KR101866924B1 - Composition for improving metabolism disorder comprising syringaresinol - Google Patents

Abstract

The present invention discloses a composition for the prevention or amelioration of metabolic dysfunction comprising Sirling's resinoid as an active ingredient.

Description

[0001] The present invention relates to a composition for improving metabolic dysfunction,

The present invention relates to a composition for improving metabolic dysfunction comprising Sirling's lysinol.

Due to changes in lifestyle and overflowing high calorie food, human beings are exposed to the risk of metabolic diseases such as obesity, type 2 diabetes, hyperlipidemia, and fatty liver. Considering that obesity is a major cause of metabolic diseases such as type 2 diabetes, hyperlipidemia, and fatty liver, prevention or improvement of obesity can prevent other metabolic diseases.

Obesity generally occurs when the energy input is greater than the energy expenditure in the body. Specifically, the surplus energy is stored in adipose tissue in the form of triglycerides. Adipose tissue can store large amounts of surplus energy, such as rubber balloons, but at the same time increases the size of adipocytes. In addition, if the amount of surplus energy to be stored is not covered by fat tissue alone, lipid dysregulation occurs in which energy is stored in other tissues such as muscle, liver, and lipotoxicity. In addition, fat stored in each tissue is transformed into free fatty acid through lipolysis. This free fatty acid is known to neutralize insulin signaling through signal transduction mechanisms such as JNK and PKC. Inhibition of the insulin signaling system inevitably leads to insulin resistance, which leads to various metabolic diseases such as hyperglycemia, hyperlipidemia, hypercholesterolemia, type 2 diabetes and fatty liver. Thus, obesity can be said to be more serious because it is accompanied not only by external problems but also by various adult diseases.

Korean Patent Laid-Open No. 10-2011-0110053 (Published on Jun. 10, 2011) Specification

The present invention aims to provide a composition having excellent metabolic dysfunction prevention or improvement effect, specifically preventing or improving metabolic dysfunction by controlling lipid metabolism. The present invention also provides a food and pharmaceutical composition having an excellent metabolic dysfunction prevention or improvement effect.

An aspect of the present invention provides a composition for preventing or ameliorating metabolic dystrophy comprising syringaresinol as an active ingredient.

Another aspect of the present invention provides a food and pharmaceutical composition for preventing or ameliorating metabolic dystrophy which comprises Sirling's resinoid as an active ingredient.

The composition according to the present invention increases the expression of SIRT 1 (Sirtuin 1), inhibits fatty acid synthesis, accelerates fatty acid oxidation and increases the expression of PGC 1 by incorporating Siring Gelsinol as an active ingredient, Metabolic dysfunction, specifically obesity, type 2 diabetes, hyperlipidemia or fatty liver.

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a schematic view showing a method for separating and purifying Siringagrelin from a ginseng fruit extract. FIG.
Figure 2 is the chemical structure of Sirling's lycinol.
FIG. 3 is a graph showing changes in the expression of SIRT 1 gene after treatment with Sirling's lycinol 20, 50, 100 μM in human adipocytes, hepatocytes and myocytes.
FIG. 4 is a graph showing the amount of decrease in the expression of genes involved in fatty acid synthesis in human adipocytes treated with 50 μM Sirling's resinol. FIG.
FIG. 5 is a graph showing a decrease in the expression levels of genes involved in fatty acid synthesis in human hepatocytes treated with 50 μM Sirling's resinol. FIG.
FIG. 6 is a graph showing the decrease in the expression levels of genes involved in fatty acid synthesis in human myocytes treated with 50 .mu.M Sirengarceinol.
FIG. 7 is a graph showing an increase in the expression levels of genes involved in fatty acid oxidation in human adipocytes treated with 50 μM Sirengarceinol. FIG.
FIG. 8 is a graph showing the increase in expression of genes involved in fatty acid oxidation in human hepatocytes treated with 50 μM Sirling's resinol. FIG.
FIG. 9 is a graph showing an increase in the expression levels of genes involved in fatty acid oxidation in human myocytes treated with 50 μM Sirlinggarisin.
FIG. 10 is a graph showing that fatty acid oxidation is increased in human adipocytes, hepatocytes and myocytes treated with 50 mg of Ringer's Resinol.
FIG. 11 is a graph showing the degree of increase in the expression of PGC 1a, an energy metabolism-regulating gene in human adipocytes, hepatocytes and muscle cells treated with 50 μM Sirling's resinol.
FIG. 12 is a graph showing the degree of increase in expression of PGC 1b, an energy metabolism control gene, in human adipocytes, hepatocytes and myocytes treated with 50 μM Sirling's resinol.

