KR101791631B1 - Composition for Anti-obesity Using an Extract of Trigonostemon reidioides - Google Patents

Abstract

The present invention discloses an anti-obesity composition using trigone nostemone radiodes extract having the activity of inhibiting the differentiation of precursor adipocytes into adipocytes.

Description

TECHNICAL FIELD The present invention relates to a composition for an anti-obesity using an extract of Trigonosynthomonadilis,

The present invention relates to the use of Trigonostemon reidioides extract of the present invention.

Obesity refers to the state of excess energy accumulation in body fat due to the imbalance of energy intake and consumption (Korean J Obes 2002; 11 (3): 263-65).

Obesity is caused by a variety of causes including dietary, environmental effects and changes in eating habits such as high fat and high calorie diet, lack of exercise due to busy social environment, and endocrine abnormalities (Am J Clin Nutr 1998: 67: 563 And it is known that it induces various endocrine diseases such as diabetes, hyperlipidemia, hypertension, coronary artery disease, and the like. (Endocrinol Metab. 2010. 25 (4): 301-304).

The World Health Organization (WHO) has classified obesity as a disease, not a phenomenon or symptom, and reported that by 2015, the global obesity population will increase to 1.5 billion people and become a major health problem (Ann Epidemiol. 2005. 15: 87-97; J Life Sci., 2013. 23: 69-78).

In Korea, according to the National Health and Nutrition Examination Survey (2013), the prevalence of obesity (over 19 years old, standardized) is 31.8%, and 3 out of 10 Korean adults are obese (Knhanes, Health Behavior and Chronic Disease Statistics, 2013)

The energy in the body is stored in the form of triglyceride in the fat cells. When the energy source in the body is exhausted, the stored fat is decomposed into free fatty acid and glycerol and used as an energy source. However, And increases the amount of stored fat in the body, which is a direct cause of obesity.

The mechanism of pharmacological action for the development of obesity therapy has been divided into three categories: the mechanism of interfering with the absorption of fat in the small intestine, the mechanism of suppressing the appetite, and the excess energy entering the body into fat And promote the metabolism of energy in the body and release it into heat.

Xenical ™ (Roche Pharmaceuticals, Switzerland) is a representative treatment for obesity using a pharmacological mechanism to inhibit fat digestion and absorption, and Reductil ™ (Abbott Laboratories, Inc.) is a representative treatment for obesity using a pharmacological mechanism to suppress appetite. , USA). Exorise (Exorise ™, Acopama, France) is a representative treatment for obesity using a pharmacological mechanism for promoting energy metabolism in the body.

Most of the currently used treatments for obesity have adverse side effects such as abdominal pain, nausea, vomiting, headache, insomnia, gastrointestinal disorders, and elevated blood pressure. Reducetil (sibutramine) has already been withdrawn from the market in 2010 due to controversy over cardiovascular side effects. Therefore, efforts are being actively made to develop new drugs from natural products with relatively few side effects (J Korean Med Obes Res 2013, 13 (2): 74-75).

In addition, fat cells are differentiated from lipid precursors, which triggers the accumulation of triglycerides and induces the expression of adipocyte-specific proteins (aP2, FAS, GLUT4, LPL, leptin) C / EBR?, C / EBR? and C / EBR?), adipocyte determination differentiation factor 1 (SREBP1c) / (sterol regulatory element binding protein 1c (Genes De 2000, 14 (11) 1293-1307) (Physiol Rev 1998, 78 (3): 783-809), which are known to play a pivotal role in transcription factors called adipokines and adipokines Annu Rev Biochem 2008, 77: 289-312; Genes Dev 1996, 10: 1096-1107).

Thus, inhibition of adipocyte differentiation and the associated transcription factors and adipokines are targets for the development of new therapeutic agents for obesity.

Meanwhile, Trigonostemon reidioides is a plant originating in Cambodia, Vietnam, Thailand, Myanmar and Laos. Root extracts have traditionally been used as expectorants and laxatives (Journal of Natural Products, 53 (5): 1148 -1151, 1990), and rediocides B to E isolated therefrom have been proposed as candidates for insecticides (J Nat Prod. 2004 Feb; 67 (2): 228-31). However, no anti-obesity activity of Trigonosynthomonadhiides has been proposed to date.

The present invention has been completed by confirming that the extract of Trigonostemmonadioides has an activity of inhibiting the differentiation of adipose precursor cells into adipocytes.

It is an object of the present invention to provide an anti-obesity composition using Trigonostomene radiodes extract.

Other and further objects of the present invention will be described below.

