KR20120119160A - Composition comprising an extract of curcuma longa l. or curcuma aromatica l. isolated therefrom having il-6 induced stat3 inhibitory activity - Google Patents

Abstract

PURPOSE: A composition including extract of ground part in curcumae longae rhizoma or the non-polar organic solvent fractions thereof are provided to be useful for preventing and treating IL-6 induced STAT3 mediated diseases, cancer or inflammatory diseases. CONSTITUTION: A composition for preventing and treating IL-6 induced STAT3 mediated diseases includes extract of ground part in curcuma longa L or curcuma aromatica L as active ingredient. The extract is obtained by extracting the ground part of curcuma longa L or curcuma aromatica L by using water, organic solvent or a mixed solvent thereof. The organic solvent is methanol, ethanol, isopropanol, butanol, ethylene, acetone, hexane, ether, chloroform, ethyl acetate, butylacetate, dichloromethane, N,N- dimethylformamid (DMF), dimethyl sulfoxide (DMSO), 1,3- butylene glycol, propylene glycol or a mixed solvent thereof. A non-polar organic solvent fraction is obtained by disjunct-extracting the extract with hexane, ether, dichloromethane, chloroform, ethyl acetate or a mixed solvent thereof. The IL-6 induced STAT3 mediated disease is cancer or inflammation disease.

Description

Composition comprising an extract of Curcuma longa L. or Curcuma aromatica L. isolated therefrom having IL-6 induced STAT3 with a turmeric or turmeric extract of turmeric or turmeric having an inhibitory effect on IL-6 induced SAT3 activation inhibitory activity}

The present invention relates to a composition for treating IL-6-induced STAT3-mediated disease comprising turmeric extract of Curcuma longa L or Curcuma aromatica L, or a nonpolar organic solvent fraction thereof as an active ingredient. Specifically, the present invention is a composition for treating IL-6 induced STAT3 mediated disease comprising turmeric or turmeric ground extract, or a nonpolar organic solvent fraction thereof as an active ingredient, IL-6 induced STAT3 mediated comprising the composition as an active ingredient A method of treating IL-6 induced STAT3-mediated disease in an animal other than a human, comprising administering a functional food for preventing or ameliorating the disease, and administering the composition to a subject in need thereof.

Interleukin-6 (IL-6) is a cytokine, also called B cell stimulating factor 2 (BSF2) or interferon β2 (INF-β2). IL-6 was found to be a differentiation factor involved in the activation of B lymphocytes (Hirano, T. et al., Nature (1986) 324, 73-76). Subsequently, it was found to be a multifunctional cytokine affecting the function of various cells (Akira, S. et al., Adv. In Immunology (1993) 54, 1-78). IL-6 delivers its biological activity through two proteins on the cell membrane. One is the IL-6 receptor, a protein to which IL-6 binds. IL-6 receptor is a membrane-bound protein of about 80 kDa expressed through the cell membrane. The other is the membrane protein gp130, which has a molecular weight of about 130 kDa pertaining to signal transfer of nonligand binding. IL-6 and IL-6 receptors form an IL-6 / IL-6 receptor complex and then bind to gp130 (Taga et al., J. Exp. Med. (1987) 166, 967). After binding of the ligand to the receptor, Janus Kinases 2 (JAK2) is activated by transphosphorylation in the cell. Activated JAK2 phosphorylates several tyrosine residues in the receptor cytoplasmic domains, which are STAT3 (signal transducers and activators of SH2 or other phosphotyrosine binding motifs). It acts as a docking site for proteins in the cytoplasm such as transcription 3). STAT3 bound to the cytoplasmic domain of the receptor is released from the receptor after phosphorylation by JAK2. Activated STAT3s are known to bind to each other in the cytoplasm to form a homo- or heterodimer and then enter the nucleus to bind the recognition sequence of the gene of interest to increase transcription. (Levy, DE, et al., Nat Rev Mol Cell Biol, 2002, 3, 651-62, Darnell, JE, Jr, Science, 1997, 277, 1630-1635).

