, b, c} of the rods by Tukey test The value is P <0.05, which is remarkable Showed a difference.

Licorice extract or roasted licorice extract showed an improvement in glucose tolerance in OGTT. Licorice extract did not decrease the peak concentration of serum glucose during the OGTT experiment compared to the control. However, from 30 minutes to 120 minutes serum glucose concentrations were drastically reduced (FIG. 1A), indicating an improvement in insulin action. Unlike licorice extract, baked licorice extract and exendin-4 decreased the peak concentration of serum glucose, indicating an increase in insulin secretion. Serum glucose concentration was decreased from 30 minutes to 120 minutes in the baked licorice extract or exendin-4 treated mice group in the same manner as the mice treated with licorice extract (Fig. 1a). However, the lower area of the serum insulin curve was higher in the mouse group to which the roasted licorice extract was administered than the other group (FIG. 1B).

< Experimental Example  2> Baked Licorice  Extracts Glycyrrhizin  or Glycyrrhetinic acid  Differentiation into adipocytes and triglycerides ( triglyceride Investigating the effect on accumulation

Baked licorice extract of the present invention, glycyrrhizin or glycyrrhetinic acid compounds isolated from the following experiments to determine the effect on the differentiation and triglyceride (triglyceride) accumulation in adipocytes.

<2-1> Cell Culture

The 3T3-L1 cells used in the experiment were purchased from the American Cell Line Bank, and added DMEM with 1% fetal bovine serum (FBS), gentamycine (100 units / ml) and streptomycin (streptomycin (100 µg / ml)). (Dulbecco's modifiedEagle's medium) culture.

3T3-L1 fibroblasts were washed with phosphate buffer saline at 3 days intervals in culture, and then 1 ml of 0.25% trypsin-EDTA solution per 50 ml flask was treated for 1 minute at room temperature, followed by trypsin. The solution was discarded and stored at 37 ° C. for 5 minutes to detach and passage cells. The detached cells were suspended in 10 ml of DMEM medium added with 10% FBS and then transferred to a new culture vessel (50 ml culture flask) with a CO ₂ incubator (37 ° C., 5% CO) at a split ratio of 1:20. ₂ ) were incubated.

<2-2> Differentiation into Adipocytes Triglyceride  Investigate the impact on accumulation

3T3-L1 fibroblasts were incubated until completely confluent in the same manner as the passage. Two days after the bottom of the culture vessel was completely filled, 0.25 μM of derivatized dexamethasone (dexamethasone) was added and cultured for 4 days, followed by DMSO (negative control), rosiglitazone (positive control, 2 uM), and licorice extract (50 ug / mL). Roasted licorice extract (50 ug / mL), glycyrrhizin (5 uM) and glycyrrhetinic acid (5 uM) were added. In addition, 6 days or more DMSO, rosiglitazone (5 uM), licorice extract (50 ug / mL), baked licorice extract (50 ug / mL), glycyrrhizin (5 uM) and glycyrrhetinic acid (5 uM) ) Was added. Until the cells were incubated, DMSO, extracts (or licorice extract or roasted licorice extract) or compounds (glycirizine or glycyrrhetinic acid) were also added each time the medium was changed. After 6 days of incubation with extracts or compounds, cells were obtained with lysis buffer without glycerol and triglycerides. Glycerol and triglyceride concentrations of the cells were measured by Trinder kit (Youngdong Pharmaceutical Co., Seoul). ^* Was significantly different from other groups with P <0.05, and the ^{a, b} values of the rods by Tukey's test were P <0.05 with P <0.05. ^† P <0.05, significantly different from the control group (DMSO administration).

Licorice Extract and Roasted Licorice Extract of Triglycerides and Differentiation of 3T3-L1 Fibroblasts into Adipocytes Accumulation was increased (FIG. 2). However, glycyrrhizin and glycyrrhetinic acid did not improve the differentiation of adipocytes and triglyceride accumulation.

