KR20130133493A - Curcumin extracts as an effective components for lipid metabolism improvement and obesity enhancement - Google Patents

Abstract

The present invention relates to a use of a Curcuma longa extract for lipid metabolism improvement and obesity treatment. According to the present invention, the Curcuma longa extract has effects on lipid metabolism improvement and obesity treatment, and natural Curcuma longa can be used as pharmaceutical agents and various functional health foods for lipid metabolism improvement and obesity treatment.

Description

Curcumin extracts as an effective components for Lipid Metabolism Improvement and Obesity Enhancement}

The present invention relates to the use of turmeric as a medicament or food, improving liver lipid metabolism or improving obesity.

The prevalence of lifestyle-related diseases such as cardiovascular disease, cancer, diabetes, and dementia has increased significantly due to changes in dietary patterns, stress, environmental pollution, and lack of exercise, which lead to malnutrition and nutritional imbalance such as high calorie and high fat diet. In Korea alone, about 20 trillion won was spent on treatment of diseases in 2002, which greatly affects the national economic development.

Meanwhile, Ulgeum has been used as herbal medicine, spices, and edible and has herbal names such as Eulgeum, Gumgeum, Okgeum (玉 金), Turmeric, and Emperor. The Chinese herbal herb has been recorded to stop blood, remove bad blood, and heal blood, bleeding, and gold spears. In addition to lowering the qi and bleeding (血 林), bleeding (尿 血), Jinchang (金 瘡), blood vessels (심 心痛) to treat. It has been used as a placebo, pain medication, etc., and it has been used for nosebleeds, hematuria, and bleeding.

Turmeric, harvested from powdered turmeric roots, is a spice and an ingredient in curry powder. The turmeric contains 0.3% of the yellow pigment curcumin and its derivatives, p-hydroxycinnamiyl feruloylmethane and p, p'-dihydroxydicinnamoylmethane, 1-5% essential oils with unique flavors such as turmerone and dehydroturmerone, 2.4% non-volatile oil, and 50% starch. It contains 5% crude fiber, 4% ash and 16% moisture. Recently, studies on the physiological activity of turmeric have been reported, including the antioxidant activity of curcuminoids, the antioxidant activity of curcumin, anticancer, antimutagenic, anti-inflammatory and antimicrobial effects, and the anti-snake effect of tumerone and ar -tumerone.

Recently, researches have been conducted to find a substance that modulates physiological activity using various natural products or to find a substance that is safe and has no side effects and has an improvement effect. Accordingly, the present inventors have investigated the effect of improving the lipid metabolism and the reversal of turmeric and completed the present invention based on the data.

The present invention has a technical problem to provide a natural product that can be safely used for improving liver lipid metabolism or obesity.

The present invention has been developed to solve the above technical problem, proposes a liver lipid metabolism improvement to obesity improvement of natural turmeric extract.

According to the present invention, it can be seen that turmeric extract is effective in improving liver lipid metabolism and obesity, barulum, a natural product, can be usefully used in pharmaceutical preparations or various functional health foods for improving liver lipid metabolism and obesity. .

Figure 1 shows the blood sugar content of the experimental animal.
Figure 2 shows the triglyceride content in blood of experimental animals.
Figure 3 shows the total cholesterol content in the blood of experimental animals.
4 and 5 show the HDL-cholesterol and LDL-cholesterol content in blood of experimental animals.
Figure 6 shows the results of measuring the arteriosclerosis index of experimental animals.
Figure 7 shows the total lipid content of liver tissue of the experimental animal.
Figure 8 shows the neutral lipid content of liver tissue of the experimental animal.
Figure 9 shows the total cholesterol content of liver tissue of the experimental animal.
10 shows the neutral lipid content of feces of experimental animals.
Figure 11 shows the total cholesterol content of feces of experimental animals.
12 shows cell viability for 3T3-L1 cells.
Figure 13 shows the free fatty acid concentration produced during lipolysis.
Figure 14 shows the concentration of glycerol produced during lipolysis.
Figure 15 shows the leptin concentration produced during lipolysis.

The present invention relates to the use of liver lipid metabolism improvement to obesity improvement for turmeric extract. Through the following experimental example it was confirmed that the liver lipid metabolism to improve the obesity effect in the experimental animal administered turmeric extract, while turmeric can be used as a safe health material because it is an edible food.

In the present invention, turmeric can be used without limitation, the one that is collected, cultured or commercially available, and the extract can be obtained by conventional extraction methods in the art, such as ultrasonic extraction, filtration and reflux extraction. Preferably, the ground turmeric powder is extracted in cold water and then lyophilized.