The IL-6-induced signaling system has been reported to be associated with inflammatory diseases and various cancer diseases. Therefore, inhibition of the IL-6-induced signaling system is therapeutically useful. Currently, anti-IL-6 R antibodies are the most studied for the inhibitory function of IL-6 signaling system. This anti-IL-6 R antibody has been reported as a synovial cell growth inhibitor against rheumatoid arthritis (International Patent Publication No. 98/11020), plasmacytosis, hyperimmunoglobulinemia, anemia, nephritis, cachexia, rheumatoid arthritis, It is known to be used for the treatment of cattle breeder diseases and diseases that contribute to IL-6 products such as vasculitis (International Patent Publication No. 96/12503). Also known as a prophylactic / protective agent for sensitive T cell-related diseases such as multiple sclerosis, uveitis, chronic thyroiditis, hypersensitivity, contact dermatitis and atopic dermatitis (International Patent Publication No. 98/42377), used as a therapeutic agent for systemic erythematoses Patents have also been reported (International Patent Publication No. 98/42377). In addition, in the report used as a therapeutic agent for Crohn's disease (International Patent Publication No. 99/47170), the active ingredient is known as an anti-IL-6R antibody. A patent used as an active ingredient for the treatment of pancreatitis has also been reported. (International Patent Publication No. 00/10607), International Patent Publication No. 02/3492, which is a patent for the treatment of psoriasis, is also known as an anti-IL-6R antibody as an active ingredient. The active ingredient is also an anti-IL-6R antibody in Patent Publication No. 02/080969. However, these proteins may have epitopes that can be recognized as foreign proteins and may still be immunogenic when used as a therapeutic agent. Because of the problem that non-small molecule compounds are not recognized by the immune system, much research is currently being conducted.

In addition, the IL-6 signaling system in association with cancer is associated with a number of intermediate mediator STAT3. It has been reported to be involved in several forms of cancer, including myeloma, breast carcinoma, prostate cancer, brain tumors, head and neck carcinoma, melanoma, leukemia and lymphoma, especially chronic myeloid leukemia and multiple myeloma (Niu, et al., Cancer Res. , 1999, 59, 5059-5063). Cells derived from both rat and human prostate cancers have been found to have structurally activated STAT3, which has some acute leukemias (Gouilleux-Gruart, V. et al., Leuk. Lymphoma, 1997, 28, 83-88) and T It has been shown to be structurally activated in cellular lymphomas (Yu, CL et al., J. Immunol., 1997, 159, 5206-5210). Interestingly, STAT3 has been found to structurally phosphorylate on serine residues in chronic lymphocytic leukemia (Frank, DA, et al., J. Clin. Invest., 1997, 100, 3140-3148). STAT3 has been found to be structurally active in myeloma tumor cells in both myeloid mononuclear cells and cultures from patients with multiple myeloma. These cells are resistant to Fas-mediated cell death and express high levels of Bcl-xL. STAT3 signaling has been shown to be essential for the survival of myeloma tumor cells by conferring resistance to apoptosis (Catlett-Falcone, R. et al., Immunity, 1999, 10, 105-115). On the other hand, recently, IL-6 is ideally secreted in a group of cancer patients induced by Ras, including pancreatic cancer, and the removal of IL-6 inhibits tumor cell growth and angiogenesis by Ras as well as reducing tumor size. Has been reported (Brooke Ancrile et al., Gene & Development, 2007, 21, 1714-1719). In addition, the gp130 / JAK / STAT3 pathway caused by IL-6 is expected to be a new target in anticancer therapy, as it has been shown that STAT3 is activated by IL-6 overexpression in EGFR-mutated lung adenocarcinoma (Sizhi). Paul Gao et al., J. Clin.Invest. 2007, 117, 38463856).

Meanwhile, Curcuma longa L) and Curcuma aromatica L are perennial grasses of the Zingiberaceae, native to tropical Asia, cultivated in all regions except southern China and mountainous areas of northern Korea. Ingredients include turmerone, zingerene, phellandrene, 1,8-cineole, bornole, dehydroturmerone, and arabinose. , Fructose, glucose, starch, organic acid, etc., root is yellow crystalline diketone compound curcumin and its derivative p-hydroxy cinnamoyl feruloyl methane And about 0.3% of a yellow pigment of p, p'-dihydroxy dicinnamoyl methane; other essential oils 1 to 5%, nonvolatile oil about 2.4%, starch 50% It contains 5% crude fiber, 4% ash and 16% moisture. All. It promotes blood circulation and is used as a treatment for bruises and fish blood as well as shoulder joint pain.It is known to exhibit blood cholesterol lowering effect and inhibitory effect on liver virus (Jung Bo-seop and Shin). Mingyo: Doha Chinese Herbal Medicine Dictionary, Younglimsa, pp874-875, 1998), especially curcumin, is known to be effective in the treatment of anti-cancer and anti-inflammatory diseases (Korea Patent Registration No. 10 / 0821490), angiogenesis inhibition, apoptosis induction, cancer metastasis suppression, cholesterol lowering, immunosuppressive effect, HIV therapeutic effect is known (Bharat B. Aggarwal et al., Phytopharmaceuticals in Cancer Chemoprevention. 2004).