< Experimental Example  3> Baked Licorice  Extracts Glycyrrhizin  or Glycyrrhetinic acid Into fat cells  Glucose absorption probe

To determine glucose uptake by insulin stimulation in adipocytes, 3T3-L1 fibroblasts of Experimental Example 2 were 2-deoxy in 3T3-L1 adipocytes between 9 and 10 days after the differentiation into adipocytes first. -D- [3H] glucose uptake was measured (Sung, MW et al ., Electrophoresis 25: 3434-3440, 2004; Shimaya, A. et al ., J. Biol . Chem . 279: 55277-55282, 2004). ^* Was significantly different from other groups with P <0.05, and the ^{a, b, c} values of the bars by Tukey's test were P <0.05 with P <0.05 Showed a difference.

Insulin dependent mode glucose uptake in 3T3-L1 adipocytes was stimulated by insulin up to 10 nM. As a result of administration of 0.2 nM and 10 nM insulin, glucose uptake was 1.6 + 0.3 fold and 6.6 + 0.8 fold higher than control (non-insulin), respectively. Insulin administration above 10 nM no longer increased glucose uptake, so 10 nM was used as the maximum glucose uptake (FIG. 3).

In the absence of insulin, glucose uptake was not changed by licorice extract, roasted licorice extract, or glycyrrhizin and glycyrrhetinic acid. When licorice extract and roasted licorice extract were previously administered to 3T3-L1 adipocytes before being stimulated with 0.2 nM insulin, glucose uptake by insulin stimulation was moderately increased in a dose dependent manner by licorice extract and roasted licorice extract. Baked licorice extract also increased the absorption more than licorice extract (Fig. 3). Glycirizine and glycyrrhetinic acid, the main components of licorice and baked licorice, also increased glucose uptake by insulin stimulation by 80% of 10 nM insulin administration. Therefore, it was found that the roasted licorice extract of the present invention, glycyrrhizin or glycyrrhetinic acid compound isolated therefrom increased glucose uptake by insulin stimulation.

< Experimental Example  4> Baked Licorice  Of extract PPAR -γ As agonist  Action investigation

Baked licorice extract according to the present invention, glycyrrhizin or glycyrrhetinic acid compounds isolated from the following experiments to determine whether it acts as an agonist of peroxisome proliferation-activated receptor-γ (PPAR-γ).

Human fetal kidney (HEK) 293 cells were introduced into 96-well plates for 24 hours in 1 × 10 4 cell well-1 prior to transformation. According to the manufacturer's protocol, PPRE-luciferase (firefly pGL3-DR-1-luciferase; 0.12 ug DNA / well), pSV-SPORT-PPAR-γ expression vector (Lipofectamine PLUS reagent (Invitrogen, USA)) Cells were instantaneously transformed with 0.12 ug DNA / well) and pSV-SPORT-retinoid X receptor (RXR) -vector (0.08 ug DNA / well). The efficiency of transformation was determined using a renilla phRTK vector (Promega, USA) of 10 ng DNA per well. 42 hours after transformation, cells were treated with DMEM (Dulbecco's modified Eagle's medium) containing 0.1% BSA and without serum for 6 hours, and then licorice extract (0, 0.5, 5, 50 ug / mL) for 24 hours. Roasted licorice extract (0, 0.5, 5, 50 ug / mL), glycyrrhizin (0, 0.05, 0.5, 5 uM) and glycyrrhetinic acid (0, 0.05, 0.5, 5 uM) and positive control rosiglitazone (0 , 0.02, 0.2, 2 uM). After incubation, the cells were washed three times with phosphate buffer solution and lysed in 1 × floating solution (Promega, USA). Cell lysates were analyzed for firefly (PPRE-luciferase) activity and renilla luciferase activity using the Dual-Luciferase Reporter Assay System (Promega, USA). Luciferase activity was measured by a luminometer by a dual luciferase assay. For analysis, the ratio of Firefly luciferase activity to Renilla luciferase activity was calculated (Sellers, WR et al ., Genes Dev . 12: 95-106, 1998). ^* Was significantly different from other groups with P <0.05, and the ^{a, b, c, d} values of rods by Tukey's test were P <0.05 with P <0.05 Showed a difference.

