KR101495607B1 - Composition comprising s-allyl-l-cysteine for treating obesity-induced inflammation - Google Patents

Abstract

The present invention relates to a composition for treating inflammation induced by obesity comprising S-arylcysteine as an active ingredient, wherein the composition according to the present invention induces expression of adiponectin and inhibits IL-6 and MCP-1 Lt; RTI ID = 0.0 > inflammation < / RTI > induced by obesity can be prevented and treated.

Description

TECHNICAL FIELD [0001] The present invention relates to a composition for treating inflammation induced by obesity containing S-arylcysteine as an active ingredient. BACKGROUND OF THE INVENTION 1. Field of the Invention [0001]

The present invention relates to a composition for treating inflammation induced by obesity containing S-arylcysteine as an active ingredient.

Obesity is a direct cause of the development of insulin resistance, type 2 diabetes, atherosclerosis, hyperlipidemia, and nonalcoholic fatty liver disease and is associated with a number of metabolic diseases including ischemic heart disease, dementia, cancer, rheumatoid arthritis, reflux esophagitis, hypertension, It can be a cause. Recently, there is a growing body of evidence that obesity induces mild inflammation leading to related metabolic diseases. In particular, adipose tissue has been identified as an endocrine organ that produces a variety of physiologically active substances as well as a role of storing surplus energy. When the obesity degree is high or the fat cell function abnormality occurs, the physiologically active substance secreted from the adipose tissue is abnormally expressed and the immune response changes, which affects the generation and progress of many metabolic diseases.

The physiologically active components secreted from adipose tissue are mainly cytokine and chymocaine, which can be classified into pro-inflammatory, anti-inflammatory and metabolic regulation components. Representative inflammatory components include tumor necrosis factor-alpha, TNF-a, interleukin-6, IL-6, monocyte chemoattractant protein 1, MCP-1 ), And antiinflammatory components include adiponectin. Finally, leptin and adiponectin are the regulators of metabolic function.

Recent studies have shown that MCP-1 derived from adipose tissue induces migration of macrophages into adipose tissue, thereby amplifying the inflammatory response in adipose tissue. In contrast, adiponectin enhances insulin sensitivity by increasing the expression of insulin receptor substrate-1 in skeletal muscle, inhibits the expression of adherent molecules in vascular endothelial cells, accumulates vascular endothelial mononuclear cells / macrophage-derived foam cells Interferes with the atherosclerotic lesion process.

This finding suggests that the regulation of the secretion of physiologically active components secreted by adipose tissue plays an important role in the progression of obesity, and thus the regulation of such physiologically active components controls not only obesity-induced inflammation but also the progression of obesity Suggest a useful target.

Accordingly, the present inventors have discovered a substance capable of regulating secretion of a physiologically active ingredient secreted from adipose tissue, and have reached the present invention.

It is an object of the present invention to provide a composition for improving obesity-induced inflammation containing S-arylcysteine as an active ingredient.

In order to achieve the above object, there is provided a pharmaceutical composition for preventing and treating inflammation comprising S-Allyl-L-Cysteine as an active ingredient in one embodiment of the present invention.

In another embodiment, there is provided a health functional food for preventing and improving inflammation containing S-Allyl-L-Cysteine as an active ingredient.

In another embodiment, there is provided a pharmaceutical composition for preventing and treating metabolic diseases containing S-Allyl-L-Cysteine as an active ingredient.

In another embodiment, there is provided a health functional food for preventing and improving metabolic diseases containing S-Allyl-L-Cysteine as an active ingredient.

In the present invention, the S-Allyl-L-Cysteine inhibits the expression of IL-6 and MCP-1, and the Tetrandrine is characterized in that the secretion of adiponectin is increased , Wherein the composition is in the form of a capsule, tablet, granule, powder or beverage.

In the present invention, S-arylcysteine is a water-soluble sulfur compound and has been reported to have a pharmacological action such as an antioxidative action, a liver disorder prevention action, a cancer prevention action, a cancer cell proliferation inhibitory action, and the like.

[Chemical Formula 1]

In the present invention, adiponectin is a hormone-like component having a size of about 30 kDa and plays an anti-inflammatory, anti-arteriosclerosis and insulin resistance improvement. Since adiponectin levels in obese people have been reported to be significantly lower than those in normal people, many studies have shown that blood adiponectin levels are inversely proportional to body mass index (BMI), and diabetes and obesity with cardiovascular disease The patient's serum adiponectin levels were found to decrease. Recent studies also show that plasma adiponectin levels are inversely proportional to the size of visceral fat, which is closely related to metabolic disease in adipose tissue.