In the present invention, curcumin, demethoxy curcumin, and bisdemethoxy curcumin were not detected in the stem portion (ground part) of turmeric or turmeric (Korean Patent Publication No. 2011/0004763), but the turmeric or turmeric ground portion Although the extract, or a fraction thereof, inhibited the STAT3 activation induced by IL-6 and confirmed that the activity of inhibiting the IL-6 signaling system was excellent, the base was used only for a long time. It has been confirmed that the use of turmeric or turmeric that has been discarded without any special use can be used for the treatment of cancer or inflammatory diseases, and thus the present invention has been completed.

Accordingly, it is an object of the present invention to provide a composition for treating IL-6 induced STAT3-mediated disease comprising extracts of turmeric or turmeric ground, or nonpolar organic solvent fractions thereof as an active ingredient.

It is still another object of the present invention to provide a functional food for preventing or ameliorating IL-6 induced STAT3-mediated diseases, including extracts of turmeric or turmeric ground, or non-polar organic solvent fractions thereof.

Still another object of the present invention is to provide a method for treating IL-6 induced STAT3 mediated disease in animals other than humans, comprising administering the therapeutic composition to a subject in need thereof.

In one embodiment, the present invention relates to a composition for treating IL-6-induced STAT3-mediated disease comprising extracts of turmeric or turmeric ground, or non-polar organic solvent fractions thereof as an active ingredient.

The turmeric or turmeric extract included in the composition for treating IL-6-induced STAT3-mediated disease of the present invention includes any of all extracts, soluble extracts, dilutions or concentrates thereof, or dried products obtained at each step of the extraction process. Preferably, methanol cold needle extract of the turmeric or turmeric ground portion is used, and more preferably ethyl acetate soluble extract of methanol cold needle extract is used.

In addition, the non-polar organic solvent fraction contained in the composition includes all fractions and purified products obtained in each step of the purification treatment using the extract, any one of diluents or concentrates thereof or dried products thereof. Preferably, the hexane: acetone fraction of the methanol cold extract of turmeric or turmeric turbidity is used.

The turmeric or turmeric extract of turmeric or turmeric having an inhibitory effect on IL-6-induced STAT3 activation from the turmeric or turmeric ground can be prepared by the following method.

Specifically, the method for producing a turmeric or turmeric ground extract of the present invention includes extracting the turmeric or turmeric ground portion with water, an organic solvent or a mixed solvent thereof.

Preferably, the ground portion of turmeric or turmeric pulverized by drying for a predetermined time may be extracted according to various extraction methods such as cold needle extraction, heat extraction, ultrasonic extraction, reflux cooling extraction, and the like as known in the art. The extraction method is not particularly limited and may be extracted by room temperature or warming under conditions in which the active ingredient is not destroyed or the destruction thereof is minimized.

The turmeric or turmeric ground portion can be used without limitation, such as cultivated or commercially available, it is used to clean and dry. Organic solvents suitable for the present invention include methanol, ethanol, isopropanol, butanol, ethylene, acetone, hexane, ether, chloroform, ethyl acetate, butyl acetate, dichloromethane, N, N-dimethylformamide (DMF), dimethyl Sulfoxide (DMSO), 1,3-butylene glycol, propylene glycol or a mixed solvent thereof, and preferably a lower alcohol having 1 (C ₁ ) to 4 (C ₄ ) carbon atoms such as methanol and ethanol, more preferably. May be extracted using methanol.

In a preferred embodiment of the present invention, the ground portion of turmeric or turmeric is washed, dried and ground in a grinder to powder, and then at 2 to 20 times, preferably 3 to 5 times the weight of the ground powder of dried turmeric or turmeric. After extracting with a volume of water, an organic solvent or a mixed solvent thereof using a method such as hot water extraction, cold extraction, reflux cooling extraction or ultrasonic extraction at about 15 to 100 ° C. for about 12 hours to 4 days, and then the upper layer by vacuum filtration. Recover the liquid. This extraction process may be repeated several times, preferably by repeating twice to collect the supernatant, which may be concentrated under reduced pressure or lyophilized to obtain a ground extract of turmeric or turmeric.

In addition, by obtaining a highly active non-polar organic solvent fraction from the turmeric extract of turmeric or turmeric contained in the composition of the present invention, and further isolated by chromatography or the like method to inhibit the IL-6 induced STAT3 activation effect according to the present invention Having turmeric or turmeric fractions can be separated.

