WO2018230931A2 - Composition for preventing or treating metabolic diseases - Google Patents

Abstract

The present invention relates to a composition for preventing or treating metabolic diseases and, more particularly, to a pharmaceutical composition and a food composition for preventing, alleviating, or treating metabolic diseases, comprising an extract of Gentianae Macrophyllae Radix as an active ingredient. The method of the present invention promotes AMPK activity; inhibits fat accumulation, fat granulation, lipogenesis transcription factor SREBP-1c activity, and lipogenic enzyme expression; and reduces body weight, fat tissue and liver tissue weight, blood glucose, triglycerides, and cholesterol content, and thus may be effectively used for preventing or treating metabolic diseases such as obesity, diabetes, hypertriglyceridemia, hypercholesterolemia, and the like.

Description

 【Specification】

[Name of Invention] Metabolic Disease Prevention or Charity Composition

TECHNICAL FIELD This application claims priority to Korean Patent Application No. 10-2017-0074193, filed on June 13, 2017, the entire disclosure of which is incorporated herein by reference.

The present invention relates to a composition for preventing or treating metabolic diseases, and more specifically, metabolic diseases such as obesity, diabetes mellitus, hypertriglyceridemia, hypercholesterolemia, etc., which include the extract of Gentian (Gent ianae Macrophyl lae Radix) as an active ingredient. It relates to a pharmaceutical composition and food composition for preventing, improving or treating.

BACKGROUND OF THE INVENTION In modern society, quality of life is improving and lifespan is being extended. However, with the increase of lifespan, cardiovascular diseases and metabolic diseases are increasing. According to the recently released statistics of the World Health Organization, it is reported that diseases that cause high deaths worldwide include various cancers, cardiovascular diseases, metabolic diseases, and neuropsychiatric diseases. The metabolic disease acts as a common disease mechanism with metabolic syndrome, such as diabetes, obesity, hypertension, hyperlipidemia, cardiovascular disease. The symptoms of metabolic syndrome are not fatal, but because they have a predisposition to develop serious diseases such as diabetes and ischemic cardiovascular diseases, they are the most threatening diseases of modern people. This metabolic syndrome has recently increased in Korea, and has been reported to exceed the level of developed countries such as the United States and Western Europe (Albert, KG Zi 瞧 et DZ.Definition, diagnosis, and classification of di betes mel 1 itus and its). Compl icicat ion, Parti; diagnosis and classification of diabetes melilite Provisional report of WHO Consultation. Was recently called by the World Health Organization and the US National Institute of Health,

Adult Treatment Program m (Adult Treatment Program ΠΙ)

It was officially called metabolic syndrome.

Obesity is a condition in which the body fat amount is abnormally increased than the standard weight, and when more calories are consumed than consumed calories, extra calories accumulate in the fat tissue in the body. Complications due to obesity include hypertension; Myocardial infarction; Varicose veins; Pulmonary embolism; Coronary artery disease; Cerebral hemorrhage; dementia; Parkinson's; Type 2 diabetes; Hyperlipidemia; stroke; Cancers such as uterine cancer, breast cancer, prostate cancer and colon cancer; heart disease; Gallbladder disease; Apnea during sleep; arthritis; sterility; Venous ulcers; Sudden death; Fatty liver; Hypertrophic cardiomyopathy; Thromboembolism; Esophagitis; Abdominal wall hernia; Urinary incontinence; Cardiovascular disease; High blood pressure; Endocrine diseases. Diabetes is a systemic metabolic disease caused by genetic or environmental factors. It is a condition caused by the absolute or relative lack of insulin in the body and refers to an abnormally high blood sugar level. Diabetes complications include hypoglycemia, ketoacidosis, hyperosmotic complications, macrovascular complications, diabetic retinopathy, diabetic neuropathy, and diabetic nephropathy. Hypertriglyceridemia is dyslipidemia (dysl ipidemia) and refers to the state of increased triglycerides in the blood. In most cases, hypertriglyceridemia can be caused by causes such as obesity, diabetes and drinking.Families with hypertriglyceridemia due to genetic factors are autosomal dominant hereditary diseases. May occur. Hypertriglyceridemia is also known to cause pancreatic cancer. Hypercholesterolemia refers to a condition in which the concentration of cholesterol in serum is 220 to 250 rag / dL or more, and atherosclerosis is a disease that is likely to occur. Primary and secondary can be classified as primary dominant, which means that dominant genetics are caused by deterioration of LDL receptor function in liver and other cell membranes. Secondary is obesity, nephrosis, hypothyroidism, obstructive jaundice, It means that it is caused by diabetes.

Meanwhile, candidates for the treatment of obesity and related metabolic diseases are typically AMP-acted protein kinase (AMPK) and sterol regulatory element-binding. protein (SREBP). AMPK is an enzyme that plays an important role in cellular energy metabolism mainly expressed in tissues such as liver, muscle, and fat, and is activated by ATP reduction and AMP increase due to depletion of intracellular energy. SREBP (Sterol regulatory element-binding protein) is an important transcriptional activator that induces the synthesis of cholesterol and fatty acids in liver and adipocytes by expressing enzymes involved in the biosynthetic pathway of fatty acids and cholesterol. It acts as a transcription factor to induce the expression of major enzymes. Activated AMPK is known to inhibit fat synthesis by inhibiting SREBP-lc (Yang J et al., J Cel l Biochem, 106: 414-426, 2009; Yap F et al., Int J Biol Sci 7 : 645-650, 2011).

Until now, the drug for the treatment of metabolic syndrome has not been developed and attempts to treat the metabolic syndrome using only drugs for treating diabetes, hyperlipidemia and hypertension, but has limitations as a drug. Currently available drugs include biguanide compounds used for the treatment of diabetes, such as metformin and chiazolidinedione compounds such as rosigl i tazone and piogl i tazone. This is attracting attention. Metformin is a representative AMPK promoter, but gastrointestinal side effects may occur, and rosiglitazone is banned due to cardiovascular side effects, and side effects such as fracture risk and weight gain have been reported. Pioglitazone is also known to cause heart failure and side effects such as weight gain or fluid pooling when administered with insulin.

Therefore, there is a need for research on substances that have fewer side effects and can effectively treat metabolic syndrome. Therefore, through the development of candidate substances that effectively inhibit the synthesis and accumulation of fat through the regulation of AMPK and SREBP-lc, it proposes an effective method to improve or treat the pathology of metabolic diseases associated with obesity or fat excess accumulation.

