WO2014163262A1 - Composition for treating or preventing obesity, containing chili seed extract - Google Patents

Abstract

The present invention relates to a composition for treating or preventing obesity, containing a chili seed extract as an active ingredient. Particularly, the chili seed extract, which is the active ingredient of the present invention, can inhibit the differentiation of a preadipocyte to an adipocyte, can inhibit an increase in weight and body fat by inhibiting an accumulation of adipocytes, inhibits blood sugar and insulin levels and reduces neutral fat and cholesterol, thereby treating and preventing obesity, and has no cytotoxicity. In addition, there are no side effects since the active ingredient is a natural substance. Particularly, the effects of the chili seed extract are far superior compared with a chili flesh extract, and thus can be widely used for treating or preventing obesity.

Description

Obesity treatment or prevention composition comprising red pepper seed extract

The present invention relates to a composition for treating or preventing obesity, which comprises red pepper seed extract as an active ingredient.

The prevalence of various lifestyle-related diseases and chronic degenerative diseases caused by over-nourishment, environmental pollution, lack of exercise, and increased stress due to economic level has been a big problem in our society. Of these, obesity is one of the most recently-focused diseases. Obesity is a surplus of energy because energy intake is generally not balanced with energy expenditure due to physical activity. It is a condition in which fat tissue is excessively accumulated due to quantitative and numerical increase of adipocytes in the body, and due to genetic factors, environmental factors, mental factors or lifestyle habits such as eating habits and lack of exercise, etc. It means a disease caused by the collapse of my energy balance.

In relation to obesity, studies on adipogensis are being conducted. The localization refers to a process in which fat cells are differentiated from progenitor cells to accumulate fat, and localization is known to cause metabolic diseases such as obesity, diabetes, fatty liver, and coronary heart disease. The fat cells not only act as energy stores but also secrete protein hormones called adipocytokine as endocrine organs to perform various functions for maintaining energy homeostasis in the body. However, excessive differentiation of fat cells and disproportionate energy metabolism can lead to abnormal gene expression and signaling system abnormalities of adipocytes, leading to abnormal secretion of adipocytokine.

Transcription factors that induce differentiation of adipocytes include adipocyte determination and differentiation dependent factor 1 / sterol response element binding protein 1c (ADD1 / SREBP1c), peroxisome proliferator activated receptor γ (PPARγ), and C / EBP (CCAAT). enhancer binding protein) has been reported. The transcription factors are induced at different times during the adipocyte differentiation process, and interact with each other to regulate the expression of adipocyte specific genes and gradually induce the activation of adipocyte metabolism and adipocyte differentiation.

First, peroxisome proliferator activated receptor γ (PPARγ) belongs to nuclear receptors and induces the expression of many other genes as well as aP2, a fat cell-specific fatty acid binding protein. In this regard, previous studies have reported that when PPARγ is overexpressed in fibroblasts rather than progenitor cells using retroviruses, adipocyte differentiation occurs in normal fibroblasts.

Differentiation of adipocytes induced by the transcription factors proceeds to confluence, hormonal induction, clonal expansion, growth arrest and terminal differentiation. First, when progenitor cells become confluence, growth arrest occurs when the cell cycle is G0 / G1. Thereafter, the cell enters the clonal expansion stage in which one or two cell divisions are caused by appropriate differentiation stimulation and expression of C / EBβ and C / EBP. Through the expression of PPARγ and C / EBPa, pro-adipocytes enter the phase of growth arrest, just before the stage of complete differentiation. The final stage, terminal differentiation, takes days to weeks, and mature growth cells are characterized by continuous growth arrest.

Specifically, progenitor cells, which were similar to fibroblasts at the beginning of differentiation, form morphological rounding-up, mRNAs such as lipoprotein lipase begin to be expressed, and transients of the transcription factors C / EBPβ and C / EBPδ. induction occurs. Then, PPARγ and C / EBPa are expressed to regulate or activate most of the genes that actually determine the phenotype of adipocytes. Through this process, lipid droplets appear in the cytoplasm and grow and merge over time to form one or several large droplets.

In addition, the obesity may be a problem with metabolic syndrome such as diabetes, obesity caused by the metabolic syndrome or metabolic syndrome may be caused by obesity.

Diabetes and related insulin resistance may also occur when blood glucose levels are within normal glucose tolerance during the development of type 2 diabetes. Insulin resistance is also affected by free fatty acids in the blood. The free fatty acid is produced during the lipolysis process in which intracellular triglycerides are hydrolyzed to free fatty acids and glycerol and secreted from the adipocytes. Inflow of large amounts of free fatty acids from the intraperitoneal fat with high lipolytic activity into the liver lowers glucose utilization in the liver and interferes with insulin binding and action. As a result, the hepatic insulin elimination rate drops, resulting in higher insulin concentrations in the peripheral. Free fatty acids also reduce glucose utilization in the periphery of fat, muscle, etc., leading to increased insulin resistance.

Obesity treatment mechanisms to relieve metabolic syndrome such as obesity or diabetes and maintain proper weight include control of appetite, obstruction of digestion and absorption of fat, increase of energy consumption, and regulation of lipid metabolism. It has been reported that there are significant side effects.

Therefore, the development of drugs that can control the growth and differentiation of splenocytes and the treatment of metabolic diseases caused by adipose tissue excess or fat metabolism among natural products that are expected to minimize the possibility of safety problems are relatively minimized. It is required.

Red pepper is one of the high temperature crops originated in South America, and it was introduced to Korea before and after Imjin War and used for food. Fruits are cone-shaped berries with little moisture, red ripe fruits can be dried and used as spices, ornamental, medicinal, etc., and leaves can be used as herbs.

