KR101113202B1 - Use of triterpenoid for prevention and treatment of autoimmune disease - Google Patents

Abstract

PURPOSE: A composition of triterpenoid for preventing and treating autoimmune diseases is provided to suppress IL-12, IL-6, and TNF-alpha. CONSTITUTION: A pharmaceutical composition for preventing and treating autoimmune diseases contains triterpenoid of chemical formula 1 or pharmaceutically acceptable salt thereof as an active ingredient. In chemical formula 1, R1 is CHO or CH_3; and R2 is O or CH_2. The composition additionally contains a carrier, excipient, disintegrant, sweetener, coating agent, lubricant, flavoring agent, anti-oxidant, buffer solution, diluents, dispersion agent, surfactant, or binder. The pharmaceutical composition is used in the form of a granule, powder, coating tablet, capsule, suppository, syrup, juice, suspension, emulsion, or liquid.

Description

Use of Triterpenoid for Prevention and Treatment of Autoimmune Disease

The present invention relates to the use of prophylaxis and treatment of autoimmune diseases of lupan type triterpenoids.

Acanthopanax koreanum Nakai (Araliaceae) is an indigenous plant widely distributed in Korea. The root and stem bark of A. koreanum has traditionally been administered as a tonic and sedative and has been used to treat hepatitis and diabetes. The leaves of the plant contain diterpenoids, lignans, triterpenoids, polyacetylenes, phenylpropanoids and flavonoids.

Autoimmune disease is a disease caused by the body's immune function attacking itself. It is formed over a long period of time, the symptoms are chronically persistent, and usually cause permanent damage to organs. It is a reality.

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 (ⅳ) Inflammatory Bowel Diseases, a disease caused by the immune system attacking the intestine (ⅴ), 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. Systemic lupus and the like that can hit (Systemic Lupus Erythematosus, SLE).

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) Inhibition of interleukin-12 may be helpful in the treatment of autoimmune diseases, a hyperimmune response to cells in the human body.

Sepsis is a condition in which a microbial infection causes a severe inflammatory response throughout the body. More specifically, fever symptoms that rise above 38 degrees, or hypothermia falling below 36 degrees, respiratory rate increases to more than 24 times per minute (empty breathing), heart rate of 90 or more times per minute (tachycardia), or an increase in white blood cell counts on blood tests, or If there is more than one symptom of a significant decrease, it is called systemic inflammatory response syndrome (SIRS), which is called sepsis when the systemic inflammatory response syndrome is caused by a microbial infection.

Lipopolysaccharide (LPS) is a component of the cell wall of Gram-negative bacteria and causes excessive sepsis shock when exposed to the human body. It stimulates antigen-providing cells, such as host macrophages and dendritic cells, to cause host-induced inflammatory processes, in which overproduced interleukin-6 and TNF-α cause endotoxic shock, the leading cause of sepsis. Known.

The inventors of the present invention found that the novel triterpenoid compounds extracted from steamed A. koreanum leaves inhibit the production of Interleukin-12, Interleukin-6, and Tumor Necrosis Factor (TNF). The present invention has been completed by finding out that there is activity.

The present invention is to provide a composition for the prevention and treatment of autoimmune diseases containing a compound that inhibits interleukin-12, interleukin-6 and TNF-α production as an active ingredient.

The present invention provides a medicament for preventing and treating autoimmune diseases comprising at least one selected from the group consisting of triterpenoids having a structure of Formula 1, derivatives thereof and all pharmaceutically acceptable salts thereof as an active ingredient. To provide a composition.

[Formula 1]

[Wherein R ¹ is CHO or CH ₃ and R ² is O or CH _2. ]

As can be seen through the following examples, the triterpenoids according to the present invention have an excellent interleukin-12 production inhibitory effect. These effects can prevent and treat autoimmune diseases, specifically MS, multiple sclerosis, 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.

Triterpenoids of Formula 1 include both derivatives thereof and salts thereof. Wherein the derivative includes both glycosides and nonglycosides of the triterpenoids.