[Detailed Description of the Invention]

[Technical problem] Therefore, the inventors of the present invention have no cytotoxicity and have good therapeutic effects. While researching the activity, jinkyo extract has the effect of promoting the activity of AMPK, reducing the activity of SREBP-lc, inhibiting fat accumulation, and reducing the content of blood sugar, triglycerides and cholesterol, which is useful for treating metabolic diseases. The present invention has been completed by revealing that it can be used.

Accordingly, it is an object of the present invention to provide a pharmaceutical composition for preventing or treating metabolic diseases, including as an active ingredient Gent ianae Macrophyl lae Radix. It is also an object of the present invention to provide a pharmaceutical composition for preventing or treating metabolic diseases consisting of Gentian extract (Gent ianae Macrophyl lae Radix). It is also an object of the present invention to provide a pharmaceutical composition for the prevention or treatment of metabolic diseases consisting essentially of the extract (Gent ianae Macrophyl lae Radix) as an active ingredient.

It is another object of the present invention to provide a food composition for preventing or improving metabolic diseases, including the extract of Orthodontic as an active ingredient. It is another object of the present invention to provide a food composition for preventing or improving metabolic diseases consisting of extracts of jinjagyo. In addition, another object of the present invention is to provide a food composition for preventing or improving metabolic diseases consisting essentially of the extract of the jinchuan as an active ingredient.

Still another object of the present invention is to provide a use of Gent ianae Macrophyl lae Radix for the preparation of an agent for treating metabolic diseases.

Still another object of the present invention is to provide a method for treating metabolic disease, comprising administering to a subject in need thereof an effective amount of a composition comprising Gentian extract (Gent ianae Macrophyl lae Radix) as an active ingredient. Technical Solution In order to achieve the above object, the present invention provides a pharmaceutical composition for the prevention or treatment of metabolic diseases comprising Gentianae Macrophyllae Radix as an active ingredient. The present invention also provides a pharmaceutical composition for preventing or treating metabolic diseases consisting of Gentianae Macrophyllae Radix. The present invention also provides a pharmaceutical composition for the prevention or treatment of metabolic diseases consisting essentially of the extract (Gent ianae Macrophyllae Radix) as an active ingredient.

In order to achieve the other object of the present invention, the present invention provides a food composition for preventing or improving metabolic disease, including the extract as an active ingredient. In another aspect, the present invention provides a food composition for preventing or improving metabolic disease consisting of the extract of the jinja. In another aspect, the present invention provides a food composition for preventing or improving metabolic diseases consisting essentially of the extract of the jinjag as an active ingredient.

In order to achieve another object of the present invention, there is provided a use of Gentian extract (Gent ianae Macrophyllae Radix) for the preparation of a preparation for the treatment of metabolic diseases.

In order to achieve another object of the present invention, there is provided a method for treating metabolic disease, comprising administering to a subject in need thereof an effective amount of a composition comprising Gentianae Macrophyllae Radix as an active ingredient.

Hereinafter, the present invention will be described in detail.

The present invention provides a pharmaceutical composition for the prevention or treatment of metabolic diseases, including Gentianae Macrophyllae Radix as an active ingredient. The present invention also provides a pharmaceutical composition for the prevention or treatment of metabolic diseases consisting of Gentian extract (Gent i anae Macrophyl lae Radix). The present invention also provides a pharmaceutical composition for the prevention or treatment of metabolic diseases consisting essentially of the extract (Gent i anae Macrophyl lae Radix) as an active ingredient.

In the present invention, the word 'jinentai (Gent i anae Macrophyl lae Radix)' is called Jingyo, which means that Jingyo is produced in Qin Dynasty and roots are entangled with each other like a net. It refers to the roots of perennial herbaceous plants of coriander root plant and buttercups that grow on dreary land. It has a peculiar smell, bitter and spicy taste, and has a slightly cold nature. Also known as 'Jinbeom' or 'Odokdogi', it is a non-toxic herbal medicine that is harvested in autumn to remove foliage, beard roots, sliced clean, and dried in the sun. In oriental medicine, the same plant has been used for the treatment of pain relief, dysmenorrhea, customs pain, arthritis, yellowing, and urinary deficiency. It is used for customary joint pain, fever and swelling, hand and hand paralysis, jaundice, swelling and fever. In addition, the pharmacological action of orgy was reported to be anti-inflammatory and antibacterial against skin fungi and dysentery. The shape is conical, the upper part is rough, the lower part is smooth, and the outer surface is grayish yellow with vertical or horizontal grooves. The head is swelled, attached to several roots, and remains a short fibrous duct. The quality is hard and brittle, so it is easy to bend. The face of the face is yellow or yellowish brown, and the wood part is yellow. The other names are left Jingu (左 秦 Jinkyo (秦 膠), Jingyu (ᅳ) ᅳ Jinjo (秦 爪), Jingyu (秦 Λ)).

In the present invention, the "metabolic di sease" refers to a disease caused by excessive synthesis or accumulation of fat due to abnormal energy metabolism in the body due to various causes such as excessive energy intake or hormonal imbalance. The metabolic disease is not particularly limited, but is characterized in that it is selected from the group consisting of obesity, diabetes, hypertension, hyperlipidemia, hypercholesterolosis, arteriosclerosis, fatty liver and cardiovascular disease. Preferably it is selected from the group consisting of obesity, diabetes, hypertriglyceridemia, hypercholesterolemia and fatty liver. Examples of the extracting solvent of the extract of the present invention include ethanol, methane, propanol, isopropanol, butanol, 1 to 6 carbon atoms, acetone ether, chloroform, ethyl acetate, It can be extracted using at least one solvent selected from the group consisting of methylene chloride, nucleic acid, cyclonucleic acid, petrolem ether, diethyl ether, benzene. Extract of the present invention can be extracted using ethane as a solvent, preferably 20 to 80% ethane can be extracted using a solvent, more preferably 20 to 45% ethanol as a solvent It can be extracted, and most preferably can be extracted using 25% ethanol as a solvent.

The pharmaceutical composition according to the present invention may be formulated in a suitable form either alone or with a pharmaceutically acceptable carrier, and may further contain excipients or diluents. As used herein, 'pharmaceutically acceptable' refers to a nontoxic composition that, when administered to human beings, is physiologically acceptable and typically does not cause allergic reactions such as gastrointestinal disorders, dizziness, or the like.