Turmeric extract, which has been found to improve liver lipid metabolism or improve obesity, may be prepared according to a conventional method as a pharmaceutical composition, a pharmaceutical formulation, a functional food, and the like.

The pharmaceutical compositions may be used in the form of pharmaceutically acceptable salts, or may be used alone or in combination with other pharmaceutically active compounds to a suitable collection. The salt is not particularly limited as long as it is pharmaceutically acceptable so long as it is pharmaceutically acceptable and includes, for example, hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, hydrofluoric acid, hydrobromic acid, formic acid acetic acid, tartaric acid, lactic acid, citric acid, fumaric acid, , Benzenesulfonic acid, toluenesulfonic acid, and naphthalenesulfonic acid. The pharmaceutical composition may be administered orally or parenterally, and during parenteral administration, it is preferable to select an external skin or intraperitoneal, rectal, intravenous, intramuscular, subcutaneous, intrauterine dural or cerebrovascular injection method, most preferably. Is used for oral administration.

Pharmaceutical formulations are prepared using commonly used diluents or excipients, such as fillers, extenders, binders, wetting agents, disintegrating agents, surfactants, and the like. Solid form preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, which form at least one excipient such as starch, calcium carbonate, sucrose or lactose (at least one compound). lactose), gelatin and the like are mixed. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid preparations for oral administration include suspensions, liquid solutions, emulsions, and syrups, and various excipients such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin, may be included. have. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations and suppositories, where non-aqueous solvents and suspensions are propylene glycol, polyethylene glycol and olive oil. Vegetable oils, injectable esters such as ethyl oleate, and the like may be used, and suppository bases such as witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like may be used. have.

The functional food may be added with turmeric extract as it is or used with other food or food ingredients, and may be appropriately used according to a conventional method. Specific functional foods include chewing gum, caramel products, candy, ice cream, sweets, various foods, soft drinks, mineral water, alcoholic beverages, and health functional foods including vitamins and minerals. In the foodstuff acceptable food supplement additives can be added various flavors or natural carbohydrates. Natural carbohydrates include glucose, monosaccharides such as fructose, disaccharides such as maltose and sucrose, and polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol and erythritol. As a zero, natural sweeteners such as taumartin, stevia extract, or synthetic sweeteners such as saccharin or aspartame may be used. Functional foods are also used in various nutrients, vitamins, electrolytes, flavors, colorants, pectic and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH regulators, stabilizers, preservatives, glycerin, alcohols, carbonated drinks It may be prepared to contain a carbonation agent and the like used, and may also contain a flesh for preparing natural fruit juice, fruit juice beverage and vegetable beverage.

Hereinafter, the present invention will be described based on Examples and Experimental Examples. However, the following Examples and Experimental Examples are only for illustrating the present invention, and the scope of the present invention is not limited thereto.

[ Example ] Turmeric  Preparation of powder

After receiving turmeric at Jindo, it was dried at 80 ℃ using a farm-type hot air dryer and pulverized with a pulverizer (Daesung Power Mixer / Pulverizer DA-280G, Seoul, Korea) and 6 ℃ of distilled water (w / v) was added. Extracted for 24 hours. Repeat three times under the same conditions as above and collect the supernatant. The filtrate was filtered through 1 filter paper, and the filtrate was concentrated under reduced pressure using a rotary vacuum evaporator (HS-2001N, Hanshin Science CO. Korea) and dried with a lyophilizer (Bondiro, Ilshin, Korea) to obtain turmeric powder.

[ Experimental Example 1 in vivo Anti-obesity  Functional evaluation

1. Outline of Experiment Method

(1) Breeding and dieting of experimental animals

Experimental animals were purchased from Bio genomics, Inc., Seoul, Korea, Sprague-Dawley males of about 100 ± 10g body weight. After preliminary breeding with general mixed feed (Purina Co., Seoul, Korea) for a week before the start of the experimental formula, divided into control and experimental groups by randomized complete block design so that the average weight is similar. The animals were divided for 4 weeks. The diet was stored at 4 ° C. during the experimental period, and fed at a certain time every day for free intake. The temperature of the feeding room was maintained at 22 ± 2 ℃ and relative humidity 50 ± 10. The diet group was divided into the normal group (N) and the 1% high fat high cholesterol test group (HF, CPA, CPB), and the high fat high cholesterol test group was again divided into the high fat high cholesterol control group (HF) and the high fat high cholesterol + 0.05% turmeric feed group (CPA). ), High fat high cholesterol + 0.1% turmeric feed group (CPB) divided into a total of four groups were bred.

