KR20140093573A - Composition for Anti-obesity Containing Dehydrozingerone - Google Patents

Abstract

The present invention relates to a composition for treating or preventing obesity and a health food for alleviating obesity, wherein dehydrozingerone is contained as an active ingredient. According to the present invention, dehydrozingerone has excellent effects in losing weight, reducing body fat, and decreasing total cholesterol and leptin so as to be useful for obesity treatment or prevention.

Description

Technical Field [0001] The present invention relates to a composition for treating or preventing obesity containing dihydrogingerol,

The present invention relates to a composition for treating or preventing obesity, which contains dehydrozingerone as an active ingredient, and a health food for improving obesity.

Obesity refers to the state of excess fat tissue accumulation in the body due to the increase in the size or number of adipocytes, which means that there is more fat than the amount of fat needed for the body.

The causes of obesity are food intake, lack of exercise, and genetic susceptibility. Obesity has negative consequences for health and quality of life, such as type 2 diabetes, hypertension, hypercholesterolemia, and cardiovascular disease, and the social costs are gradually increasing. In the United States, obesity causes more than 300,000 deaths annually, making it the second most preventable cause of death (McGinnis JM and Foege WH, JAMA 270: 2207-2212, 1993) (Colditz GA, Am. J. Clin. Nutr. 55: 503S-507S, 1992).

As such, the metabolic diseases caused by obesity are diverse and serious, and prevention and treatment are urgently needed to prevent them.

 Currently, obesity treatment drugs are largely classified into satiety suppressants, lipid absorption inhibitors, and psychotropic appetite suppressants depending on the action mechanism.

Saturation stimulants inhibit appetite by inhibiting the reuptake of the neurohormones serotonin and noradrenalin, which regulate appetite in the brain, and increase energy expenditure by increasing basal metabolic rate. Reductil, which is a representative product, was withdrawn from the market after the decision to discontinue the final sale at KFDA in October 2010 due to the adverse effects of cardiovascular factors such as myocardial infarction and stroke in the product, Sibutramine.

The fat absorption inhibitor suppresses the function of lipase, a digestive enzyme that absorbs fat into the body, and discharges the fat that is ingested to the outside of the body. As such a lipid absorption inhibitor, Orlistat component is Xenical. Xenical, which is known to have the least side effects, also shows adverse effects such as fat stasis, intestinal gas production, and abdominal bloating. Recently, patients who complain of kidney trouble have also appeared.

Psychotropic appetite suppressants treat obesity by promoting the production of the neurohormones norepinephrine and dopamine, which regulate appetite in the brain, and by reducing the appetite itself, and its components are phendimetrazine, (phentermine).

Leptin (leptin) is another candidate for obesity treatment. It releases blood from the adipocytes and passes through the blood-brain barrier, acts on receptors in the central nervous system, inhibiting food intake, reducing body weight, and promoting energy consumption. In obese patients, the hypothalamus is constantly exposed to leptin, resulting in resistance to leptin and hyperleptinemia. Although there is a high concentration of leptin in the blood, it is difficult to develop an obesity-controlling drug using leptin because it can not transmit appetite suppression and signals to metabolism.

On the other hand, dehydrozingerone is a compound having a structure represented by the following general formula (1) as a component that can be extracted from ginger, and has antiinflammation (Elias G et al., Indian J Exp Biol, 26 (7): 540 -2, 1988), antioxidant (Rajakumar DV et al., Molecular and Cellular Biochemistry, 140: 73-79, 1994) and anticancer agents (Noriko Motohashi et al., Cancer Letters, 134: 3742, 1998) It is known, but its association with obesity treatment or prevention is unknown.

[Chemical Formula 1]

Accordingly, the present inventors have made intensive efforts to develop an obesity inhibitor, and as a result, they have found that dehydrozingerone is superior in the effect of inhibiting obesity through the expression or activity of AMPK (AMP kinase) .

It is an object of the present invention to provide a composition for treating or preventing obesity containing dehydrozingerone as an active ingredient and a health functional food for improving obesity.

