KR101081451B1 - Composition for Preventing or Treating of Obesity Comprising Secoiridoid Derivatives as Active Ingredients - Google Patents

Abstract

The present invention relates to a composition for the prevention or treatment of obesity, comprising sequoidoid derivative (secoiridoid) derivative as an active ingredient. The secoirioid derivatives of the present invention can inhibit adipocyte differentiation, decrease body fat mass, decrease visceral fat mass, decrease total cholesterol concentration, decrease plasma triglyceride and hepatic triglyceride, decrease fasting blood glucose and decrease blood insulin concentration. Resulting in a prophylactic or therapeutic activity of obesity.

Obesity, oleuropein, ash, secoirioid

Description

Composition for Preventing or Treating of Obesity Comprising Secoiridoid Derivatives as Active Ingredients}

The present invention relates to a composition for the prevention or treatment of obesity, including the ash plant or secoirioid derivatives.

Due to the change in living environment, the visceral fat type obesity of modern people has increased, and the incidence of metabolic syndrome accompanying diabetes, hypertension, lipid metabolism abnormality, insulin resistance, etc. is increasing rapidly. These diseases increase the risk of mutual development and are common diseases associated with multiple metabolic changes such as aging, stress, and immune dysfunction.

According to the 2005 National Health and Nutrition Survey, 32% of Korean adults aged 20 and over were obese (35.2% of adult men and 28.3% of women). The incidence of childhood obesity in Korea has also increased rapidly.In 2005, 11.3% of elementary school students, 10.7% of middle school students, and 16% of high school students were classified as obese (BMI ≥ 25 kg / m ² ), and overweight (BMI ≥ 23 kg / m ^2). Or 17% of obese adolescents had metabolic syndrome.

This increase in overweight and obesity leads to an increase in the prevalence of chronic diseases, such as high blood pressure (30.2% male, 25.6% male), diabetes (9.0% male, 7.2% female), and high cholesterol in Koreans aged 30 and over in 2005. The prevalence of bloodemia (7.5% male and 8.8% female) is very high compared to other countries. In 2005, the mortality rate from diabetes was 35.5 per 100,000 people in Korea, more than 3-7 times higher than in Japan (5.9), the UK (7.5), or Germany (16.6). The increase in the number of diabetic patients in Korea is expected to increase to 3,000,000 and to 5,450,000 by 2030, which means that 10% of Koreans will become diabetic.

According to the statistics of the Korea Institute of Health and Social Affairs, the socioeconomic losses from obesity and obesity complications in 2006 are estimated to total KRW 2.1 trillion, including indirect expenses such as medical expenses and income loss from treatment. Accordingly, the government sets the main goal of national health promotion in 2010 to reduce adult obesity rate to less than 20% and adolescent obesity rate to less than 15%, and precisely define obesity and metabolic diseases as an implementation strategy to achieve the goal. And the method of measurement was decided.

Efficacy products have been imported and sold in Korea as a major obesity treatment agent. Among them, anti-obesity products such as xenical, reductyl, and excoriant are widely known. Xenical, which is an orlistat-based ingredient, is the world's first anti-obesity agent that inhibits the action of lipase to inhibit fat absorption, decreases total cholesterol and LDL cholesterol levels, improves blood sugar and lowers blood pressure. see. Reductil, the main ingredient of sibutramine (sibutramine), was approved by the FDA in 1997 and is sold in more than 30 countries around the world.It maintains high levels of serotonin and noradrenaline in the sympathetic nervous system, inducing sympathetic nervousness, appetite and satiety There is this. Lastly, Exorix is a non-prescription semi-finished product imported from France, which increases heat generation, increases the body's basic metabolism, inhibits lipase activity, reduces intestinal fat absorption by 30%, and increases the production of noradrenaline. There is an action to increase.

Obesity can be the best treatment effect in combination with diet therapy, exercise therapy and behavioral therapy, but this method takes a lot of time and effort and difficult to implement, so many obesity treatments or diet products are used. However, Olistat, which is currently used as a treatment for obesity, has side effects such as fatty stool, intestinal gas generation, and bloating. Sibutramine is known to have side effects such as headache, dry mouth, anorexia, insomnia, and constipation. Orlistat also inhibits the absorption of vitamin E and vitamin D, while phentermine and sibutramine have side effects that lead to increased heart rate, palpitations, or dizziness.