Specifically, the method for purifying the turmeric or turmeric fraction from the ground portion of turmeric or turmeric according to the present invention comprises the steps of: 1) fractionating the ground portion extract of turmeric or turmeric with a nonpolar organic solvent to obtain a nonpolar organic solvent soluble extract; And 3) purifying the obtained non-polar organic solvent soluble extract by chromatography.

In the step 1), water is added to the ground extract of turmeric or turmeric and suspended, and fractional extraction is performed sequentially using a nonpolar organic solvent to obtain a nonpolar organic solvent soluble extract. At this time, a conventional fractional extraction method can be used, and preferably a fractionation funnel can be used. Non-polar organic solvents suitable for the present invention include hexane, ether, dichloromethane, chloroform, ethyl acetate, or a mixed solvent thereof, and preferably fractional extraction using ethyl acetate.

Step 2) is a step of separating the turmeric or turmeric fraction by purifying the obtained non-polar organic solvent soluble extract of turmeric or turmeric by chromatography. In the present invention, the active ingredient can be separated by performing chromatography on the above-mentioned nonpolar organic solvent soluble extract of turmeric or turmeric, and the type and developing solvent of the chromatography column can be variously controlled.

According to an embodiment of the present invention, 3 l of ethanol was added to 1 kg of powdered turmeric or turmeric ground, followed by cold extraction for 3 days at room temperature, followed by filtration and concentration under reduced pressure to obtain 60 g of turmeric or turmeric crude extract. Fractional extraction of the extract with ethyl acetate yielded 12.73 g of a non-polar organic solvent soluble extract. After concentration under reduced pressure, silica gel column chromatography (hexane: acetone = 100/0 to 0/100 concentration gradient) was performed to obtain 900 mg of a fraction.

In addition, the therapeutic composition of the present invention may include a pharmaceutically effective amount of the above-ground extract of turmeric or turmeric, a nonpolar organic solvent fraction thereof alone or may include one or more pharmaceutically acceptable carriers, excipients or diluents. have.

As used herein, the term "IL-6-induced STAT3-mediated disease" refers to a disease mediated by excessive activation of IL-6, which is known to be associated with an existing inflammatory response, and excessive activation of STAT3, which is known to be involved in cancer induced. do.

In the present invention, the term "cancer" refers to a condition in which normal cell division, differentiation and death control functions occur, abnormally overproliferating, invading surrounding tissues and organs, forming agglomerates, and destroying or modifying existing structures. Examples include pancreatic cancer, breast cancer, prostate cancer, brain tumor, head and neck cancer, melanoma, myeloma, leukemia, lymphoma, liver cancer, gastric cancer, colon cancer, bone cancer, uterine cancer, ovarian cancer, rectal cancer, esophageal cancer, small intestine cancer, anal muscle cancer , Colon cancer, fallopian tube carcinoma, endometrial carcinoma, cervical carcinoma, vaginal carcinoma, vulvar carcinoma, Hodgkin's disease, bladder cancer, kidney cancer, ureter cancer, renal cell carcinoma, renal pelvic carcinoma and central nervous system tumor It doesn't work.

In the present invention, the term "inflammation" refers to a complex lesion that involves three kinds of tissue tissue defense, circulatory disorder and exudation, and tissue proliferation as one of the defense responses of biological tissues to a certain stimulus. In addition, various types of infection and expression in the in vivo defense system against irritants in metabolites in vivo, various chemical mediators are involved in the mechanism of expression of inflammation, and the pathogenesis thereof is very complicated. It is a topical protective response caused by tissue injury or destruction, which acts to destroy, weaken or mask both injurious and injurious tissues. The characteristic of this inflammation is that the microvessels are perforated, the blood components leak into the interstitial space, and the white blood cells migrate to the inflammatory tissues, usually accompanied by clinical symptoms such as erythema, edema, hyperalgesia and pain. Examples of diseases related to such inflammation are rheumatoid arthritis, osteoporosis, plasmacytosis, hyperimmunoglobulinemia, anemia, nephritis, cachexia, herders disease, vasculitis, multiple sclerosis, uveitis, chronic thyroiditis, delayed hypersensitivity, atopic dermatitis Dermatitis, systemic erythematoses, Crohn's disease, pancreatitis, psoriasis, combustive idiopathic atrophy, diabetes and Alzheimer's, and the like.

In the present invention, the term "prevention" refers to the induction of IL-6 by administration of a composition for the prevention or treatment of IL-6 induced STAT3-mediated diseases, which comprises turmeric or turmeric ground extract, nonpolar organic solvent fraction thereof as an active ingredient. By any action that inhibits or delays the development of a STAT3-mediated disease.