The reason that adiponectin is inversely proportional to the obesity index while fat tissue produces most of adiponectin is because the inflammatory factor inhibits the production of adiponectin. Tumor necrosis factor-alpha, a typical inflammatory factor, and lipopolysaccharide (LPS), a typical inflammatory agent, inhibit adiponectin expression. In addition, adiponectin increases the production of IL-10, IL-1 receptor antagonist (IL-1 RA), an anti-inflammatory component, in immune cells such as monocytes, macrophages and dendritic cells. In addition, the plasma concentration of C-reactive protein (CRP), which is a typical inflammatory factor in obese or diabetic patients, is inversely proportional to adiponectin and increases with increasing adiponectin concentration even when normal weight or diabetes is not experienced. In mice lacking adiponectin, the mRNA level of TNF-a is increased, leading to an increase in TNFa in the blood. Induction of overexpression of adiponectin in a representative obesity animal model, ob / ob mice, leads to obesity but improves the metabolism, decreases the concentration of macrophages infiltrating adipose tissue, and decreases the expression of TNF in adipose tissue Effect appears. Injection of recombinant adiponectin into ob / ob mice also reduces fatty liver improvement and TNF production. Therefore, adiponectin is closely related to inflammation, and when the expression of adiponectin is increased, metabolic diseases such as arteriosclerosis caused by obesity-induced inflammatory reaction (obesity inflammation) or obesity inflammation are improved without improvement of obesity .

The composition of the present invention comprises the above S-aryl cysteine relative to the total weight of the composition 0.1 to 50% by weight. The compositions comprising S-arylcysteine of the present invention may further comprise suitable carriers, excipients or diluents according to conventional methods. Examples of carriers, excipients and diluents that can be included in the composition of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, Cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. The composition according to the present invention may be formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols or the like, oral preparations, suppositories or sterilized injection solutions according to a conventional method have. More specifically, when formulating the composition, it can be prepared using a diluent or an excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, a surfactant, and the like. Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like, which may contain at least one excipient such as starch, calcium carbonate, Sucrose, lactose, gelatin, and the like. In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used. Examples of the liquid preparation for oral use include suspensions, solutions, emulsions, syrups and the like, and various excipients such as wetting agents, sweeteners, fragrances, preservatives, etc. in addition to commonly used diluents such as water and liquid paraffin . Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations and suppositories. Examples of the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like. Examples of the suppository base include witepsol, macrogol, tween 61, cacao paper, laurin, glycerogelatin and the like.

The present invention may be varied depending on the age, sex and body weight of the patient, but it is generally administered in an amount of 0.01 to 500 mg / kg, preferably 0.1 to 100 mg / kg, once to several times per day . The dosage may also be increased or decreased depending on the route of administration, degree of disease, sex, weight, age, and the like. Thus, the dosage amounts are not intended to limit the scope of the invention in any manner.

The composition of the present invention can be administered to mammals such as rats, mice, livestock, humans, and the like in various routes. All modes of administration may be expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intra-uterine or intracerebroventricular injections. Since the S-aryl cysteine of the present invention has little toxicity and side effects, it can be safely used for prolonged use even for prophylactic purposes.

The present invention provides a health functional food comprising the above-mentioned S-aryl cysteine and a pharmaceutically acceptable food supplementary additive, and it can be various foods such as beverage, gum, tea, vitamin complex, Pills, powders, granules, precipitates, tablets, capsules or beverages. In this case, the amount of the S-arylcysteine in the food or beverage may be generally 0.01 to 15% by weight of the total food weight of the health food composition of the present invention, and 0.02 to 100% 10 g, preferably 0.3 to 1 g.

Food supplementary additives as defined herein include food additives customary in the art, such as flavoring agents, flavoring agents, coloring agents, fillers, stabilizers, and the like. The health beverage composition according to the present invention is not particularly limited as to the ingredient to be added in addition to the S-aryl cysteine as an essential ingredient in the indicated ratio, and may contain various flavors or natural carbohydrates as an additional ingredient have. Examples of the natural carbohydrate include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose and the like; Polysaccharides such as dextrin, cyclodextrins; And sugar alcohols such as xylitol, sorbitol, and erythritol. As natural flavors other than those described above, natural flavors (such as tau martin, stevia extract (e.g., rebaudioside A, glycyrrhizin)) and synthetic flavors (saccharin, aspartame, etc.) have. The ratio of the natural carbohydrate is generally about 1 to 20 g, preferably about 5 to 12 g per 100 ml of the composition of the present invention.