The main ingredients contained in the flesh of the red pepper are capsanthin, capaorubin, vitamins, capsaicin and organic acids including capsaicin, which are spicy flavors. The component is a capsaicinoid. The main components of the spicy taste of the capsaicinoid including the capsaicin and its analogs are capsaicin and dihydrocapsaicin among the five homologues of the capsaicin. For example, the capsaicinoid content of red pepper powder, which is made of varieties that are not spicy depending on the degree of spicy pepper, averages about 10 mg%, but the capsai of red pepper powder made of cheongyang pepper, known as spicy pepper, is on average. The content of synoid (capsaicinoid) is 250 mg% to 350 mg%, and it is reported that the pulp is not included in the pulp of relatively low capsaicinoid content.

The capsaicin is known to have a variety of effects, such as humoral immune activity and cancer gene expression control and anti-geriatric effects, functional dyspepsia, energy metabolic rate, bactericidal action.

Meanwhile, red pepper is mainly used for pulp, and is removed from the manufacturing process of red pepper powder, which is the main method of using red pepper, and treated as waste. It is true. Therefore, the development of various application methods for the red pepper seed is required, but unlike the red pepper flesh of the red pepper portion, there are almost no studies on the red pepper seed including the study on the physiological activity or the active ingredient related to the physiological activity.

An object of the present invention is to solve the problems of the prior art as described above, an object of the present invention is to provide a composition for treating, improving or preventing metabolic diseases comprising a red pepper seed extract as an active ingredient.

In order to achieve the above object, the present invention provides a pharmaceutical composition for the treatment or prevention of metabolic diseases comprising red pepper seed extract as an active ingredient. The metabolic disease treatment or prevention composition may be a pharmaceutical composition or a pharmaceutical composition.

The composition for treating or preventing metabolic diseases may include pepper seed extract, specifically, pepper seed water extract extracted with water.

The metabolic disease may be obesity, diabetes or hyperlipidemia, specifically obesity or diabetes, for example obesity.

In addition, the present invention provides a composition for improving or preventing metabolic diseases in order to achieve the above object. The metabolic disease improvement or prevention composition may be a food composition. The food composition may be a functional food composition.

The metabolic disease improvement or prevention composition may include a pepper seed extract as an active ingredient. The pepper seed extract may be a hot pepper seed hot water extract.

In this aspect, the present invention may be a food composition for improving or preventing obesity or diabetes comprising red pepper seed extract as an active ingredient.

The food composition may be a dietary supplement for improving or preventing obesity or diabetes.

Red pepper seed extract, the active ingredient of the present invention, inhibited the proliferation of pro-dipotent cells into adipocytes, inhibited the increase and accumulation of adipocytes, and was found to exhibit an anti-obesity effect. Therefore, the effects of lowering insulin resistance and lowering blood cholesterol levels through the effects of weight loss and treatment, improvement or prevention of obesity are also recognized. In addition, the red pepper seed extract has a significantly superior inhibitory effect on adipocyte differentiation compared to the red pepper flesh extract, but also has low cytotoxicity, and is manufactured from red pepper used for a long time for food, so no side effects, etc. Since it uses the treated part, it is recognized as an excellent industrial effect because of its economic effect.

1 is a graph showing the results of confirming the cytotoxicity of the pepper seed extract according to an embodiment of the present invention. The vertical axis of the graph shows the survival rate of proliferative cells (3T3-L1) relative to the control (PBS). The horizontal axis of the graph represents the control group and the experimental group according to the content of the pepper seed extract, specifically, PBS is a control group without the pepper seed extract, and 10, 25, 50, 75 and 100 are 10 ㎍ / ml, 25 of the pepper seed extract, respectively. The experimental group which added μg / ml, 50 μg / ml, 75 μg / ml and 100 μg / ml was shown.

Figure 2 shows the effect of inhibiting the differentiation of red pepper seed extract into adipocytes, according to an embodiment of the present invention, Figure 2a shows a photograph stained with Oil Red O dye reagent showing the effect of inhibiting the differentiation of red pepper seed extract into adipocytes. . In FIG. 2a, PBS refers to a control group without addition of red pepper seed extract, and red pepper seed 10, red pepper seed 25, red pepper seed 50, red pepper seed 75 and red pepper seed 100 are red pepper seed extracts, respectively, 10 μg / ml, 25 μg / ml and 50 μg / ml. , 75 ㎍ / ml and 100 ㎍ / ml treated experimental group, pepper powder 10, pepper powder 25, pepper powder 50, pepper powder 75 and pepper powder 100 are 10 ㎍ / respectively of the extract of red pepper powder made of red pepper flesh Experimental groups treated with ml, 25 μg / ml, 50 μg / ml, 75 μg / ml and 100 μg / ml are shown. Figure 2b is a graph showing the effect of inhibiting the differentiation of red pepper seed extract into adipocytes, the vertical axis of the graph means a value representing the differentiation into adipocytes relative to the control (PBS). The horizontal axis of the graph shows each experimental group, and PBS means a control group without adding pepper seed extract, and pepper seeds 10, pepper seeds 25, pepper seeds 50, pepper seeds 75, and pepper seeds 100 were 10 ㎍ / ml and 25 ㎍ /, respectively. Experimental groups treated with ml, 50 μg / ml, 75 μg / ml and 100 μg / ml are shown, and pepper powder 10, red pepper powder 25, red pepper powder 50, red pepper powder 75 and red pepper powder 100 are made of red pepper powder. Experimental groups treated with 10 μg / ml, 25 μg / ml, 50 μg / ml, 75 μg / ml and 100 μg / ml, respectively, are shown.

