KR101206370B1 - Use of Ginsenosides for Prevention and Treatment of Autoimmune Disease - Google Patents

Abstract

The present invention is a food, medicament for preventing and ameliorating / treating autoimmune diseases comprising at least one compound selected from the group consisting of floralginsenoside J and ginsenoside I as an active ingredient. It relates to a cosmetic composition.
Floringinsenoside J or ginsenoside I according to the present invention is excellent in inhibiting interleukin-12 production and is useful for the treatment of autoimmune diseases caused by interleukin-12. Can be utilized.

Description

Use of Ginsenosides for Prevention and Treatment of Autoimmune Disease

The present invention relates to the use of floral ginsenoside J or ginsenoside I for the prophylaxis and treatment of autoimmune diseases.

Autoimmune diseases are diseases caused by the body's immune function attacking itself, and for the treatment of autoimmune diseases, the immune function that protects our body must be suppressed. However, there are many difficulties in treatment because of exposure to cancer or infectious diseases. In addition, autoimmune diseases are formed over a long period of time, symptoms are chronically persistent and generally cause long-term permanent damage, and there is little to be cured.

While knowledge of autoimmune diseases has evolved over the past 20-30 years, the exact mechanism of production, the identity of autoantigens, and regulatory genes are still unclear. Autoimmune diseases can be broadly divided into organ-specific diseases and systemic diseases.

Organ-specific autoimmune diseases are caused by the immune response to organ-specific antigens and can occur in almost every organ in our body. Systemic autoimmune diseases are caused by immune responses to antigens expressed throughout the body rather than an immune response to any particular cell. Such systemic autoimmune diseases can also cause disease selectively in specific organs.

Examples of autoimmune diseases include i) Rheumatoid Arthritis in which the immune system attacks tissues of various joints, and ii) autoimmunity of the central nervous system induced by T cells. Multiple Sclerosis (MS), which can lead to blindness, paralysis, and premature death, i.e., immune mediators that destroy the insulin-producing cells of the pancreas and play an important role in the MHC gene Immune-Mediated or Type I Diabetes Mellitus (공격) Inflammatory Bowel Diseases, a disease caused by the immune system attacking the intestine, 피부) Scleroderma, which induces thickening of the skin or blood vessels (Scleroderma), ⅵ) Systemic autoimmunity, accompanied by symptoms such as deep fatigue, rash, joint pain, and in severe cases, damage to the kidneys, brain, lungs, etc. Can systemic lupus (Systemic Lupus Erythematosus, SLE) with the like.

Interleukin-12 is a kind of interleukin produced in antigen-providing cells such as dendritic cells and macrophages by antigen stimulation. It acts to stimulate T cells to differentiate into type 1 helper T cells, and NK (natural killer) cells. In addition, it plays an important role in the activity of T lymphocytes. It is a heterodimer form of IL-12A (p35) and IL-12B (p40), the expression of IL-12A (p35) is constitutive, so the biological function of interleukin-12 is mainly IL-12B (p40) Depends on its expression.

Research has been reported that the inhibition of the interleukin-12 may be helpful in the treatment of autoimmune diseases, which is a hyperimmune response to cells in the human body, and thus the inventors of the present invention, while studying the substances that inhibit them, ginseng The present invention was completed by finding out that floral extracts (floralginsenoside) J or ginsenoside I extracted from leaves and flowers have interleukin-12 production inhibitory activity.

The present invention is to provide a composition for the prevention and treatment of autoimmune diseases containing a compound that inhibits the production of interleukin-12 as an active ingredient.

Therefore, the present invention is to prevent and improve / treat autoimmune diseases comprising at least one compound selected from the group consisting of floralginsenoside J and ginsenoside I as an active ingredient to solve the above problems. Provided are food, pharmaceutical and cosmetic compositions.

The composition comprising floralginsenoside J or ginsenoside I according to the present invention as an active ingredient has an excellent inhibitory effect on the production of interleukin-12, resulting in the activity of interleukin-12. It can be usefully used for the treatment of induced autoimmune diseases.

1 shows the structure of ginsenosides of the present invention. (a) is floralginsenoside J, and (b) is ginsenoside I.
Figure 2 measures the inhibitory effects of floralginsenoside J (a) and ginsenoside I (b) on the production of interleukin 12 (IL-12) in LPS-stimulated myeloid-derived dendritic cells. It is a graph of the experimental results of Example 1.
Figure 3 measures the inhibitory effects of ginsenoside Rg1, ginsenoside Km and ginsenoside II on the production of interleukin 12 (IL-12) in LPS-stimulated myeloid-derived dendritic cells. It is a graph of the experimental result of one comparative example.

The present invention provides a food composition for the prevention and improvement of autoimmune diseases comprising at least one compound selected from the group consisting of floralginsenoside J and ginsenoside I as an active ingredient.

