KR101458062B1 - Pharmaceutical composition containing Dipterocarpus tuberculatus extract or fractions for prevention or treatment of metabolic disease - Google Patents

Abstract

The present invention relates to Dipterocarpus < RTI ID = 0.0 > The present invention relates to a composition for preventing and treating metabolic diseases, which comprises an extract of T. tuberculatus or a fraction thereof as an active ingredient. The Dipteractus persulacea extract or a fraction thereof according to the present invention is a composition for preventing and treating metabolic diseases comprising glycerol- -3-phosphate, GPAT), inhibits triglyceride biosynthesis in hepatocytes, inhibits fat accumulation in hepatocytes, increases glucose uptake in skeletal muscle cells, increases animal glucose uptake By confirming the blood glucose lowering effect in the oral glucose tolerance test (OGTT), the composition containing the extract of Diptera luciferus tuberculatus or its fraction as an active ingredient of the present invention can be used for the treatment of obesity, type 2 diabetes, insulin resistance, (hepatic steatosis) and non-alcoholic fatty liver (fatty liver). Lt; / RTI >

Description

[0001] The present invention relates to a pharmaceutical composition for preventing or treating metabolic diseases containing Dipterocarpus tuberculatus extract or fractions thereof,

The present invention relates to Dipterocarpus < RTI ID = 0.0 > The present invention relates to a pharmaceutical composition for preventing and treating metabolic diseases such as obesity, type 2 diabetes, insulin resistance, hepatic steatosis, and non-alcoholic fatty liver, which comprises extracts or fractions thereof, will be.

It is one of the mechanism of inducing chronic diseases caused by obesity. Excessive energy supply is accumulated in the form of triglyceride in non-fat tissue such as liver, muscle, pancreas and heart beyond the limit of fat tissue which is energy storage tissue. Inflammation, increased fatty acid synthesis, decreased fatty acid oxidation rate, increased insulin resistance in muscle and liver, reduced insulin production in the pancreas and beta cell death, heart failure in heart, myocardial infarction, nonalcoholic fatty liver fatty liver, NAFLD). Therefore, it can be an efficient strategy for prevention and treatment of insulin resistance, diabetes and metabolic syndrome which inhibits lipid accumulation of tissue through inhibition of fat biosynthesis and increase of lipid oxidation.

Biosynthesis of triglyceride in a multistage reaction is the first step glycerol-3-phosphate acyltransferase is catalyzed by (glycerol-3-phosphate acyltransferase, GPAT), glycerol-3-phosphate in sn (glycerol-3-phosphate) - 1 catalyzes the ester reaction to produce lysophosphatidic acid (LPA) by transferring a fatty acid (fatty acyl-CoA) in the form of acyl-coenzyme A to glycerol-3 Limiting step that regulates the rate of the glycerol-3-phosphate pathway (Bell et al, Annu Rev Biochem 49: 459-487, 1980). The last step is the biosynthesis of triglycerides by diacylglycerol acyltransferase (DGAT).

To date, GPAT has been found to have four isoenzymes in mammalian tissues and is distinguished by their susceptibility to and presence in N-ethylmaleimide (NEM). GPAT3 and GPAT4 present in the endoplasmic reticulum (ER) are highly susceptible to sulfhydryl reagent containing NEM, and mtGPAT1, which is present in the mitochondrial outer membrane (MOM) mtGPAT2 exhibits resistance to NEM and is characterized by the preference of saturated fatty acyl-CoA as a substrate (Gonzanlez-Baro et al., Biochim. Biophys. Acta, 1771: 830-838, 2007).

Although mtGPAT accounts for about 10% of the total GPAT activity in most tissues of the human body, it is known that the liver tissue accounts for up to 50% of total GPAT activity and is also active in adipose tissue (Bell et al., Annu Rev Biochem 49: 459-487, 1980; Lewin et al. Arch. Biochem. Biophys. 396: 119-127, 2001). This suggests that mtGPAT may be a useful target for fatty liver formation, obesity, and insulin resistance treatment.

Among the four isoforms of GPAT, only mtGPAT is known to be affected by diet and exercise. Studies have shown that mtGPAT mRNA expression is increased and mtGPAT activity is increased when high calorie diets are consumed in excess of caloric intake. Similarly, after constant exercise, In mice, the activity of mtGPAT was steadily increased as compared with those of mice that did not exercise at all, resulting in a significant increase in the synthesis of triglyceride in the blood (KuMp et al., 2006).

In rats, selective overexpression of mtGPAT in the liver increased lipid biosynthesis in the liver compared to the control group, but significantly decreased fatty acid oxidation and increased fat and dyslipidemia and insulin resistance, In particular, insulin resistance in the liver has increased significantly (Linden et al., FASEB J , 20: 434-443, 2006; Linden et al., J. Lipid Res. 45: 1279-1288, 2004). This implies that lipid metabolism in the liver is mainly involved in the development of insulin resistance. In particular, mtGPAT can be an attractive molecular target for the development of dyslipidemia and insulin resistance treatments associated with non-alcoholic fatty liver disease, since the incidence of fatty liver is significantly higher in obese patients (Linden et al . , FASEB J , 20: 434-443, 2006).

In a related study, when a high fat or high sugar diet was fed to mtGPAT1 ^- deficient mice (mtGPAT1 ^{- / -} ) to induce obesity, CPT-1 and beta-oxidation (β oxidation) In addition, mtGPAT1-deficient mice (mtGPAT1 ^{- / -} ) showed a 37% decrease in triglyceride level compared with the control group and a 15% decrease in blood serum level of very low density lipoprotein (VLDL) Secretion was reduced by 30% and as a result, mtGPAT1 - / - mice were observed to increase insulin sensitivity after decreasing body weight and fat mass (Hammond et al, Mol Cell Biol 22: 8024-8214, 2002; Hammond et al, J Biol Chem 280: 25629-25636, 2005).

Thus, GPAT inhibition may be a point of inhibiting intracellular accumulation of triglycerides. Development of low molecular weight inhibitors that regulate the fat accumulation and energy metabolism of GPAT may be associated with obesity, type 2 diabetes, dyslipidemia, insulin resistance, It may be a strategy to develop a therapeutic agent for metabolic diseases such as hepatic insufficiency and nonalcoholic fatty liver.