As used herein, the term " extract "is a broad concept that encompasses all of the substances obtained by extracting components of natural products, regardless of the type of extraction method, extraction solvent, extracted component or extract.

When controlling the fat metabolism, excessive accumulation of fat can be prevented, so that obesity can be prevented and improved. One way to prevent overaccumulation of fat is dietary restriction, that is, calorie restriction. Limiting diet can not only reduce body weight but also improve blood lipid levels and improve metabolic diseases. It is known that the expression of SIRT 1 (Sirtuin 1, sirtuin 1) protein is increased when the diet is restricted, and when SIRT 1 is induced to increase the activity without dietary restriction, have. SIRT 1 is a NAD ⁺ -dependent histone protein deacetylase that regulates energy metabolism such as glucose synthesis, fatty acid oxidation, and the like. Therefore, substances capable of regulating the expression of SIRT1 may be able to control fat metabolism and further prevent or ameliorate metabolic dysfunction, such as obesity, type 2 diabetes, hyperlipidemia, and fatty liver.

One aspect of the present invention provides a composition for preventing or ameliorating metabolic dystrophy, which comprises Sirling's resinoid as an active ingredient.

Life consumes nutrients to maintain life, digests and absorbs them to make body components, and stores them as energy sources. In addition, it disassembles it and performs various bio-activities with the energy liberated at that time. Such a phenomenon is called "metabolism". As used herein, the term " metabolic disorder " means a state in which a living being including a human or an animal is unable to perform the metabolism smoothly, and includes a glucose metabolism disorder or a lipid metabolism disorder. A lipid metabolism abnormality or a lipid metabolism abnormality includes a symptom or a disease caused by a hyperglycemia or lipid metabolism disorder, specifically, a lipid accumulation-caused symptom or a disease caused by a fatty acid metabolic disorder, examples of which include obesity, diabetes mellitus, Hyperlipemia or fatty liver.

Siringar Recinol is a lignan compound having the chemical structure shown in FIG. 2, which can be obtained through chemical synthesis or extracted from one or more of flaxseed, white, white, sesame and ginseng. The above flaxseed, yellow, white, and sesame seeds include all parts of a plant such as leaf, stem, root, fruit or seed of each plant, and the ginseng fruit includes ginseng fruit rind or flesh.

Sirring regicin increases the expression of SIRT 1, inhibits fatty acid synthesis, promotes oxidation of fatty acids, and inhibits accumulation of fat in the body. This is confirmed by inhibiting the expression of fatty acid synthesis related genes such as SINGULAR RECYNOLES ADD1 / SREBP1c, ACC and FAS, promoting the expression of fatty acid oxidation-related genes such as ACO, CPT1, and mCAD, and increasing fatty acid oxidation . In addition, Silinggecinol promotes energy metabolism, specifically, fat metabolism, thereby increasing body fat consumption and inhibiting the accumulation of excess fat, which is known as PGC (peroxisome), which regulates the expression of genes related to Sirling's recurrence energy metabolism proliferator-activated receptor coactivator) 1 expression. Thus, a composition comprising Sirling's rescinol may prevent or ameliorate metabolic dysfunction, such as obesity, second-line diabetes, hyperlipidemia or fatty liver, due to saccharide or lipid metabolism disorders.