Empirical formula Ingredients N HF CPA CPB Cornstarch 539 429 428.5 428 Casein 200 200 200 200 Sucrose 100 100 100 100 Cellulose 50 50 50 50 Mineral mixture ^{1 )} 35 35 35 35 Vitamin mixture ^{2 )} 10 10 10 10 DL-methionine 3 3 3 3 Choline chloride 3 3 3 3 Corn oil 60 60 60 60 Cholesterol 0 10 10 10 Lard 0 100 100 100 Curcumin 0 0 0.5 One Total 1000 1000 1000 1000 ¹⁾ AIN-76 mineral mixture (g / kg mixture).
²⁾ AIN-76 vitamin mixture (g / kg mixture).

2. weight gain, Dietary intake  And Dietary efficiency

(1) Experimental method

Dietary intake was measured every day during the entire experimental period, body weight was measured every three days at a certain time. The food efficiency ratio (FER) was calculated by dividing the total weight gain by the food intake over the same period.

(2) Experimental results

The results of observing weight gain, dietary intake, and dietary efficiency are shown in Table 2 below.

Weight gain, dietary intake and dietary efficiency Groups Body wight gain (g) Food intake (g / day) FER N 134.4 ± 11.45 ^b   19.40 ± 0.51   0.392 ± 0.050 HF 158.4 ± 5.610 ^a 20.03 ± 0.03  0.453 ± 0.024 CPA 155.0 ± 10.34 ^ab 19.98 ± 0.02  0.440 ± 0.027 CPB 149.3 ± 5.69 ^ab 19.72 ± 0.03 0.431 ± 0.05

Body weight gain was significantly increased in the high fat high cholesterol control group (HF) compared to the normal group (N), and decreased in both the turmeric feeding group (CPA, CPB) compared to the high fat high cholesterol control group (HF), Dietary intake also showed a similar trend. The dietary efficiency was increased in the high fat high cholesterol control group (HF) compared to the normal group (N) and decreased in both the turmeric feeding group (CPA, CPB) compared to the high fat high cholesterol control group (HF).

3. liver, Abdominal fat  And epididymal fat weight

(1) Experimental method

Completion of breeding period Hue The animal was fasted for 12 hours, blood was collected from the abdominal aorta under light ether anesthesia, and tissues were taken immediately and rinsed with saline solution. Store at -80 ° C.

(2) Experimental results

Liver tissue, abdominal fat and epididymal fat weight comparison results are shown in Table 3 below.

Liver tissue, abdominal fat and epididymal fat weight Groups Liver index Abdominal Epidydimal (g / 100g body weight) N 9.64 ± 0.41 ^c 2.00 ± 0.55 ^b 2.30 ± 0.99 ^NS HF 15.98 ± 0.75 ^a 6.20 ± 1.54 ^a 4.60 ± 1.35 CPA 11.30 ± 1.01 ^bc 2.55 ± 0.51 ^a 2.29 ± 0.11 CPB 11.56 ± 0.84 ^b 2.30 ± 0.10 ^a 2.55 ± 0.51

As described above, liver tissue was significantly increased in the high fat high cholesterol control group (HF) compared to the normal group (N), and decreased in both the turmeric feeding group (CPA, CPB) compared to the high fat high cholesterol control group (HF) Indicated. Abdominal fat was significantly increased in the high fat high cholesterol control group (HF) compared to the normal group (N), and decreased in all groups fed the turmeric (CPA, CPB) compared to the high fat high cholesterol control group (HF). . In epididymal fat, it was increased in the high fat high cholesterol control group (HF) compared to the normal group (N), and decreased in all groups fed the turmeric (CPA, CPB) compared to the high fat high cholesterol control group (HF).

4. Blood glucose ( glucose ) content

The result of observing blood glucose is as shown in FIG. 1. Compared to the normal group (N), it was significantly increased in the high fat high cholesterol control group (HF), and in all groups fed turmeric (CPA, CPB) decreased to 6% and 14%, respectively, compared to the high fat high cholesterol control group (HF). In particular, the 0.1% turmeric feed group (CPB) was significantly reduced compared to the high fat high cholesterol control group (HF).