In the present invention, the term "treatment" refers to IL-6 induction by administration of a composition for the prevention or treatment of IL-6 induced STAT3-mediated diseases, which comprises turmeric or turmeric ground extract, nonpolar organic solvent fraction thereof as an active ingredient. Any action that improves or beneficially changes the symptoms of a STAT3-mediated disease.

As used herein, the term "pharmaceutically effective amount" means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment, and the effective dose level refers to a patient's sexually transmitted disease, age, type of disease, severity, It can be determined according to the activity of the drug, sensitivity to the drug, the time of administration, the route of administration and the rate of release, the duration of treatment, factors including the concurrent drug and other factors well known in the medical field. The therapeutic compositions of the present invention may be administered as individual therapeutic agents or in combination with other therapeutic agents and may be administered sequentially or simultaneously with conventional therapeutic agents. In addition, the therapeutic composition of the present invention may be administered in a single or multiple doses. Taking all of the above factors into consideration, it is important to administer an amount that can obtain the maximum effect in a minimum amount without side effects, and can be easily determined by those skilled in the art. Specifically, the therapeutic composition of the present invention is preferably oral administration or intravenous administration.

Examples of pharmaceutically acceptable carriers, excipients and diluents that may be used in the therapeutic compositions of the invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate , Gelatin, calcium phosphate, calcium silicate, calcium carbonate, cellulose, methyl cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxy benzoate, talc, magnesium stearate, mineral oil and the like.

The pharmaceutical composition of the present invention may be used in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, oral dosage forms, external preparations, suppositories, and sterile injectable solutions according to conventional methods. . When formulated, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents and surfactants are usually used. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and such solid preparations may contain at least one excipient such as starch, calcium carbonate, sucrose or lactose, gelatin in the therapeutic composition. It is prepared by mixing. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid preparations for oral administration include suspensions, liquid solutions, emulsions, and syrups, and include various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin. Can be. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories. As the non-aqueous solvent and suspending agent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate and the like can be used. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.

In a preferred embodiment of the present invention, the present invention relates to the above extract of turmeric or turmeric, whose nonpolar organic solvent fraction inhibits the expression of the protein induced by IL-6 (FIGS. 1 and 2), and IL-6 induced STAT3 Inhibiting the phosphorylation of (Fig. 3), it was confirmed to inhibit the migration into the nucleus of phosphorylated STAT3 (Fig. 4). It was also confirmed that the expression of SOCS-3 induced by STAT3 was also inhibited.

Therefore, the pharmaceutical composition according to the present invention contains turmeric or turmeric extract, which has an inhibitory effect on IL-6 induced STAT3 activation, and a nonpolar organic solvent fraction thereof as an active ingredient, which is useful for the prevention or treatment of IL-6 induced STAT3 mediated diseases. It is expected to be able to be used as well as to prevent or treat the symptoms or complications caused thereby.

As another aspect, the present invention relates to a method for treating IL-6 induced STAT3 mediated disease in animals other than humans, comprising administering the therapeutic composition to a subject in need thereof.

The method of treatment according to the present invention does not mean that a method of treating an animal other than a human, but such a treatment method is ineffective in humans. In addition, in the case of humans, considering that the disease can be improved by administration of the therapeutic composition according to the present invention that inhibits IL-6-induced STAT3 activation in cells, it is sufficiently used in the treatment of humans Can lose.

The term "animal except human" in the present invention refers to horses, sheep, except for humans with diseases whose symptoms may be improved by administration of a therapeutic composition according to the invention that inhibits IL-6 induced STAT3 activation in cells. Animals such as pigs, goats, camels, antelopes and dogs. IL-6-induced STAT3-mediated diseases, such as cancer, by administering to animals other than humans a therapeutic composition comprising turmeric or turmeric extract having an inhibitory effect on IL-6-induced STAT3 activation, and a nonpolar organic solvent fraction thereof as an active ingredient. And inflammatory diseases can be effectively prevented and treated.

The term "administration" in the present invention means introducing a predetermined substance into the animal by any suitable method, and the route of administration of the therapeutic composition according to the present invention is oral or via any general route as long as it can reach the target tissue. Parenteral administration. In addition, the therapeutic composition according to the present invention can be administered by any device that the active ingredient can move to the target cell.

The preferred dosage of the therapeutic composition according to the present invention varies depending on the condition and the weight of the patient, the degree of disease, the type of drug, the administration route and the period of time, but can be appropriately selected by those skilled in the art. However, for the desired effect, the pharmaceutical composition of the present invention is preferably administered at a dose of 50 to 1000 mg / kg, preferably 100 to 500 mg / kg per day, and the linolanol compound is administered at a dose of 1 to 10 mg per day / kg, preferably 1 to 5 mg / kg. Administration may be administered once a day or may be divided several times.