As Western medicine shows limitations in overcoming the side effects and chronic diseases of synthetic drugs, the value of new natural products is emerging. Accordingly, the present inventors came to pay attention to secoirioid derivatives, particularly oleuroin, which are phytochemical compounds contained in olive leaves in the process of searching for active substances that inhibit obesity from native plants.

Olerofane is a chemical mixture extracted from olive leaves and has a structural formula of C ₂₅ H ₃₂ O ₁₃ and a molecular weight of 540.514.

Oleuropine's main functions are antioxidant, antiviral and antimicrobial activity, and it is effective in lowering blood pressure, cancer and heart related diseases. Treatment of leuuropine with Caco-2 cells, a colorectal cancer cell line, delayed G2 / M phase time and blocked the cell cycle, inhibiting the proliferation of cancer cells. To determine the toxicity of oleuropine, 1 g / kg of body weight was administered to rats for 7 days. Several other experiments have shown that oleuropine is safe enough to calculate LD50. Most of the commercialization of oleuropine is classified as a dietary supplement and is sold for satisfying the aforementioned main physiological functions.

U.S. Pat. No. 70,711,95 discloses a method of treating obesity using amine and amide derivatives that act as ligands of neuropeptide Y Y5. US Pat. No. 6,702,22 discloses thiazolidinedione analogs for the treatment of diabetes, hyperlipidemia or obesity.

US Pat. No. 6,871,131 discloses a composition for treating hyperlipidemia comprising phenylacetylglutamine, phenylacetylisoglutamine phenylacetic acid. US Pat. No. 6942967 discloses apobec-1 protein as a therapeutic target for atherosclerosis, hyperlipidemia, obesity and diabetes.

Numerous papers and patent documents are referenced and cited throughout this specification. The disclosures of the cited papers and patent documents are incorporated herein by reference in their entirety to better understand the state of the art to which the present invention pertains and the content of the present invention.

The present inventors have tried to develop a natural substance having anti-obesity activity. As a result, the present invention was completed by confirming that oleuropein contained in the extract of the Oleaceae family plants has the above activity.

Accordingly, an object of the present invention is to provide a composition for the prevention or treatment of obesity, including oleuropein or derivatives thereof as an active ingredient.

Other objects and advantages of the present invention will become more apparent from the following detailed description of the invention, claims and drawings.

According to an aspect of the present invention, the present invention provides a composition for preventing or treating obesity, comprising as an active ingredient a compound of Formula 2, which is a sequoidoid derivative of Formula 1 or a hydrolysis product thereof:

Formula 1

Formula 2

R in the formula is a glycosyl group; R ₁ is hydrogen, methyl, 2- (4-hydroxyphenyl) ethyl (2- (4-hydroxyphenyl) ethyl) or 2- (3,4-dihydroxyphenyl) ethyl (2- (3,4-dihydroxyphenyl ethyl).

The present inventors have tried to develop a natural substance having anti-obesity activity. As a result, it was found that the sequoidoid derivative (such as oleuropine) or the hydrolyzate thereof contained in the ash family has the above activity.

Secoiridoid derivatives or hydrolysates thereof are very effective in the prevention or treatment of obesity.

As demonstrated in the examples below, oleuropine leads to a high fat diet by inhibiting adipocyte differentiation, decreasing body fat mass, decreasing visceral fat mass, decreasing total cholesterol concentration, decreasing plasma triglycerides and hepatic triglycerides Efficacy in relieving marked obesity.

The following example demonstrates anti-obesity efficacy by using leuuropine as a representative compound as a secoirioid derivative. However, it is apparent to those skilled in the art that the secoirioid derivatives included in Formula 1, which are known to exhibit the same or similar level of biological activity as oleuropine, will also exhibit anti-obesity efficacy similar to oleuropine. For example, US Pat. Nos. 6,117,844 and 6,455,580 disclose secoiridoid derivatives included in Formula 1 that exhibit the same or similar level of biological activity as oleuropine, which exhibits anti-obesity efficacy similar to oleuropine. Can be represented.