Conventional mtGPAT inhibitor compounds include cyclopentenyl acetic acid derivatives (Eydysh et al. Bioorg. Med. Chem. 2010, 18: 6470-6479), 2- (nonylsulfonamido) and benzoic acid derivatives Eydysh et al., J. Med. Chem. 2009, 52: 3317-3327), but the IC ₅₀ value was in the range of 25 μM to 350 μM, showing a slight inhibitory activity as an enzyme inhibitor. The enzyme source used here is interpreted as the result of the rat mitochondrial fraction still at an early stage. Patents include Fasgen and Princeton University in the United States, and patent 1, which studies that genetic inhibition of mtGPAT and lipid metabolism enzymes is effective in inhibiting and treating various viral infections (WO 2011/019498).

On the other hand, Dipterocarpus Tuberculatus is a plant belonging to the genus Dipterocarpus, distributed in Bangladesh, Myanmar, Cambodia, India, Laos, Thailand and Vietnam, and is used as wood. The components and activity are not known.

Accordingly, the present inventors have found that Dextroctapus tuberculatus extract or its fractions effectively inhibited the enzyme activity of mtGPATl, inhibited the biosynthesis of triglycerides in the cells, and inhibited the production of skeletal muscle cells , Obesity, type 2 diabetes, insulin resistance, diabetes mellitus, and nonalcoholic fatty liver disease (OGTT) by increasing the glucose uptake in obese, The present invention has been completed based on this finding.

It is an object of the present invention to provide a pharmaceutical composition for preventing and treating metabolic diseases containing Dipterocarpus tuberculatus extract as an active ingredient.

Another object of the present invention is to provide a pharmaceutical composition for the prevention and treatment of metabolic diseases containing as an active ingredient a fraction obtained by fractionating the Dipterolokappus tuberculatus extract with an organic solvent.

In order to solve the above-mentioned problems, the present invention provides a pharmaceutical composition for preventing and treating metabolic diseases containing Dipterocarpus tuberculatus extract as an active ingredient.

The present invention also provides a pharmaceutical composition for the prevention and treatment of metabolic diseases, which comprises an active ingredient in a fraction obtained by fractionating Diptera luciferus tuberculatus extract with an organic solvent.

The present invention also provides a composition for a health food for preventing and improving metabolic diseases containing Diptera luciferus tuberculatus extract as an active ingredient.

In addition, the present invention provides a composition for a health food for preventing and improving metabolic diseases, which contains Diptera luciferus tuberculatus fraction as an active ingredient.

The Dipterocarpus < RTI ID = 0.0 > tuberculatus extract or its fractions have been found to effectively inhibit the activity of mtGPAT1 causing metabolic diseases and inhibit biosynthesis of intracellular triglycerides and increase insulin-dependent glucose uptake activity in skeletal muscle cells. Therefore, Tuberculous extract or its fractions can be usefully used for the prevention and treatment of metabolic diseases such as obesity, type 2 diabetes, gonadal hyperplasia and non-alcoholic fatty liver.

Figure 1 is a schematic representation of the Dipterocarpus < RTI ID = 0.0 > tuberculatus extract or fractions thereof in the HepG2 cells (human-derived hepatocytes).
FIG. 2 is a graph showing glucose uptake activity in L6 cells of rat skeletal muscle cells of extracts or fractions thereof of Diptera locaprus tuberculatus.
FIG. 3 is a graph showing an effect of inhibiting lipid accumulation by fatty acid induction in hepatocytes of Diptera locaprus tuberculatus extract or a fraction thereof.

Hereinafter, the present invention will be described in detail.

The term Dipterocarpus tuberculatus , as used in the present invention, means all organs of a natural, hybrid or variant of water, including, for example, roots, branches, stems, leaves and flowers, Is the bark of Dipterocarpus tuberculeus.

The present invention relates to Dipterocarpus < RTI ID = 0.0 > The present invention provides a pharmaceutical composition for preventing and treating metabolic diseases containing, as an active ingredient, an extract of P. tuberculatus .

The extract may be extracted with a solvent such as water, a C ₁ to C ₂ alcohol, or a mixture thereof. Specifically, the alcohol may be ethanol or methanol, but is not limited thereto.

The present invention also provides a pharmaceutical composition for the prevention and treatment of metabolic diseases containing as an active ingredient a fraction obtained by fractionating an extract of Diptera luciferus tuberculatus with an organic solvent.

The organic solvent may be chloroform or butanol, but is not limited thereto.

The fraction may be a chloroform fraction, a butanol fraction or a water fraction obtained by phylogenetically fractionating Diptera luciferus tuberculatus extract in the order of chloroform, butanol and water, but is not limited thereto.

The Diptera luciferus tuberculatus extract may be produced by, but not limited to, the following methods:

1) extracting Dextrolofus tuvaculatus with an extraction solvent;

2) cooling the extract of step 1) and filtering; And

3) Concentrating the filtered extract of step 2) under reduced pressure and drying.

In the above method, the Diptera luciferus tuberculatus of step 1) can be used without limitation such as cultivated or commercially available. The dipterocarpus tuberculatus may be, but not limited to, using a dipterocarpus tuberculeus bark.

As the extraction method of the Diptera luciferus tuberculatus extract, a conventional method in the art such as filtration, hot water extraction, immersion extraction, reflux cooling extraction and ultrasonic extraction can be used, and the extraction is performed once to 5 times by the hot water extraction method And may be, but is not limited to, repeating extraction three times more specifically. The extraction solvent may be added in an amount of 0.1 to 10 times, preferably 0.3 to 5 times, to the dried Diptera lycopersa tuberculatus. The extraction temperature may be 20 to 40 占 폚, but is not limited thereto. In addition, the extraction time may be 12 to 48 hours, but is not limited thereto.

In this method, the vacuum concentration of step 3) may be by using a vacuum decompression concentrator or a vacuum rotary evaporator, but is not limited thereto. The drying may be, but not limited to, vacuum drying, vacuum drying, boiling, spray drying or lyophilization.

The metabolic diseases may be selected from the group consisting of obesity, type 2 diabetes, insulin resistance, hepatic steatosis and non-alcohol fatty liver, but are not limited thereto.