Pharmaceutically acceptable carriers may further include, for example, carriers for oral administration or carriers for parenteral administration. Carriers for oral administration may include lactose, starch, cellulose derivatives, magnesium stearate, stearic acid and the like. In addition, it may include various drug delivery materials used for oral administration to the peptide formulation. Carriers for parenteral administration may also include water, suitable oils, saline, aqueous glucose, glycols, and the like, and may further include stabilizers and preservatives. Suitable stabilizers include antioxidants such as sodium hydrogen sulfite, sodium sulfite or ascorbic acid. Suitable preservatives include benzalkonium chloride, methyl- or propyl-parabens and chlorobutane. The pharmaceutical composition of the present invention may further include a lubricant, a humectant, a sweetener, a flavoring agent, an emulsifier, a suspension agent, and the like, in addition to the above components. Other pharmaceutically acceptable carriers and formulations may be referred to those described in Remington's Pharmaceut i cal Sciences, 19th ed., Mack Pub 1 i sh i ng Compan, East on, PA , 1995). The composition of the present invention may be administered to any mammal, including humans. For example, it can be administered orally or parenterally. Parenteral administration methods include, but are not limited to, intravenous, intramuscular, intraarterial, intramedullary, intradural, intracardiac, transdermal, subcutaneous, intraperitoneal, intranasal, intestinal, topical, sublingual or rectal administration. Can be.

The pharmaceutical composition of the present invention may be formulated into a preparation for oral or parenteral administration according to the route of administration as described above. In the case of preparations for oral administration, the compositions of the present invention may be formulated using powders, granules, tablets, pills, dragees, capsules, liquids, gels, syrups, slurries, suspensions, etc. using methods known in the art. Can be. For example, oral formulations can be obtained by tablets or dragees by combining the active ingredients with solid excipients, milling them and adding suitable auxiliaries and then processing them into granular mixtures. Examples of suitable excipients include sugars and corn starch, wheat starch, rice starch and potato starch, including lactose, dextrose, sucrose, solbi, manny, xili, erysri and malty, etc. Fillers such as cellulose, gelatin, polyvinylpyridone, and the like, including starch, cellulose, methyl cellulose, sodium carboxymethyl cellulose and hydroxypropylmethyl cellulose. In some cases, crosslinked polyvinylpyridone, agar, alginic acid or sodium alginate may be added as a disintegrant. Furthermore, the pharmaceutical composition of the present invention may further include an anticoagulant, a lubricant, a humectant, a perfume, an emulsifier, a preservative, and the like. Formulations for parenteral administration may be formulated by methods known in the art in the form of injections, creams, lotions, external ointments, oils, humectants, gels, aerosols and nasal inhalants. These formulations are described in Remington's Pharmaceut i cal Science, 19th ed., Mack Publ i Shing Company, East on, PA, 1995, a prescription generally known in all pharmaceutical chemistries.

The total effective amount of the composition of the present invention may be administered to a patient in a single dose (s ingle dose), and may be administered by a fract ionated treatment protocol administered for a long time in a mul t iple dose. Can be. The pharmaceutical composition of the present invention may vary the content of the active ingredient depending on the extent of the disease. Preferably seen Preferred total doses of the pharmaceutical compositions of the invention may be from about 0.01 / g to 10,000 mg, most preferably O.lig to 3000 mg per kg of patient weight per day. However, the dosage of the pharmaceutical composition is determined in consideration of various factors such as the age, weight, health status, sex, severity of the disease, diet and excretion rate as well as the formulation method, route of administration and frequency of treatment. In view of this, one of ordinary skill in the art will be able to determine the appropriate effective dosage of the compositions of the present invention. The pharmaceutical composition according to the present invention is not particularly limited to its formulation, route of administration and method of administration as long as the effect of the present invention is shown.

The present invention provides a food composition for preventing or ameliorating metabolic disease, including an extract of jinja as an active ingredient. In another aspect, the present invention provides a food composition for preventing or improving metabolic disease consisting of the extract of the jinja. In another aspect, the present invention provides a food composition for preventing or improving metabolic diseases consisting essentially of the extract of the jinjag as an active ingredient.

The composition for foods using the extract of jinjag according to the present invention includes all forms such as functional food, nutritional supplement, health food and food additives. These types can be prepared in various forms according to conventional methods known in the art.

For example, as a health food, the composition for food itself of the present invention may be prepared in the form of tea, juice and drink for drinking, or granulated, encapsulated and powdered. In addition, the composition for food of the present invention can be prepared in the form of a composition by mixing with known substances or active ingredients known to have the effect of reducing body fat, improving cholesterol, lowering blood pressure.

Functional foods also include beverages (including alcoholic beverages), fruits and processed foods (e.g. canned fruit, canned foods, jams, marmalade, etc.), fish, meat and processed foods (e.g. ham, sausage and conveyor). If you like), breads and noodles (for example udon, Soba, Ramen, Spaghetti, Macaroni, etc., Juice, Various drinks, Cookies, Sweets, Dairy (e.g. butter, Cheese), Edible vegetable oil, Margarine, Vegetable protein, Retort food, Wild food, Seasonings ( For example, it can be prepared by adding the food composition of the present invention to miso, soy sauce, sauce, and the like.

The preferred content of the food composition according to the present invention is not limited thereto, but is preferably 0.01 to 50 weight ¾ of the total weight of the finally prepared food. In order to use the food composition of the present invention in the form of a food additive, it may be prepared and used in powder or concentrate form.

In addition, the food composition of the present invention may contain various flavors, natural carbohydrates, and the like as additional components, as in general beverages. The carbohydrates are sugars such as monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, polysaccharides such as textine and cyclodextrin, xylide, sorbitol and erythritol. As the sweetener, natural sweeteners such as tautin, stevia extract, synthetic sweeteners such as saccharin, aspartame, and the like can be used. The ratio of the natural carbohydrate is generally about 0.01-0.04g, preferably about 0.02 ~ 0.03g per 100 mL of the composition of the present invention, but is not limited thereto.

Definitions of the excipients, binders, disintegrants, lubricants, copulation agents, flavoring agents, etc. of the present invention are those described in the literature known in the art and include those having the same or similar functions. Sacrament, Korean College of Pharmacy, 5th Edition, P33-48, 1989).

In one embodiment of the present invention, water, 25%, 50% or 70% ethane (EtOH) as a solvent to prepare a powdery extract, each of the extracts treated with 3T3-L1 adipocytes, respectively, AMPK assay kit As a result of quantifying the activity of AMPK, the effect of promoting AMPK activity was found to be the highest in the case of orthodontic extract extracted with 25% ethane (Example 1, Table 1). In one embodiment of the present invention, after treatment with 3T3-L1 adipocytes, orthogonal extract prepared by using water, 25%, 50% or 7 ethane (EtOH) as a solvent, quantifying fat granules and inhibiting fat accumulation result. Treatment with 25% ethanol extract showed the best effect of inhibiting fat granules. In addition, the amount of fat accumulation was lower when the ethanol extract was treated than the water extract, and it was confirmed that the fat accumulation inhibitory effect was best when the ethanol extract was treated (see Example 1 and Table 2).