In addition, it is known that elenolic acid of Formula 2 formed by hydrolyzing glycosyl groups of secoirioid derivatives exhibits the same or similar biological activity as oleuropine (see US Patent Nos. 6,117,844 and US Pat. 6,455,580). These elenolic acids are also formed when the secoirioid derivatives are metabolized in vivo. Thus, it is clear to those skilled in the art that the compound of formula (II), the hydrolysis product of the secoirioid derivative, will exhibit similar anti-obesity efficacy as oleuropine.

Secoiridoid derivatives or hydrolysates thereof can be prepared according to the contents described in PCT Publication WO96 / 14064, US Pat. No. 6,455,580 and US Pat. No. 6,117,844.

According to a preferred embodiment of the present invention, in Formula 1 or 2 R ₁ is 2- (3,4-dihydroxyphenyl) ethyl, and most preferably oleuropane having the structure of formula (3) as an active ingredient It is to include.

Formula 3

According to a preferred embodiment of the present invention, the secoirioid derivative is included in the extract or fraction of the ash family.

Secoirioid derivatives are found in large quantities in the fruits, roots, stems, especially leaves of plants of the Oleaceae family. It is known that the ash family containing a large amount of secoirioid derivatives (especially oleuropine) contains about 600 species of 24 genera. Oleaceae plants used in the present invention is not specially limited, including the seco yirido Id derivative, particularly the oleic ah Europa wind straight-O (olive tree, Olea europaea), Liguria strum (Ligustrum) In a plant, when Manly (Syringa) in the plant, a proxy Nurse (Fraxinus) in plants, well over Smith (Jasminum) in plants or ottoman Tuscan (Osmanthus) in plants.

Ash tree plant extracts containing secoirioid derivatives can be obtained by using a conventional extraction solvent for ash tree (preferably, the leaves of the ash tree), and preferably (a) anhydrous having 1 to 4 carbon atoms. Or a hydrous lower alcohol (e.g. methanol, ethanol, propanol, butanol, normal-propanol, iso-propanol and normal-butanol, etc.), (b) a mixed solvent of the lower alcohol with water, (c) acetone, (d) Ethyl acetate, (e) chloroform, (f) 1,3-butylene glycol, (g) hexane, (h) diethyl ether, (i) butyl acetate or (j) water can be obtained as an extraction solvent.

Ash plant fraction comprising a secoirioid derivative means a more isolated / purified form obtained by further separating / purifying the ash plant extract. For example, fractions obtained by passing an ash plant extract through an ultrafiltration membrane having a constant molecular weight cut-off value, separation by various chromatography (manufactured for separation according to size, charge, hydrophobicity or affinity), etc. The fractions obtained through the various purification methods described above are also included in the ash fraction. Ole O by the use of the O leaf extract in Europa method for obtaining oleic right pane is described in detail in U.S. Patent Application Publication No. 2003-0017217.

In addition, the secoirioid derivatives can be synthesized chemically.

According to a preferred embodiment of the present invention, the secoirioid derivatives include secoirioid derivatives prepared by synthesis in addition to those isolated from the ash tree and plants.

Methods of synthesizing secoirioid derivatives are described in detail in PCT Publication WO 96/14064.

According to another aspect of the present invention, the present invention provides a pharmaceutical composition or a food composition for the prevention or treatment of obesity, including secoirioid derivatives.

When the composition of the present invention is made into a pharmaceutical composition, the pharmaceutical composition of the present invention includes a pharmaceutically acceptable carrier. Pharmaceutically acceptable carriers included in the pharmaceutical compositions of the present invention are those commonly used in the preparation, such as lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia rubber, calcium phosphate, alginate, gelatin, Calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methyl cellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil, and the like It doesn't happen. In addition to the above components, the pharmaceutical composition of the present invention may further include a lubricant, a humectant, a sweetener, a flavoring agent, an emulsifier, a suspending agent, a preservative, and the like. Suitable pharmaceutically acceptable carriers and formulations are described in detail in Remington's Pharmaceutical Sciences (19th ed., 1995).