As another aspect, the present invention provides a functional food for preventing or ameliorating IL-6 induced STAT3-mediated diseases, including extracts of turmeric or turmeric ground, or nonpolar organic solvent fractions thereof.

Specifically, the ground extract of turmeric or turmeric according to the present invention, a nonpolar organic solvent fraction thereof may be added to food or beverage for the purpose of improving or preventing IL-6 induced STAT3-mediated diseases, but the type of food is not particularly limited. For example, various foods such as confectionery, bread, and noodles, drinks such as water, soft drinks, fruit drinks, gums, teas, vitamin complexes, seasonings, and health functional foods. At this time, the amount of the extract or fraction in the food or beverage is generally in the case of the dietary supplement composition of the present invention can be added to 0.01 to 15% by weight, preferably 0.1 to 5% by weight of the total food weight, the health beverage composition It may be added to the ratio of 0.01 to 5.0 g, preferably 0.01 to 1.0 g based on 100 ml. The health functional food of the present invention thus obtained is a food which can fully utilize the health prophylactic and therapeutic effects of the extract or fraction according to the present invention because it contains the composition of the present invention.

The health beverage composition of the present invention is not particularly limited to the liquid component except for containing the extracts or fractions as essential ingredients in the indicated proportions, and may contain various flavors or natural carbohydrates as additional ingredients, such as ordinary drinks. . The above-mentioned natural carbohydrates include monosaccharides such as glucose, fructose and the like: disaccharides such as maltose and sucrose; Polysaccharides such as dextrin, cyclodextrin, and the like; And sugar alcohols such as xylitol, sorbitol, erythritol, and the like. As flavoring agents other than those mentioned above, natural flavoring agents (tauumakin, stevia extract, etc.), and synthetic flavoring agents (saccharin, aspartan, etc.) can be advantageously used. The proportion of said natural carbohydrate is generally from about 0.1 mg to 2.0 g, preferably from about 0.1 mg to 1.0 g per 100 ml of the composition of the present invention.

 The health functional food of the present invention is a step of adding the above-mentioned extract or compound of the present invention during the manufacturing process of the base food or by adding the extract or fraction of the present invention as described above after the preparation of the base food. It can be obtained easily by adding. At this time, a taste and odor correction agent may be added as needed.

In addition to the above, the health functional food of the present invention includes various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, 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 adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated beverages, and the like. In addition, the health functional food of the present invention may contain natural fruit juice and fruit flesh for the production of fruit juice drinks and vegetable drinks. Such components may be used independently or in combination. The proportion of such additives is generally selected within the range of about 20 parts by weight or less per 100 parts by weight of the health functional food of the present invention.

Turmeric or turmeric ground extract according to the present invention, its nonpolar organic solvent fractions effectively inhibit IL-6 induced STAT3 activation, and thus can be effectively used for the prevention and treatment of IL-6 induced STAT3 mediated diseases such as cancer or inflammatory diseases. have.

FIG. 1 is a graph showing the inhibitory activity of IL-6-induced luciferase expression of the methanol extract and ethyl acetate fraction of the ground wart.
Figure 2 is a graph showing the expression inhibitory activity of IL-6 induced luciferase of turmeric ground ethyl acetate fraction.
Figure 3 is a graph showing the IL-6 induced STAT3 phosphorylation inhibitory activity of turmeric ground ethyl acetate fraction.
Figure 4 is a photograph showing the effect of inhibiting migration in STAT3 nuclei phosphorylated by IL-6 of turmeric ground ethyl acetate fraction.
5 is a graph showing SOCS-3 expression inhibitory activity induced by STAT3 of turmeric ground ethyl acetate fraction.

Hereinafter, the present invention will be described in more detail with reference to examples. However, these examples are for illustrative purposes only, and the scope of the present invention is not limited to these examples.

Example 1 Extraction and Purification of an Active Substance with IL-6 Induced STAT3 Activation Inhibitory Activity from Turmeric or Turmeric

 Turmeric or turmeric ground (leaves and stems) were washed thoroughly with water, dried in the shade, and then powdered under the Waring brand. The powdered samples were each put in methanol, extracted by cold extraction at room temperature for 3 days, filtered under reduced pressure with a filter paper (Watman, USA), and the filtrate was extracted with methanol in a vacuum rotary concentrator at room temperature, followed by turmeric and 60 g of each crude extract of turmeric were obtained.