In one aspect of the present invention, Siringaglisinol can be obtained by extracting at least one of flaxseed, yellowtail, sesame gum, sesame and ginseng fruit with at least one selected from the group consisting of water, an organic solvent and a mixture of water and an organic solvent have. The organic solvent includes, but is not limited to, at least one selected from the group consisting of alcohol, acetone, ether, ethyl acetate, diethyl ether, ethyl methyl ketone and chloroform. Wherein the alcohol comprises a C ₁ to C ₅ lower alcohol and the C ₁ to C ₅ lower alcohol is selected from the group consisting of methanol, ethanol, isopropyl alcohol, n-propyl alcohol, n-butanol and isobutanol But is not limited thereto.

In another aspect of the present invention, the Sirling's lecithin may be contained in the composition as an extract of flaxseed, yellowtail, sesame, sesame and ginseng fruit, among which a fraction particularly effective for the improvement of the metabolic dysfunction may be included.

In one aspect of the present invention, a method for separating and purifying Sirling's lycinol from ginseng fruit may comprise the following steps. Preparing an alcoholic extract of the ginseng fruit pulp; Eluting the alcohol extract with a solvent containing at least one of water and alcohol to obtain a fraction; And performing chromatography, specifically Thin Film Chromatography (TLC), on the obtained fractions using an organic solvent as a developing solvent. The organic solvent includes at least one selected from the group consisting of alcohol, acetone, ether, ethyl acetate, diethyl ether, ethyl methyl ketone and chloroform, and the alcohol includes C ₁ to C ₅ alcohols. The composition according to one aspect of the present invention may contain the purified syringes lecinol as an active ingredient as described above.

The composition according to one aspect of the present invention comprises from 1% to 80% by weight, in particular from 5% to 60% by weight, more specifically from 10% to 30% by weight, based on the total weight of the composition, can do. When it is included in the above range, it is not only suitable for exhibiting the intended effect of the present invention but also can satisfy both the stability and safety of the composition and may be suitably used within the above range in terms of cost effectiveness. Concretely, when the amount of Sirling's Lysinol is less than 1% by weight, the sufficient effect of improving metabolic dysfunction can not be obtained. When it exceeds 80% by weight, safety and formulation stability may be lowered.

One aspect of the present invention provides a food composition comprising Sirling's resinol as an active ingredient. The food composition can prevent or ameliorate metabolic syndrome such as obesity, second-line diabetes, hyperlipidemia or fatty liver, and includes a preference food or health food composition.

The formulation of the food composition is not particularly limited, but may be formulated into, for example, tablets, granules, powders, liquid preparations such as drinks, caramels, gels, bars and the like. The food composition of each formulation can be blended with the ingredients commonly used in the field in addition to the active ingredient without difficulty by those skilled in the art depending on the purpose of formulation or use, and synergistic effect can be obtained when the composition is applied simultaneously with other ingredients.

Determination of the dosage of the active ingredient is within the level of ordinary skill in the art and its daily dose is, for example, from 0.1 mg / kg / day to 5000 mg / kg / day, more specifically from 50 mg / kg / day to 500 mg / kg / day, but it is not limited thereto, and may be varied depending on various factors such as the age, health condition, and complication of the subject to be administered.

One aspect of the present invention provides a pharmaceutical composition comprising Sirling's rescinol as an active ingredient. The pharmaceutical composition can prevent or ameliorate metabolic dysfunction, and specifically can prevent or ameliorate obesity, diabetes mellitus, hyperlipidemia or fatty liver.

The pharmaceutical composition according to one aspect of the present invention may be administered orally, parenterally, rectally, topically, transdermally, intravenously, intramuscularly, intraperitoneally, subcutaneously, and the like.

Formulations for oral administration may be in the form of tablets, pills, soft and hard capsules, granules, powders, granules, solutions, emulsions or pellets, It is not. These formulations may contain, in addition to the active ingredient, a diluent such as lactose, dextrose, sucrose, mannitol, sorbitol, cellulose or glycine, a lubricant such as silica, talc, stearic acid or polyethylene glycol, or a binder such as magnesium aluminum Silicate, starch paste, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose or polyvinylpyrrolidine). And may optionally contain pharmaceutical additives such as disintegrants, absorbents, colorants, flavors, or sweeteners. The tablets may be prepared by conventional mixing, granulating or coating methods.