Rosiglitazone (positive control), a widely used PPAR-γ agonist, increased luciferase activity by 4.5 + 0.6 times than DMSO administration (P <0.001). In contrast, licorice extract and roasted licorice extract improved luciferase activity by 2.8 + 0.4 and 3.3 + 0.4, respectively (Figure 4). However, glycyrrhizin and glycyrrhetinic acid did not increase luciferase activity. Thus, licorice extract and roasted licorice extract can be said to contain other PPAR-γ agonists in addition to glycyrrhizin and glycyrrhetinic acid. The results showed that the roasted licorice extract improved glucose uptake by insulin stimulation by activating PPAR-γ.

< Experimental Example  5> Baked Licorice Extract Glycyrrhizin  or Glycyrrhetinic acid  Investigation of Insulin Secretion by Glucose Stimulation in Langerhans Island.

Baked licorice extract according to the present invention, glycyrrhizin or glycyrrhetinic acid compound isolated from the following experiment was performed to see if it acts as an insulin secreting agent.

The pancreatic islets of male mice were isolated by collagen degrading factors (Hennige, AM et. al ., J. Clin . Invest . 112: 1521-1532, 2003) High concentrations (20 mM) containing fetal bovine serum, 50 uM β-mercaptoethanol, penicillin, and streptomycin in cattle to remove and regenerate acina cells ) Was incubated with CO ₂ incubator (37 ° C., 5% CO ₂ ) for 10 hours (v / v) for 24 hours. Twenty Langerhans islands were first incubated for 16 hours in low concentration (2 mM) glucose DMEM medium containing bovine serum albumin (5 mg / mL). Add Langerhans Island to glucose Krebs-Ringe solution (2 mM and 20 mM) containing 20 mM Hepes (5 mg / mL) and bovine serum albumin (5 mg / mL) at pH 7.4, and add DMSO, licorice extract, roasted licorice extract, glycyrrhizin and glyci Retinic acid was treated for 30 minutes each. Insulin concentrations of each medium were measured by radioimmunoassay (Linco Research, St. Charles, MO) in low glucose medium (2 mM) and high glucose medium (20 mM). Exendin-4 (2.5 nM) was used as a positive control. ^* Was significantly different from other groups with P <0.05, and the ^{a, b} values of the rods by Tukey's test were P <0.05 with P <0.05. ^† P <0.05, significantly different from the control group (DMSO administration).

Insulin secretion in the Langerhans islets isolated from mice increased 4.8 + 0.6 fold in high glucose (20 mM) DMEM medium than in low glucose (2 mM) DMEM medium. Licorice extract, roasted licorice extract, glycyrrhizin, and glycyrrhetinic acid did not alter insulin secretion in low glucose medium, but in high glucose medium, roasted licorice extract or glycyrrhetinic acid showed significantly higher insulin secretion than DMSO-administered groups ( 5). Unlike baked licorice extract and glycyrrhetinic acid in high concentration of glucose medium, licorice extract and glycyrrhizin did not improve insulin secretion by glucose stimulation (FIG. 5). Therefore, the roasted licorice extract or glycyrrhetinic acid compound isolated therefrom acts as an insulin secreting agent.

< Experimental Example  6> Baked Licorice  Extracts Glycyrrhizin  or Glycyrrhetinic acid  Investigation of improvement of pancreatic beta cell function and viability

Baked licorice extract of the present invention, glycerin or glycyrrhetinic acid compounds isolated from the pancreatic beta cells to investigate the relationship between the function and viability of insulin receptor substrate-2 (IRS2), pancreas MRNA expression of homeobox-1 (PDX-1) and glucokinase and glucokinase were examined.