5. triglycerides in serum, 촐 Cholesterol , HDL -cholesterol, LDL -Cholesterol content and arteriosclerosis index ( atherogenic index , AI )

(1) Experimental method

The serum triglyceride content was calculated by measuring the absorbance at 550 nm using a kit (Asan Co., Gyeonggi, Korea) by the standard enzyme method. Total cholesterol content was calculated by measuring the absorbance at 500 nm using a standard enzyme kit (Asan Co., Gyeonggi, Korea), and the HDL-cholesterol content was 2%, dextron sulfate solution and 1M Mgcl ₂ precipitate. The mixture was mixed 1: 1 and centrifuged at 12,000 rpm for 8 minutes, and the supernatant was calculated by measuring the absorbance at 500 nm using a kit (Asan Co., Gyeonggi, Korea) by the standard enzyme method. Serum LDL-cholesterol content was calculated by Friedewald's calculation, and serum atherosclerosis (atherogenic index, AI) was calculated by Fiordaliso calculation.

(2) triglyceride content in the blood

The result of observing triglyceride in serum is shown in FIG. 2. As can be seen, the triglyceride concentration in serum tended to increase by 28% in the high fat high cholesterol control group (HF) compared to the normal group (N), and compared with the high fat high cholesterol control group (HF). CPB) showed a decrease of 5% and 20%, respectively.

(3) Total cholesterol content of blood

In cardiovascular disease, an increase in blood cholesterol and lipid concentrations can often be observed. The result of the total-cholesterol content, which is an indicator reflecting this condition, is shown in FIG. 3. Serum total cholesterol concentration increased 27% in the high fat high cholesterol control group (HF) compared to the normal group (N), 19% decrease in the high fat high cholesterol control group (HF) in the 0.05% turmeric fed group (CPA) In particular, the group fed 0.1% turmeric (CPB) showed a 26% decrease. Thus, when the cholesterol level is decreased in the group fed with turmeric than the high fat high cholesterol control group (HF), turmeric is considered to be effective in improving hypercholesterolemia.

(4) HDL-cholesterol and LDL-cholesterol content in blood

 The results of observing the levels of HDL and LDL cholestero in the blood are shown in Figures 4 and 5. HDL-cholesterol decreased 23% in the high fat / high cholesterol control group (HF) compared to the normal group (N), but increased to 3% and 8% in the high-fat and high cholesterol control group (CPA and CPB) compared to the normal group (N). Showed a tendency to. On the other hand, LDL-cholesterol increased in the high fat / high cholesterol control group (HF) compared to the normal group (N), but decreased in the turmeric feed group (CPA, CPB) to 12% and 28%, respectively.

(5) atherosclerotic index (AI)

The atherogenic index results are shown in FIG. 6. 17% increase in high fat high cholesterol control group (HF) compared to normal group (N), and 3%, 17% decrease in high fat high cholesterol control group (HF) in all groups fed turmeric (CPA, CPB), respectively Can be seen. These results suggest that turmeric not only reduces the incidence of obesity, hyperglycemia and fatty liver due to high fat and high cholesterol diet, but also lowers the risk of cardiovascular diseases by controlling abnormalities of cholesterol content in tissues.

6. Liver tissue  Total Lipid, Triglycerides and Total Cholesterol Content

(1) Experimental method

The total lipid content of liver tissue was extracted and quantified by Folch et al., And the quantification of liver tissue lipid was modified by Sale et al. With 0.5% triton X-100 as an emulsifier in the enzyme solution for measuring triglyceride and cholesterol. The absorbance of triglyceride and cholesterol in liver was measured at 550 nm and 500 nm, respectively, by removing turbidity from color development by mixing 3 mM sodium cholate.

(2) Total lipid content of liver tissue

The result of observing the total lipid content of liver tissue is shown in FIG. Lipid content in liver tissue was 65% higher than that of normal group (N), but increased in high fat high cholesterol control group (HF), but in the turmeric feeding group (CPA, CPB), 5%, respectively, compared to high fat high cholesterol control group (HF). The tendency was to decrease to 11%.

(3) Neutral lipid content of liver tissue

The result of observing the neutral lipid content of liver tissue is shown in FIG. 8. The triglyceride content increased to 85% in the high fat high cholesterol control group (HF) compared to the normal group (N), and 30% and 32% in all the turf fed groups (CPA and CPB), respectively, compared to the high fat high cholesterol group. It showed a tendency to decrease.

(4) the total cholesterol content of liver tissue

The results of observing the total cholesterol content of liver tissue is shown in FIG. The total cholesterol content of liver tissue was increased to 78% in the high fat high cholesterol control group (HF) compared to the normal group (N), 7% in the turmeric feeding group (CPA, CPB) compared to the high fat high cholesterol control group (HF), respectively. There was a tendency to decrease by 8%.