In another embodiment of the present invention, 3T3-L1 adipocytes were treated with extract 25% ethane, extract (Q) or metformin (METformin, MET) at different doses, and then fat accumulation and cell viability were measured and compared. As a result, it was confirmed that 25% ethanol extract of Gyogyo showed superior fat accumulation inhibitory activity compared to metformin, and that cell viability did not decrease even if the dose of Gyogyo 25% ethanol extract was increased. (See Examples 1-3, FIGS. La and lb).

In another embodiment of the present invention, 3T3-L1 adipocytes were treated with orthogonal 25% ethanol extract (Q), followed by Western blot to confirm the phosphorylation activity of AMPK by extracting protein, which is a substrate protein of AMPK. It was confirmed that phosphorylation of AMPK, ACC and SREBP-lc increased in a concentration-dependent manner, and showed stronger activity than metformin (MET), a representative AMPK promoter (Example 2-1, see FIG. 2).

In another embodiment of the present invention, 3T3-L1 adipocytes were treated with 25% ethanol extract, followed by ELISA to confirm target DNA binding activity of SREBP-lc. It was confirmed that the target protein binding activity decreases in a concentration-dependent manner, it was confirmed that more inhibit the activity than metformin (Example 2-2, see Figure 3).

In another embodiment of the present invention, after processing 25% ethanol extract in 3T3-L1 adipocytes, the RNA was extracted, followed by real time PCR, resulting in fat synthesis. Expression levels of transcription factors SREBP-1C and liposynthesis enzymes ACCl, FAS, SCD1 were confirmed to decrease in a concentration-dependent manner, and it was confirmed that the expression levels were suppressed more than metformin (Example 3, FIGS. 4A to 4). 4d).

In another embodiment of the present invention, a high fat diet was supplied to a mouse, and oral administration of 25% ethanol extract at a different dose once daily was performed, followed by body weight, retroperitoneal adipose tissue, and epididymal fat. The weight of epididymal adipose tissue and liver was increased, and the weight of control, post-renal adipose tissue, epididymal adipose tissue and liver was increased in the control group compared to the normal group. When the extract treated with% ethane, it was confirmed that the weight, post-renal adipose tissue, epididymal adipose tissue and liver weight decreased in a concentration-dependent manner (see Example 4-1, FIGS. 5A to 5D).

In another embodiment of the present invention, the mice fed high fat diet were orally administered 25% ethanol extract once daily at different doses, followed by anesthesia to collect blood from the heart, and to coagulate blood to centrifuge. After the serum was obtained, the glucose and triglyceride contents were measured, and the control and sugar contents were higher in the control group than in the normal group. When the extract was treated, it was confirmed that the content of sugar and triglyceride in the serum was reduced (see Example 4-2, FIG. 6, FIG. 7).

In another embodiment of the present invention, the mice fed high fat diet were orally administered with 25¾ ethanol extract once daily at different doses, and then anesthetized, and blood was collected from the heart. LDL cholesterol and total cholesterol content were measured to obtain LDL cholesterol and total cholesterol in the control group compared to the normal group. However, when treated with 25% ethanol extract, the content of LDL cholesterol and total cholesterol in serum was decreased (see Example 4-3, FIGS. 8A and 8B). In one embodiment of the present invention, AMP-activated protein kinase, which is an important therapeutic target protein for metabolic diseases that regulates energy metabolism in 3T3-L1 adipocytes and is involved in fat production and accumulation in 3T3-L1 adipocytes It was confirmed that the activity of kinase (AMPK) is promoted and the activity of SREBP-lc (Sterol regulatory element-binding protein-lc) is inhibited. In addition, it was confirmed that the expression of fat synthase such as ACC-KAcetyl-CoA carboxylase 1), SCD-1 (St Ear oy 1 -CoA desaturase 1), and fatty acid synthase (FAS), which are transcribed by SREBP-lc, was inhibited. . The AMPK activation and SREBP-lc activity inhibitory effect of the above-mentioned oleaginous extract was more effective than metformin (met formin) currently used as an antidiabetic agent as an AMPK promoter, and it was confirmed that there is no cytotoxicity.

Therefore, the skilled artisan uses safety of AMPK activation and intracellular fat accumulation inhibitory effect of the present inventors to identify and improve the pathology and prevent metabolic diseases associated with fat overproduction or fat accumulation such as obesity and safety. Can be developed as an effective drug candidate.

The present invention provides the use of Gentian extract (Gent i anae Macrophyll ae Radix) for the preparation of an agent for treating metabolic diseases.

The present invention provides a method for treating metabolic disease, comprising administering to a subject in need thereof an effective amount of a composition comprising Gentian extract (Gent ianae Macrophyl lae Radix) as an active ingredient.

The 'effective amount' of the present invention, when administered to an individual, refers to an amount that shows the effect of improving, treating, preventing, detecting, diagnosing or inhibiting metabolic disease or metabolic disease, and the term 'individual' is an animal, preferably It may be a mammal, particularly an animal including a human, and may be a cell, tissue, organ, or the like derived from the animal. The subject may be a patient (pat i ent) in need of the effect. The term 'treatment' of the present invention refers generically to ameliorating a metabolic disease or symptom of a metabolic disease, which cures or substantially It may include preventing or ameliorating the condition, including but not limited to alleviating, healing or preventing one or most symptoms resulting from metabolic disease.

The term 'comprising' of the present invention is used in the same way as 'containing' or 'characteristic', and does not exclude additional component elements or method steps not mentioned in the composition or method. . The term 'consisting of' means to exclude additional elements, steps or components, etc., unless otherwise noted. The term “essentially consisting of” means in the scope of a composition or method, including the component elements or steps described, as well as those component elements or steps that do not substantially affect its basic properties, and the like.

[Effect of the Invention] Accordingly, the present invention provides a composition for the prevention or treatment of metabolic disease, comprising the extract of Orthodontic as an active ingredient. The method of the present invention promotes AMPK activity, inhibits fat accumulation, fat granules, fat transcriptase activity and the expression of fat synthase, and decreases the content of body weight, blood sugar, triglycerides and cholesters to prevent metabolic diseases or It can be usefully used for treatment.

Fig. La and lb are the results of confirming the effect of the extract (Q) on fat accumulation suppression in fat cells compared to metformin (MET) of orthogonal 25% ethane (Fig. La) and As a result of confirming the effect on cell viability (Fig. Lb) is shown graphically.