The structure of the floral ginsenoside J (floralginsenoside J) and ginsenoside (ginsenoside) I is shown in Figure 1, which can be extracted and used in ginseng.

The ginseng is Korean ginseng ( Panax ginseng ), P. quiquefolius , P. notoginseng , P. japonicus , P. trifolium , P. pseudoginseng , P. vietnamensis , or Vietnamese ginseng American Panax quinquefolium ) and the like, but is not limited thereto. Preferably, Korean ginseng ( Panax ginseng ) can be used, in particular, it can be used to extract from the leaves and flowers.

The food composition has an effect of inhibiting the production of interleukin-12, it can be usefully used in the manufacture of health foods and general foods that can exhibit the prevention and improvement of autoimmune diseases.

In one embodiment of the present invention, the food composition for preventing and improving autoimmune diseases is selected from the group consisting of floralginsenoside J and ginsenoside I based on 100 parts by weight of the total food composition. One or more compounds may be included in 0.01 to 90 parts by weight, 0.1 to 90 parts by weight, 1 to 90 parts by weight, or 10 to 90 parts by weight, but is not limited thereto.

In another embodiment of the present invention, the food composition for preventing and improving the autoimmune disease further comprises at least one additive selected from the group consisting of organic acids, phosphates, antioxidants, lactose casein, dextrin, glucose, sugar and sorbitol. can do. The organic acid may be, but is not limited to, citric acid, fumaric acid, adipic acid, lactic acid or malic acid, and the phosphate may be, but is not limited to, sodium phosphate, potassium phosphate, acid pyrophosphate or polyphosphate (polymeric phosphate), antioxidant The agent may be a natural antioxidant such as, but not limited to, polyphenols, catechins, alpha-tocopherols, rosemary extracts, licorice extracts, chitosan, tannic acid or phytic acid.

In another embodiment of the present invention, the food composition for preventing and ameliorating autoimmune diseases is various nutritional agents in addition to at least one compound selected from the group consisting of floralginsenoside J and ginsenoside I , Flavoring agents such as vitamins, minerals (electrolytes), synthetic and natural flavoring agents, coloring and neutralizing agents (such as cheese and chocolate), pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH Regulators, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated beverages, and the like. In addition, the food composition for preventing and improving autoimmune diseases according to an embodiment of the present invention may contain a flesh for preparing natural fruit juice, fruit juice beverage and vegetable beverage. The proportion of such additives is generally not limited to, but is selected from the range of 0 to about 20 parts by weight, 5 to 20 parts by weight, or 5 to 15 parts by weight per 100 parts by weight of the composition of the present invention.

 According to one embodiment of the invention, the formulation of the food composition for preventing and improving the autoimmune disease may be in the form of a solid, powder, granules, tablets, capsules, liquids or beverages, but is not limited thereto.

In addition, the food composition for the prevention and improvement of the autoimmune disease is not limited thereto, but not limited to confectionery, sugar, ice cream products, dairy products, meat products, fish products, tofu or jelly, edible oils and fats, noodles, teas, beverages, special nutrition products, Health Supplement, Seasoned Food, Ice, Ginseng Products, Pickled Kimchi, Raisins, Fruits, Vegetables, Dried Products of Fruits or Vegetables, Cutting Products, Fruit Juice, Vegetable Juice, Mixed Juice, Chips, Noodles, Livestock Processing It can be used in the manufacture of foods, processed foods, processed foods, dairy products, fermented milk foods, soybean foods, cereal foods, microbial fermented foods, bakery, condiments, meat processing, acidic beverages, licorice, herbs.

According to an embodiment of the present invention, when using a food composition comprising at least one compound selected from the group consisting of the floral ginsenoside J and ginsenoside I in the manufacture of a health functional food It may be used as 0.01 to 15% by weight, or 0.1 to 10% by weight of the total food weight, when used in the manufacture of beverages may be used as 0.02 to 10% by weight, or 0.3 to 1% by weight of the total beverage.

The present invention also provides a pharmaceutical composition for the prevention and treatment of autoimmune diseases comprising at least one compound selected from the group consisting of floralginsenoside J and ginsenoside I as an active ingredient.

As can be seen through the following examples, the floral ginsenoside J or ginsenoside I of the present invention has an excellent interleukin-12 production inhibitory effect. These effects can prevent and treat autoimmune diseases, and in particular, multiple sclerosis (MS), psoriasis, rheumatoid arthritis, Crohn's disease, ulcerative colitis, type I diabetes (diabetes mellitus), It may be applied to the prevention and treatment of inflammatory bowel disease or autoimmune diseases such as systemic lupus, but is not limited thereto.