In order to isolate and purify the active substance from the crude extract, turmeric crude extract is suspended in 1 L of water and mixed by adding the same amount of ethyl acetate. The process is repeated four times, and the water-soluble fraction is 1 L and ethyl acetate soluble. After obtaining 4 L of fraction, the ethyl acetate soluble fraction was concentrated under reduced pressure to give 12.73 g of an ethyl acetate soluble extract.

12.73 g of the ethyl acetate soluble extract obtained above were subjected to column chromatography of silica gel using a step gradient solvent system consisting of hexane: acetone = (100/0 to 0/100, v / v). The active fractions were separated to yield 900 mg of ethyl acetate fractions.

< Example  2> curcuma  or Turmeric Local Curcuminoids  Investigation of the content of compounds

The concentration of curcumin, demethoxycurcumin and bisdemethoxycurcumin in order to confirm the presence of curcuminoid compounds in the ground portion of each turmeric or turmeric through the present Example was 15.625, 31.25, 62.5, 125, 250, 500 and It was prepared at 1000 μg / ml and analyzed under the following conditions to obtain a calibration line.

The HPLC analysis used in this example used our pump system with an Agilent 1200 Series HPLC instrument. The detector used in this example was tested using the company's variable wavelength detector (VWD) at the best analytical detection wavelength of 260 nm, and the solvent flow rate was 1.0 ml / min. The sample injection amount was 10 μl, and was prepared at a concentration of 10 mg / ml each. Columns of HPLC analysis were analyzed using ZORBAX-SB-18 (5 μm, 150 mm × 4.6 mm). Analysis of the mobile phase was performed with 20% acetonitrile, 0 min; under polarization conditions of water (containing 0.1% TFA) and acetonitrile (containing 0.1% TFA); 25% acetonitrile, 10 min; 35% acetonitrile, 20 min; 50% acetonitrile, 30 min; 60% acetonitrile, 40 min; 70% acetonitrile, 50 min; 100% acetonitrile, 60 min.

The contents of curcumin, demethoxy curcumin and bisdemethoxy curcumin in methanol extracts of turmeric or turmeric were determined on the basis of the above-mentioned calibration curve.

Sample used Content (g / kg, extract) Curcumin Demethoxycurcumin Bisdemethoxycurcumin Tube Root Ethanol Extract 17.0 5.3 3.4 Stem Ethanol Extract - - - Root stem ethanol extract 2.8 0.4 6.8

As shown in Table 1, curcumin 17.0 g / kg (extract), demethoxy curcumin 5.3 g / kg (extract), and bisdemethoxy curcumin 3.4 g / kg (extract) were detected at the root root site, and at the root stem site. Curcumin 2.8 g / kg (fraction), demethoxycurcumin 0.4 g / kg (fraction), and bisdemethoxycurcumin 6.8 g / kg (fraction), but at the stem site curcumin, demethoxycurcumin and bisdemethoxycurcumin Was not detected.

In addition, similar results were also confirmed in the extract of each part of turmeric.

These results indicate that curcumin and its derivatives are not present in the extract of turmeric or turmeric, and the efficacy of the extracts and fractions according to the invention is caused by an active substance different from curcumin.

< Example  3> extract of the present invention and Fractions IL -6 Influence on induction

<3-1> Turmeric  Ground extract and Fraction IL -6 induction Luciferase  Inhibitory Activity Assay

In order to investigate the effect of the ground extract and fractions of turmeric of the present invention on the expression mechanism of the IL-6-related protein, the experiment was carried out as follows.

After dispensing HepG2 cells (ATCC HB-8065) at 5 x 10 ⁴ cells / well in 96 well plates, 10% FBS (v / v), 60.0 mg / L kanamycin sulfate (Gamyco., USA) and 2.0 DMEM culture medium containing g / l sodium hydrogen carbonate (NaHCO ₃ ; Sigma, USA) was used to incubate at 37 ° C. with 5% CO ₂ until 80% confluent in the culture dish. Subsequently, 50 μl of serum-free medium was exchanged, and a mixture of 0.1 μg pSTAT3-TA-Luc (Clontech, Calif.) And 0.3 μl lipofectamin reagent (Invitrogen, USA) was added to each well and reacted for 3 hours. -TA-Luc was transfected, and further changed to freshly prepared 200 μl DMEM culture medium and incubated for an additional 24 hours.

The transfected cells were cultured serum-free (serum starvation) with 1% BSA / DMEM, and the samples were treated for 1 hour as follows, followed by incubation for 3 hours with the addition of 10 ng / ml IL-6 (R & D system, USA). .