The present inventors extracted Diptera lycopersa tuberculatus by pulverizing and dipping it in methanol to prepare Diptera lokapus tubaucuratus extract or fractions thereof. The extract was filtered and concentrated under reduced pressure to obtain a methanol extract. To extract the active substance, the Dextrocarpus tubercularis methanol extract was subjected to solvent fractionation with chloroform, butanol and water to obtain respective fractions. The fractions of human glycerol -3-phosphate acyltransferase (hGPAT1) inhibitory activity was measured. As a result, excellent inhibitory activity was confirmed.

Human hGPAT1 cDNA (NCBI accesstion No. NM_020918) was cloned into pFastBac1 vector in order to isolate hGPAT1 (human GPAT1) from hGPAT1 (human GPAT1) and to isolate hGPAT1 enzyme source. Then, recombinant bacmid DNA obtained was transformed into Sf9 cells and human hGPAT1 cDNA (Baculovirus) were assembled and amplified. Cells were harvested and homogenized using an ultrasonic cell scraper. Only the supernatant was taken and centrifuged. The obtained precipitate was suspended in sucrose buffer and used as an enzyme source of mitochondrial hGPAT1 (mitochondrial hGPAT1). The supernatant obtained by centrifuging the supernatant after removing the precipitate was suspended in a sucrose buffer and used as a microsomal hGPAT1 enzyme source.

In order to measure the inhibitory effect of human hGPAT1 on the activity of the microsomal hGPAT1 enzyme, its activity is lost by N-ethylmaleimide (NEM). When measuring only mitochondrial hGPAT1 activity, Ethylmaleimide was pretreated to disrupt microsomal hGPAT1 activity and then the experiment proceeded. HGPAT1 mitochondrial activity of the enzyme in the resulting reaction product ^[14 C] resources phosphatides diksan ^([14 C] Lysophosphatidic acid) was measured by the amount of radiation. The activity of mitochondrial hGPAT1 was measured by pretreatment of 2 mM N-ethylmaleimide in an ice bath for 15 minutes before the experiment to inactivate the activity of microsomal hGPAT1, and the activity of microsomal hGPAT1 The activity of the microsomal hGPAT1 enzyme source was corrected by measuring the ratio of total hGPAT1 activity and microsomal hGPAT1 enzyme activity by pre-treating the microsomal hGPAT1 enzyme source with N-ethylmaleimide (2 mM).

The substrates used for the enzyme reaction were [ ¹⁴ C] glycerol-3-phosphate (1.8 μM) and palmitoyl-CoA (100 μM) The reaction was stopped by water. The reaction mixture was separated into a water layer and a butanol layer by centrifugation and an upper layer (butanol layer) containing [ ¹⁴ C] lysophosphatidic acid as a reaction product was taken. The supernatant was separated into water layer and butanol layer by centrifugation with the same volume of water, and 600 μl of the supernatant was removed and the amount of radioactivity (Disintegrations per minute, DPM) was measured with a liquid scintillation counter (LSC) Respectively. The extract of Diptera luciferus tuberculatus prepared in Example 1 was treated to measure hGPAT1 enzyme activity. As a result, the extract of Diptera lokapus tuberculatus or its fraction showed excellent hGPAT1 inhibitory activity and hGPAT1 inhibitory activity in a concentration-dependent manner (see Table 1).

In order to examine the effect of the extract and fraction of the present invention on the triglyceride synthesis in cells, the inhibitory activity of triglyceride biosynthesis in a cell against one type of substrate was measured using human hepatocyte HepG2 cells . As a result, when each of the fractions of Dipteracificus tuberculatus or its extract was treated at a concentration of 10 and 30 μg / ml and [ ¹⁴ C] glycerol was used as a substrate, as shown in Table 2, each fraction contained triglycerides And inhibited strong neutral fat biosynthesis in the CHCl3 fraction (see Table 2 and Figure 1).

To measure glucose uptake in L6 cells (rat skeletal myoblast cell line) of extracts or fractions of Diptera locapus tuberculatus, the differentiated L6 cells were treated with Dipteractococcus tabacuratus extract and fractions including insulin And cultured in Krebs-Ringer Buffer (KRB). 2-deoxy-D-glucose and labeled 2-deoxy-D- [ ¹⁴ C] glucose, 0.2 μCi / ml) and allowed to react for 10 minutes. After the reaction, the glucose uptake into the cells was measured by a scintillation counter. As a result, when Dipteractifus tuberculatus extract or fraction was treated at 30 ㎍ / ml for 3 hours or 6 hours, glucose intake was significantly increased in the aqueous and chloroform fractions compared to the control (DMSO). Glucose uptake was increased 1.4 times (chloroform fraction) and 2.2 times (water fraction) compared to the control group at 24 hours treatment (see FIG. 2).

Oral glucose tolerance test was carried out to examine the blood glucose lowering effect of oral administration of Dextroceropus tuberculatus extract. Five week old ICR mice were obtained and after one week of purification, the mice were fasted for 16 hours on the day before the test. In the test group, the fasted mice were orally administered with 100 mg / kg or 300 mg / kg of Diptera luciferus tuberculatus fraction at 90 minutes before administration of D - (+) - glucose. D - (+) - Glucose was orally administered to each mouse in an amount of 0.2 ml per 20 g. After taking D - (+) - glucose, blood samples were collected by time (15, 60, 120 min) and blood glucose level was measured. 0.5% CMC in the normal control group and 500 mg / kg metformin in the positive control group. Eight mice per group were used. The results were evaluated by the t-test to determine the statistical significance of the inhibition rate (%) of the blood glucose increase in the test substance-administered group compared to the solvent control group. In the case of 300 mg / kg of water fraction, the blood glucose level was increased by 25.2% in the 15th minute and 23.8% in the 60th minute (see Table 3).

Therefore, the Diptera locaprus tuberculatus extract or fraction thereof according to the present invention effectively inhibits the activity of mtGPAT1 causing metabolic diseases, and inhibits biosynthesis of intracellular triglycerides and glucose uptake activity in skeletal muscle cells The Dipterolokapus tubaucuratus extract of the present invention or a fraction thereof is used as an active ingredient of a pharmaceutical composition for the prevention and treatment of metabolic diseases such as obesity, type 2 diabetes, insulin resistance, hepaticopathy, and nonalcoholic fatty liver .

The composition of the present invention may contain 0.1 to 99.9% by weight of the Dextroceropus tuarvacularis extract of the present invention or a fraction thereof as an active ingredient, and may include a pharmaceutically acceptable carrier, excipient or diluent.