The pharmaceutical composition comprising at least one compound selected from the group consisting of floralginsenoside J and ginsenoside I according to the present invention as an active ingredient can be used for the treatment of autoimmune diseases. Therefore, the present invention provides a pharmaceutical composition for the prevention and treatment of autoimmune diseases comprising at least one compound selected from the group consisting of floralginsenoside J and ginsenoside I, preparation of an autoimmune disease treatment agent. Use of at least one compound selected from the group consisting of floralginsenoside J and ginsenoside I, and therapeutically effective amounts of floralginsenoside J and ginsenoside I Provided is a method of treating an autoimmune disease comprising administering to a subject one or more compounds selected from the group consisting of:

In one embodiment of the invention, the pharmaceutical composition for the prevention and treatment of autoimmune diseases is suitable carriers, excipients, disintegrants, sweeteners, coatings, swelling agents, lubricants, lubricants, flavors commonly used in the manufacture of pharmaceutical compositions It may further comprise one or more adjuvants selected from the group consisting of agents, antioxidants, buffers, bacteriostatics, diluents, dispersants, surfactants, binders and lubricants.

Specifically, the carriers, excipients and diluents are lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline Cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil can be used, and solid preparations for oral administration include tablets, pills, powders, granules, capsules. And the like, and such solid preparations may be prepared by mixing at least one excipient such as starch, calcium carbonate, sucrose or lactose, gelatin and the like in the composition. In addition to simple excipients, lubricants such as magnesium styrate and talc may also be used. Oral liquid preparations include suspensions, solvents, emulsions, syrups, and the like, and may include various excipients such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories, and the like. 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. Witsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like may be used as the base material of the suppository.

In another embodiment of the present invention, the pharmaceutical composition for preventing and treating autoimmune diseases is granules, powders, coated tablets, tablets, pills, capsules, suppositories, gels, syrups, juices, suspensions according to conventional methods. It can be formulated into emulsions, drops, or solutions.

According to one embodiment of the invention the pharmaceutical composition is intravenous, intraarterial, intraperitoneal, intramuscular, intraarterial, intraperitoneal, intrasternal, transdermal, nasal, inhaled, topical, rectal, oral, intraocular or intradermal Via the route can be administered to the subject in a conventional manner.

Preferred dosages of one or more compounds selected from the group consisting of floralginsenoside J and ginsenoside I include the condition and weight of the subject, type and extent of disease, drug form, route and duration of administration. And may be appropriately selected by those skilled in the art. According to one embodiment of the present invention, but not limited thereto, the daily dosage may be 0.01 to 200 mg / kg, specifically 0.1 to 200 mg / kg, more specifically 0.1 to 100 mg / kg. Administration may be administered once a day or divided into several times, thereby not limiting the scope of the invention.

In the present invention, the 'subject' may be a mammal including a human, but is not limited thereto.

In another aspect, the present invention provides a cosmetic composition for the prevention and improvement of autoimmune diseases comprising at least one compound selected from the group consisting of floralginsenoside J and ginsenoside (I) as an active ingredient. Floringinsenoside J and ginsenoside I have excellent inhibitory effects on interleukin-12 production, as shown in the following examples, to prevent skin inflammatory reactions such as atopic dermatitis, an autoimmune disease. And cosmetic compositions for improvement.

In one embodiment of the invention, the cosmetic composition for the prevention and improvement of autoimmune diseases is usually in cosmetics with one or more compound components selected from the group consisting of floralginsenoside J and ginsenoside I The additives used may further comprise one or more additives selected from the group consisting of vitamins, surfactants, emulsifiers, perfumes, pigments, stabilizers, preservatives, antioxidants, sunscreens, pH adjusters and chelating agents.

According to one embodiment of the present invention, the cosmetic composition using the cosmetic composition for preventing and improving the autoimmune disease is not limited thereto. For example, the flexible cosmetics, nourishing cosmetics, massage cream, nutrition cream, pack , Gels, essences, lipsticks, makeup bases, foundations, lotions, ointments, gels, creams, cleansing, face wash, soaps, shampoos, rinses, treatments and cosmetics. Such cosmetics may contain conventional ingredients such as aqueous vitamins, oily vitamins, high molecular weight peptides, polymeric polysaccharides, sphingolipids and the like, and may be easily prepared according to techniques well known to those skilled in the art.

According to one embodiment of the present invention, the content of at least one compound component selected from the group consisting of floralginsenoside J and ginsenoside I is not limited thereto, but is 0.001 to 20 based on the total weight of the cosmetic composition. Weight%, 0.001 to 5 weight%, or 0.001 to 1 weight%.

[Example]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in detail with reference to the following examples. However, the following examples are intended to illustrate the contents of the present invention, but the scope of the present invention is not limited to the following examples. Embodiments of the present invention are provided to more fully describe the present invention to those skilled in the art.