3 is a graph showing the effect of inhibiting the expression of adipocyte differentiation gene according to the content of red pepper seed extract according to an embodiment of the present invention, a picture showing the expression level of PPARγ, PBS of the horizontal axis, 10, 25, 50, 75 and 100 represent a control group treated with PBS and an experimental group to which 10 ㎍ / ml, 25 占 // ml, 50 占 // ml, 75 占 // ml and 100 占 // ml were added, respectively.

Figure 4 is a graph showing the toxicity in the animal model of pepper seed extract, according to an embodiment of the present invention, the vertical axis of the graph represents the liver weight / weight, the horizontal axis is the control (control), pepper seed extract 200mg / kg And experimental groups treated with 400 mg / kg, respectively.

Figure 5 is a graph showing the effect on the body weight in the animal model of pepper seed extract, according to an embodiment of the present invention, the vertical axis represents the weight (g), the horizontal axis represents the number of experimental days control is a control, pepper seed ex . 200 mg / kg of pepper seed extract 200 mg / kg administration group and pepper seed ex. 400 mg / kg represents a 400 mg / kg dose group of red pepper seed extract.

Figure 6 is a graph showing the effect on the blood sugar, insulin and insulin resistance of the pepper seed extract, according to an embodiment of the present invention, the horizontal axis of the graph is the control (control), pepper seed extract 200mg / kg and 400 mg The experimental group treated / kg each, Figure 6a is a graph showing the effect on the blood sugar of pepper seed extract, the vertical axis represents the blood sugar concentration (m mol / L), Figure 6b is a graph showing the effect of pepper seed extract on insulin The vertical axis of the graph shows the insulin concentration (μL U / ml), Figure 6c is a graph showing the insulin resistance of the pepper seed extract, the vertical axis represents the degree of insulin resistance.

Figure 7 is a graph showing the effect on the serum triglycerides and cholesterol of the red pepper seed extract, according to an embodiment of the present invention, the horizontal axis of each graph control (control), red pepper seed extract 200mg / kg and 400 mg / kg Figure 7a shows the experimental group treated, respectively, the vertical axis in the graph showing the serum triglyceride reduction effect of red pepper seed extract, the vertical axis represents the concentration of serum triglyceride (mg / dl), Figure 7b is the graph showing the cholesterol reduction effect of red pepper seed extract Indicates cholesterol concentration (mg / ml).

Figure 8 is a graph showing the effect on the free fatty acid of pepper seed extract, according to an embodiment of the present invention, the horizontal axis of the control group (control), pepper group 200mg / kg and experimental group treated 400 mg / kg, respectively The vertical axis represents the concentration of free fatty acid (mM).

Hereinafter, embodiments of the present invention will be described in detail so that those skilled in the art can easily practice the present invention. As those skilled in the art would realize, the described embodiments may be modified in various different ways, all without departing from the spirit or scope of the present invention.

All experimental results were repeated at least three times and expressed as average value, and the comparison with each group was determined to be significant in each case of p <0.05 using the ANOVA test.

[Preparation example. Preparation and Analysis of Red Pepper Seed Extract]

Preparation Example 1 Preparation of Red Pepper Seed Extract

Red pepper seeds were purchased commercially to remove red pepper seeds. 100 ml of red pepper seeds was added to 900 ml of distilled water, extracted for 30 minutes, filtered, concentrated under reduced pressure in a water bath of 40 ° C. or lower, and dried again using a freeze dryer system. It is shown in Table 1 below. A sample of the powder obtained as a result of the above was obtained and used for the experiment. The yield of lyophilisate was 11.4% on average.

Table 1

	Chilli Seed Powder	menstruum	percolation	concentration	Freeze drying
Extraction 1	100 g	900 ml	720 ml	355 ml	12 g
Extract
2	100 g	900 ml	680 ml	275 ml	11.5 g
Extract 3	100 g	900 ml	720 ml	260 ml	11.5 g
Extract 4	100 g	900 ml	670 ml	310 ml	11.5 g
Extract
5	100 g	900 ml	690 ml	330 ml	10 g
Extract
6	100 g	900 ml	700 ml	600 ml	12 g

As a result of high-speed liquid chromatography (HPLC) analysis of the red pepper seed extract, capsaicinoid, which is a major bioactive substance of red pepper flesh, was not found, so it was confirmed that capsaicinoid, that is, capsaicin and its derivatives were not included. It became.

Experimental Example 1. Confirmation of Cellular Anti-obesity Effect of Red Pepper Seed Extract]

Experimental Example 1-1. Cultivation of Profat Cells

Preadipocytes 3T3-L1 cell line was used from the American Type Culture Collection (ATCC, USA). Preadipocytes 3T3-L1 cells were treated with 5% CO ₂ under Dulbecco's Modified Eagle Medium (DMEM, Hyclone) medium containing 100 Units / mL penicillin, 100 μg / mL streptomycin and 10% newbone calf serum (FCS, Hyclone). Subcultured at 37 ℃ cell culture was used for the experiment.

Experimental Example 1-2. Cytotoxicity Evaluation of Pepper Seed Extract

MTT assay was performed to evaluate the cytotoxicity of the red pepper seed extract on the proliferative cells. After incubating 3T3-L1 cells in a 96-well plate, red pepper seed extract was added to each of 10 ㎍ / ml, 25 ㎍ / ml, 50 ㎍ / ml, 75 ㎍ / ml and 100 ㎍ / ml, respectively. ), Proliferative capacity of pro-adipocytes using MTT [3- (4,5-methylthiazol-2-yl) 2,5-diphenyl tetrazolium bromide] assay at 2 days (48 hours) and 3 days (72 hours), respectively. Survival rate) was measured and the results are shown in FIG. 1.