"Pharmaceutically acceptable salt" as used herein means a salt suitable for use in contact with tissues of humans and lower animals without causing excessive toxicity, irritation, allergic reactions, etc. within the scope of medical judgment. Kinds of such pharmaceutically acceptable salts are well known in the art. For example, pharmaceutically acceptable salts are described in detail in S. M. Berge et al., J. Pharmaceutical Sciences, 1977, 66: 1. Pharmaceutically acceptable salts can be broadly divided into acid addition salts and basic addition salts. Acid addition salts of the triterpenoid compounds according to the invention can be prepared in situ during the final separation and purification of the compounds of the invention or by reacting the free base functional groups with suitable organic acids in separate reaction systems. Representative acid addition salts include, but are not limited to, acetate, adipate, alginate, citrate, aspartate, benzoate, benzenesulfonate, bisulfate, butyrate, camphorate, camphorsulfonate, digluconate, glycerol Phosphate, hemisulfate, heptanoate, hexanoate, fumarate, hydrochloride, hydrobromide, hydroiodide, 2-hydroxyethanesulfonate (isothionate), lactate, maleate, methanesulfonate, Nicotinate, 2-naphthalenesulfonate, oxalate, palmitoate, pectinate, persulfate, 3-phenylpropionate, picrate, pivalate, propionate, succinate, tartrate, thiocyanate, Phosphate, glutamate, bicarbonate, p-toluenesulfonate and udecanoate It is included. Examples of acids that can be used to form acid addition salts include inorganic acids such as hydrochloric acid, bromic acid, sulfuric acid and phosphoric acid and organic acids such as oxalic acid, maleic acid, succinic acid and citric acid. Basic addition salts may be used to convert carboxylic acid moieties in situ during the final separation and purification of the compounds of the invention into suitable bases (e.g., hydroxides, carbonates or bicarbonates of pharmaceutically acceptable metal cations). Nate), ammonia, organic primary amines, secondary amines or tertiary amines. Pharmaceutically acceptable basic addition salts include, but are not limited to, alkali metal or alkaline earth metal cations such as lithium, sodium, potassium, calcium, magnesium and aluminum salts, nontoxic quaternary ammonia and amine cations (ammonium, tetramethyl Ammonium, tetraethylammonium, methylammonium, dimethylammonium, trimethylammonium, triethylammonium, diethylammonium and ethylammonium). Other representative organic amines useful for the formation of base addition salts include ethyleneamine, ethanolamine, diethanolamine, piperidine, piperazine and the like.

The pharmaceutical composition for the prevention and treatment of autoimmune diseases comprising at least one selected from the group consisting of triterpenoids, derivatives thereof and all pharmaceutically acceptable salts thereof according to the present invention as an active ingredient It can be used for treatment. Therefore, the present invention provides a pharmaceutical composition for the prevention and treatment of autoimmune diseases comprising triterpenoids as an active ingredient, the use of triterpenoids for the preparation of therapeutic agents for autoimmune diseases, and therapeutically effective amounts of triterpenoids. Provided is a method of treating an autoimmune disease comprising administering to a subject.

The present invention also provides a pharmaceutical composition for the prevention and treatment of sepsis comprising at least one selected from the group consisting of the triterpenoids, derivatives thereof and all pharmaceutically acceptable salts thereof as an active ingredient. As can be seen through the following examples, the triterpenoids according to the present invention has an excellent inhibitory effect on the production of interleukin-6 and TNF (Tumor Necrosis Factor) -α, which cause sepsis shock, preventing sepsis and It can be used for treatment. Therefore, the present invention provides a pharmaceutical composition for the prevention and treatment of sepsis, which contains triterpenoids as an active ingredient, the use of triterpenoids for the preparation of the treatment of sepsis, and a therapeutically effective amount of triterpenoids to the subject. It provides a method of treating sepsis comprising the step.