Formulations for parenteral administration may be, but are not limited to, injections, drops, lozenges, ointments, gels, creams, suspensions, emulsions, suppositories, patches or spraying agents.

The effective ingredients of the pharmaceutical composition according to one aspect of the present invention will vary depending on the age, sex, weight, pathological condition and severity of the subject to be administered, route of administration, or judgment of the prescriber. Determination of the amount of application based on these factors is within the level of ordinary skill in the art and its daily dose is, for example, from 0.1 mg / kg / day to 100 mg / kg / day, more specifically from 5 mg / kg / day. < / RTI >

One aspect of the present invention provides a cosmetic composition comprising Sirling's recinol as an active ingredient. The cosmetic composition can prevent or ameliorate metabolic dysfunction, and can specifically prevent or ameliorate obesity, diabetes, hyperlipidemia or fatty liver.

The cosmetic composition according to the present invention may be provided in all formulations suitable for topical application. For example, it may be provided as a solution, an emulsion obtained by dispersing an oil phase in an aqueous phase, an emulsion obtained by dispersing an oil phase in water, a suspension, a solid, a gel, a powder, a paste, a foam or an aerosol composition. Compositions of such formulations may be prepared according to conventional methods in the art.

The cosmetic composition according to the present invention may further comprise a moisturizing agent, an emollient agent, a surfactant, an ultraviolet absorber, an antiseptic, a bactericide, an antioxidant, a pH adjusting agent, organic and inorganic pigments, a fragrance, . The compounding amount of the above components can be easily selected by those skilled in the art within a range not to impair the objects and effects of the present invention. The amount thereof may be 0.01 to 5% by weight, specifically 0.01 to 3% by weight, have.

Hereinafter, the constitution and effects of the present invention will be described in more detail with reference to Examples and Experimental Examples. However, these examples and experimental examples are provided for illustrative purposes only in order to facilitate understanding of the present invention, and the scope and scope of the present invention are not limited thereto.

EXAMPLES Isolation and Analysis of Syringal Resinol

1. Pretreatment of ginseng fruit

The raw ginseng fruit was harvested and the seeds were separated and removed. Then, the ginseng fruit was removed, and only the flesh was dried with sunlight or hot air to produce dried ginseng fruit pulp.

2. Isolation and Analysis of Syringal Resinol from Extracts of Fruits and Ginseng Fruits

To 1 kg of dried ginseng fruit pulp prepared above, 3 liters of water or alcohol was added, and the mixture was extracted at room temperature or reflux, filtered, and concentrated under reduced pressure at 40 to 45 ° C to obtain 300 g of ginseng fruit pulp extract. The extract was treated with ether to remove lipid soluble components, crude saponin was extracted with butanol and concentrated. This was separated and purified to obtain syringal lysinol. Specific methods are as follows. First, 194 g of the sample was purified by reversed-phase column chromatography. 100% water was initially used as the elution solvent, methanol was gradually increased by 10%, and finally 100% methanol solvent was used . As a result, GB-1 to GB-10 fractions were obtained. The fractions GB-3 showing the SIRT1 expression activity were selected and concentrated. Then, 50% aqueous methanol was used to separate the fractions from the Sephadex LH-20 column Followed by chromatography (Sephadex LH-20 column chromatography). GB-3-6 (3F) showing the SIRT1 expression activity was selected and concentrated. TLC of preparative silica gel was performed using chloroform: methanol (10: 1) as a developing solvent. The active fraction having an Rf value of 0.67 was purified. The separation and purification method is schematically shown in FIG.

NMR spectroscopic analysis and database search were performed to identify the active compound isolated and purified as syringaresinol. Mass spectrometry was performed to confirm this. ESI-mass was measured in positive mode, and [M + Na] + was observed at m / z 440.9 and [2M + Na] + at m / z 858.9 The molecular weight was found to be 418. NMR spectroscopy was also performed to determine the chemical structure, and the results are shown in FIG. As can be seen in Fig. 2, the active compound isolated and purified has the chemical structure of siringa regicinol.