As shown in FIG. 1, when each pepper seed extract was added to 3T3-L1 cells, it was confirmed that up to 100 μg / ml concentration did not induce cell death compared to the normal group, and the anti-obesity effect of the pepper seed extract was In order to confirm the anti-diabetic effect, pepper seed extract was used in the experiment up to a concentration of 100 μg / ml.

Experimental Example 1-3. Confirmation of the Differentiation Inhibitory Effect of Preadipocytes into Adipocytes

In order to confirm the effect of inhibiting the differentiation of red pepper seed extract into adipocytes of the adipocytes, the progenitor cells 3T3-L1 cells passaged in Experimental Example 1-1 were dispensed on 6-well plates and cultured for 2 days. Even if the cells were completely grown in the well plate, the cells were cultured again for 2 days, and then differentiated into induction culture medium (DMEM medium containing 10 μg / ml insulin, 0.5 μM dexamethasone, and 0.8 mM isobutylmethyl xanthine) to induce differentiation for 2 days. Then, the cells were replaced with DMEM medium containing only 10 μg / ml insulin and incubated for 2 days, and then exchanged with DMEM medium containing 10% FBS for 4 days.

The differentiation degree was tested by adding pepper seed extract with differentiation induction to the 6-well plate cultured cells. The control group (PBS) was added nothing, 10 ㎍ / ml, 25 ㎍ / ml, 50 ㎍ / ml, 75 ㎍ / ml and 100 ㎍ / ml, respectively, to each sample was added to each sample, red pepper flesh Red pepper powder extract prepared as 10 μg / ml, 25 μg / ml, 50 μg / ml, 75 μg / ml and 100 μg / ml were added, respectively. After inducing differentiation by adding the red pepper seed extract or the red pepper flesh extract, respectively, the amount of fat produced was washed with PBS for 30 minutes at room temperature with 10% formalin after inducing differentiation-induced cells for 30 minutes with 4% Oil Red O solution. The fat was dyed red by the Oil Red O solution to evaluate the efficacy of fat staining under a microscope to evaluate the efficacy, the results are shown in Figures 2a and 2b.

As shown in FIG. 2A and FIG. 2B, it was confirmed that fat production was suppressed in a concentration-dependent manner when the red pepper seed extract or the red pepper powder extract prepared with red pepper flesh was treated as compared to the PBS-treated control group. In particular, the red pepper seed extract was found to significantly inhibit the fat production from the 50 ㎍ / ml treated group, and when 75 ㎍ / ml treated, the fat production was less than about 50%, specifically about 40% It was confirmed to decrease to a degree. On the other hand, in the case of red pepper powder, it was confirmed that the degree of inhibition of fat production was lower than the red pepper seed extract in the whole range, and the inhibitory effect of the production was not so great up to the amount of 75 ㎍ / ml. It was confirmed that the fat production of about 60% compared to the control group, pepper seed, that is, pepper seed extract compared to the red pepper pulverized extract extract was found to have a significantly superior fat production inhibitory ability.

Experimental Example 1-4. Confirmation of the inhibitory effect on the expression of lipogenesis

3T3-L1 adipocytes cultured in Experimental Example 1-1 were divided into 1 × 10 ⁵ cells / well, put together differentiation-inducing substance and sample red pepper seed extract, and induced cell differentiation on day 8 after inducing differentiation. Specifically, the cultured cells are washed twice with PBS solution, and then lysis buffer (PRO-PREP protein extraction solution, Intron Biotechnology, South Korea) is added and lysed at 4 ° C. for 10 minutes. The lysed cells were harvested and centrifuged at 13,000 rpm and 4 ° C. for 20 minutes to extract the supernatant and stored at -70 C. At the same time, cell proteins were extracted and subjected to immunoblot analysis. The cells were washed once with refrigerated phosphate buffer, followed by lysis buffer (20 mM Tris, pH7.0, 5 mM EDTA, 1 mM EGTA, 1% Triton X-100, 0.2 mM PMSF, 1 μg / μL aprotinin, 20 μg). / μL leupeptin, 1 mM Na ₃ VO ₄ , 10mMNaF, 1mMpyrophosphate, 1mMß-glycerophosphate) was added to react for 10 minutes on ice. Cells were centrifuged at 20,000 × g and 4 ° C. for 15 minutes to extract supernatant, and protein was quantified using the Bio-Rad protein quantitative kit using Bradford method. After mixing with a sample buffer containing SDS and ß-mercaptoethanol corresponding to the volume of sample 1 and heated at 100 ℃ for 5 minutes. The heated sample was developed on SDS polyacrylamide gel and then transferred to the sorbent. After confirming the extent of development and transition using molecular markers for proteins, the sorbents were placed in a blocking solution (TTBS containing 5% nonfat dry milk and 0.1% Tween 20) and allowed to react at room temperature for 1 hour. After washing twice with Tris buffer containing 0.1% Tween 20, the reaction was performed with a primary antibody for 2 hours, followed by washing twice. After reacting with a secondary antibody containing peroxidase for 1 hour and washing twice, detection of the secondary antibody was visualized using an enhanced chemiluminescence reagent (Amersham Life Science, Little Chalfont, England, UK) and quantified by densitometer. The results are shown in FIG.