As shown in the following Examples and Experimental Examples, the inventors of the present invention found that the extract of aqueous solution of trigonostomonadhiosidethanol (70% (v / v)) extracts the differentiation of mouse preadipocytes 3T3-L1 into adipocytes by concentration Dependent inhibition. Here, 3T3-L1 cells are lipogenic precursor cells derived from mouse embryos which are widely used as an in vitro model of obesity research.

In view of the above experimental results, the composition for anti-obesity of the present invention is characterized in that it contains Trigonostemon radiodi extract as its active ingredient.

In the present specification, the term " Trigonostomene radiodes extract "refers to an extract of Trigonostemmonadioides, a leaf, a fruit, a flower, a root, and a mixture thereof in water, methanol, ethanol, But are not limited to, lower alcohols such as methylene chloride, ethylene, acetone, hexane, ether, chloroform, ethyl acetate, butyl acetate, N, N-dimethylformamide (DMF), dimethylsulfoxide (DMSO) Or an extract obtained by leaching using a mixed solvent thereof, an extract obtained by using a supercritical extraction solvent such as carbon dioxide or pentane, or a fraction obtained by fractionating the extract, and the extraction method is a method of extracting the polarity, It is possible to apply any method such as cold rolling, reflux, warming, ultrasonic irradiation, supercritical extraction, etc. In the case of the fractionated extract, the fraction is suspended in a specific solvent and then mixed with a solvent having a different polarity. The extract is adsorbed on a column packed with silica gel or the like, and then a hydrophobic solvent, a hydrophilic solvent, Quot; means fractions obtained as a mobile phase. Also, the meaning of the extract includes a concentrated liquid extract or a solid extract in which the extraction solvent is removed by a method such as freeze drying, vacuum drying, hot air drying, spray drying and the like. Preferably an extract obtained by using water, ethanol or a mixed solvent thereof as an extraction solvent, and more preferably an extract obtained by using a mixed solvent of water and ethanol as an extraction solvent.

In the present specification, the term " active ingredient "alone means an ingredient which exhibits the desired activity or which can exhibit activity together with a carrier which is not itself active.

In the present specification, "anti-obesity" means a decrease in body fat and / or a decrease in body weight. Thus, it includes the prevention of obesity and the treatment of obesity, and further includes the reduction of weight / body fat for beauty or health purposes (aka diet) although the weight is not classified as obesity or overweight.

In the present specification, the term "obesity" means an abnormally increased state of adipose tissue, whether it is obesity due to genetic factors or obesity due to environmental factors. When the body mass index (BMI) It is meant to include obesity (for BMI> 30.0), obesity (for BMI 25-30), and overweight (for BMI between 23 and 25).

The anti-obesity composition of the present invention may contain the active ingredient in any amount (effective amount) as long as it can exhibit anti-obesity activity, depending on the purpose of use, formulation, compounding purpose, etc. A typical effective amount is based on the total weight of the composition To < RTI ID = 0.0 > 0. < / RTI > Here, "effective amount" refers to the amount of active ingredient capable of inducing an anti-obesity effect. Such effective amounts can be determined experimentally within the ordinary skill of those skilled in the art.

The subject to which the composition of the present invention can be applied (prescription) is preferably a mammal and a person, particularly a human.

The anti-obesity composition of the present invention may further comprise, in addition to the active ingredient, any compound or natural extract which is already known to have safety and has anti-obesity activity for the purpose of raising or supplementing the anti-obesity effect. Specific examples of such compounds or extracts include Garcinia cambogia bark extract, conjugated linolenic acid (free fatty acid), conjugated linolenic acid (triglyceride) in the Health Functional Foods Act Lactobacillus gasseri BNR17, L-carnitine tartrate, green matte extract, green coffee bean extract, sesame leaf extract, soybean embryo extract, etc., which are individually recognized according to the Act on Health Functional Foods, in addition to green tea extract and chitosan (Extract), Lactobacillus (Lactobacillus sp.), Lactobacillus (Lactobacillus sp.), Lactobacillus (Lactobacillus sp. Extract), Lactobacillus Preserved diglycerides, wild mango seed extract, medium chain fatty acid (MCFA) containing preservatives, cholesterol Seuposeu there may be mentioned E. coli extract, chitooligosaccharide, finger root extract powder, such as a composite, such as hibiscus extract. Such compounds or natural extracts may be included in the anti-obesity composition of the present invention in combination with one or more thereof.

The anti-obesity composition of the present invention can be identified as a food composition in a specific embodiment.