In this way, singlingcecinol was isolated from the ginseng fruit pulp.

[Experimental Example 1] Evaluation of promoting effect of SIRT1 expression in adipocytes, hepatocytes and myocytes

The following experiments were performed to evaluate the promoting effect of SIRT 1 gene expression in human adipocyte, hepacyte and myocyte of Siringagrelin.

Human adipocytes, hepatocytes, and myocytes were purchased from ZENBIO (Research Triangle Park, NC, USA) and cultured in medium supplemented with OM-AM, ZENBIO, hepatocyte- (SKM-D, SKM-M, ZENBIO) in a 5% CO ₂ incubator. Each cell was treated with 20, 50, and 100 μM Syringal lysinol dissolved in DMSO for 24 hours, and negative control was treated with DMSO at a volume of 1/1000.

Cells treated with each sample were washed twice with cold PBS, and RNA was extracted from them using TRIzol agent (Invitrogen). CDNA was synthesized using 5 mg of RNA extracted and quantified from the above using a reverse system (Fermentas, Glen Burnie, MD, USA). Expression patterns of each gene were determined by qRT-PCR using primers designed for the synthesized cDNA and SIRT 1 and GAPDH genes. PCR reaction and analysis were performed using a Rotor-Gene 3000 system (Corbett Research, Sydney, Australia). The mRNA relative expression results are shown in Fig.

As can be seen in Fig. 3, Sirling's lycinol can increase the expression of SIRT1 in human adipocytes, hepatocytes and myocytes in a concentration-dependent manner. Based on this, it can be seen that siringagrelinol can improve metabolism abnormality, specifically lipid metabolism abnormality.

[Experimental Example 2] Evaluation of regulation of lipid metabolism-related gene expression in adipocytes and hepatocytes

Human adipocytes, hepatocytes and myocytes were treated with ringgarcinol at 50 [mu] M in the same manner as in Experimental Example 1, washed with PBS, and RNA was extracted to synthesize cDNA. Expression patterns of fatty acid synthesis-related genes such as ADD1 / SREBP1c, ACC, and FAS and fatty acid oxidation-related genes such as ACO, CPT1, and mCAD were measured using qRT-PCR. The results of comparison with the control group treated with DMSO only as a sample are shown in Figs.

As can be seen from Figs. 4 to 6, Sirling's rescinol inhibited the expression of genes inducing fatty acid synthesis. As can also be seen from Figs. 7 to 9, siring ginsenosin increased the expression of genes promoting fatty acid oxidation. Based on these results, it can be seen that Sirring regicin inhibits lipid synthesis and increases fat consumption and inhibits fat accumulation.

[Experimental Example 3] Evaluation of fatty acid oxidation promoting ability

In a substantially same manner as in Experimental Example 1, ringer recipin was treated at 50 [mu] M to human adipocytes, hepatocytes and muscle cells. Cells were washed with PBS, cultured in a fatty acid oxidation assay medium for one day, and the amount of ³ H ₂ O contained in the medium was measured by counting the medium. The results are shown in Fig. 10 in comparison with the untreated group.

As can be seen from Fig. 10, Siringagrelin can increase fatty acid oxidation in human adipocytes, hepatocytes and myocytes. Based on this, it can be seen that siringagrecinol can inhibit accumulation of fat in the body.

[Example 5] Increase in expression of PGC 1 of Siringagrelinol

In a substantially same manner as in Experimental Example 1, ringer recipin was treated with human adipocytes, hepatocytes and myocytes at 50 μM, washed with PBS, and RNA and cDNA were sequentially extracted. MRNA expression of PGC 1α and PGC 1β, which regulate the expression of genes related to energy metabolism, was analyzed by qRT-PCR using a dedicated primer. Expression results of PGC 1α and PGC 1β compared with the control group treated with DMSO alone were shown in FIGS. 11 and 12, respectively.