As shown in FIG. 3, it was confirmed that the pepper seed extract inhibited the expression of the lipogenesis-related transcription factor PPARγ as compared to the control group (PBS) to which nothing was added, and in particular, the expression of the transcription factor when the concentration of the pepper seed extract was increased. It was confirmed that more effectively suppressed. Therefore, from the above results, it was confirmed that the red pepper seed extract can treat, improve or prevent obesity by inhibiting the expression of genes that induce localization, inhibiting the localization of profat cells and inhibiting the fat festival.

Experimental Example 2. Anti-obesity effect of red pepper seed extract in animal model]

Experimental Example 2-1. Breeding and Diet of Laboratory Animals

Five-week-old male C57BL / 6Jms Slc mice were fed from a central laboratory animal (South Korea) and used for the experiment. The diet was fed to a high-fat diet containing 60% fat in pellet form based on AIN-93G (Table 2), and divided into experimental groups fed control and pepper seed extract. The red pepper seed extract dose was administered orally daily for 6 weeks, and the diet and water were supplied fresh daily.

TABLE 2

Formula	high fat diet
Product	gm%	kcal%
Protein	26.2	20
Carbohydrate	26.3	20
Fat	34.9	60
Total	-	100
Kcal / gm	5.24	-
Ingredient	gm	Kcal
Casein
	200	800
L-cystein	3	12
Corn starch	0	0
Maltodextin 10	125	500
Sucrose	68.8	275.2
Cellulose	50	0
Soybean oil	25	225
Lard	245	2205
Mineral mix	10	0
DiCalcium Phosphate	13	0
Calcium Carbonate	5.5	0
Potassium citrate	16.5	0
Vitamin mix	10	40
Choline Bitarate	2	0

Experimental Example 2-2. Toxicity Evaluation of Red Pepper Seed Extract

After the end of the breeding period, the animals were anesthetized, the abdomen was cut in the liver, and the liver was weighed. Liver weight / weight ratio was measured to determine the toxicity of the pepper seed extract to the experimental animals and the results are shown in FIG.

As shown in FIG. 4, the results of the experiment did not show a significant difference between the control group and the control group that did not administer the pepper seed extract. Therefore, it was confirmed that there was no toxicity until the dose of the pepper seed extract was 400 mg / kg. The anti-obesity effect of red pepper seed extract was measured for the concentration.

Experimental Example 2-3. Check the effect of weight and fat loss

While raising the experimental animals of Experimental Example 2-1, the body weight was measured weekly and the food intake was measured. Food intake was calculated by subtracting the remaining amount from the previous day's feed. The measured change in body weight is shown in FIG. 5.

In addition, after the experiment was completed, the total amount of abdominal fat was excised to excise the abdomen of the experimental animal, and to remove all subcutaneous fat, epididymal fat, mesenteric fat, and back fat, which are the fat around the epididymis, and the weight of the abdominal fat. Table 3 shows.

TABLE 3

	Epididymal fat	Mesenteric fat	Vixceralfat	Totalfat
Control	0.02 ± 0.01	0.26 ± 0.04	1.53 ± 0.15	2.21 ± 0.25
Pepper seed extract 200 mg / kg	0.02 ± 0.01	0.19 ± 0.01	1.42 ± 0.12	2.01 ± 0.16
Pepper seed extract 400 mg / kg	0.02 ± 0.01	0.17 ± 0.02	1.39 ± 0.11	1.91 ± 0.16

As shown in FIG. 5, it was confirmed that the increase in body weight was smaller in the experimental group administered with red pepper seed extract compared to the control group. In addition, as shown in Table 3, the total abdominal fat content of the experimental group treated with red pepper seed extract was reduced, and it was confirmed that the red pepper seed extract had an anti-obesity effect of inhibiting weight gain and accumulation of body fat based on the above results.

When accumulated in the abdomen of the body, visceral fat forms are more likely to become obese, visceral fat mass has a strong correlation with insulin resistance, and with elevated blood sugar, abnormal trilipidemia such as elevated serum triglycerides and lower HDL-cholesterol It is known to increase the risk of metabolic syndrome, and further experiments were conducted on the effect of reducing the red pepper seed insulin resistance.

Experimental Example 2-4. Confirmation of Insulin Resistance Reduction Effect

The blood glucose of the experimental animal of Experimental Example 2-1 was measured by heart blood collection after fasting for 8 hours. Insulin was measured using a mouse insulin ELISA kit (Shibayagi) in the serum separated after the end of the experiment. In addition, in order to evaluate insulin resistance, the HOMA-IR was calculated by the following formula, and the results are shown in FIG. 6.

[formula]

As shown in FIG. 6A, the blood glucose level of the experimental group to which the red pepper seed extract was administered was decreased compared to the control group, and as shown in FIG. 6B, the fasting insulin concentration of the experimental group to which the red pepper seed extract was administered was significantly reduced. Since the HOMA model is used to evaluate insulin sensitivity and β-cell function from fasting insulin and blood glucose, it was confirmed that the red pepper seed extract reduced fasting insulin concentration and blood glucose through the results shown in FIGS. 6A and 6B. It was confirmed that the pepper seed extract can reduce insulin resistance.

Experimental Example 2-5. Confirmation of lowering serum lipid level

After the breeding period was completed, the experimental animals were sacrificed, blood was separated from the abdominal aorta of the experimental animals, and then serum was separated using a centrifuge. Total cholesterol, triglycerides and free fatty acids in serum were measured using the kit of Yeongdong Pharm. (Korea) and the results are shown in FIGS. 7 and 8.