The regenerated Langerhans island was treated with DMSO, licorice extract, roasted licorice extract, glycyrrhizin and glycyrrhetinic acid for 8 hours. Total RNA was isolated from the island of Langerhans treated with control or trizol (GIBCO BRL, Life Technologies, Inc., Grand Island, New York). CDNA was synthesized with a RETRO script kit (Ambion Inc., Austin, Texas) using oligo dT. And quantitative Realtime PCR [4 minutes at 94 ° C., 30 minutes at 94 ° C., 55 minutes] using iCycler PCR instrument (Bio-Rad Laboratories, Hercules, California) and QuantiTect SYBR Green PCR kit (Qiagen Inc., Valencia, California). 30 seconds at &lt; RTI ID = 0.0 &gt;

PCR reaction was performed according to the manufacturer's method. Primers of IRS2, PDX-1, glucokinase and cyclophillin genes of mice are shown in Table 3 below.

IRS2 , PDX -One, Glucokinase  And Cyclophilin  Gene primer   IRS2  Forward direction   5'-CATCGACTTCCTGTCCCATCA-3 '  SEQ ID NO: 1  Reverse   5'-CCCATCCTCAAGGTCAAAGG-3 '  SEQ ID NO: 2   PDX-1  Forward direction   5'-AGGAAAACAAGAGGACCCGTACT-3 '  SEQ ID NO: 3  Reverse   5'-CGGGAGATGTATTTGTTAAATAAGAATTC-3 '  SEQ ID NO: 4   Glucokinase  Forward direction   5'-CCTGAGGCTGGAGACCCATGA-3 '  SEQ ID NO: 5  Reverse   5'-TGGGGTGGAGCGCACGTA-3 '  SEQ ID NO: 6   Cyclophilin  Forward direction   5'-CAGACGCCACTGTCGCTTT-3 '  SEQ ID NO: 7  Reverse   5'-TGTCTTTGGAACTTTGTCTGCAA-3 '  SEQ ID NO: 8

Quantitative analysis was performed by calculating the relative ratios of the internal control cyclophilin and the gene PCR product of interest. Cell viability was measured at 0, 6, 12, 24, 36 and 48 hours with the WSE-1 measuring instrument (Roche). This experiment was repeated four times. ^* Was significantly different from other groups with P <0.05, and the ^{a, b} values of the rods by Tukey's test were P <0.05 with P <0.05. ^† P <0.05, significantly different from the control group (DMSO administration).

MRNAs of IRS2, PDX-1 and glucokinase were determined by incubating the isolated Langerhans islands with licorice extract, roasted licorice extract, glycyrrhizin or glycyrrhetinic acid for 8 hours. In real-time PCR, roasted licorice extract and glycyrrhetinic acid increased the expression of IRS2 and PDX-1 (FIG. 6A). Baked licorice extract and glycyrrhetinic acid increased glucokinase according to the results of insulin secretion by glucose stimulation, but baked licorice extract was more inducible than glycyrrhetinic acid.

Cell viability was decreased over time when DMSO was administered, but baked licorice extract and glycyrrhetinic acid increased cell viability (FIG. 6B). However, licorice extract and glycyrrhizin did not inhibit cell death. As a result, Baked Licorice extract and glycyrrhetinic acid showed the possibility of acting as an insulin secretant like exendin-4 by enhancing pancreatic beta cell function and viability.

< Experimental Example  7> Baked Licorice  extract, Glycyrrhizin  or Glycyrrhetinic acid  Acute Toxicity Test of Compounds

In order to determine the acute toxicity for the baked licorice extract of the present invention, glycyrrhizin or glycyrrhetinic acid compound isolated therefrom, the following experiment was performed.

SPF (specific pathogens free) ICR mice were divided into 4 groups (3 males and 3 females / experimental group) at 4 weeks of age, temperature 22 ± 3 ℃, humidity 55 ± 10%, illumination 12L / 12D It was bred in a condition animal room. Mice were allowed to acclimate for about a week before being used in the experiment. Feed for experimental animals (for mice and rats, Dyets, USA) and negative water were supplied after sterilization and free intake.