As can be seen from Figs. 11 and 12, Sirling's recurin can increase the expression of PGC 1? And PGC 1? In human adipocytes, hepatocytes and myocytes. Based on this, it can be seen that Siringagresinol promotes energy metabolism and inhibits accumulation of fat in the body.

Formulation examples of compositions according to one aspect of the present invention are described below, but may be applied to various other formulations, which are not intended to be limiting but merely illustrative of the invention.

[Formulation Example 1] Health food

Siringa glycine ................... 1000 mg

Vitamin mixture

Vitamin A Acetate ............... 70 ㎍

Vitamin E ....................... 1.0 mg

Vitamin B1 ...................... 0.13 mg

Vitamin B2 ...................... 0.15 mg

Vitamin B6 ........................ 0.5 mg

Vitamin B12 ....................... 0.2 g

Vitamin C .......................... 10 mg

Biotin ............................. 10 μg

Nicotinic acid amide ... 1.7 mg

Folic acid ............................... 50 ㎍

Calcium pantothenate ..................... 0.5 mg

Mineral mixture

Ferrous sulfate ........................ 1.75 mg

Zinc oxide .......................... 0.82 mg

Magnesium carbonate ...................... 25.3 mg

Potassium Phosphate ......................... 15 mg

Secondary Calcium Phosphate ..................... 55 mg

Potassium citrate .......................... 90 mg

Calcium carbonate ........................... 100 mg

Magnesium chloride ...................... 24.8 mg

Although the composition ratio of the above-mentioned vitamin and mineral mixture is comparatively mixed with the ingredient suitable for health food as a preferred embodiment, the compounding ratio thereof may be arbitrarily modified.

[Formulation Example 2] Health drinks

Siringa glycine .......................... 1000 mg

Citric acid ................................ 1000 mg

Oligosaccharides ................................ 100 g

Taurine .................................... 1 g

Purified water ............ ...................... Remaining amount

The above components are mixed according to a conventional health drink manufacturing method, and the mixture is stirred and heated at 85 DEG C for about 1 hour, and then the solution is sterilized by filtration.

[Formulation Example 3] Tablets

100 mg of siringagrecinol, 50 mg of soybean extract, 100 mg of glucose, 50 mg of red ginseng extract, 96 mg of starch and 4 mg of magnesium stearate were mixed and 40 mg of 30% ethanol was added to form granules, Dry and tablet with tablets using a tablet machine.

[Formulation Example 4]

100 mg of siringagrecinol, 50 mg of soybean extract, 100 mg of glucose and 600 mg of starch were mixed and 100 mg of 30% ethanol was added to form granules, followed by drying at 60 ° C to form granules, .

[Formulation Example 5] Cream

Creams are prepared according to a conventional method with the composition shown in the following table.

ingredient Content (% by weight) Siringa Greshin 3.0 Polyethylene glycol monostearate 2.0 Glycerin monostearate 5.0 Cetyl alcohol 4.0 Squalene 3.0 Tri-2-ethylhexane glyceryl 6.0 Sphingoglycolipids 1.0 1,3-butylene glycol 7.0 Purified water Balance

Claims (8)

A composition for preventing or ameliorating a lipid metabolism disorder comprising syringaresinol as an active ingredient.
delete The method according to claim 1,
Wherein the lipid metabolism disorder comprises at least one selected from the group consisting of obesity, hyperlipidemia and fatty liver.
The method according to claim 1,
Wherein the singing griseol is separated from one or more extracts selected from flaxseed, white, white, sesame and ginseng.
The method according to claim 1,
Wherein the composition comprises from 1% to 80% by weight, based on the total weight of the composition, of a syringal lysinol.
The method according to claim 1,
The composition inhibits fatty acid synthesis and promotes fatty acid oxidation.
7. The method according to any one of claims 1 to 6,
Wherein the composition is a food composition.
7. The method according to any one of claims 1 to 6,
Wherein the composition is a pharmaceutical composition.

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