As shown in Fig. 7a and 7b, both the serum triglyceride and cholesterol concentration in the pepper seed extract administration group was significantly reduced compared to the control group, especially in the case of 400mg per kg body weight significantly reduced both triglyceride and cholesterol compared to the control group The effect could be observed.

In addition, as shown in FIG. 8, free fatty acid was measured from serum, and the free fatty acid of the experimental group administered with red pepper seed extract was decreased compared with the control group, and especially when administered at 400 mg / kg, the tendency to decrease compared to the control group was observed. Seemed. As a result of this study, pepper seed extract administered at 400 mg / kg tended to reduce the concentration of free fatty acids when obesity was induced with high fat, and it was confirmed that pepper seed extract may reduce insulin resistance due to obesity.

Although the preferred embodiments of the present invention have been described in detail above, the scope of the present invention is not limited thereto, and various modifications and improvements of those skilled in the art using the basic concepts of the present invention defined in the following claims are also provided. It belongs to the scope of rights.

The present invention relates to a composition for treating or preventing metabolic diseases, such as obesity. The metabolic disease, for example, a composition for treating or preventing obesity may be a pharmaceutical composition or a pharmaceutical composition. The composition for treating or preventing obesity may include pepper seed extract, specifically, pepper seed water extract extracted with water.

In addition, the present invention provides a composition for improving or preventing metabolic diseases, such as obesity, in order to achieve the above object. The composition for improving or preventing obesity may be a food composition. The food composition may be a functional food composition.

The inventors of the present invention, while studying the natural plant-derived ingredients effective in obesity, pepper seeds, which are mostly used as waste, unlike pepper pulp, have superior obesity treatment, improvement and prevention effect compared to chili pulp, obesity treatment and improvement Or it can be used as a preventive composition to complete the present invention.

Unless otherwise specified herein, an active ingredient means a component that provides an anti-obesity effect in a composition, specifically a pharmaceutical composition or a food composition.

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

The present invention relates to a composition for treating or preventing obesity, which comprises red pepper seed extract as an active ingredient. The composition for treating or preventing obesity may be a pharmaceutical composition or a pharmaceutical composition.

The obesity refers to a state in which fat tissue is excessively accumulated due to quantitative and numerical increase of adipocytes in the body, and the quantitative increase of such fat cells is due to localization, ie, differentiation of fat cells and accumulation of fat. It means to happen.

The pepper seed refers to the seeds contained in the flesh of the pepper, the pepper (pepper, Capsicumannuum ) is a high-temperature crop of South America origin, mainly pulp and leaves have been used for food.

The main physiologically active substance of the red pepper flesh extract is capsanthin, capaorubin, vitamin, capsaicin, or organic acid, and the like. In relation to the capsaicin has been reported effects such as humoral immune hyperactivity and oncogene expression regulation, functional dyspepsia, energy metabolic rate or bactericidal action.

The study of the pepper has been conducted mainly to study the pepper pulp, the research on the pepper seeds is rarely progressed at home and abroad.

The red pepper seed extract inhibits the differentiation of pro-dipotent cells into adipocytes, inhibits the expression of transcription factors that induce differentiation into adipocytes, inhibits the accumulation of fat in the body and the increase in body weight, reduces resistance to insulin, and In addition to lowering the levels of triglycerides and cholesterol, obesity was not only treated or prevented, and the anti-obesity effect was found to be remarkably superior to the red pepper extract, and further analysis showed that the content of capsaicin was not high unlike the red pepper extract. It was confirmed that the excellent effect was derived by the ingredient different from the active ingredient exhibiting the effect of the existing pepper flesh extract or pepper extract.

Specifically, as a result of analyzing the pepper seed extract by HPLC, it was confirmed that capsicinoid, which is a main active substance of the red pepper flesh extract, was not included. In particular, as a result of comparing the effect of inhibiting the differentiation of the progenitor cells into adipocytes of the red pepper seed extract and red pepper flesh extract, it was experimentally confirmed that the red pepper seed extract is remarkably superior to the red pepper flesh extract.

In addition, as a result of confirming the effect on the liver weight / weight of the experimental animal by the toxicity evaluation of the pepper seed extract confirmed that there is no significant change of liver weight / body weight in the experimental animal to which the pepper seed extract was administered, It was confirmed that it has an obesity effect but does not exhibit cytotoxicity. Specifically, when the toxic substance is administered to the body, the size and weight of the liver increases, and it was confirmed that the ratio of liver weight / body weight did not change in the experimental animals administered the red pepper seed extract.

In addition, the red pepper seed extract inhibits weight gain and body fat accumulation and inhibits blood glucose and insulin concentrations to reduce insulin resistance, thereby treating, improving or preventing metabolic syndrome caused by obesity.

The extract may be prepared by extracting with an extraction solvent or by adding a fractional solvent to the extract prepared by extracting with an extraction solvent.

The extraction solvent of the red pepper seed extract may be any one selected from the group consisting of water, an organic solvent and a combination thereof, and the organic solvent may be a polar solvent such as alcohol having 1 to 5 carbon atoms, dilute ethyl acetate or acetone, and the like. Non-polar solvents of ether, chloroform, benzene, hexane or dichloromethane or mixed solvents thereof. The alcohol having 1 to 5 carbon atoms may be methanol, ethanol, propanol, butanol, isopropanol, and the like, but is not limited thereto. In addition, the alcohol dilution water may be diluted with water to 50% (v / v) to 99.9% (v / v) alcohol.

Extraction solvent of the red pepper seed extract may be preferably at least one selected from the group consisting of water, alcohol having 1 to 5 carbon atoms, alcohol dilution water and mixtures thereof, more preferably water, alcohol having 1 to 4 carbon atoms and It may be any one selected from the group consisting of a mixture thereof, even more preferably may be water.