The compositions of the present invention may be of various oral or parenteral formulations. In the case of formulation, a diluent or excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, or a surfactant is usually used. Solid formulations for oral administration include tablets, pills, powders, granules, capsules, and the like, which may contain one or more excipients such as starch, calcium carbonate, sucrose or lactose lactose, gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate, talc, and the like may also be used. Liquid preparations for oral administration include suspensions, solutions, emulsions, syrups and the like. Various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included in addition to water and liquid paraffin, which are simple diluents commonly used. have. Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories.

Examples of non-aqueous solvents and suspensions include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, injectable esters such as ethyl oleate, and the like. Examples of the suppository base include witepsol, macrogol, tween 61, cacao paper, laurin, glycerogelatin and the like.

The composition of the present invention may be administered orally or parenterally, and it is preferable to select the intraperitoneal, rectal, rectal, intravenous, intramuscular, subcutaneous, intrauterine or intracerebral injection methods for parenteral administration, It is used for external skin.

The dosage of the composition of the present invention varies depending on the patient's body weight, age, sex, health condition, diet, time of administration, administration method, excretion rate and severity of disease, and the daily dose is Dipterolokapus tuberculatus Preferably from 30 to 500 mg / kg, more preferably from 50 to 300 mg / kg, based on the amount of the extract, and may be administered 1 to 6 times a day.

The composition of the present invention may be used alone or in combination with methods using surgery, radiation therapy, hormone therapy, chemotherapy, and biological response modifiers.

The present invention also provides a method for the prevention or treatment of metabolic diseases comprising the step of administering to said individual a pharmaceutically effective amount of said composition.

The metabolic diseases may be selected from the group consisting of obesity, type 2 diabetes, insulin resistance, hepatic insufficiency, and non-alcoholic fatty liver, but is not limited thereto.

The pharmaceutically effective amount is 0.0001 to 100 mg / kg, and 0.001 to 10 mg / kg, but is not limited thereto. The dose may vary depending on the weight, age, sex, health condition, diet, administration period, method of administration, rate of elimination, severity of disease, and the like of a particular patient.

The composition can be administered orally or parenterally at the time of clinical administration and can be administered orally or parenterally in the case of parenteral administration by intraperitoneal injection, rectal injection, subcutaneous injection, intravenous injection, intramuscular injection, intrauterine injection, intracerebral injection, And may be used in the form of a general pharmaceutical preparation.

The subject is a vertebrate animal, specifically a mammal, and more specifically, an experimental animal such as a mouse, a rabbit, a guinea pig, a hamster, a dog, or a cat, and more specifically an ape-like animal such as a chimpanzee or a gorilla have.

In the present invention, "administering" means introducing a predetermined substance into a patient in any appropriate manner, and the administration route of the substance can be administered through any conventional route so long as it can reach the target tissue. But are not limited to, intraperitoneal, intravenous, intramuscular, subcutaneous, intradermal, oral, topical, intranasal, intrathecal, rectal. In addition, the pharmaceutical composition may be administered by any device capable of moving the active substance into the target cell.

Also, the phrase "administering" means that the composition of the present invention is introduced into a pancreatic cancer cell by "systemic delivery" or "topical delivery "."Systemicdelivery" refers to delivery which results in a broad-spectrum biodistribution of compounds within an organism. Some administration techniques may lead to systemic delivery of certain compounds, while others may not. Systemic delivery means that a useful, preferably therapeutically effective amount of a compound is exposed to the majority of the body. Generally, in order to obtain a global bio-distribution, it is desirable that the compound not be rapidly degraded or removed prior to reaching the diseased site far from the site of administration (e.g., by first passage organ (liver, lung, etc.) In the blood) is required. As used herein, "topical delivery" refers to direct delivery of a compound to a target site in an organism. For example, the compound may be delivered locally by direct injection into a diseased site, such as a tumor or other target site, e.g., a target organ such as the pancreas.

The present invention also provides a composition for a health food for preventing and improving metabolic diseases, which contains Diptera locaprus tuberculatus extract as an active ingredient.

The organic solvent may be chloroform or butanol, but is not limited thereto.

The Diptera luciferus tuberculatus extract may be produced by, but not limited to, the following methods:

1) extracting Dextrolofus tuvaculatus with an extraction solvent;

2) cooling the extract of step 1) and filtering; And

3) Concentrating the filtered extract of step 2) under reduced pressure and drying.

In the above method, the Diptera luciferus tuberculatus of step 1) can be used without limitation such as cultivated or commercially available. The dipterocarpus tuberculatus may be, but not limited to, using a dipterocarpus tuberculeus bark.

As the extraction method of the Diptera luciferus tuberculatus extract, a conventional method in the art such as filtration, hot water extraction, immersion extraction, reflux cooling extraction and ultrasonic extraction can be used, and the extraction is performed once to 5 times by the hot water extraction method And may be, but is not limited to, repeating extraction three times more specifically. The extraction solvent may be added in an amount of 0.1 to 10 times, preferably 0.3 to 5 times, to the dried Diptera lycopersa tuberculatus. The extraction temperature may be 20 to 40 占 폚, but is not limited thereto. In addition, the extraction time may be 12 to 48 hours, but is not limited thereto.

In this method, the vacuum concentration of step 3) may be by using a vacuum decompression concentrator or a vacuum rotary evaporator, but is not limited thereto. The drying may be, but not limited to, vacuum drying, vacuum drying, boiling, spray drying or lyophilization.

The metabolic diseases may be selected from the group consisting of obesity, type 2 diabetes, insulin resistance, hepatic steatosis and non-alcohol fatty liver, but are not limited thereto.

In addition, there is provided a composition for a health food for preventing and improving metabolic diseases, which contains Dipteractifus tuberculatus fraction as an active ingredient.

The fraction may be a chloroform fraction, a butanol fraction or a water fraction obtained by phylogenetically fractionating Diptera luciferus tuberculatus extract in the order of chloroform, butanol and water, but is not limited thereto.

The metabolic diseases may be selected from the group consisting of obesity, type 2 diabetes, insulin resistance, hepatic steatosis and non-alcohol fatty liver, but are not limited thereto.