In order to achieve the above objects, there is provided a composition for treating or preventing obesity comprising dehydrozingerone as an active ingredient.

The present invention also provides a health functional food for improving obesity containing dehydrozingerone as an active ingredient.

According to the present invention, dehydrozingerone is excellent in the effects of reducing weight, reducing body fat, decreasing total cholesterol and leptin, and being useful for the treatment or prevention of obesity.

1 shows the AMPK (AMP kinase) protein expression ability according to the concentration (A) and time (B) of dehydrozingerone in muscle cells.
Figure 2 shows the weight loss effect of dehydrozingerone.
Figure 3 shows the effect of dehydrozingerone on abdominal fat loss.
Figure 4 shows the effect of dehydrozingerone on the fat accumulation of each major tissue.
5 shows the total cholesterol-lowering effect of dehydrozingerone.
FIG. 6 shows the effect of dehydrozingerone on leptin concentration in animals treated with hyperlipemia.

In one aspect, the present invention relates to a composition for treating or preventing obesity containing dehydrozingerone as an active ingredient.

The dehydrozingerone of the present invention may be characterized in that the expression or activity of AMPK (AMP kinase) is increased to control lipid metabolism.

In one embodiment of the present invention, the activity of AMPK was analyzed by treating the precursor cells of the muscle with dehydrogenase, and as a result, phosphorylation of ACC, which is regulated by AMPK and AMPK by dihydrogingerism, Respectively.

In another embodiment of the present invention, mice that received only high-fat diet and high-fat diets combined with dihydroergensin were compared to mice that received dihydroergensin, indicating that weight reduction, body fat reduction, Cholesterol concentration and leptin concentration were decreased.

The dihydroergensin of the present invention increases the activity of AMPK through phosphorylation of AMPK and decreases weight gain, and thus can be used as an active ingredient of a composition for treating or preventing obesity and a health functional food for obesity improvement.

Therefore, in another aspect, the present invention relates to a health food for improving obesity containing the composition for treating or preventing obesity as an active ingredient.

The compositions of the present invention may further comprise suitable carriers, excipients and diluents conventionally used in the manufacture of the compositions.

The composition of the present invention may be administered orally or parenterally, and it is preferable to select parenterally when injecting parenterally or intraperitoneally, intramuscularly, subcutaneously, intravenously, intramuscularly or intrasternally , But is not limited thereto.

The composition of the present invention can be formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, oral preparations, suppositories and sterilized injection solutions according to conventional methods . Examples of carriers, excipients and diluents that can be included in the composition include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, Methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. 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 at least one excipient such as starch, calcium carbonate, sucrose ), Lactose, gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used. Examples of the liquid preparation for oral use include suspensions, solutions, emulsions, and syrups. In addition to the commonly used simple diluent, liquid paraffin, various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included.

Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Examples of the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like. Examples of suppository bases include witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin, and the like.

The preferred dosage of the composition of the present invention varies depending on the condition and the weight of the patient, the degree of disease, the type of drug, the route of administration and the period of time, but can be appropriately selected by those skilled in the art. However, for the desired effect, the composition is preferably administered at a dose of 0.0001 to 1 g / kg per day, preferably 0.001 to 200 mg / kg per day, but is not limited thereto. The above administration may be carried out once a day or divided into several times. The dose is not intended to limit the scope of the invention in any way.

The health food of the present invention can be used as it is or in combination with other food or food ingredients, and can be suitably used according to conventional methods.

There is no particular limitation on the kind of the food. Examples of the food include dairy products including drinks, meat, sausage, bread, biscuits, rice cakes, chocolates, candies, snacks, confectionery, pizza, ramen noodles, other noodles, gums, ice cream, various soups, And a combination thereof, all of which include health foods in a conventional sense.

The dihydrogingerrone according to the present invention can be added directly to food or used together with other food or food ingredients, and can be suitably used according to a conventional method. The amount of the active ingredient to be mixed can be suitably determined according to its use purpose (for prevention or improvement). Generally, the amount of dihydroxygermanium in the health food may be added in an amount of 0.01 to 15% by weight of the total food, and the health beverage composition may be added in an amount of 0.02 to 5 g, preferably 0.3 to 1 g, . However, in the case of long-term intake intended for health and hygiene purposes or for the purpose of controlling health, the amount may be less than the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount exceeding the above range.