Figure 2 shows the results of Western blot to confirm the effect of the jinkyo 25% ethanol extract (Q) on the phosphorylation of AMPK substrate proteins AMPK, ACC and SREBP-lc in adipocytes compared to metformin (MET) will be. FIG. 3 shows the results of conducting SREBP-1 transcription factor ELISA in order to confirm the effect of the extract (Q) on the target DNA binding activity of SREBP-lc compared to metformin (MET) in orthodontic 25¾ ethane. (* P <0.05, ** p <0.01, *** p <0.001).

4A to 4D show the amount of expression of SREBP—lc (Sterol regulatory element-binding protein-lc), which is a liposynthetic transcription factor, compared to metformin (MET), with extract of 25% ethane from orthognathic acid (FIG. 4A) and fat Effect of the expression of ACC1 (Acetyl-CoA carboxylase 1), a synthase (FIG. 4B), the expression of fatty acid synthase (FAS) (FIG. 4C), and the expression of SCD KStearoyl-CoA desaturase 1 (FIG. 4D) The graph shows the results of real time—PCR to confirm the results. Ορ <0 · 05, ** ρ <0.01, *** ρ <0.001).

5a to 5d are extracts of orthodontic 25% ethane (Q) according to the dose of the mouse body weight (FIG. 5A), the weight of retroperitoneal adipose tissue (FIG. 5B), epididymal adipose tissue ) And the effect on the weight of the liver (Fig. 5C) and the weight of the liver (Fig. 5D) is a graph p <0.05, ** p <0.01 ₍ *** p <0.001).

FIG. 6 is a graph showing the effect of 25% ethanol extract (Q) on the blood glucose (glucose) content according to the dose Op <0.05, ** p <0.01, *** p <0.001).

7 is a graph illustrating the effect of 25% ethanol extract (Q) on the content of triglyceride in the blood according to the dose (* p <0.05, ** p <0.01, *** p <0.001) ).

8a and 8b graphically show the effect of Orthogium 2 ethanol extract (Q) on the contents of LDL cholesterol (FIG. 8A) and total cholesterol (FIG. 8B) according to the dose (* P <0.05, ** p <0.01, *** p <0.001). Figure 9 shows the result of Western blot to confirm the effect of the extract (Q) in the orthogonal 25% ethane on the expression of AMPK phosphorylation, SREBP-lc, ACC and FAS protein in adipose tissue and liver tissue of the mouse.

EMBODIMENT OF THE INVENTION Hereinafter, this invention is demonstrated in detail. However, the following examples are merely to illustrate the present invention, and the content of the present invention is not limited to the following examples.

Method of Preparation Extract Extract Gentianae Macrophyllae Radix was purchased through CK Co., Ltd., and sensory test, plant trace analysis, heavy metal test, residue pesticide test, drying at Acinetum Herbal Analysis Center (www.dhac.kr). A weight loss test, an ash test, an acid insoluble ash test, and an X content test were used to determine the suitability. 25 g of oleaginous water, 200 ml of 25% ethane, 200 ml of 50% ethanol, 200 ml of 50% ethanol or 200 ml of h ethane, refluxed at 65 ^° C for 4 hours, and filtered to obtain a primary extract, which was repeatedly extracted under the same solvent and conditions. A secondary extract was obtained. Then, the first and second extracts were combined, concentrated under reduced pressure at 50 ^° C to remove ethane, and the concentrated extract was frozen and lyophilized to obtain an extract in powder form. As a result of measuring the yield of the fruit extract, it was confirmed that the water extract 34.8%, 25% ethanol extract 31.6%, 50% ethanol extract 25.1%, 70% ethanol extract 34.9%.

Cell culture

3T3-L1 adipocytes were purchased from the American Type Culture Collection (Manassas, VA, USA) and cultured using Dulbecco's Modified Eagle's Medium (DMEM) under conditions of 5% CO ₂ , 37 ° C. To induce intracellular fat accumulation, cells filled in culture vessels were treated with lug / mL insulin, 0.25 μΜ dexamethasone, 0.5 mM 3-isobutyl-1-methylxanthine (3-isobutyl-1-l-). methylxanthine) was added. Every 2 days thereafter Fat accumulation was continued for 7 days with medium replacement with DMEM containing ly / mL insulin.

Oil red 0 stained cultured 3T3-L1 adipocytes were fixed for 1 hour with 4% paraformaldehyde solution. Then remove 4¾ paraformaldehyde, wash twice with PBS, add Oil red 0 solution and react in the dark for 30 minutes / then remove the solution and wash with distilled water 3 times, then isopropyl alcohol (isopropyl The absorbance was measured at 510 nm by eluting with alcohol (Kasturi et al. J. Biol. Chem. 257: 12224-12230, 1982).

A PK activity quantification AMPK activity was measured using the AMPK assay kit (Cyclex Inc., Columbia, MD, USA) according to the manufacturer's instructions. Briefly, cultured adipocytes were collected and lysed, and then added to a 96 well plate coated with a peptide containing serine 789 amino acids of insulin receptor substrate-1 (IRS-1), and 50 μΜ ATP was added. After addition, phosphorylation reaction was performed at 30 ^° C. for 30 minutes. After reaction, an anti-phospho-IRS-1 antibody was added, a secondary antibody conjugated with HRPChorse-radish peroxidase was added, and a substrate solution provided in the kit was added to develop a color reaction and measure absorbance at 450 nm. The activity of AMPK was quantified.

Cell Viability Quantification Cell viability was quantified to assess cytotoxicity. Cell viability was quantified using the Cel 1 Count EZ Cell Survival Assay Kit (Rockl nd Immunochemicals, Limerick, PA, USA) as a method of quantifying the activity of cells converting hydroxyethyl disulfide to mercaptoethan.

Western Blot

3T3-L1 adipocytes were treated with varying concentrations of 25% ethanol extract of Orthodontic. That The medium was then removed and the protein extracted from the cells. Then, isolated from a 12% SDS-PAGE gel, transferred to a nitrocellulose membrane (Bi Rad Laboratories Inc.), the membrane was blocked with 5% skim milk powder, and then the primary antibody and 2 was dilute at 1: 1000. Reacted with primary antibodies respectively. The membranes reacted with the antibody were reacted with PBST solution, and then reacted with Enhancecd Chemi-Lumescence reagent (Thermo Fisher Scientific, Inc. Waltham, MA, USA) and exposed to X-ray film to analyze protein bends. Antibodies used in the method are as follows.

Primary Antibodies: Anti—phoshorylated (p) -AMPK, anti—AMPK, anti-p-SREBP-lc, ant i -p-ACC, ant i -ACC, anti-SREBP-lc, anti-FAS (Cel 1 Signaling) Technology, Danvers, MA, USA), Anti— bet a— act in (Santa Cruz, Biotechnology, Dal las, TX, USA)

Secondary Antibodies: anti-mouse IgG, anti-rabbit IgG secondary antibodies (Cell Signaling Technology, Danvers, MA, USA).