The food composition of the present invention can be prepared in any form and can be used in various forms such as beverages such as tea, juice, carbonated drink, ionic drink, processed milk such as milk and request route, gum, rice cake, Korean confectionery, Such as foods, tablets, capsules, rings, granules, liquids, powders, flakes, pastes, syrups, gels, jellies, bars and the like. In addition, the food composition of the present invention may be classified into any product category as long as it meets the laws and regulations on the time of manufacture and distribution in the legal and functional category. For example, it may be a health functional food according to the Act on Health Functional Foods, or a food functional food according to the Food Sanitation Act (standards for food additives, food standards and specifications), confectionery, pulses, bean oil, fermented beverages, Particularly food preparations for weight control).

The food composition of the present invention may contain food additives in addition to the active ingredients thereof. Food additives are generally understood to be substances that are added to foods and mixed or infiltrated into food in the manufacture, processing or preservation of food, and their safety must be ensured since they are taken daily with food and for long periods. Food additives according to the Food Hygiene Act (food additives notification, food additive standards and standards) are limited by the classification of safe synthetic food additives as chemical synthetic products, natural additives and mixed preparations.

These functional food additives can be classified into sweeteners, flavors, preservatives, emulsifiers, acidifiers, and thickeners.

A sweetener is used to impart a sweet taste suitable for foods, and natural or synthetic sweeteners can be used. Preferably, natural sweeteners are used. Examples of natural sweeteners include sugar sweeteners such as corn syrup solids, honey, sucrose, fructose, lactose and maltose.

Flavors may be used to enhance taste or flavor, both natural and synthetic. Preferably, a natural one is used. When using natural ones, the purpose of nutritional fortification can be performed in addition to the flavor. Examples of natural flavoring agents include those obtained from apples, lemons, citrus fruits, grapes, strawberries, peaches, and the like, or those obtained from green tea leaves, Asiatica, Daegu, Cinnamon, Chrysanthemum leaves and Jasmine. Also, those obtained from ginseng (red ginseng), bamboo shoots, aloe vera, banks and the like can be used. The natural flavoring agent may be a liquid concentrate or a solid form of extract. Synthetic flavors may be used depending on the case, and synthetic flavors such as esters, alcohols, aldehydes, terpenes and the like may be used.

As the preservative, calcium sorbate, sodium sorbate, potassium sorbate, calcium benzoate, sodium benzoate, potassium benzoate and EDTA (ethylenediaminetetraacetic acid) can be used. As the emulsifier, acacia gum, carboxymethyl cellulose, Pectin and the like. As the acidulant, math, malic acid, fumaric acid, adipic acid, phosphoric acid, gluconic acid, tartaric acid, ascorbic acid, acetic acid, phosphoric acid and the like can be used. The acidulant may be added so that the food composition has a proper acidity for the purpose of inhibiting the growth of microorganisms other than the purpose of enhancing the taste.

Examples of the thickening agent include suspending agents, sedimentation agents, gel-forming agents, bulking agents and the like.

The food composition of the present invention may contain physiologically active substances or minerals which are known in the art and which are stable as a food additive in addition to the above-mentioned food additives in order to supplement and supplement functional and nutritional properties.

Examples of such physiologically active substances include catechins contained in green tea and the like, vitamins such as vitamin B1, vitamin C, vitamin E and vitamin B12, tocopherol, dibenzoyl thiamine, etc. Examples of minerals include calcium preparations such as calcium citrate, magnesium stearate , Iron preparations such as iron citrate, chromium chloride, potassium iodide, selenium, germanium, vanadium, zinc and the like.

The food composition of the present invention may contain an appropriate amount of the above-mentioned food additives according to the product type so as to achieve the purpose of addition thereof.

With regard to other food additives that can be included in the food composition of the present invention, reference may be made to the Food Code or the Food Additive Code.

In another specific embodiment, the composition of the present invention can be identified as a pharmaceutical composition.

The pharmaceutical composition of the present invention may be prepared into oral formulations or parenteral formulations according to the route of administration by conventional methods known in the art, including pharmaceutically acceptable carriers in addition to the active ingredient. The term "pharmaceutically acceptable" as used herein means that the application (prescribing) subject does not have the above-mentioned toxicity that is adaptable without inhibiting the activity of the active ingredient.

When the pharmaceutical composition of the present invention is prepared into an oral formulation, it may be formulated into powder, granules, tablets, pills, sugar tablets, capsules, solutions, gels, syrups, suspensions, wafers And the like. Examples of suitable pharmaceutically acceptable carriers include sugars such as lactose, glucose, sucrose, dextrose, sorbitol, mannitol, xylitol, starch such as corn starch, potato starch and wheat starch, cellulose, methylcellulose, ethylcellulose, Cellulose derivatives such as sodium carboxymethyl cellulose and hydroxypropylmethyl cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, magnesium stearate, mineral oil, malt, gelatin, talc, And the like. In case of formulation, a diluent such as a filler, an extender, a binder, a wetting agent, a disintegrant, a surfactant, and / or an excipient may be formulated according to need.