The pharmaceutical composition of the present invention may be administered orally or parenterally, and preferably applied by oral administration.

Suitable dosages of the pharmaceutical compositions of the present invention may vary depending on factors such as the formulation method, mode of administration, age, weight, sex, morbidity, food, time of administration, route of administration, rate of excretion and response to the patient. Can be. Preferred dosages of the pharmaceutical compositions of the invention are in the range of 0.001-100 mg / kg on an adult basis.

The pharmaceutical compositions of the present invention may be prepared in unit dose form by formulating with a pharmaceutically acceptable carrier and / or excipient according to methods which can be easily carried out by those skilled in the art. Or may be prepared by incorporation into a multi-dose container. The formulation may be in the form of solutions, suspensions, syrups or emulsions in oils or aqueous media, or in the form of extracts, powders, powders, granules, tablets or capsules, and may further comprise dispersants or stabilizers.

When the composition of the present invention is made of a food composition, as an active ingredient, as well as sequoidoid derivatives, it contains components that are commonly added during food production, for example, proteins, carbohydrates, fats, nutrients, seasonings and Contains flavors. Examples of the above carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose, oligosaccharides and the like; And sugars such as conventional sugars such as polysaccharides such as dextrin, cyclodextrin and the like and xylitol, sorbitol, erythritol. As the flavoring agent, natural flavoring agents [tautin, stevia extract (for example, rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be used.

For example, when the food composition of the present invention is prepared with a drink, the cicolic acid, liquid fructose, sugar, glucose, acetic acid, malic acid, fruit juice, tofu extract, jujube extract, licorice extract, etc. You can.

The composition of the present invention comprising a secoirioid derivative as an active ingredient, inhibits adipocyte differentiation, decreases body fat amount, decreases visceral fat amount, decreases total cholesterol concentration, decreases plasma triglycerides and hepatic triglycerides, and decreases fasting blood glucose And a decrease in blood insulin levels, ultimately exhibiting prophylactic or therapeutic activity of obesity.

The features and advantages of the present invention are summarized as follows.

(Iii) The present invention provides a composition for the prevention or treatment of obesity comprising a secoirioid derivative as an active ingredient.

(Ii) The composition of the present invention can be separated using the ash plant, and can also be synthesized through chemical methods.

(Iii) The composition of the present invention comprising an ash plant extract or a secoirioid derivative as an active ingredient, inhibits adipocyte differentiation, decreases body fat amount, decreases visceral fat amount, decreases total cholesterol concentration, plasma triglycerides and liver tissue It results in a decrease in triglycerides, a decrease in fasting blood sugar and a decrease in insulin concentration in the blood, ultimately exhibiting a prophylactic or therapeutic activity of obesity.

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

Example 1: Inhibitory effect of oleuropine on adipocyte differentiation using mouse adipocyte line (3T3-L1)

Cell culture and oil red O staining

Mouse fat cell lines (3T3-L1, ATCC, American Type Culture Collection, Manassas, VA, USA) were used to assess the effects of oleuropine (Extrasynthese, France) on the differentiation and growth of adipocytes. Adipocytes, 3T3-L1 cells, were dispensed in 12-well plates and added Dulbecco-modified Eagle with 1% penicillin-streptomycin, 1% non-essential amino acids, and 10% fetal bovine serum (FBS). medium) was used to incubate in a confluent state at 37 ℃, 5% CO ₂ incubator. Confluent and grown 3T3-L1 cells were cultured for two days in a culture medium containing MDI (0.5 mM isobutyl-methylxanthine, 1 μM dexamethasone and 1 μg / ml insulin). After making adipocytes (differentiation adipocytes), the cells were differentiated into mature adipocytes while incubated for two more days in a DMEM medium containing 1 μg / ml insulin. Thereafter, the cells were incubated for 10 days while replacing the DMEM medium every two days to form fully differentiated adipocytes.