Extraction time of the pepper seed extract is not particularly limited, but may be extracted for 30 minutes or more, for example, may be extracted for 28 minutes to 35 minutes.

Extraction temperature of the red pepper seed extract may be carried out at the extraction temperature that is usually made at the time of plant extraction in the technical field to which the present invention belongs.

The extracting method of the red pepper seed extract may be prepared according to a conventional method of preparing a plant extract, but may be, for example, cold needle extraction method, hot needle extraction method, heat extraction method, ultrasonic extraction method, but is not limited thereto. Ultrasonic grinding extractors or fractionators may be used.

The fraction is an extract extracted with an extraction solvent to any one solvent selected from the group consisting of hexane, methylene chloride, acetone, ethyl acetate, ethyl ether, chloroform, water and mixtures thereof, preferably hexane, methylene chloride and ethyl acetate The fractionation process may be further performed with one or more solvents selected from the group consisting of.

Two or more solvents may be used in the fractionation, and the fractions of each extract may be prepared using sequentially or mixed according to the polarity of the solvent.

For example, the fractionation process may be performed at 4 ° C. to 120 ° C., or 50 ° C. to 90 ° C., or 60 ° C. to 80 ° C., but is not limited thereto.

The red pepper seed extract or the fraction obtained by performing the fractionation process may be filtered or concentrated or dried to remove the solvent, it can be carried out both filtration, concentration and drying. Specifically, the filtration may be performed using a filter paper or a reduced pressure filter, the concentration may be concentrated under reduced pressure using a reduced pressure concentrator, for example, a rotary evaporator, and the drying may be performed by, for example, a lyophilization method.

The red pepper seed extract may be preferably concentrated in a vacuum and concentrated in a freeze-dried powder form to extract and filtered the red pepper seeds in the extraction container with the extraction solvent. The obtained extract can be stored in a deep freezer until use.

Obesity treatment or prevention composition comprising the red pepper seed extract as an active ingredient, in addition to the active ingredient, nutrients, vitamins, electrolytes, flavors, coloring agents, neutralizing agents, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protection Sex colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated drinks, and the like may further be included.

In addition, the carrier, excipient or diluent may be lactose, dextrose, sucrose, sorbitol, mannitol, ziitol, erythritol, maltitol, starch, acycia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline In the group consisting of cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil, dextrin, calcium carbonate, propylene glycol, liquid paraffin, physiological saline It may be one or more selected, but is not limited to any conventional carrier, excipient or diluent can be used. The ingredients may be added independently or in combination with the active ingredient, ie pepper seed extract.

Obesity treatment or prevention composition comprising the red pepper seed extract as an active ingredient is 0.001% to 99.9% by weight, preferably 0.1% to 99% by weight, more preferably 1% by weight of the active ingredient relative to the total weight of the composition % To 50% by weight. In addition, the content of the additional component may be added in the range of 0.1% to 20% by weight based on the total weight of the composition for treating or preventing obesity, but is not limited thereto.

In addition, when pharmaceutical compositions for treating or preventing obesity containing the red pepper seed extract as an active ingredient, conventional fillers, extenders, binders, disintegrants, surfactants, anti-coagulants, lubricants, wetting agents, flavors, emulsifiers or preservatives, etc. It may further include, can be used orally or parenterally.

Specifically, solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and the solid preparations include at least one excipient such as starch, calcium carbonate ( It is prepared by mixing calcium carbonate, sucrose or lactose, gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid preparations for oral use include suspensions, solvents, emulsions, and syrups.In addition to the commonly used simple diluents, water and liquid paraffin, various excipients may include, for example, wetting agents, sweeteners, fragrances, and preservatives. have.

In addition, the formulation of the composition for treating or preventing obesity comprising the red pepper seed extract of the present invention as an active ingredient may be in a preferred form depending on the method of use, and in particular, provides rapid, sustained or delayed release of the active ingredient after administration to a mammal. It can be formulated by adopting a method known in the art to do so. Examples of specific formulations include granules, powders, syrups, solutions, suspensions, tablets, injections, spirits, cataplasma, capsules, soft or hard gelatin capsules, and the like.

Furthermore, a composition for treating or preventing obesity comprising the red pepper seed extract of the present invention as an active ingredient may be prepared using Remington's Pharmaceutical Sciences (Remington's Pharmaceutical Science, recent edition), Mack Publishing Company, Easton PA Formulated preferably using the method disclosed herein.

The dosage of the composition for treating or preventing obesity comprising the red pepper seed extract according to the present invention as an active ingredient may be appropriately selected by those skilled in the art in consideration of the method of administration, the age, sex and weight of the taker, and the severity of the disease. have. As an example, the composition for treating or preventing obesity comprising the red pepper seed extract of the present invention as an active ingredient is 0.0001 mg / kg to 1000 mg / kg, based on the active ingredient, in order to be more effective, from 0.01 mg / kg to It may be administered at 500 mg / kg. Administration may be administered once a day or may be divided several times. The dosage does not limit the scope of the invention in any aspect.

In addition, the composition for treating or preventing obesity comprising the red pepper seed extract of the present invention as an active ingredient may further include an extract for a compound or natural product having a known obesity treatment or prophylactic effect in addition to the active ingredient, and the active ingredient 5 parts by weight to 200 parts by weight with respect to 100 parts by weight, respectively.

In addition, the present invention relates to a food composition for improving or preventing obesity, including red pepper seed extract as an active ingredient. The food composition may be a dietary supplement composition.