In one embodiment of the invention, for the prevention and treatment of autoimmune diseases or sepsis comprising at least one selected from the group consisting of the triterpenoids, derivatives thereof and all pharmaceutically acceptable salts thereof as an active ingredient. Pharmaceutical compositions are suitable carriers, excipients, disintegrants, sweeteners, coatings, swelling agents, lubricants, lubricants, flavoring agents, antioxidants, buffers, bacteriostatic agents, diluents, dispersants, surfactants, binders commonly used in the manufacture of pharmaceutical compositions. And one or more adjuvants selected from the group consisting of 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, for the prevention and treatment of autoimmune diseases or sepsis comprising at least one selected from the group consisting of the triterpenoids, derivatives thereof and all pharmaceutically acceptable salts thereof as an active ingredient. Pharmaceutical compositions can be formulated into granules, powders, coated tablets, tablets, pills, capsules, suppositories, gels, syrups, juices, suspensions, emulsions, drops or solutions according to conventional methods.

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.

The preferred dosage of the triterpenoid may vary depending on the condition and weight of the subject, the type and extent of the disease, the form of the drug, the route of administration, and the duration, 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 food composition comprising at least one selected from the group consisting of triterpenoids having a structure of Formula 1, derivatives thereof, and all pharmaceutically acceptable salts thereof as an active ingredient. The food composition has an inhibitory effect on the production of Interleukin-12, Interleukin-6, and Tumor Necrosis Factor (TNF), and thus may be particularly effective in preventing and treating autoimmune diseases and sepsis. It can be usefully used for the production of dietary supplements and general foods.

In one embodiment of the invention, the food composition comprising the triterpenoids as an active ingredient, 0.01 to 90 parts by weight, 0.1 to 90 parts by weight, 1 to 1 part by weight of the triterpenoids with respect to 100 parts by weight of the total food composition 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 may further include one or more additives selected from the group consisting of organic acids, phosphates, antioxidants, lactose casein, dextrin, glucose, sugar and sorbitol. 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, α-tocopherols, rosemary extracts, licorice extracts, chitosan, tannic acid or phytic acid.

In another embodiment of the present invention, the food composition comprising at least one selected from the group consisting of the triterpenoids, derivatives thereof and all pharmaceutically acceptable salts thereof as an active ingredient, Eggplant nutrients, vitamins, minerals (electrolytes), flavors such as synthetic and natural flavors, colorants and neutralizers (such as cheese and chocolate), pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners , pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated drinks, and the like. In addition, the food composition for preventing and treating 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 not limited thereto but is generally 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 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 is not limited thereto, but confections, sugars, ice cream products, dairy products, meat products, fish products, tofu or jelly, edible oils, noodles, teas, beverages, special nutrition products, health supplements, seasoned foods, ice , Ginseng products, pickled kimchi, raisins, fruits, vegetables, dried products of fruits or vegetables, cut products, fruit juices, vegetable juices, mixed juices, chips, noodles, livestock processed foods, fish processed foods, dairy products , Fermented milk food, legume food, cereal food, microbial fermented food, bakery, condiments, meat processing, acidic beverages, licorice, herbs and the like can be used in the manufacture of food.

According to one embodiment of the invention, the food composition comprising at least one selected from the group consisting of the triterpenoids, derivatives thereof and all pharmaceutically acceptable salts thereof as an active ingredient in the manufacture of health functional food When used, it can 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 can be used as 0.02 to 10% by weight, or 0.3 to 1% by weight of the total beverage have.

In another aspect, the present invention provides a cosmetic composition comprising at least one selected from the group consisting of triterpenoids having a structure of Formula 1, derivatives thereof, and all pharmaceutically acceptable salts thereof as an active ingredient.

Triterpenoids having the structure of Formula 1 have an inhibitory effect on the production of Interleukin-12, Interleukin-6, and Tumor Necrosis Factor (TNF), as can be seen through the following examples. Excellent, it can be used as a cosmetic composition for preventing and treating skin inflammatory reactions such as atopic dermatitis.