Oleuropine was treated in culture at concentrations of 0.1, 1, 10, 50 and 100 μM at two-day intervals from the first day of differentiation by adding MDI to 3T3-L1 cells. Oluopepine was dissolved in DMSO and used for negative control (negative control) in which only DMSO was added. After incubation for a total of 14 days, the culture solution was removed at the time of differentiation was completed, and stained fat cells contained in the differentiated adipocytes. To do this, wash the cells twice with PBS (phosphate buffered saline), fix the cells for 1 hour with 10% BNF (Buffered Neutral Formalin), wash once again with PBS, and then oil red specifically to stain red fat. 1 ml of O dye was added to a 12-well plate to stain the fat globules for 1 hour and washed twice with distilled water.

In order to measure the concentration of triglycerides contained in the differentiated 3T3-L1 cells, stained fat globules were dissolved in 1 ml of isobutanol, and the O.D values were measured at 600 nm.

Inhibition of Adipocyte Differentiation by Oluuropine

Treatment of oleuropine with 3T3-L1 cells as shown in panel A of FIG. 1 significantly reduced the differentiation of adipocytes in a concentration dependent manner. As a result of quantitative determination of the amount of intracellular fat stained with oil red O by spectrophotometry, the concentration of O.D also decreased (FIG. 1, Panel B).

Example 2: Body weight and visceral fat reduction effect of oleuropine using a mouse

Experimental diet preparation and breeding of laboratory animals

The obesity induction diet used in this experiment was a high fat diet (HFD: 40% fat calorie, 17 g Laad + 3% corn oil / 100 g diet), and the diet containing oleuropine is HFD and its composition. The same, but the oleuropein contained 0.03% level. Normal diet (ND) was prepared based on the composition of the AIN-76 rodent diet (American Institute of Nutrition, Report of the American Institute of Nutrition ad hoc committee on standards for nutritional studies. J. Nutr. 107: 1340-1348, 1977). (Table 1).

Experimental Formula ingredient Normal diet
(g / kg diet) Control diet
(g / kg diet) Indole-3-carbinol diet
(g / kg diet) Casein 200 200 200 DL-methionine 3 3 3 Corn starch 149.99 110.96 109.96 Sucrose 500 370 370 cellulose 50 50 50 Corn oil 50 30 30 Laad - 170 170 Vitamin complex 10 12 12 Mineral complex 35 42 42 Choline Bitartrate 2 2 2 cholesterol - 10 10 tert-butyhydroquinone 0.01 0.04 0.04 Indole-3-carbinol - - 1.00 Total (g) 1,000 1,000 1,000 Fat (% calories) 11.5 39.0 39.0 Total calories, kJ / kg diet 16,439 19,315 19,315

Five-week-old male C57BL / 6J mice (Orient, Korea) were adapted to the laboratory environment for 1 week with solid feed, and then randomly placed into the high fat diet control group and the experimental group according to the egg mass method, and reared for a total of 10 weeks. The diet was fed with water between 10 and 11 am daily, and dietary intake was measured daily and body weight was measured every three days. In order to prevent sudden weight change due to feed intake, body weight was measured 2 hours after removing the feed container, and the dietary efficiency was the total test period from the feeding date to the sacrifice day, and the cumulative weight gain during the test period was determined by the total diet. Calculated by dividing by intake. After fasting the test animals for 12 hours or more, blood, liver and visceral fat tissues (diplordial fat, perirenal fat, mesenteric fat, and abdominal fat) were collected under anesthesia with diethyl ether to prepare 0.1 M phosphate buffer solution (pH). 7.4), and then weighed. Blood collected from the abdominal aorta was centrifuged at 1000 x g for 15 minutes to separate plasma.

Body weight and visceral fat weight

The final weight and the weight gain of the 10 weeks after ingesting the experimental diet for 10 weeks, compared to the high-fat diet control group (HFD), the final weight was 32%, and the cumulative weight gain in the group fed the oleuropine 52% significantly decreased (FIG. 2).

After eating the experimental diet for 10 weeks, the weight of epididymal fat, peripheral fat, mesenteric fat, and abdominal fat were measured. As a result, the epididymal fat weight in terms of unit weight was higher in the oleuropaine group than the control group (HFD). 51%, peripheral fat mass 82%, mesenteric fat weight 59%, posterior cavity fat weight 60%, and total visceral fat weight 56% ( P <0.001). Therefore, it was confirmed that oleuropine has a very excellent weight loss and visceral fat reduction effect (Fig. 3).