Statistical Analysis All analyzes were carried out using SPSS 21.0 software (SPSS Inc. USA), and all data were expressed in means-based SEM.

Example 1 Effect of Concentrated Extract

1-1. Measurement of AMPK Activity Promoting Effect According to Concentration of Orthodontic Extracts The following experiments were conducted to determine the effect of orthodontic extracts extracted with ethanol at different concentrations in adipocytes. According to the experimental method, 25%, 50% or 70% ethanol (EtOH) extract was prepared by the jingae. Adipocytes were cultured 3T3-L1 cells, and the cells were treated with extracts of different concentrations. Orthodontic extract was dissolved in DMS0 (dimethyl su If oxide) and treated with a final volume of 0.2%. 0.2% DMS0 was not toxic to 3T3-L1 cells and treated with 0.2% DMS0 in the control group, 100% water extract (100% water extract), 25% ethane (EtOH) extract, 50% ethanol ( EtOH) extract, 70% Ethane (EtOH) extracts were treated at 250, 120 and 62yg / mL, respectively. Then, the cells cultured according to the above experimental method were collected and lysed, and then lysed in a 95 well plate, and AMPK activity was quantified using an AMPK assay kit (CycLex Co. Japan). As a result, as shown in Table 1, the 100% water extract of jinkyo was found to be similar to the AMPK activity of the control, while ethanol extract was found to increase the AMPK activity compared to the control. When ethanol extract was treated with 250yg / mL, the AMPK activity was accelerated when the extract was treated with 25% ethane, and the AMPK activity was the lowest when the extract was treated with 70% ethane. appear. As a result, it was confirmed that the 25 ethanol extract of Jingyo had the best AMPK activity promoting effect.

[Table 1] Promotion of AMPK Activity According to Concentration of Orthodontic Extracts

AMPK activity T-test AMPK activity compared to unpaired control

 (Mean standard deviation, n = 4) (p-value) Acceleration rate control (adi ocyte) 1.000 cm 0.236

100% Water Extract (250yg / ml) 0.922 士 0.182 0.620-100% Water Extract (125yg / ml) 0.876 士 0.118 0.384-100% Water Extract (62yg / ml) 0.908 士 0.305 0.651-25¾ EtOH Extract 250yg / ml) 1.788 士 0.208 0.002 78.84% Ortho 25% EtOH Extract (125yg / ml) 1.373 士 0.042 0.021 37.33% Ortho 25% EtOH Extract (62yg / ml) 0.952 士 0.237 0.784-Ortho 50% EtOH Extract (250yg / ml ) 1.509 士 0.132 0.009 50.90% Ortho 50% EtOH extract (125yg / ml) 1.212 士 0.090 0.145 21.16% Orthogonal 5 (»EtOH extract (62yg / ml) 0.858 士 0.116 0.322-Ortho 70% EtOH extract (250yg / ml) 1.230 0.179 0.172 22.95% Jinkyo 7OT EtOH Extract (125yg / ml) 0.946 士 0.093 0.685- Jinkyo 70¾ EtOH Extract (62yg / ml) 0.900 土 0.207 0.548-

1-2. Inhibitory Effect of Adipose Accumulation by Concentration of Oral Extracts Cultured 3T3-L1 cells were treated with different concentrations and doses. The extract was dissolved in DMS0 (dimethyl sulfoxide) and the final volume was treated to 0.¾. 0.2% DMS0 was not toxic to 3T3-L1 cells and treated with 0.2% DMS0 in the control group, 100% water extract (100% water extract), 25% ethanol (EtOH) extract, 50% ethanol (EtOH ), 70% ethanol (EtOH) extract was treated with 250, 120, 62 _U g / mL respectively. Fat granules were quantified by Oil red 0 staining as in the above experimental method.

 As a result, as shown in Table 2, the amount of fat accumulation of the 100% water extract of Jingyo was similar to that of the control group, whereas the amount of fat accumulation of the ethanol extract was lower than that of the control group. In addition, the amount of fat accumulation was the lowest when 250iig / mL of 25% ethanol extract was treated. As a result, the 25% ethanol extract of Jingyo showed the best fat suppression effect.

[Table 2] Inhibitory Effect of Fatty Acid Extracts on Concentrations of Fatty Acid Extracts Fat Concentration Treated Concentrations compared to Unpaired Controls

 (Mean 土 standard deviation, n = 4) (p-value) Inhibition rate control (adipocyte) 1.000 士 0.067-Orthogonal 100% water extract (250yg / nil) 0.970 士 0.068 0.549

Orgy 100% water extract (125yg / ml) 1.006 sul 0.130 0.935

Orgy 100% water extract (62yg / ml) 1.022 士 0.126 0.764

Ortho 25% EtOH extract (250ug / ml) 0.515 t 0.011> 0.001 48.46% Ortho 25% EtOH extract (125yg / ml) 0.592 t 0.029> 0.001 40.82% 25% EtOH extract (62yg / ml) 0658 土 0.024> 0.001 34 18% 50% EtOH extract (250yg / ml) 0 630 士 0.025> 0.001 37 02% 50% EtOH extract (125yg / ml) 0 710 士0.009> 0.001 29 02% Oyster Extract 50% EtOH Extract (62yg / ml) 0 745 土 0.020> 0.001 25 47% Oyster Extract 70% EtOH Extract (250yg / ml) 0 793 0.01 0.014 0.001 20 73% Oyster Extract 70% EtOH Extract (125yg / ml) 0 778 士 0.008 0.001 22 21% Oregano 70% EtOH Extract (62yg / ml) 0 778 士 0.013> 0.001 22 21%

In the above example, since 25% ethanol extract had the best AMPK activation effect and fat accumulation inhibitory effect, the following examples were all carried out using 25¾ ethanol extract.