In one embodiment of the invention, the cosmetic composition is commonly used in cosmetics, with one or more selected from the group consisting of triterpenoids having a structure of Formula 1, derivatives thereof, and all pharmaceutically acceptable salts thereof The additive may further include 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 is used in the formulation is not limited to this, for example, supple cosmetics, nourishing cosmetics, massage cream, nutrition cream, pack, gel, essence, lipstick, makeup Base, foundation, lotion, ointment, gel, cream, cleansing, face wash, soap, shampoo, rinse, treatment and essence. Such cosmetics may include conventional ingredients such as aqueous vitamins, oily vitamins, polymer peptides, polymer polysaccharides, sphingolipids, and the like, and may be readily prepared according to techniques well known to those skilled in the art.

According to one embodiment of the present invention, the at least one content selected from the group consisting of the triterpenoids, derivatives thereof and all pharmaceutically acceptable salts thereof 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%.

The triterpenoids having the structure of Formula 1 according to the present invention are excellent in inhibiting the production of Interleukin-12, Interleukin-6, and TNF (Tumor Necrosis Factor) -α. It can be useful for the treatment of autoimmune diseases and sepsis caused by.

BRIEF DESCRIPTION OF THE DRAWINGS The structure of the luphen type triterpenoid compounds 1-13 is shown.
Figure 2 is a graph of the experimental results of Example 1 measuring the inhibitory effect of the triterpenoids of the present invention on the production of interleukin 12 (IL-12) of LPS-stimulated bone marrow-derived dendritic cells.
Figure 3 is a graph of the experimental results of Example 2 measuring the inhibitory effect of the triterpenoids of the present invention on the production of interleukin-6 (IL-6) of LPS-stimulated bone marrow-derived dendritic cells.
Figure 4 is a graph of the experimental results of Example 3 measuring the inhibitory effect of the triterpenoids of the present invention on TNF-α production of LPS-stimulated bone marrow-derived dendritic cells.

Hereinafter, examples will be described in detail to help understand the present invention. However, the following examples are merely to illustrate the content of the present invention is not limited to the scope of the present invention. The embodiments of the present invention are provided to more completely explain the present invention to those skilled in the art.

The following preparation examples are to provide a preparation example commonly applied to the embodiment according to the present invention.

Manufacturing example  1: A. koreanum  Separation of Ethyl Acetate Fraction from Leaves

A. koreanum leaves were collected from Susin Ogapi in Cheonan, Korea in August 2006, and evidence specimens (CNU 060810) are stored in a herbarium at the College of Pharmacy, Chungnam National University, Korea.

The dried leaves of A. koreanum (4.0 kg) were extracted three times with methanol (MeOH) under reflux for 15 h, yielding 460.3 g of a black solid extract. The extract was suspended in water and separated with ethyl acetate (EtOAc) to give an ethyl acetate extract (AK1, 156.0 g) and a water extract (AK2, 204.3 g).

Manufacturing example  2: Triterpenoids  Compound Silica Gel In the column  detach