The functional food of the present invention may contain various flavors or natural carbohydrates as an additional ingredient. Such natural carbohydrates are monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, and polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol and erythritol. Examples of sweeteners include natural sweeteners such as tau martin and stevia extract, synthetic sweeteners such as saccharin and aspartame, and the like. The ratio of the natural carbohydrate may be selected from the range of 0.01 to 0.04 part by weight, specifically about 0.02 to 0.03 part by weight per 100 parts by weight of the health food of the present invention.

In addition to the above, the functional food of the present invention may contain various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusting agents, stabilizers, preservatives, , A carbonating agent used in carbonated drinks, and the like. In addition, the functional food of the present invention may contain flesh for the production of natural fruit juice, fruit juice drink and vegetable drink. These components may be used independently or in combination. The proportion 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 health food of the present invention.

Hereinafter, the present invention will be described in detail with reference to Examples, Experimental Examples and Production Examples.

It should be noted, however, that the following Examples, Experimental Examples and Preparation Examples are merely illustrative of the present invention, and the content of the present invention is not limited by the following Examples, Experimental Examples and Preparation Examples.

< Example  1> Dipter Rocarpus Tuberculatus  Preparation of extract

<1-1> Dipter Rocarpus Tiberaculatus  Preparation of methanol extract

100 g of dried Dipter rotifus tuvaculatus (Korea Plant Extract Banks, Korea Research Institute of Bioscience and Biotechnology) was pulverized and immersed in 2 L of methanol and extracted twice for 7 days. The extract was filtered and concentrated under reduced pressure to obtain about 15 g of a methanol extract.

<1-2> Dipter Rocarpus Tiberaculatus  Preparation of ethanol extract

100 g of the dried Dipter rotifers tuberculatus was pulverized and immersed in 2 L of ethanol and extracted twice for 7 days. The extract was filtered, and concentrated under reduced pressure to obtain 13 g of an ethanol extract.

<1-3> Dipter Rocarpus Tiberaculatus  Preparation of water extract

100 g of dried Dipter rotifers tuberculatus was pulverized and immersed in 2 L of water and extracted twice for 7 days. The extract was filtered and concentrated under reduced pressure to obtain 10 g of a water extract.

< Example  2> Dipter Rocarpus Tuberculatus Fraction  Produce

In order to track the active substance, 10 g of the Diptera lokapus tsuberculosis methanol extract obtained in Example <1-1> was suspended in 200 ml of distilled water, and then chloroform 100 ml was added thereto to carry out fractionation. The chloroform fraction 3 g of methanol extract was concentrated under reduced pressure. The methanol extract was suspended in water and then extracted first with chloroform. Then, 100 ml of butanol was added to the water layer and fractionated to obtain 3 g of butanol fraction. The fractions were fractionated with methanol and butanol, To obtain 4 g of a water fraction.

< Example  3> Human origin hGPAT1 ( human GPAT1 ) &Lt; / RTI &gt; Enzyme source  detach

Human-derived hGPAT1 cDNA (NCBI accesstion No. NM_020918) was cloned into pFastBac1 vector (Invitrogen), and the resulting recombinant bacmid DNA was transformed into Sf9 cells to assemble and amplify baculovirus containing human hGPAT1 cDNA . Sf9 cells (1 × 10 ⁶ cells / ml) were infected with 10 MOI of virus. After 48 hours, the cells were recovered by centrifugation and homogenized buffer (250 mM sucrose, 10 mM Tris 7.4), 1 mM EDTA) and homogenized using an ultrasonic cell crusher. The supernatant was centrifuged at 8,000 g for 15 minutes, and the resulting precipitate was suspended in sucrose buffer (250 mM sucrose, 10 mM Tris (pH 7.4), 1 mM EDTA, 1 mM DTT ), And the concentration of the protein was determined by the Bradford Method, which was stored at -80 ° C and used in the experiment.

< Experimental Example  1> Dipter Rocarpus Tuberculatus  Extract and its Fraction  Identification of human hGPAT1 activity

Mitochondrial proteins isolated from sf9 cells overexpressing human-derived hGPAT1 were used as enzyme sources

HGPAT1 mitochondrial activity of the enzyme is measured by the radiation amount of the reaction product of ^[14 C] resources phosphatides diksan ^([14 C] Lysophosphatidic acid) produced by mitochondria hGPAT1 enzyme source derived from a human body. The activity of mitochondrial hGPAT1 was measured by pretreatment of 2 mM N-ethylmaleimide in an ice bath for 15 minutes before the experiment to inactivate the activity of microsomal hGPAT1, and the activity of microsomal hGPAT1 The activity of the microsomal hGPAT1 enzyme source was corrected by measuring the ratio of total hGPAT1 activity and microsomal hGPAT1 enzyme activity by pre-treating the microsomal hGPAT1 enzyme source with N-ethylmaleimide (2 mM).

The substrate used for the enzyme reaction was [ ¹⁴ C] glycerol-3-phosphate (1.8 μM) and palmitoyl-CoA (100 μM) , 4 mM MgCl ₂ , 8 mM NaF, 2 mg / ml BSA) at 26 ° C for 20 minutes, and the reaction was stopped by water-saturated butanol and water. The reaction product was separated into a water layer and a butanol layer by centrifugation and 800 μl of an upper layer (butanol layer) containing [ ¹⁴ C] lysophosphatidic acid as a reaction product was taken. The supernatant was separated into water layer and butanol layer by centrifugation with the same volume of water, and 600 μl of the supernatant was removed and the amount of radioactivity (Disintegrations per minute, DPM) was measured with a liquid scintillation counter (LSC) Respectively. The hGPAT1 enzyme activity was measured by treating the final concentration of the Diptera lokapus tubaucuratus extract or its fraction prepared in Example 1 or Example 2 at a concentration of 30 and 100 占 퐂 / ml. The inhibition rate of hGPAT1 enzyme activity by the sample was calculated by the following formula (1).

[Equation 1]

(%) = {1 - [(T-B) / (C-B)]} 100

T: DPM value of the test solution containing the sample in the enzyme reaction solution,

C: DPM value of the control sample not containing the sample in the enzyme reaction solution, and

B: DPM value of the control sample without the enzyme source added.

The hGPAT1 inhibitory activity of the Diptera locusta Tuberculosis extract and fraction of the present invention is shown in [Table 1].

As a result, as shown in Table 1, the extract of Dipteracificus tuberculatus or its fraction showed excellent hGPAT1 inhibitory activity and hGPAT1 inhibitory activity in a concentration-dependent manner.