7. Fecal  Determination of Total Cholesterol and Neutral Lipid Content

(1) Experimental method

After measuring the wet weight of the stool in the last 3 days of the experiment period, freeze-dried until reaching the constant in the freeze dryer (-70 ℃) and the dry weight was measured to calculate the moisture content of the stool. Total lipid excretion of feces was quantified by Folch et al., And cholesterol was quantified at 550 nm by Pearson et al.

(2) Neutral lipid content of feces

The result of observing the content of the neutral lipid of the feces to determine the excretion of lipid into feces is as shown in FIG. The content of triglyceride in feces increased 24% in the high fat high cholesterol control group (HF) compared to the normal group (N). In the turmeric feeding group (CPA, CPB), 2% and 27%, respectively, tended to increase slightly compared to the high fat high cholesterol control group (HF). It is believed that turmeric is effective in suppressing the absorption of dietary fat by promoting the excretion of triglycerides as feces, and is believed to be due to the fiber and physiological effects contained in turmeric. This result is consistent with the decrease of the neutral lipid content in the blood supply group (CPA, CPB).

(3) total cholesterol content of feces

The result of observing the total cholesterol content in the feces is as shown in FIG. The total cholesterol content of feces was increased by 28% in the high fat high cholesterol group compared to the normal group, and increased to 6% and 29% in all the groups fed the turmeric (CPA, CPB) compared to the high fat high cholesterol control group (HF), respectively. The trend was shown.

[ Experimental Example 2 ] in vitro Anti-obesity  effect

1. Experimental Method

Using 3T3-L1 fibroblasts and adipocytes in Lipolytic ability, insulin-sensitive substances and fat metabolism regulators were investigated in vitro . 3T3-L1 preadipocytes (ATCC) were incubated in an incubator at 5% CO ₂ using DMEM medium containing 10% fetal bocine serum, 100 unit / ml penicillin, and 100 mg / ml strptomycin. After fusion, the cells were separated by treatment with 0.05% trypsin / EDTA, centrifuged to collect the cells, and a suspension solution was prepared so that the cell uniformity was 3.3 × 10 ³ cells / cm ³ . , After 3-4 days, the cells were fused and differentiated into adipocytes by changing the medium to differentiation medium. About 10 days after the differentiation medium treatment, more than 90% of the cells differentiated into adipocytes.

2. Cytotoxicity

The results of examining the cytotoxicity of turmeric against 3T3-L1 cells by performing MTT colorimeter assay after 24 hours by treating turmeric by concentration are shown in FIG. 12. Survival rates at 0, 2.5, 5, 10, 20, and 40 μM concentrations of turmeric were 100, 97.72, 90.97, 34.94, and 16.77%, respectively (p <0.05). Cell viability decreased.

3. Effect on Free Fatty Acid Concentration

The treatment of turmeric by concentration was performed 24 hours later, and the free fatty acid concentration generated during lipolysis was measured. As a result, curcumin concentrations increased by 76.36, 93.18, and 171.82%, respectively.

4. glycerol  Impact on concentration

The glycerol concentration produced during lipolysis measured by treating the turmeric by concentration and performing the assay 24 hours later is as shown in FIG. 14. Therefore, turmeric has been observed to have an effect of inhibiting fat accumulation as a mechanism for breaking down fat in adipocytes, thereby inhibiting obesity.

5. leptin  Impact on concentration

Leptin is a hormone expressed in adipocytes that acts on the hypothalamus to inhibit food intake, increases energy expenditure, and controls obesity. Leptin secretion is known to increase with increasing fat accumulation in adipocytes. In order to determine the correlation between the concentration of leptin and the lipid lowering effect of turmeric, the leptin concentration was measured during curcumin treatment, and the results were measured by running the assay 24 hours after treating turmeric by concentration. As shown, leptin secretion was decreased by 11.86, 24.68 and 30.27%, respectively, compared to the control group.

Claims (4)

Liver lipid metabolism improving composition comprising the turmeric extract as an active ingredient. In claim 1,
The turmeric extract, liver lipid metabolism improving composition, characterized in that the lyophilized after extracting the powder in water. A composition for improving obesity, comprising turmeric extract as an active ingredient. 4. The method of claim 3,
The turmeric extract is a composition for improving obesity, characterized in that lyophilized after extracting turmeric powder in water.

Images