Baked licorice extract prepared in Example, glycyrrhizin or glycyrrhetinic acid compound isolated therefrom was prepared at a concentration of 50 mg / ml in 0.5% tween 80, and then 0.04 ml (100 mg / kg) per 20 g of mouse body weight. ), 0.2 ml (500 mg / kg) and 0.4 ml (1,000 mg / kg), orally. Samples were administered orally once and observed for side effects or lethality for 7 days after administration. That is, on the day of administration, changes in general symptoms and the presence or absence of dead animals were observed at least one hour, four hours, eight hours, twelve hours after the administration, and one or more mornings and afternoons every day from the next day until the seventh day. In addition, on the 7th day of administration, animals were killed and dissected, and the internal organs were visually examined. The change in body weight was measured at the interval of 1 day from the day of administration, and the weight loss phenomenon of the animal by the baked licorice extract, glycyrrhizin or glycyrrhetinic acid compound isolated therefrom was observed.

As a result, no significant clinical symptoms were observed in all the mice treated with the sample, no mice died, and no toxicity change was observed in weight change, blood test, blood biochemistry test, autopsy findings, etc.

Therefore, the roasted licorice extract according to the present invention, glycyrrhizin or glycyrrhetinic acid compound isolated therefrom did not show toxicological changes up to 1,000 mg / kg in all mice, and the minimum lethal dose (LD ₅₀ ) was 1,000 mg / kg or more. It was considered safe.

Examples of preparations for the compositions of the present invention are illustrated below.

< Formulation example  1> Preparation of Pharmaceutical Formulations

<1-1> Powder  Produce

2 g of roasted licorice extract, glycyrrhizin or glycyrrhetinic acid compound

1 g lactose

After mixing the above components, the airtight cloth was filled to prepare a powder.

<1-2> Preparation of Tablet

Roasted Licorice Extract, Glycirizine, or Glycyretinic Acid Compound 100 mg

Corn starch 100 mg

Lactose 100 mg

2 mg magnesium stearate

After mixing the above components, tablets were prepared by tableting according to a conventional method for producing tablets.

<1-3> Preparation of Capsule

Roasted Licorice Extract, Glycirizine, or Glycyretinic Acid Compound 100 mg

Corn starch 100 mg

Lactose 100 mg

2 mg magnesium stearate

After mixing the above components, the capsule was prepared by filling in gelatin capsules according to the conventional method for producing a capsule.

<1-4> Preparation of Injection Solution

Roasted Licorice Extract, Glycirizine or Glycyretinic Acid Compound 10 μg / ml

Dilute hydrochloric acid BP until pH 3.5

Injectable sodium chloride BP up to 1 ml

Dissolve the roasted licorice extract, glycyrrhizin or glycyrrhetinic acid compound according to the invention in an appropriate volume of sodium chloride BP for injection, adjust the pH of the resulting solution to pH 3.5 with dilute hydrochloric acid BP and inject the sodium chloride BP for injection. Volume to adjust and thoroughly mix. The solution was filled into a 5 ml Type I ampoule made of clear glass, encapsulated under an upper grid of air by dissolving the glass, and sterilized by autoclaving at 120 ° C. for at least 15 minutes to prepare an injection solution.

< Formulation example  2> Manufacture of food

Food products containing roasted licorice extract, glycyrrhizin or glycyrrhetinic acid compound were prepared as follows.

<2-1> Preparation of Flour Food

Baked licorice extract, glycyrrhizin or glycyrrhetinic acid compound each 0.1 to 10.0 parts by weight is added to the flour, using the mixture to prepare bread, cakes, cookies, crackers and noodles in a conventional manner to prepare foods for health promotion It was.

<2-2> soup  And juicy ( gravies Manufacturing

Baked licorice extract, glycyrrhizin or glycyrrhetinic acid compound was added 0.1 to 1.0 parts by weight to the soup and broth, respectively, to prepare a health-producing meat products, noodles soup and gravy in a conventional manner.

<2-3> ground Ground beef  Produce

10 parts by weight of the roasted licorice extract, glycyrrhizin or glycyrrhetinic acid compound was added to ground beef to prepare ground beef for health promotion in a conventional manner.

<2-4> dairy products ( dairy products Manufacturing

Baked licorice extract, glycyrrhizin or glycyrrhetinic acid compound each 0.1 to 1.0 parts by weight was added to the milk, using the milk to prepare a variety of dairy products such as butter and ice cream in a conventional manner.