The hGPAT1 inhibitory activity of the extracts of Diptera lokapus toubaculatus and each fraction Extract / fraction Final concentration ([mu] g / ml) Inhibition rate (%) hGPAT1 hDGAT1 hDGAT2 Methanol extract 30 73.6 16.1 22.7 100 91.9 35.7 47.7 Chloroform fraction 30 3.3 5.2 35.3 100 29.7 23.9 40.1 Butanol fraction 30 57.1 19.4 31.4 100 86.1 30.2 55.1 Water fraction 30 68.3 15.5 12.7 100 91.7 23.8 12.5

As shown in [Table 1] and [Fig. 1], the extracts and fractions of Diptera luciferus tuberculatus of the present invention had excellent hGPAT1 inhibitory activity and hGPAT1 inhibitory activity in a concentration-dependent manner. However, another enzyme, acyltransferase, catalyzes the last stage of triglyceride biosynthesis, and the hDGAT1 and hDGAT2 enzymes exhibit weak inhibitory activity. Thus, the extract of Diptera luciferus tuberculatus or its fractions selectively inhibited hGPAT1.

< Experimental Example  2> Dipter Rocarpus Tuberculatus  Extract and its The fraction HepG2  Confirmation of neutral fat biosynthesis inhibition in cells

In order to examine the effect of the extract and fraction of the present invention on the triglyceride synthesis in cells, the inhibitory activity of triglyceride biosynthesis in one cell was measured using HepG2 cells as a human derived hepatocyte . HepG2 cells were purchased from ATCC and cultured in minimal essential medium (MEM; 2 mM L-glutamine; 1.5 g / L sodium bicarbonate, 0.1 mM nonessential amino acids and 1 mM (BSS) medium supplemented with sodium pyruvate was supplemented with 10% fetal bovine serum (FBS) and 1% antibiotic (100 U / ml penicillin and 100 g / ml streptomycin ) Was added thereto and cultured in a 37 ° C and 5% CO ₂ incubator. The activity of hGPAT1 enzyme was measured by the amount of triglyceride produced in cultured HepG2 cells. After the addition of the extract and fraction as an enzyme inhibitor, the effect of the enzyme inhibitor was determined according to the decrease rate of triglyceride production. 24 well (well) as a culture seeded in a plate of 1 × 10 ⁶ cells / ml per well of cells and replaced with 24 hours FBS is DMEM (Dulbecco's modified Eagle's medium ) that does not exist after incubation medium substrate ^[14 C ] Glycerol ([ ¹⁴ C] glycerol) was added and reacted for 18 hours. Samples were dissolved in dimethyl sulfoxide (DMSO), and the control in the neutral fat production reaction was carried out with dimethyl sulfoxide alone without adding the sample. The yield of the resulting triglyceride was 100 .

In order to measure the amount of triglyceride produced in the cells after the reaction, [ ¹⁴ C] glycerol, which is a substrate remaining in the medium, which was not absorbed into the cells, was removed and removed once with phosphate-buffered saline (PBS) 0.5 ml of a post-extraction solvent (hexane: isopropanol = 3: 2, v: v) was added to extract whole fat including neutral fat. After extracting with 0.5 ml of extraction solvent twice for 30 minutes, 1 ml of the extract was concentrated through nitrogen gas. After removing the extraction solvent, whole fat was dissolved in an organic solvent (chloroform: methanol = 2: 1) and thin layer chromatography (TLC: (Hexane: diethyl ether: acetic acid = 80: 20: 1, v: v: v) on a silica gel 60 F ₂₅₄ , thickness 0.5 mm, Merck) Respectively. After separating the triglyceride (Rf value: 0.4) on the TLC, the TLC plate was exposed to a radiation-sensitive film for 3 hours, and then analyzed by image analysis (BAS-1500, Fuji Photo Film Co. Ltd.) Fat [ ¹⁴ C] radioactivity was measured. After the extraction, the remaining cells were dissolved in 0.3 ml of 0.1 N sodium hydroxide and used to measure the protein concentration of the cells used in the reaction. The amount of neutral fat produced by the Diptera lokapus tubaucuratus extract of the present invention or its fractions was calculated by measuring the amount of radioactivity in triglyceride and dividing the protein concentration by the experimental value and correcting the experimental error between the test groups.

As a result, when [ ¹⁴ C] glycerol was used as a substrate, the production of triglyceride in the cells was inhibited by methanol (30 μg / ml) and the fractions of Dipteracificus tuberculatus extract or its fractions were treated at a concentration of 30 μg / 31.0% of the extract, 58.7% of the chloroform fraction, 75.4% of the butanol fraction and 5.6% of the water fraction were inhibited (Table 2 and Fig. 1).

Inhibitory activity of neutral lipid biosynthesis in hepatocyte (HepG2 cell) of Dipter rotifus tuberculatus extract or its fraction Extraction / fraction ([mu] g / ml) Triglyceride production (% of control) The control (DMSO) 10 [mu] g / ml 30 [mu] g / ml Methanol extract 100 84.8 69.0 Chloroform fraction 100 50.9 41.3 Butanol fraction 100 36.5 24.6 Water fraction 100 96.3 94.4

< Experimental Example  3> Dipter Rocarpus Tuberculatus  Extract and its Fraction  Increased glucose uptake in skeletal muscle cells

L6 myoblasts were cultured in DMEM (4 mM L-glutamine, 1.5 g / L sodium hydrogencarbonate, 4.5 g / L glucose) medium containing 10% FBS. Cells cultured on a 24-well plate were washed twice with PBS in a state where 80% of the cells were grown on the whole surface of the medium, and then cultured in 0.2% FBS DMEM (4 mM L-glutamine, 1.5 g / L sodium hydrogencarbonate and 1 g / L glucose) medium and cultured for 24 hours. Under these conditions, cells in the myoblastes state differentiate into myotubes. Differentiated L6 cells were transfected with insulin and Dipterocarpus tuberculeus

The extract and butanol fractions were treated at a concentration of 30 μg / ml for a certain period of time (1, 3, 6 and 24 hours) and then cultured in Krebs-Ringer Buffer (KRB) for 30 minutes. To the cells cultured in KRB, 0.1 mM 2-deoxy-D-glucose and labeled 2-deoxy-D- [ ¹⁴ C] glucose, 0.2 μCi / ml) was treated and reacted for 10 minutes. KRB buffer was removed from the cells after the reaction, washed three times with KRB buffer, and the cells were lysed with 1 M sodium hydroxide (NaOH). Cells dissolved in 1 M sodium hydroxide were measured with a scintillation counter to determine glucose uptake.