1-3. Cytotoxicity and Fat Accumulation Inhibitory Effects of Orthodontic Extracts Compare the cytotoxicity and fat accumulation inhibitory effects of 25% ethanol extracts with the best effect on AMPK activation and fat accumulation inhibition in comparison with metformin commercialized as a representative AMPK promoter Experiments were carried out as follows. According to the experimental method, 3T3-L1 adipocytes were treated with 0, 30, 100, 300, 100Og / mL of 25% ethanol extract (Q) for 7 days. In addition, metformin (MET) commercialized as a representative AMPK promoter was treated with 0, 30, 100, 300, 100Og / mL. The fat accumulation and cell viability in the cells were then measured and compared. As a result, as shown in Fig. La and lb, the fat accumulation inhibitory activity was increased according to the dose of both when treated with orthogonal 25¾ ethanol extract (Q) and treated with metaformin (MET). The 25% ethanol extract of Orthogyo showed better fat accumulation inhibitory activity than metoformin (FIG. La). In addition, both 25% ethanol extract (Q) and metformin (MET) were found not to decrease cell viability until the concentration of lOOOyg / mL (Fig. Lb). As a result, the 25% ethanol extract of Jingyo was found to have better fat accumulation inhibitory activity than metformin, and it was confirmed that there was no cytotoxicity like commercialized metformin. Example 2: Effect of Orthodontic Extract on the Activity of AMPK and Adipose Synthetic Transcription Factor SREBP—lc

2-1. Effect of Orthodontic Extract on the Activity of AMPK Using the Orthodontic 25% ethanol extract which showed the best effect in Example 1, the following experiment was carried out to confirm the effect of the orthodontic extract on the activity of AMPK.

AMPK is a serine / threonine kinase. It is activated by ATP reduction and AMP increase due to energy depletion in cells. AMPK activation inhibits the synthesis of fat in human cells and promotes its degradation. Therefore, AMPK is well known as a therapeutic target for metabolic diseases such as obesity, diabetes, fatty liver, hyperlipidemia (Zhang BB et al., Cell Metab, 9: 407-416, 2009; Fogarty S et al., Biochimica et Biophysica Acta, 1804) : 581-591; Hardie DG, Diabetes, 62: 2164-2172, 2013). Substrate proteins phosphorylated by AMPK are known as AMPK, acetyl-CoA carboxylase (ACC), and SterBP-lc (Sterol regulatory element-binding protein_lc) (Gowans GJ et al., Cell Metab 18: 556-). 566, 2013; Li Y et al., Cell Metab 13: 376-388, 2011). According to the experimental method, 3T3-L1 adipocytes were treated with 0% 3, 10, 30, 100, 300, 100 g / mL of 25% ethanol extract (Q) for 7 days. In addition, metformin (MET) commercialized as a representative AMPK promoter was treated with 100 mg / mL. Then, proteins were extracted from the cells and subjected to western blot.

As a result, as shown in Figure 2, when treated with the extract (Q) in 25% ethane of jinchuo, phosphorylation of AMPK, ACC and SREBP-lc increased with the concentration. In addition, treatment with 25% ethanol extract at 100 g / mL of jinchuan showed similar effects to 1000 yg / ml of metformin, and the same phosphorylation increased with lOOOOyg / mL. Appeared. This resulted in 25% ethanol extract of Jingyo phosphorylated SREBP-lc, a fat transcriptase, and ACC and AMPK, a fat synthase, and stronger activity than metformin. It was confirmed that it was shown.

2-2. Effect of Orthodontic Extract on SREBP-lc Activity In order to confirm the effect of Orthodontic extract on SREBP-lc activity using 25% ethanol extract having the best effect in Example 1, Was carried out.

Sterol regulatory element-binding protein (SREBP) is an important transcriptional activator that induces the synthesis of cholesterol and fatty acids in liver and adipocytes by expressing enzymes involved in the biosynthetic pathways of fatty acids and cholesterol. SREBP-la, SREBP- lc and SREBP-2 are classified into three isoforms. Among these, SREBP-lc is most expressed in tissues such as fat, liver, and muscle, and the major enzymes involved in the synthesis of fat are acetyl-CoA carboxylase 1 (ACCl), fatty acid synthase (FAS), and SCD 1 (st ear). oy 1 -CoA desaturase 1) and SREBP-lc itself are known to act as transcription factors (Jeon TI and Osborne TF, Trends Endocrinol Metab, 23: 65-72, 2012). It is also known that phosphorylation of SREBP-lc by AMPK reduces the activity of SREBP-lc (Yang J et al., J Cel l Biochem, 106: 414-426, 2009; Li Y et al., Cel l Metab 13: 376-388, 2011). According to the experimental method, the extract (Q) was treated with 0, 3, 10, 30, 100, 300, 100 mg / mL of ookgwa 25% ethane to 3T3-L1 adipocytes for 7 days. Among the commercialized drugs, metformin (MET), a representative AMPK promoter, was treated at 1000 _U g / mL. Then, the SREBP-1 transcription factor ELISA (Cayman Chemical Co. Ann Arbor, MI, USA) was used to measure the binding activity of SREBP-lc's target DNA (5'-TCACCTGA-3 ^' : SEQ ID NO: 1). .

As a result, as shown in Fig. 3, the target DNA binding activity of SREBP-lc was decreased with concentration when the ethanol extract (Q) of Orthogonal malaria 25¾>. In addition, when treated with orthogonal 25% ethanol extract, 30 300 μ g / raL, the effect was similar to that of metformin lOOOO yg / mL, and in the same treatment with lOOOO yg / mL, the target DNA binding activity was decreased. It appeared to decrease further. Through this, the extract of orthodontic 25% ethane was the target of SREBP-lc, a fat synthesis transcription factor. Inhibiting DNA binding, and showed a stronger inhibitory activity than metformin.

Example 3 Inhibitory Effects of Oral Extracts on Lipid Synthesis Transcripts and Lipid Synthesis Enzymes In Example 2, the AMPK activity was promoted by 25% ethanol extract of lycopene and the phosphorylation of SREBP-lc was increased. It was confirmed that the target DNA binding activity is inhibited. In order to determine the effect of the extract on the expression level of liposynthetic transcription factor and liposynthase was carried out as follows. According to the experimental method, 3T3-L1 adipocytes were treated with 0 31, 62, 250, 500, and 1000 ug / mL of 25% ethanol extract for 7 days. RNA was then extracted from the cells using the RNeasy Kit (Qiagen, Germany) and cDNA was synthesized using the cDNA Reverse Transcription kit (Applied Biosys terns, Foster City, CA, USA). Then, real time PCR of the Taqman method was performed, and SREBP-lc (Mm00550338_ml, Applied Biosystems), which is a liposynthetic transcription factor, ACCl (Mm0130425g, Applied Biosystems), and FAS (Mm01253292_ml, Applied Biosystems), which are liposynthetic transcription factors, and The expression level of SCDl (Mm00772290_ml, Applied Biosystems) was measured, and the ratio of expression level was measured based on the control group. 18S rRNA (Hs99999901_sl, Applied, Biosystems) was used as a control.