Example 3 Efficacy and Prevention of Obesity Hyperlipidemia, Fatty Liver and Type 2 Diabetes with Olerofane

Plasma total cholesterol, triglyceride and glucose concentration were measured twice each using a commercial clinical kit (Bio Clinical system), insulin concentration was measured by ELISA using a mouse insulin kit (Shibayaki, Japan). The lipid component of liver tissue was extracted according to the method of Folch et al. 1 mL of distilled water was added to 0.25 g of liver tissue and homogenized using a polytron homogenizer (IKA-WERKE GmbH & Co., Ultra-Turrax, Staufen, Germany). 5 mL of chloroform: methanol solution (2: 1, v / v) was added to the homogeneous solution, mixed well, and the lower layer was separated by centrifugation at 1000 xg for 10 minutes, and the chloroform: methanol solution (2: 1, v / v) 2 mL was added, and the same procedure was repeated to completely separate the liver lipid components. 3 mL of chloroform: methanol: 0.05% CaCl ₂ (3:48:47, v / v / v) solution was added to the lower layer solution, mixed for 1 minute, and centrifuged at 1000 xg for 10 minutes. After completely drying with nitrogen gas, the dried lipid was dissolved in 1 mL of methanol and used for lipid component analysis. Triglyceride concentrations in hepatic lipid extracts were measured using the same commercial lipid analysis kit (Bio Clinical system) used for the analysis of plasma.

Plasma lipid concentrations of mice fed the experimental diet shown in Table 1 for 10 weeks were 76% triglyceride, 40% total cholesterol, and LDL + compared to the high-fat diet control group (HFD). VLDL cholesterol concentration was reduced by 30% and free fatty acid concentration by 40% (Table 2).

Dietary obesity It is well known that animal model or human obesity is accompanied by type 2 diabetes, which is accompanied by an increase in blood insulin concentration and fasting blood glucose. In addition, the term 'metaflammation' has recently appeared for inflammatory reactions caused by nutrient or metabolic oversupply, and obesity is interpreted as 'chronic and low-level inflammation'. There is an ongoing research into the relationship between obesity and the immune system. In other words, a variety of obesity complications (type 2 diabetes, insulin resistance, arteriosclerosis, cancer and asthma, etc.) is a new view that is caused by the interaction with the immune system in the course of obesity. For example, TLR4 (toll-like receptor 4), which is involved in the innate immune response, uses dietary fats (particularly saturated fatty acids) as ligands, acting as an important factor in the inflammatory response and insulin resistance pathways, while in the central nervous system It is also suggested to be involved in appetite control. Therefore, the concentration of free fatty acids in blood and tissues has recently been recognized as a major indicator of the development of insulin resistance and metabolic diseases caused by obesity.

In this experiment, oleuropine was ingested for 10 weeks in mice fed high-fat diet, and the fasting blood glucose was decreased by 29% compared to the high-fat diet control group, and the blood insulin concentration was also significantly reduced by 32%. Insulin resistance index (IRI) also decreased significantly by 52% (Table 2). Therefore, oleuropine has an effect of improving type 2 diabetes or insulin resistance, and is also expected to improve the metabolic inflammatory response closely related thereto.

Obesity-related Biochemical Indicators of Mouse Blood Containing Olerofane Normal diet.
(ND) High Fat Diet Control Group
(HFD) Oleuropine County Triglycerides (mmol / L) 0.60 ± 0.09 1.41 ± 0.12 0.34 ± 0.09 ^* Total Cholesterol (mmol / L) 3.07 ± 0.09 6.20 ± 0.54 3.71 ± 0.43 ^* HDL cholesterol (mmol / L) 1.33 ± 0.09 2.33 ± 0.27 1.02 ± 0.06 ^* LDL + VLDL Cholesterol (mmol / L) 1.74 ± 0.06 3.87 ± 0.57 2.69 ± 0.45 ^* Free fatty acid (uEq / L) 357 ± 26 534 ± 8 ^* 321 ± 46 ^* Glucose (mmol / L) 6.16 ± 0.95 8.49 ± 0.53 6.03 ± 0.31 ^* Insulin (ng / mL) 0.51 ± 0.06 0.76 ± 0.10 0.52 ± 0.08 ^* IRI ^a 0.54 ± 0.07 1.10 ± 0.10 0.53 ± 0.08 ^*

^* Significantly different from the value for HFD group by Student's t-test at P <0.05.