In addition to the above-mentioned composition, the composition of the present invention can be used as a flavoring agent such as various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, coloring agents and intermediates (cheese, chocolate etc.), pectic acid and its salts, Salts, organic acids, protective colloid thickening agents, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated beverages and the like. In addition, the compositions of the present invention may contain flesh for the production of natural fruit juices and fruit juice drinks and vegetable drinks. These components may be used independently or in combination. The proportion of such additives is not so critical, but is generally selected in the range of 0 to about 20 parts by weight per 100 parts by weight of the composition of the present invention.

As described above, the composition of the present invention can prevent and treat inflammation induced by obesity by inducing the expression of adiponectin and reducing the expression of IL-6 and MCP-1, which are involved in an obesity-mediated inflammatory reaction.

1 is a graph showing the concentration of adiponectin in the treatment group treated with S-arylcysteine at a concentration.
FIG. 2 is a graph showing the IL-6 concentration in the treatment group treated with S-arylcysteine at different concentrations.
FIG. 3 is a graph showing the MCP-1 concentration of the treatment group treated with S-arylcysteine at different concentrations.
Fig. 4 is a graph showing the toxicity test result of S-arylcysteine.

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. Culture of adipocytes

(Insulin 10 μg / ml, 3-isobutyl-1-methylxanthine 0.5 mM, and dexamethasone 1 μg / ml) was added to 3T3-L1 cells (purchased from American Tissue Culture Collection, USA) Were mixed in a culture medium, treated for two days, and insulin 10 μg / ml was added to the culture medium for two days. Finally, the culture medium was induced to induce adipocyte differentiation.

Example  2. S-aryl cysteine (S- Allyl -L- Cysteine ) Of inflammatory factor concentration

The adipocytes of Example 1 were starvated overnight in serum-free medium and then treated with TNF-alpha at a concentration of 20 ng / ml to induce inflammation, while S - S-Allyl-L-Cysteine was cultured for 24 hours.

After culturing for 24 hours, the cultures were separated and the contents of adiponectin, IL-6 and MCP-1 secreted by ELISA were measured. As a result, it was confirmed that the expression of adiponectin was induced in S-arylcysteine-treated treatment (see FIG. 1), and the concentrations of IL-6 and MCP-1, which are not specific to adipose tissue, (See Figs. 2 and 3).

Example  3. S-aryl cysteine (S- Allyl -L- Cysteine ) To vascular endothelial cell toxicity test

The anti-inflammatory effects of S-arylcysteine were not due to toxicity and toxicity tests were performed for clinical use and food use. Vascular endothelial cells were mixed with 0, 6.25, 12.5, 25, and 50 μM S-arylcysteine for 16 hours, and cell viability was measured using a WST-1 kit (Roche Applied Science, Indianapolis, IN, USA).

As shown in FIG. 4, the survival rate of vascular endothelial cells was not changed in 0, 6.25, 12.5, 25, and 50 μM S-aryl cysteine. Experimental results with S-aryl cysteine demonstrate that this is not a toxic effect. From these results, it was confirmed in Examples 1 and 2 that the active ingredient ebola diamine in the present invention inhibits inflammation without giving toxicity to vascular endothelial cells.

Examples of formulations for the composition of the present invention are illustrated below. However, the following formulation examples are merely illustrative of the present invention, and the content of the present invention is not limited by the following formulation examples.

Formulation example  One: Sanje  Produce

S-aryl cysteine ------------------------------- 300 mg

Lactose ------------------------------------------ 100 mg

Talc ------------------------------------------- 10 mg

The above components are mixed and filled in airtight bags to prepare powders.

Formulation example  2: Preparation of tablets

S-aryl cysteine -------------------------------- 50 mg

Corn starch ------------------------------------- 100 mg

Lactose ------------------------------------------ 100 mg

Magnesium stearate ------------------------------ 2 mg

After mixing the above components, tablets are prepared by tableting according to the usual preparation method of tablets.

Formulation example  3: Preparation of capsules

S-aryl cysteine 50 mg

Corn starch ------------------------------------- 100 mg

Lactose ------------------------------------------- 100 mg

Magnesium stearate ------------------------------- 2 mg

The above components are mixed according to a conventional capsule preparation method and filled in gelatin capsules to prepare capsules.