The ethyl acetate extract was separated on a silica gel column and eluted with a mixture of CHCl ₃ : MeOH (slope 50: 1 to 5: 1 v / v) to give five fractions AK1A to AK1E. Fraction AK1C was eluted with fractions AK1C1-AK1C4 on a silica gel column using eluent CHCl3: MeOH: H2O (90: 10: 1, v / v / v). The AK1C3 fraction was eluted with eluent MeOH: H ₂ O (8: 2 v / v) on YMC RP-18 column to give compound 1 (50.0 mg). Fraction AK1C4 was eluted with eluent MeOH: H2O (6: 4 v / v) on a YMC RP-18 column to give compound 2 (20.2 mg). The water soluble fraction (AK2) was increased on a Diaion HP-20P column (Mitshubishi Chem. Ind. Co., Japan) to increase the concentration of MeOH (100% H ₂ O, 20% MeOH, 40% MeOH, 60% MeOH, 80%). MeOH and 100% MeOH) chromatography gave five fractions AK2A to AK2E. The AK2A and AK2B fractions were combined and eluted with eluent CHCl ₃ : MeOH: H ₂ O (75: 20: 3, v / v / v) on a silica gel column to give four fractions AK2A1 to AK2A4. Fraction AK2A2 was eluted with eluent CHCl ₃ : MeOH: H ₂ O (75: 20: 3, v / v / v) on a silica gel column to give compound 7 (120.9 mg). Fraction AK2A3 was further eluted with eluent CH ₂ Cl ₂ : MeOH: H ₂ O (60: 20: 2, v / v / v) on a silica gel column to give five smaller fractions AK2A3A to AK2A3E. Fraction AK2A3B was eluted with eluent acetone: H ₂ O (1: 1, v / v) on a YMC RP-18 column to give compound 8 (20.7 mg). Fraction AK2A3E was eluted with CH ₂ Cl ₂ : MeOH: H ₂ O (40: 20: 3, v / v / v) on a silica gel column to give compound 6 (6.5 mg) and compound 9 (10.4 mg). . Fraction AK2A4 was further eluted with eluent acetone: MeOH: H ₂ O (1: 2: 2, v / v / v) on a YMC RP-18 column to give compound 5 (6.0 mg). Fraction AK2C was eluted with eluent acetone: H ₂ O (2: 1, v / v) on a YMC RP-18 column to give four fractions AK2C1 to AK2C4. Fraction AK2C1 was eluted with silica gel column (50 g, 2 x 50 cm) with eluent CHCl ₃ : MeOH: H ₂ O (30: 10: 1, v / v / v) to afford compound 11 (10 mg). It was. Fraction AK2C2 was further eluted with eluent CH ₂ Cl ₂ : MeOH: H ₂ O (35: 10: 1, v / v / v) on a silica gel column (50 g, 2 × 50 cm) to give Compound 12 (10 mg) and compound 13 (10 mg) were obtained. Fraction AK2E was eluted with eluent acetone: H ₂ O (1: 1, v: v, 1.5 L) on a YMC RP-18 column to give three fractions AK2E1 to AK2E3. Fraction AK2E1 was eluted with eluent CHCl ₃ : MeOH: H ₂ O (30: 10: 1, v / v / v) on a silica gel column to give compound 3 (5 mg). Fraction AK2E2 was eluted with eluent CHCl ₃ : MeOH: H ₂ O (35: 10: 1, v / v / v) on a silica gel column to give compound 4 (8 mg) and compound 10 (7 mg).

That is, successive separations of specific fractions were performed on YMC RP-18 and silica gel columns, ultimately resulting in 13 lupan type triterpenoids 3α, 11α-dihydroxy-20,23-dioxo-30-norlupan-28 -Noic acid (3α, 11α-dihydroxy-20,23-dioxo-30-norlupane-28-oic acid) ( 1 ), 3α, 11α-dihydroxyloop-20 (29) -ene-28-noic acid (3α, 11α-dihydroxylup-20 (29) -en-28-oic acid) ( 2 ), acankoreoside M ( 3 ), acancoreoside N ( 4 ), acancoreoside I ( 5 ), Acancoreoside A ( 6 ), acancoreoside D ( 7 ), acancoreoside F ( 8 ), and acantriposide A ( 9 ), acancoreoside O ( 10 ), acancoreoside J ( 11 ), acancoreoside K ( 12 ), and acancoreoside L ( 13 ) were obtained (FIG. 1).

Example  1: Assessing Inhibitory Activity of Interleukin-12 Production

In order to evaluate the anti-inflammatory activity of the compounds, the inhibitory effects of compounds 1 to 13 on the production of IL-12B (p40) in myeloid derived dendritic cells stimulated with LPS were tested.