^a Insulin resistance index (IRI) = 10 ^-3 pmol insulin x mmol glucose x L ^-2

The liver weight of the mice fed the experimental diet for 10 weeks was significantly reduced by 24% in the oleuropein group compared to the high-fat diet control group. The lipid concentrations of liver tissue were significantly lower in oleuropine-treated group than in the high-fat diet control group, with 83% triglyceride concentration, 82% cholesterol, and 66% free fatty acid concentration (Table 3). Therefore, it can be seen that oleuropine significantly relieves fatty liver phenomenon in high fat diet-induced obesity and significantly improves obesity-inflammation and insulin resistance in liver tissue.

Obesity-related Biochemical Indices of Mouse Liver Tissue Ingested with Olerofane Normal diet.
(ND) High Fat Diet Control Group
(HFD) Oleuropine County Liver weight (g / 100 g body wt) 3.6 ± 0.1 5.5 ± 0.3 4.2 ± 0.3 ^* Triglyceride (μmol / g) 20.4 ± 0.30 35.1 ± 0.32 5.9 ± 0.40 ^* Cholesterol (μmol / g) 21.6 ± 0.58 74.8 ± 0.68 13.1 ± 0.09 ^* Free fatty acids (uEq / g) 8.56 ± 0.35 24.3 ± 0.22 ^* 8.25 ± 0.07 ^*

^* Significantly different from the value for HFD group by Student's t-test at P <0.001.

Having described the specific part of the present invention in detail, it is apparent to those skilled in the art that the specific technology is merely a preferred embodiment, and the scope of the present invention is not limited thereto. Thus, the substantial scope of the present invention will be defined by the appended claims and equivalents thereof.

1 is a diagram showing the effect of inhibiting the differentiation of oleuropine in 3T3-L1 cells.

2 is a diagram showing the body weight and weight gain of the mice ingested the experimental diet. The blue solid line represents the normal diet group (ND), the red solid line represents the high-fat diet control group (HFD), and the light blue solid line represents the oleuropine administration group.

3 is a diagram showing the weight vs. epididymal fat, peripheral kidney fat, mesenteric fat, celiac fat and total visceral fat weight of mice fed the experimental diet. The blue bar graph represents the normal diet group (ND), the red bar graph represents the high-fat diet control group (HFD), and the light blue bar graph represents the oleuropine-administered group.

Claims (7)

A food composition for inhibiting adipocyte differentiation comprising a sequoidoid derivative of Formula 1 or a compound of Formula 2 that is a hydrolysis product thereof as an active ingredient: Formula 1

Formula 2

R in the formula is a glycosyl group; R ₁ is hydrogen, methyl, 2- (4-hydroxyphenyl) ethyl or 2- (3,4-dihydroxyphenyl) ethyl. The composition of claim 1, wherein in Formulas 1 and 2, R ₁ is 2- (3,4-dihydroxyphenyl) ethyl. The composition of claim 1, wherein the secoirioid derivative is oleuropine of Formula 3 below: Formula 3

The composition of claim 1, wherein the secoirioid derivative is included in an extract or fraction of the Oleaceae family plants. The method of claim 4, wherein the Oleaceae plants ah (Olea europaea) in oleic ah Europa, Liguria strum (Ligustrum) In, when Manly (Syringa), A proxy Nurse (Fraxinus), A-party over Sumi (Jasminum) and Osman in Tuscan composition being selected from the group consisting of genus (Osmanthus). delete (a) a food-effective amount of the composition of any one of claims 1 to 5; And (b) a food composition for inhibiting adipocyte differentiation comprising a food acceptable carrier:

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