When the pharmaceutical composition of the present invention is prepared into a parenteral dosage form, it may be formulated in the form of an injection, transdermal drug delivery, nasal aspirate and suppository together with a suitable carrier according to methods known in the art. Examples of suitable carrier in the case of formulation with an injectable preparation include sterilized water, ethanol, polyol such as glycerol and propylene glycol, or a mixture thereof. Preferably, the carrier is selected from the group consisting of Ringer's solution, phosphate buffered saline containing triethanolamine, Water, or isotonic solution such as 5% dextrose may be used. When formulated with a transdermal drug, it can be formulated in the form of an ointment, a cream, a lotion, a gel, a solution for external use, a pasta, a liniment, or an air-roll. The nasal inhalant may be formulated in the form of an aerosol spray using a suitable propellant such as dichlorofluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide, etc. When formulated as a suppository, witepsol, tween 61, polyethylene glycols, cacao butter, laurin, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene stearates, and sorbitan fatty acid esters.

The formulation of pharmaceutical compositions is well known in the art and can be specifically described in Remington ' s Pharmaceutical Sciences (19th ed., 1995). This document is considered part of this specification.

The preferred dosage of the pharmaceutical composition of the present invention is 0.001 mg / kg to 10 g / kg per day, preferably 0.001 mg / kg to 1 g / day, depending on the patient's condition, body weight, sex, age, / kg < / RTI > The administration can be carried out once or several times a day. Such dosages should in no way be construed as limiting the scope of the invention.

As described above, according to the present invention, it is possible to provide an anti-obesity composition using Trigonostemmonadioides extract. The composition for anti-obesity of the present invention can be commercialized as a functional food, medicine, or the like.

Fig. 1 shows the results of demonstrating the activity of inhibiting the differentiation of precursor adipocytes into adipocytes by Trigonostemmonadioides extract.

Hereinafter, the present invention will be described with reference to Examples and Experimental Examples. However, the scope of the present invention is not limited to these examples and experimental examples.

< Example > Trigo Nostemona Lady O'Deis  Preparation of extract

The dried Trigonostemon reidioides ) To 100 g of leaf, 1 L of 70% ethanol was added, and the mixture was repeatedly extracted once at room temperature for 24 hours and then filtered with a filter paper. The obtained 70% ethanol filtrate was concentrated under reduced pressure and then lyophilized to obtain a Trinhosynthomonadioides extract.

< Experimental Example > Trigo Nostemona Lady O'Deis  Experiments to improve obesity of extracts

3T3-L1 (ATCC CL-173), a mouse precursor adipocyte, was cultured in a 10% BCS DMEM medium at 37 ° C and 5% CO ₂ . 3T3-L1 precursor adipocytes were plated at a density of 5 × 10 ⁴ cells / well in a 24-well plate and maintained at 100% confluency for 2 days. The precursor adipocytes were cultured in 10% FBS DMEM medium containing 0.5 mM 3-isobutyl-1-methylxanthine (Calbiochem 410957), 1 uM dexamethasone (Calbiochem 265005) and 1 ug / ml insulin (Sigma I9278) Were induced for 2 days and cultured for 48 hours with 10% FBS DMEM containing 1 ug / ml insulin for two days. Subsequently, the cells were replaced with 10% FBS DMEM medium for 2 days every 4 days. During induction of adipocyte differentiation, the extracts of the examples were treated with 50, 100 ㎍ / ml of each culture medium, and the degree of adipocyte differentiation was observed on the 8th day when the differentiation was completed. The degree of adipocyte differentiation was firstly confirmed by microscopy through Oil Red O staining. The degree of adipocyte staining was measured at 510 nm absorbance using an ELISA reader (SPECTRAmax 340PC, Molecular Devices, USA) Respectively. The results were obtained by repeating the experiment three times by concentration.

The results of oil red O staining and quantitative analysis of fat mass are shown in Fig. 1, and the results are shown in Fig. 1, which shows that the extract of Trigonostemmonadioides attenuates fat accumulation in adipocytes in a concentration-dependent manner. .

Claims (4)

A food composition for an anti-obesity, comprising as an active ingredient, a water-ethanol mixed solvent extract of Trigonosyntheson radiodieths leaves.
The method according to claim 1,
Wherein the water-ethanol mixed solvent is 70% ethanol.
A pharmaceutical composition for anti-obesity comprising, as an active ingredient, a water-ethanol mixed solvent extract of Trigonosynthomonadiliumis leaf.
The method of claim 3,
Wherein the water-ethanol mixed solvent is 70% ethanol.

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