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 a 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 / 0.5 mL, Salmonella minnesota was treated with triterpenoids having a structure of Formula 1 at 50 μM concentration for 1 hour. 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. In the figure, the data indicate the degree of inhibition of interleukin 12 production as a percentage (%) compared to the case treated with 0.1% DMSO (vehicle).

Positive control SB203580 (p38 MAP kinase inhibitor) showed an inhibitory effect of 74.8% at 50 μM concentration. Among 13 compounds tested, compounds 1 and 2 showed inhibitory effects of 84.5% and 62.6% at 50 μM, respectively. At the same concentration, the remaining compounds showed a mild inhibitory effect of less than 40% (FIG. 2).

Example  3: Evaluation of inhibitory activity of interleukin-6 production

In Example 3, the same experiment as in Example 1 was performed except that ELISA (BD PharMingen) was performed on interleukin-6 instead of IL-12B (p40).

The results are shown in FIG. Compounds 1 and 2 showed significant inhibitory effects of 54.6% and 46.6% on IL-6 production in LPS stimulated dendritic cells, respectively (FIG. 3).

Example  4: TNF -α production inhibitory activity evaluation

In Example 4, ELISA (BD PharMingen) was performed on TNF-α instead of IL-12B (p40).

The results are shown in FIG. Compounds 1 and 2 showed significant inhibitory effects of 45.0% and 67.9% on TNF-α production in LPS stimulated dendritic cells (FIG. 4).

In the above examples, in order to confirm the inflammatory activity of the tested compound, cell viability was continuously confirmed using a colorimetric MTT assay (Sigma, MO, USA). Compounds 1 to 13 at the tested concentrations had little or no effect on cell viability.

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. Thus, the substantial scope of the present invention will be defined by the appended claims and their equivalents.

Claims (12)

A pharmaceutical composition for preventing and treating autoimmune diseases comprising a triterpenoid having a structure of Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.
[Formula 1]

[Wherein R ¹ is CHO or CH ₃ and R ² is O or CH _2. ] The method of claim 1,
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 1 or 2,
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 and solutions. Pharmaceutical composition for the prevention and treatment of autoimmune diseases. The method of claim 1,
The autoimmune diseases include multiple sclerosis (MS), psoriasis, rheumatoid arthritis, Crohn's disease, ulcerative colitis, type I diabetes mellitus, inflammatory bowel disease or pre-neoplastic Lupus factor autoimmune disease Pharmaceutical composition for prophylaxis and treatment. A pharmaceutical composition for the prevention and treatment of sepsis, comprising the triterpenoid of claim 1 or a pharmaceutically acceptable salt thereof as an active ingredient. The method of claim 5,
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 sepsis, including. The method according to claim 5 or 6,
Formulation of the pharmaceutical composition for the prevention and treatment of sepsis is selected from the group consisting of granules, powders, coated tablets, tablets, pills, capsules, suppositories, gels, syrups, juices, suspensions, emulsions, drops and solutions. Pharmaceutical composition for the prevention and treatment of phosphorus sepsis. A food composition for preventing and treating autoimmune diseases comprising a triterpenoid having a structure of Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.
[Formula 1]

[Wherein R ¹ is CHO or CH ₃ and R ² is O or CH _2. ] The method of claim 8,
A food composition for preventing and treating 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 8 or 9,
The formulation of the food composition is a food composition in the form of a powder, granules, tablets, capsules or beverages. A cosmetic composition for preventing and treating autoimmune diseases comprising a triterpenoid having a structure of Formula 1 or a pharmaceutically acceptable salt thereof as an active ingredient.
[Formula 1]

[Wherein R ¹ is CHO or CH ₃ and R ² is O or CH _2. ] The method of claim 11,
Cosmetic composition for the prevention and treatment of autoimmune diseases further comprising at least one additive selected from the group consisting of vitamins, surfactants, emulsifiers, flavorings, pigments, stabilizers, preservatives, antioxidants, sunscreens, pH adjusters and chelating agents.

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