The health functional beverage composition of the present invention is not particularly limited to the ingredients other than the above-mentioned dihydroxyzincoron as essential ingredients in the indicated ratios and may contain various flavors or natural carbohydrates . Examples of the above-mentioned natural carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose and the like; And polysaccharides, for example, conventional sugars such as dextrin, cyclodextrin and the like, and sugar alcohols such as xylitol, sorbitol and erythritol. Natural flavors (tau martin, stevia extracts (e.g., rebaudioside A, glycyrrhizin, etc.) and synthetic flavors (saccharin, aspartame, etc.) can be advantageously used as flavors other than those described above .

In addition to the above-mentioned foods, the food of the present invention may contain flavors such as various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, colorants and heavies (cheese, chocolate etc.), pectic acid and its salts, Salts, organic acids, protective colloid thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated beverages and the like.

In addition, the dihydrogingerrone of the present invention may contain natural fruit juice and pulp for the production of fruit juice drinks and vegetable drinks. These components may be used independently or in combination. The proportion of such additives is not so critical, but is generally selected in the range of from 0 to about 20 parts by weight per 100 parts by weight of the dihalo gingerolone of the present invention.

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 at least one excipient such as starch, calcium carbonate, sucrose, Or lactose, gelatin, and the like. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Examples of the liquid preparation for oral use include suspensions, solutions, emulsions, and syrups. In addition to water and liquid paraffin, simple diluents commonly used, various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included . Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried preparations, and suppositories. Propyleneglycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like can be used. Examples of the suppository base include witepsol, macrogol, tween 61, cacao paper, laurin, glycerogelatin and the like.

As used herein, the term "improvement" is meant to include preventing, ameliorating, treating, or delaying the onset of such symptoms.

As used herein, the term "improved obesity" means any action that improves or alleviates the symptoms of obesity with the administration of the composition.

As used herein, the term "functional food" means food prepared and processed using raw materials or ingredients having functionality useful to the human body according to Law No. 6727 on health functional foods, and " And function of the nutrient for the purpose of obtaining a beneficial effect in health use such as controlling the nutrient or physiological action.

Hereinafter, the present invention will be described in more detail with reference to Examples. It is to be understood by those skilled in the art that these embodiments are only for describing the present invention in more detail and that the scope of the present invention is not limited by these embodiments in accordance with the gist of the present invention .

Example 1: AMPK (AMP kinase) phosphorylation experiment

To investigate the effect of dehydrozingerone on lipid metabolism, C2C12 muscle precursor cells (ATCC, US) were treated with dihydrozincerone to determine the amount of phosphorylated protein. ACC is a protein that is activated by phosphorylated AMPK and is known to inhibit the synthesis of fatty acids.

C2C12 was cultured in DMEM and treated with concentrations of 0 μM, 1 μM, 3 μM, 10 μM, 30 μM and 100 μM of dihydroergensin for 2 hours, respectively, and the changes in the activity of AMPK and ACC in muscle precursor cells were measured by Western blotting analysis . AMPK phosphorylated antibody (Threonine 172, Millipore-Upstate, US) and ACC phosphorylated antibody (Millipore-Upstate, US) were used for detection of phosphorylated AMPK protein and ACC protein, respectively. As a result, it was confirmed that the amount of pAMPK protein and pACC protein was increased in a concentration-dependent manner by dihydrogingerol treatment, and that the process of inhibiting fatty acid synthesis by AMPK phosphorylation was shown by dehydrogingerism (FIG. 1A) .

On the other hand, C2H12 cells were treated with 30 μM of dihydroergensin at a concentration of 30 μM and the amounts of pAMPK and pACC proteins were western blotted at 0, 10, 30, 1, 3, 6, 12 and 24 hours, Respectively. As a result, as shown in FIG. 1B, after the treatment with 30 μM of dehydrogingerrone, the amount of the two phosphorylated proteins gradually increased to reach the maximum at 12 hours, and the pAMPC-regulated pACC increased to 24 hours It was confirmed to be the maximum.