As a result, the treatment of Diptera rotifus tuberculatus extract or fraction significantly increased glucose uptake in the aqueous and chloroform fractions compared to the control (DMSO). Glucose intake was increased 1.4 times (chloroform fraction) and 2.4 times (water fraction) compared to the control group for 24 hours at a concentration of 30 ug / ml (FIG. 2).

< Experimental Example  4> Dipter Rocarpus Tuberculatus  Extract and its Fraction  cell( Huh7 ) Was confirmed to inhibit fatty acid-induced fat accumulation

Hepatocyte Huh 7 was cultured for 3 days in high glucose DMEM (Dulbecco's medium Eagle's medium, glucose 25 mM) containing 10% FBS (fetal bovine serum) Cells were seeded at ⁵ cells / ml and cultured for 24 hours. Oleate (10 mM) and sample were treated simultaneously and cultured in an incubator for 24 hours. At this time, oleic acid was treated with 5% BSA (bovine serum albumin, fatty acid free) and high glucose DMEM medium free of FBS. After the medium was removed, the cells were fixed with 3.8% formaldehyde for 30 minutes at room temperature, treated with a fat-specific staining agent Nile red at a concentration of 1 μg / ml, and stained at room temperature for 10 minutes . Subsequently, the level of intracellular fat reduction was quantified using a flow cytometer (BD FACS Caliber, BD Bioscience, USA) and fluorescence image was observed using a fluorescence microscope (Nicon ELIPSETi, Nicon, Japan).

As a result, as shown in Fig. 3, the amount of fat in the sample treated with fluorescence decreased. The results were as follows: 1 mM oleate treatment showed 5 times fat accumulation compared to negative control. Methanol extract and solvent fraction, chloroform, butanol and water fraction were added at 30 ㎍ / ml (27%, 11%, 21%, and 11%, respectively) (Fig. 3).

< Experimental Example  5> Dipter Rocarpus Tuberculatus  water Fraction  Confirming the effect of inhibiting blood sugar increase

Oral glucose tolerance test was conducted to test the blood glucose lowering effect by oral administration of samples of Dipter rotifus tuberculatus water fractions.

Specifically, 5 weeks old ICR mice were obtained and after one week of purification, mice were fasted for 16 hours on the day before the test. In the test group, the fasted mice were orally administered with 100 mg / kg and 300 mg / kg of Diptera lycopersa tuberculatus fractions 90 minutes before the administration of D - (+) - glucose. D - (+) - Glucose was orally administered to mouse orbital vein immediately before administration of D - (+) - glucose and 0.2 ml per 20 g of D - (+) - glucose. After taking D - (+) - glucose, blood samples were collected by time (15, 60, 120 min) and blood glucose level was measured. Carboxy methyl cellulose (CMC) was orally administered at a dose of 500 mg / kg for metformin in the positive control group (vehicle control, vehicle control group) and 0.5% carboxymethyl cellulose (CMC) Eight mice per group were used. The results were evaluated by the t-test to determine the statistical significance of the inhibition rate (%) of the blood glucose increase in the test substance-administered group compared to the solvent control group.

As a result, as shown in Table 3, it was confirmed that blood glucose lowering effect by glucose administration was 25.2% at 15 minutes and 23.8% at 60 minutes when 300 mg / kg of water fraction was administered (Table 3).

Blood glucose lowering effects by oral administration of water fractions and positive control substances Treatment group (n = 8) Throughput (mg / kg) Glucose change before and after glucose administration (mg / dL) 0 minutes 15 minutes 60 minutes 120 minutes Vehicle control
(0.5% CMC) 0 76.9 ± 7.0 342.4 + - 43.7 149.4 ± 24.2 91.3 ± 5.0 Water fraction 100 78.3 ± 8.9 325.6 ± 51.8 140.9 ± 10.9 95.6 ± 11.6 300 78.8 ± 10.6 255.9 ± 25.9 *** 113.8 ± 9.6 ** 89.5 ± 6.1 Metformin 500 79.3 ± 10.4 137.5 ± 20.5 *** 93.1 ± 13.2 *** 81.1 ± 9.7

**: p < 0.01, ***: p < 0.001.

< Formulation example  1> Preparation of pharmaceutical preparations

<1-1> Sanje  Produce

0.1 g of Diptera locaprus tubercutatus methanol extract of Example < 1-1 >

Lactose 1.5 g

Talc 0.5 g

The above ingredients were mixed and filled in an airtight container to prepare powders.

<1-2> Manufacture of tablets

0.1 g of Diptera locaprus tubercutatus methanol extract of Example < 1-1 >

Lactose 7.9 g

Crystalline cellulose 1.5 g

0.5 g of magnesium stearate

After mixing the above ingredients, tablets were prepared by direct tableting method.

<1-3> Preparation of capsules

0.1 g of the extract of Diptera lokapus tubaucuratus ethanol of Example < 1-1 >

5.0 g of corn starch

4.9 g of carboxycellulose

After mixing the above components to prepare a powder, the powder was filled in a hard capsule according to a conventional preparation method of a capsule to prepare a capsule.

&Lt; 1-4 > Preparation of injection

0.1 g of the extract of Diptera lokapus tubaucuratus ethanol of Example < 1-1 >

Sterile sterilized water for injection

pH adjuster

(2 ml) per ampoule according to the usual injection preparation method.

<1-5> Liquid  Produce

0.1 g of the extract of Diptera lokapus tubaucuratus ethanol of Example < 1-1 >

10.0 g per isomer

Mannitol 5.0 g

Purified water quantity

Each component was dissolved in purified water in accordance with a conventional method for producing a liquid agent, and the lemon flavor was added in an appropriate amount, followed by mixing the above components. Then, purified water was added to adjust the total amount to 100, and the solution was filled in a brown bottle and sterilized to prepare a liquid preparation.

< Manufacturing example  2> Manufacture of health food

<2-1> Production of flour food

0.5 to 5.0 parts by weight of the Diptera lokapus tsubecularis water fraction of Example 2 was added to wheat flour and the mixture was used to prepare bread, cake, cookies, crackers and noodles.