As a result, as shown in Figures 4a to 4d, when the 25% ethanol extract (Q) was added, the expression level of the SREBP-lc (FIG. 4a), a liposynthetic transcription factor, was found to decrease in a concentration-dependent manner. The expression levels of the enzymes ACC1 (FIG. 4B), FAS (FIG. 4C), and SCD1 (FIG. 4D) also decreased in a concentration-dependent manner, and showed an excellent effect compared to metformin (MET). In addition, when 25% ethane extract was treated with 250-500 μg / mL of extract, similar effects were obtained when 1000 μg / mL of metformin was applied. The amount of expression was found to decrease significantly. As a result, it was confirmed that the 25% ethanol extract of Jingyo inhibited the expression of fat transcriptase and liposynthase, thereby inhibiting obesity and hyperlipidemia caused by fat accumulation. Example 4 Effect of Orthodontic Extract In Vivo To investigate the effect of orthodontic 25% ethanol extract on the living body in a high fat diet-induced obese mouse model, the following experiment was performed.

4-1. Effect of Orthodontic Extract on Body Weight Four-week-old C57BL / 6N male mice were purchased from central laboratory animals. The experiment was allowed to adapt to the laboratory environment for one week. Normal mice were fed a normal diet containing 10% fat and control and experimental groups were fed a high fat diet containing 45% fat. The experimental group was orally administered 25 mg ethanol extract (Q) at a dose of 100, 300, 900 mg / Kg once a day for 8 weeks. After 8 weeks anesthesia was taken from the heart. Then, the mice were regenerated, and the weight was measured by cutting retroperitoneal adipose tissue, epididymal adipose tissue and liver in the abdominal cavity. As a result, as shown in Figures 5a to 5d, compared to the normal group (control) compared to the weight (figure 5a), retroperitoneal adipose tissue (figure 5b) and epididymal fat tissue (epididymal) The weight of the adipose tissue (FIG. 5C) and liver (FIG. 5 (1) was increased, and the weight loss was found to be concentration-dependent in the group treated with 25% ethanol extract (Q).

4-2. Effect of Orthodontic Extract on Blood Glucose and Thickening Fat Contents The collected blood was coagulated and centrifuged at 8000 rpm for 10 minutes to obtain serum. Blood biochemical analyzer (Modular analytics, Hitachi, Japan) was used to measure the content of glucose and triglyceride in serum. As a result, as shown in Figure 6 and 7, in the control (control) compared to the normal group (control), the content of sugar in the serum (Fig. 6) and triglycerides (Fig. 7) was increased, 25% ethanol of the oak In the extract-treated group, the serum triglyceride content decreased concentration-dependently, the serum sugar content decreased, and the serum sugar content of the 300 mg / kg and 900 mg / kg administration groups was almost similar. 4-3. Effect of Orthodontic Extract on Cholesterol Content The collected blood was coagulated and centrifuged at 8000 rpm for 10 minutes to obtain serum. The blood biochemical analyzer (Modular analyt i cs, Hi tachi, Japan) was used to measure the contents of LDL cholesterol and total cholesterol in serum. As a result, as shown in Figures 8a and 8b, the control (control) compared to the normal group (control) increased the content of LDL cholesterol (Fig. 8a) and total cholesterol (Fig. 8b) in the serum, In the group treated with 25% ethane extract, the concentrations of LDL and total cholesterol in serum decreased.

4-4. Effect of Orthodontic Extracts on AMPK, SREBP-lc, and Lipid Synthesis in Adipose and Liver Tissues

 The collected epididymal adipose tissue and liver tissue were put into a lysate containing a protease inhibitor and crushed, respectively, and then crushed by using an ultrasonic device. After centrifugation to obtain a supernatant, the protein concentration in the supernatant was measured. Then, Western blot was performed as described in the above experimental method to measure the expression levels of AMPK, p-AMPK, SREBP-lc, ACC, and FAS.

. As a result, as shown in Figure 9, the phosphorylation of AMPK increased when treated with orthogonal 25% ethanol extract (Q) compared to the control (control), the fat synthesis transcription factors SREBP-lc and liposynthase ACC and FAS have been shown to decrease.

This results in 25% ethanol extract of Orthognathic extracts to reduce weight, fat tissue and liver weight, and to reduce the content of sugars, triglycerides, LDL cholesterol and total cholesterol in the blood, resulting in obesity, diabetes, hypertriglyceridemia and high cholesterol. It was confirmed that there is a therapeutic effect for metabolic diseases such as hypertension and fatty liver.

Industrial Applicability As described above, the method of the present invention promotes AMPK activity, inhibits fat accumulation, fat granules, liposomal transcription factor SREBP-lc activity and lipase expression, weight, adipose and liver tissue weight, blood sugar, and neutrality. It can be usefully used to prevent or treat metabolic diseases by reducing fat and cholesterol content.

Claims

[Range of request]  [Claim 11  Pharmaceutical composition for the prevention or treatment of metabolic diseases, including Gentian extract (Gent ianae Macrophyll ae Radix) as an active ingredient. [Claim 2] The pharmaceutical composition for preventing or treating metabolic diseases according to claim 1, wherein the extract is extracted using an alcohol having 1 to 6 carbon atoms or a mixture thereof as a solvent. 3. The pharmaceutical composition for preventing or treating metabolic diseases according to claim 1, wherein the metabolic disease is at least one disease selected from the group consisting of obesity, diabetes, hypertriglyceridemia, hypercholesterolemia and fatty liver. Composition. [Claim 4] A food composition for preventing or improving metabolic disease, comprising the extract of Jinkyo as an active ingredient. [Claim 5] The food composition for preventing or improving metabolic disease according to claim 4, wherein the extract is derived from an alcohol having 1 to 6 carbon atoms or a mixture thereof as a solvent. [Claim 6] The method according to claim 4, wherein the metabolic disease is at least one disease selected from the group consisting of obesity, diabetes, hypertriglyceridemia, hypercholesterolemia and fatty liver. A food composition for preventing or improving metabolic disease. Claim 7 Use of the extract (Gent i anae Macrophyl lae Radix) to prepare a formulation for treating metabolic diseases. 8. The use according to claim 7, wherein the extract is extracted using an alcohol having 1 to 6 carbon atoms or a mixture thereof as a solvent. [Claim 9] The method of claim 7, wherein the metabolic disease is at least one disease selected from the group consisting of obesity, diabetes, hypertriglyceridemia, hypercholesterolemia and fatty liver. [Claim 10] A method for treating metabolic disease, comprising administering to a subject in need thereof an effective amount of a composition comprising Gentian extract (Gent ianae Macrophyllae Radix) as an active ingredient. [Claim 111]  The method of claim 10, wherein the extract is extracted using an alcohol having 1 to 6 carbon atoms or a mixture thereof as a solvent. 12. The method of claim 10, wherein the metabolic disease is one or more diseases selected from the group consisting of obesity, diabetes mellitus, hypertriglyceridemia, hypercholesterolemia and fatty liver A method for treating metabolic disease.