Formulation example  4: Preparation of injection

S-aryl cysteine ------------------------------- 50 mg

Sterile sterilized distilled water for injection ------------------------------

pH adjusting agent ---------------------------------------

(2 ml) per 1 ampoule according to the usual injection preparation method.

Formulation example  5: Liquid  Produce

S-aryl cysteine ------------------------------ 100 mg

Ising Party ----------------------------------------- 10 g

Mannitol -------------------------------------------- 5 g

Purified water -------------------------------------------

Each component was added to purified water in accordance with the usual liquid preparation method and dissolved, and the lemon flavor was added in an appropriate amount. Then, the above components were mixed, and purified water was added thereto. The whole was adjusted to 100 ml with purified water, And sterilized to prepare a liquid preparation.

Formulation example  6: Manufacture of health food

S-arylcysteine ------------------------------- 1000 mg

Vitamin mixture -------------------------------------

Vitamin A Acetate ------------------------------ 70 g

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 [mu] g

Nicotinic acid amide 1.7 mg

Folic acid -------------------------------------------- 50 μg

Calcium pantothenate ----------------------------------- 0.5 mg

Inorganic mixture -------------------------------------

Ferrous sulfate -------------------------------------- 1.75 mg

Zinc oxide --------------------------------------- 0.82 mg

Magnesium carbonate - 25.3 mg

Potassium phosphate monohydrate 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 a composition suitable for health food as a preferred embodiment, the compounding ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional method for producing healthy foods , Granules can be prepared and used in the manufacture of health food compositions according to conventional methods.

Formulation example  7: Manufacture of health drinks

S-aryl cysteine 1000 mg

Citric acid --------------------------------------- 1000 mg

Oligosaccharides --------------------------------------- 100 g

Plum concentrate ------------------------------------- 2 g

Taurine ------------------------------------------- 1 g

Purified water was added to the whole to 900 ml

The above components were mixed according to a conventional health drink manufacturing method, and the mixture was stirred and heated at 85 DEG C for about 1 hour. The resulting solution was filtered and sterilized in a sterilized 2 liter container, ≪ / RTI >

Although the compositional ratio is relatively mixed with a component suitable for a favorite drink, it is also possible to arbitrarily modify the compounding ratio according to the regional or national preference such as the demand class, the demanding country, and the use purpose.

Claims (18)

A pharmaceutical composition for preventing and treating inflammation induced by obesity containing S-Allyl-L-Cysteine as an active ingredient. The method according to claim 1,
0.0 > IL-6 < / RTI > and MCP-I. The method according to claim 1,
Lt; RTI ID = 0.0 > adiponectin. ≪ / RTI > The method according to claim 1,
Capsules, tablets, granules, powders or beverages. A health functional food for preventing and improving inflammation induced by obesity containing S-Allyl-L-Cysteine as an active ingredient. 6. The method of claim 5,
IL-6 < / RTI > and MCP-I. 6. The method of claim 5,
Adiponectin, and adiponectin. 6. The method of claim 5,
Capsules, tablets, granules, powders or beverages. A pharmaceutical composition for preventing and treating obesity-induced metabolic diseases containing S-Allyl-L-Cysteine as an active ingredient. 10. The method of claim 9,
0.0 > IL-6 < / RTI > and MCP-I. 10. The method of claim 9,
Lt; RTI ID = 0.0 > adiponectin. ≪ / RTI > 10. The method of claim 9,
Capsules, tablets, granules, powders or beverages. 10. The method of claim 9,
Wherein the disease is one or more diseases selected from the group consisting of diabetes, hyperlipidemia, fatty liver, arteriosclerosis, hypertension, cardiovascular disease, or metabolic syndrome in which the diseases occur simultaneously. A health functional food for preventing and improving obesity-induced metabolic diseases containing S-Allyl-L-Cysteine as an active ingredient. 15. The method of claim 14,
IL-6 < / RTI > and MCP-I. 15. The method of claim 14,
Adiponectin, and adiponectin. 15. The method of claim 14,
Capsules, tablets, granules, powders or beverages. 15. The method of claim 14,
Wherein the disease is one or more diseases selected from the group consisting of diabetes, hyperlipidemia, fatty liver, arteriosclerosis, hypertension, cardiovascular disease, or metabolic syndrome in which the diseases occur simultaneously.

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