Example 2 Effect of Dehydrozingerone on Weight Control

In order to confirm the effect of dihydrogingerol on obesity, overweight was induced by feeding high fat diet to male mice (C57B1 / 6, Orient Bio) at 6 weeks of age. Up to 8 weeks of age, normal diet was fed and adjusted to the environment. Dihydrosuggerone (100 mg / kg) was added daily in a 60% high fat diet from 8 to 20 weeks of age.

The experimental groups were divided into three groups: low fat diet, high fat diet and high fat diet + dehydrozingerone. Ten groups of each group were composed. As shown in FIG. 2, the low fat diet (LFD) group had a body weight of 20 g to 26.5 g, and a high fat diet , HFD) group increased from 20g to 45g, while high - fat diet + dihydro - gingerol group showed weight gain from 20g to 38g compared with high fat group. This indicates that dihydrogingerrone is effective in weight control of high-fat animals.

Example 3: Reduction effect of dehydrozingerone on fat accumulation

In order to evaluate the effect of dihydrojugeron on abdominal fat changes, we compared the abdominal fat after 12 weeks of dihydrogenase treatment with high - fat diet and high fat diet animals. As a result, it was confirmed that the animals providing the high-fat diet produced very abdominal adipose tissues while the high-fat diet animals with the dihydroergensolone inhibited the abdominal fat production (FIG. 3).

In addition, changes in adipose tissue around major organs were observed. The aneurysm of the renal artery was clamped on the anterior origin of the renal artery, and the aneurysm was dissected to allow leakage of the perfused fluid. 10 cc of 10% neutral buffered formalin was perfused through the polyethylene tube until the kidney color changed. Both kidneys and liver were removed and washed with PBS (phosphate-buffered saline). As a result, adipose tissue was accumulated around liver, epididymis (epididymis) and kidney by high fat diet. However, it was confirmed that this change was not observed in the experiment group that provided dihydrogingerrone together with the high-fat diet (Fig. 4).

Example 4: Effect of dehydrozingerone on total cholesterol increase

Dihydrosuggerone was given to high - fat diet and high fat diet animals for 12 weeks, and mice were euthanized at 20 weeks of age. After exposing the aorta, a polyethylene tube was inserted into the aorta at the lower part of the origin of the renal artery to collect blood. As a result of measurement of total cholesterol from blood, the total cholesterol of the experimental group consuming the high fat diet increased by 10% as compared with the low fat diet control group as shown in FIG. 5, whereas the high fat diet group and the dihydro gingerol diet group Compared with a 5% reduction in total cholesterol.

Example 5 Effect of Dehydrozingerone on Blood Leptin Concentration

Leptin is a hormone secreted by adipocytes and is known to suppress appetite. However, obesity is associated with leptin resistance and leptinemia. The plasma leptin levels in the experimental group that were given the high fat diet method were measured, and hyperleptinemia of 10 ng / ml or more was observed. However, it was confirmed that the blood leptin concentration in the experimental group consumed with the dihydro-gingerol in combination with the high-fat diet was similar to that of the control group that provided the low-fat diet (FIG. 6).

Therefore, dihydrogingerrone has an excellent inhibitory effect on weight gain due to obesity induced by high fat diet, fat tissue formation around abdominal fat and major organs, increase in cholesterol and increase in leptin hormone concentration.

While the present invention has been particularly shown and described with reference to specific embodiments thereof, those skilled in the art will appreciate that such specific embodiments are merely preferred embodiments and that the scope of the present invention is not limited thereto will be. Accordingly, the actual scope of the present invention will be defined by the appended claims and their equivalents.

Claims (3)

A composition for treating or preventing obesity comprising dehydrozingerone as an active ingredient. The composition for treating or preventing obesity according to claim 1, wherein the dehydrozingerone increases the expression or activity of AMPK (AMP kinase) to regulate lipid metabolism. A health functional food for improving obesity containing dihydro gingerol (dehydrozingerone) as an active ingredient.

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