The present invention also relates to an obesity improvement or prevention health functional food comprising the composition for improving or preventing obesity comprising the red pepper seed extract as an active ingredient.

The food means a natural product or processed product containing one or more nutrients, and preferably means a state in which it can be directly eaten through a certain processing process. It is intended to include all beverages, food additives and beverage additives.

For example, the food includes various foods, beverages, gums, teas, vitamin complexes, and health functional foods. In addition, the food in the present invention includes special nutritional products (e.g., prepared oils, infants, baby food, etc.), processed meat products, fish products, tofu, jelly, noodles (e.g. ramen, noodles, etc.), health supplements, seasoned foods ( For example, soy sauce, miso, red pepper paste, mixed soy sauce), sauces, confectionery (e.g. snacks), dairy products (e.g. fermented milk, cheese, etc.), other processed foods, kimchi, pickles (various kimchi, pickles, etc.), beverages ( Examples include, but are not limited to, fruits, vegetable drinks, soy milk, fermented beverages, and the like, and natural seasonings (eg, ramen soup). The food, health functional food, beverages, food additives and beverage additives may be prepared by conventional manufacturing methods.

In the present invention, a health functional food is a biological defense rhythm control, disease prevention and the like having a food group or a food composition which has added value to the food by using physical, biochemical, biotechnological techniques, etc. It refers to a food that is designed and processed to fully express the weight control function related to recovery.

The dietary supplement may include food acceptable food additives, and may further include appropriate carriers, excipients and diluents commonly used in the manufacture of dietary supplements.

The drink is a generic term for drinking to quench thirst or enjoy the taste and is intended to include a health functional beverage. The beverage is not particularly limited to other ingredients other than including the red pepper seed extract as an active ingredient in the indicated proportions as an active ingredient, and may contain various flavors or natural carbohydrates as additional ingredients, such as ordinary drinks. .

Examples of such natural carbohydrates include monosaccharides such as glucose, fructose and other disaccharides such as maltose, sucrose and the like and polysaccharides such as dextrin, cyclodextrin and the like, and Sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents other than those mentioned above, natural flavoring agents (tauumatin, stevia extract (for example, rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used. The ratio of the natural carbohydrate may generally be about 1 to 20 g, preferably 5 to 12 g per 100 ml of the food composition of the present invention, in addition to the composition of the present invention for the production of natural fruit juices, fruit juice drinks, vegetable drinks It may further contain pulp for.

In addition to the above, the food composition of the present invention includes various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, coloring and neutralizing agents (such as cheese, chocolate), pectic acid and salts thereof, alginic acid and Salts, organic acids, protective colloid thickeners, pH regulators, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated beverages, and the like. These components can be used independently or in combination. The proportion of such additives is not so critical, but may be selected from 0 to 2,000 parts by weight per 100 parts by weight of red pepper seed extract of the present invention.

The health functional beverage is a biological defense rhythm control, disease prevention and recovery of a beverage group or beverage composition that has added value to the beverage by using physical, biochemical, biotechnological techniques, etc. It refers to a beverage that is designed and processed to fully express the gymnastics function in relation to the living body.

The health functional beverage is not particularly limited to other ingredients other than the red pepper seed extract of the present invention as an essential ingredient in the indicated ratio, and may contain various flavors or natural carbohydrates as additional ingredients, such as ordinary drinks.

Examples of such natural carbohydrates include monosaccharides such as glucose, fructose and other disaccharides such as maltose, sucrose and the like and polysaccharides such as dextrin, cyclodextrin and the like, and xylitol Sugar alcohols such as sorbitol and erythritol. As flavoring agents other than those mentioned above, natural flavoring agents (tauumatin, stevia extract (for example, rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used. The proportion of said natural carbohydrates is generally about 1 g to 20 g, preferably 5 g to 12 g per 100 ml of the composition of the present invention.

In addition, in the food composition for preventing or improving obesity, containing the red pepper seed extract as an active ingredient, the active ingredient may be included in 0.01 to 15% by weight of the total food weight, the beverage composition is 0.02 g based on 100 ml To 5 g, preferably 0.3 g to 1 g.

As described above, the red pepper seed extract of the present invention has been confirmed that the anti-obesity effect, in particular, the anti-obesity effect, specifically, inhibiting the effect of adipocyte differentiation and adipocyte size increase compared with the red pepper flesh extract, effective red pepper seed extract of the present invention It was confirmed that the food composition containing as an ingredient shows the outstanding obesity prevention or improvement effect.

Red pepper seed extract as an active ingredient of the present invention is not only anti-obesity effect, insulin resistance reduction effect, blood cholesterol reduction effect is recognized, but also low cytotoxicity, since it is prepared from pepper used for a long time for food, so no side effects, etc. It can be widely used in industries related to the treatment, amelioration or prevention of various metabolic diseases, including obesity, obesity and diabetes.

Claims (5)

1. A pharmaceutical composition for treating or preventing metabolic diseases comprising pepper seed extract as an active ingredient.
2. The method of claim 1,

   The extract is hot pepper seed hydrothermal extract pharmaceutical composition for treating or preventing metabolic diseases.
3. The method of claim 1,

   The metabolic disease is obesity or diabetes is a pharmaceutical composition for treating or preventing metabolic diseases.
4. Obesity or diabetes improvement or prevention food composition comprising red pepper seed extract as an active ingredient.
5. The method of claim 4, wherein

   The food composition is a food composition for improving or preventing obesity or diabetes is a health functional food for improving or preventing obesity or diabetes.

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