< Example  1> Evaluation of inhibitory activity of interleukin-12 production

The ginsenoside compound used for the test was dissolved in DMSO. Bone marrow-derived dendritic cells were recovered from wild-type C57BL / 6 mice (Taconic Farm, Inc) and used.

After bone marrow was recovered by spraying the tibia and femur from the mouse with DMEM (Invitrogen) medium, the bone marrow cells were harvested from 3% J558L lymphoma cell tumor supernatant containing GM-CSF. RPMI 1640 medium (10% heat-inactivated) FBS, 50 μM 2-ME, and 2 mM glutamine) were cultured. GM-CSF With Medium was changed every two days with the above culture medium. Six days later, non-adherent cells and loosely adherent dendritic cells were recovered and suspended in RPMI 1640 (5% FBS). After dispensing dendritic cells (DCs) in 48-well plates at 1 × 10 ⁵ cells / mL, pretreated with floralginsenoside J or ginsenoside I at a concentration of 5 to 50 μM for 1 hour. Salmonella minnesota derived LPS (Alexis, 10 ng / mL) was further treated. After 18 hours, the cell culture supernatant was recovered and the amount of IL-12B (p40) in mouse interleukin-12 was measured by ELISA (BD PharMingen). All experiments were repeated three times and the data were expressed as mean ± standard deviation of the measurements obtained from three replicates.

The results are shown in FIG. IL-12B (p40) production of dendritic cells treated with 0.1% DMSO was expressed as 100%.

It was found that floralginsenoside J or ginsenoside I had a significant inhibitory effect on IL-12 production of LPS-stimulated dendritic cells. In particular, ginsenoside I showed the highest inhibitory effect (IC ₅₀ = 6.7 μM), and floralginsenoside J showed a moderate inhibitory effect (IC ₅₀ = 25.8 μM).

< Comparative example  1> Evaluation of inhibitory activity of interleukin-12 production

In Comparative Example 1, 20 μM of ginsenoside Rg1, ginsenoside Km, and ginsenoside were used without using floralginsenoside J or ginsenoside I. II was used. Other experiments were carried out in the same manner as in Example 1.

The results are shown in Fig. IL-12B (p40) production of dendritic cells treated with 0.1% DMSO was expressed as 100%.

3, ginsenoside Rg1, ginsenoside Km and ginsenoside II of 20 μM do not inhibit the IL-12 production of dendritic cells stimulated with LPS Could.

Having described the specific parts of the present invention in detail, it will be apparent to those skilled in the art that such specific descriptions are merely preferred embodiments, and thus the scope of the present invention is not limited thereto. will be. Accordingly, the actual scope of the present invention will be defined by the appended claims and their equivalents.

Claims (9)

Food composition for the prevention and improvement of autoimmune diseases comprising at least one compound selected from the group consisting of floralginsenoside J and ginsenoside I as an active ingredient. The method of claim 1,
Food composition for the prevention and improvement of autoimmune diseases further comprising at least one additive selected from the group consisting of organic acids, phosphates, antioxidants, lactose casein, dextrin, glucose, sugar and sorbitol. The method according to claim 1 or 2,
The food composition is in the form of a powder, granules, tablets, capsules or beverages. A pharmaceutical composition for the prevention and treatment of autoimmune diseases comprising at least one compound selected from the group consisting of floralginsenoside J and ginsenoside I as an active ingredient. 5. The method of claim 4,
Add one or more additives selected from the group consisting of carriers, excipients, disintegrants, sweeteners, coatings, swelling agents, lubricants, lubricants, flavoring agents, antioxidants, buffers, bacteriostatic agents, diluents, dispersants, surfactants, binders and lubricants Pharmaceutical composition for the prevention and treatment of autoimmune diseases, including. The method according to claim 4 or 5,
Formulation of the pharmaceutical composition for the prevention and treatment of autoimmune diseases is selected from the group consisting of granules, powders, coated tablets, tablets, pills, capsules, suppositories, gels, syrups, juices, suspensions, emulsions, drops or solutions. Pharmaceutical composition for the prevention and treatment of autoimmune diseases. 5. The method of claim 4,
The autoimmune disease is MS, multiple sclerosis, psoriasis, rheumatoid arthritis, Crohn's disease, ulcerative colitis, type I diabetes, diabetes mellitus, inflammatory bowel disease, or systemic lupus autoimmune disease Pharmaceutical composition for prophylaxis and treatment. A cosmetic composition for the prevention and improvement of autoimmune diseases comprising at least one compound selected from the group consisting of floralginsenoside J and ginsenoside I as an active ingredient. 9. The method of claim 8,
Cosmetic composition for the prevention and improvement of autoimmune diseases further comprising at least one additive selected from the group consisting of vitamins, surfactants, emulsifiers, fragrances, pigments, stabilizers, preservatives, antioxidants, sunscreens, pH adjusters and chelating agents.

Images