<2-5> Linear  Produce

Brown rice, barley, glutinous rice, and yulmu were alphad by a known method, and then dried and roasted to prepare a powder having a particle size of 60 mesh.

Black beans, black sesame seeds, and perilla were also steamed and dried by a known method, and then ground to a powder having a particle size of 60 mesh.

Baked licorice extract, glycyrrhizin or glycyrrhetinic acid compound of the present invention was decompressed and concentrated in a vacuum concentrator, dried by spraying and drying with a hot air dryer, and then pulverized with a particle size of 60 mesh to obtain a dry powder.

The grains, seeds and the dried licorice extract, glycyrrhizin or glycyrrhetinic acid compound according to the present invention prepared in the above formulated in the following ratio to prepare a conventional method.

Cereals (30 parts by weight brown rice, 15 parts by weight brittle, 20 parts by weight of barley),

Seeds (7 parts by weight perilla, 8 parts by weight black beans, 7 parts by weight black sesame seeds),

Baked licorice extract, dry powder of glycyrrhizin or glycyrrhetinic acid compound (1 part by weight),

Ganoderma lucidum (0.5 parts by weight),

Foxglove (0.5 part by weight)

< Formulation example  3> Manufacture of beverage

A beverage comprising a roasted licorice extract, glycyrrhizin or glycyrrhetinic acid compound was prepared as follows.

<3-1> Health drink  Produce

Substances such as liquid fructose (0.5%), oligosaccharide (2%), sugar (2%), salt (0.5%), water (75%) and baked licorice extract, glycyrrhizin or glycyrrhetinic acid compounds After homogenizing and homogeneously blending, it was packaged in small packaging containers such as glass bottles and plastic bottles to prepare healthy drinks.

<3-2> Vegetable juice  Produce

0.5 g of the roasted licorice extract, glycyrrhizin or glycyrrhetinic acid compound was added to 1,000 ml of a vegetable juice such as tomato or carrot to prepare vegetable juice for health promotion in a conventional manner.

<3-3> Fruit juice  Produce

0.1 g of baked licorice extract, glycyrrhizin or glycyrrhetinic acid compound was added to 1,000 ml of fruit such as apples or grapes to prepare fruit juice for health promotion in a conventional manner.

Roasted licorice extract of the present invention, the glycyrrhetinic acid compound isolated therefrom acts as an insulin secreting agent in the island of Langerhans and has a hypoglycemic function by enhancing the survival and function of pancreatic beta cells, and the glycyrrhizine isolated from the roasted licorice extract is used for insulin stimulation. Increased glucose uptake and did not show acute toxicity in mice. Therefore, the composition of the present invention can be usefully used as a composition for lowering blood sugar.

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Claims (12)

A composition for lowering blood sugar, which contains roasted licorice extract as an active ingredient. The composition of claim 1, wherein the roasted licorice extract is extracted with water, a lower alcohol of C ₁ to C ₄ or a mixture thereof. delete 3. The composition for lowering blood sugar according to claim 2, wherein the lower alcohol is ethanol. The composition for lowering blood sugar according to claim 2, wherein the roasted licorice extract is extracted at a condition of 1 to 24 hours at 50 to 90 ° C. The composition of claim 1, wherein the roasted licorice extract increases the activity of peroxisome proliferation-activated receptor-γ (PPAR-γ). A blood glucose lowering composition comprising a glycyrrhetinic acid compound as an active ingredient. 8. The composition of claim 7, wherein the glycyrrhetinic acid compound is isolated from the roasted licorice extract. delete The composition for lowering blood sugar according to any one of claims 1, 2, and 4 to 8, wherein the composition is used for the prevention and treatment of diabetes. 11. The composition for lowering blood sugar according to claim 10, wherein the diabetes is type 1 diabetes or type 2 diabetes. Claim 1, 2 and 4 to claim 8 of any one diabetic health foods for improving the blood sugar comprising the composition for lowering blood sugar.

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