<2-2> soup  And juicy ( gravies )

0.1 to 5.0 parts by weight of the Diptera lokapus tsubecularis water fraction of Example 2 was added to the soup and juice to prepare a meat product for health promotion, soup of noodles and juice.

<2-3> Ground Beef  Produce

10 parts by weight of the Diptera lokapus tsuberculosis water fraction of Example 2 was added to ground beef to prepare ground beef for health promotion.

<2-4> Dairy products ( dairy products )

5 to 10 parts by weight of the extract of Diptera lokapus tsuberculosis of Example <1-1> was added to milk, and various dairy products such as butter and ice cream were prepared using the milk.

<2-5> Solar  Produce

Brown rice, barley, glutinous rice, and yulmu were dried by a known method and dried, and the mixture was granulated to a powder having a particle size of 60 mesh.

Black soybeans, black sesame seeds, and perilla seeds were steamed and dried by a conventional method, and then they were prepared into powder having a particle size of 60 mesh by a pulverizer.

The extract of Diptera locapus tuberculatus in Example <1-1> was concentrated under reduced pressure in a vacuum concentrator, dried by spraying and dried in a hot-air drier, and pulverized to a size of 60 mesh with a pulverizer to obtain a dry powder.

The grains, seeds, and the Diptera luciferus tubercularis water extract of Example <1-1> were prepared in the following proportions:

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

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

(3 parts by weight) of the Diptera locaprus tuberculatus fraction of Example 1,

(0.5 parts by weight), and

Rhubarb (0.5 parts by weight).

<2-6> Production of health supplement foods

100 mg < tb > &lt; tb &gt; &lt; tb &gt; &lt; tb &

Vitamin mixture quantity

70 [mu] g of vitamin A acetate

Vitamin E 1.0 mg

0.13 mg vitamin B1

0.15 mg of vitamin B2

0.5 mg vitamin B6

0.2 [mu] g vitamin B12

10 mg vitamin C

Biotin 10 μg

Nicotinic acid amide 1.7 mg

50 ㎍ of folic acid

Calcium pantothenate 0.5 mg

Mineral mixture quantity

1.75 mg of ferrous sulfate

0.82 mg of zinc oxide

Magnesium carbonate 25.3 mg

15 mg of potassium phosphate monobasic

Secondary calcium phosphate 55 mg

Potassium citrate 90 mg

100 mg of calcium carbonate

24.8 mg of magnesium chloride

Although the composition ratio of the above-mentioned vitamin and mineral mixture is comparatively mixed with a composition suitable for health food as a preferred embodiment, the compounding ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional method for producing healthy foods , Granules can be prepared and used in the manufacture of health food compositions according to conventional methods.

< Manufacturing example  3> Health drink  Produce

100 mg < tb > &lt; tb &gt; &lt; tb &gt; &lt; tb &

Citric acid 100 mg

100 mg of oligosaccharide

2 mg of plum concentrate

100 mg taurine

Purified water was added to 500 ml

The above components were mixed according to a conventional health drink manufacturing method, and the mixture was heated at 85 DEG C for about 1 hour with stirring, and the resulting solution was filtered to obtain a sterilized 1 liter container, sealed sterilized, It is used in the production of the health beverage composition of the invention.

Although the composition ratio is a mixture of the components suitable for the preferred beverage as a preferred embodiment, the blending ratio may be arbitrarily varied according to the regional and national preferences such as the demand level, the demanding country, and the intended use.

Claims (13)

From the group consisting of obesity, type 2 diabetes, dyslipidemia, insulin resistance, hepatic steatosis and fatty liver containing the extract of Dipterocarpus tuberculatus as active ingredient A pharmaceutical composition for the prevention and treatment of selected diseases.
The method according to claim 1, wherein the extract is extracted with a solvent that is water, a C ₁ to C ₂ alcohol, or a mixture thereof, wherein the extract is selected from the group consisting of obesity, type 2 diabetes, dyslipidemia, insulin resistance, Wherein the pharmaceutical composition is for the prevention and treatment of diseases selected from the group consisting of gastrointestinal disorders.
The pharmaceutical composition according to claim 2, wherein the alcohol is ethanol or methanol. A pharmaceutical composition for the prevention and treatment of diseases selected from the group consisting of obesity, type 2 diabetes, dyslipidemia, insulin resistance, gonadal hyperplasia and non- Gt;
delete Prevention and treatment of diseases selected from the group consisting of obesity, type 2 diabetes, dyslipidemia, insulin resistance, diabetic retinopathy and non-alcoholic fatty liver containing fractions obtained by fractionating the extract of Dipter rotifus tuberculatus with an organic solvent A pharmaceutical composition.
6. The method according to claim 5, wherein the organic solvent is chloroform or butanol. 4. A method for preventing and treating diseases selected from the group consisting of obesity, type 2 diabetes, dyslipidemia, insulin resistance, gonadal hyperplasia and non- A pharmaceutical composition.
[Claim 5] The method according to claim 5, wherein the fraction is a chloroform fraction, a butanol fraction or a water fraction obtained by phylogenetically fractionating the Dextroctapus tuberculatus extract in the order of chloroform, butanol and water. A pharmaceutical composition for the prophylaxis and treatment of diseases selected from the group consisting of hyperlipidemia, hyperlipidemia, hyperlipidemia, hyperlipidemia, hyperlipidemia, hyperlipidemia, insulin resistance,
delete A composition for a health food for preventing and ameliorating a disease selected from the group consisting of obesity, type 2 diabetes, dyslipidemia, insulin resistance, diabetic retinopathy and non-alcoholic fatty liver comprising Diptera locaprus tuberculatus extract as an active ingredient.
delete A composition for a health food for preventing or ameliorating a disease selected from the group consisting of obesity, type 2 diabetes, dyslipidemia, insulin resistance, gonadal hyperplasia and non-alcoholic fatty liver comprising Diptera luca persa Tuberculatus fractions as an active ingredient.
12. The method according to claim 11, wherein the fraction is a fraction obtained by fractionating Diptera luciferus tuberculatus extract with an organic solvent of chloroform or butanol. 12. The method according to claim 11, wherein the fraction is a fraction of obesity, type 2 diabetes, dyslipidemia, insulin resistance, And a non-alcoholic fatty liver. delete

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