1: negative control (non-treated);

2: positive control (IL-6 10 ng / mL);

3: extracts and fractions (10, 30 μg / mL); And

4: Genistein (60 μM);

The reaction cells were washed with PBS, 50 μl lysis buffer (luciferase assay system, promega, USA) was added and stirred for 1 minute, and then 30-100 μl luciferase substrate (luciferase assay system, promega, USA) was added thereto. The degree of color development was measured in 5 minutes with a luminometer (EG & G BERTHOLD, USA) and is shown in FIG. 1.

Figure 1 is a graph showing the expression inhibitory activity of IL-6 induced luciferase of turmeric ground methanol extract and ethyl acetate fraction. As shown in Figure 1, both methanol extract and ethyl acetate fractions of turmeric showed less than 0.013 luciferase activity, lower than 0.023 or more of the positive control treated only IL-6.

These results indicate that methanol extract and ethyl acetate fraction of turmeric have the effect of inhibiting the expression of STAT3 luciferase induced by IL-6.

<3-2> Turmeric  Ground extract and Fraction IL -6 induction Luciferase  Inhibitory Activity Assay

In order to investigate the effect of the turmeric extract and fractions of the turmeric extract of the present invention on the expression mechanism of the protein related to IL-6, the experiment was carried out as follows.

Hep3B cells (ATCC HB-8064) were transfected with pStat3-Luc and pcDNA3.1 (+) (Clontech laboratories, Palo Alto, Calif.) With lipofectamin plus (Invitrogen, Carlsbad, Calif., USA). . Two days later, hygromycin was treated (100 µg / mL) to obtain a clone stably expressing luciferase. Whether luciferase was stably expressed in this clone was confirmed by luciferase activity analysis.

The transfected cells were serum-free (serum starvation) with DMEM (GIBCO 119950965) and the samples were treated for 1 hour, followed by incubation for 12 hours with the addition of 10 ng / mL IL-6 (R & D system, USA). .

1: negative control (non-treated);

2: positive control (IL-6 10 ng / mL);

3: fractions (10, 30, 60 μg / mL);

The reaction cells were washed with PBS, 50 μL lysis buffer (luciferase assay system, promega, USA) was added and stirred for 20 minutes, 30-100 μL of luciferase substrate was added, and the color development was performed with a luminometer for 5 minutes. Measured in, shown in FIG.

Figure 2 is a graph showing the expression inhibitory activity of IL-6 induced luciferase of turmeric ground ethyl acetate fraction. As shown in Figure 2, ethyl acetate fraction of turmeric is similar to the activity of about 1.1 of the positive control treated only IL-6 at 10 μg / mL concentration, but the activity is inhibited with increasing concentration at 60 μg / mL concentration It was confirmed that about 0.1 activity was shown.

These results indicate that the ethyl acetate fraction of turmeric has a concentration-dependent effect of inhibiting the expression of STAT3 luciferase induced by IL-6.

< Example  4> The extract of the present invention and Fractions IL -6 induction STAT3  Investigate the effect on phosphorylation

In order to investigate the effect of extracts and fractions of the present invention on phosphorylation, a mechanism regulating the activity of IL-6 induced STAT3 protein, experiments were carried out as follows.

Hep3B cells were dispensed at 5 × 10 ⁵ cells / well in 6-well plates, cultured 80% full in a culture dish, exchanged with serum-free medium for 12 hours, and the samples were treated for 60 minutes as follows.

1: negative control (non-treated);

2: positive control (IL-16 10 ng / mL);

3: fractions (10, 30, 60 μg / mL) and,

8: Genestein treated group (60 μΜ).

After 20 ng / mL IL-6 treatment for 20 minutes, 40 μL lysis buffer (pH 8, 20 mM Tris-HCl, 137 mM NaCl, 10% glycerol, 1% Triton X-100, 1 mM Na ₃₎ Cells were lysed with VO ₄ , 2 mM EDTA, 1 mM PMSF, 20 mM leupeptin, 20 mg / mL aprotonin; Sigma, USA) and then centrifuged at 13000 g for 15 minutes. To obtain a supernatant of dissolved protein. Protein concentration was quantified using a DC protein test kit (Bio-Rad, USA), and electrophoresed at 175 mA for 2 hours by loading the protein on a 4-12% SDS polyacrylamide gel (SDS-PAGE). After electrophoresis, the protein of the gel was transferred to a PVDF membrane (Westran S, pore size 0.2 mm; Whatman, USA) at 35 V for 90 minutes. Transfer the membrane to Tris-buffer (T-TBS; 50 mM Tri-HCl, pH 7.6, 150 mM NaCl, 0.2% Tween-20, 5% skim milk; Sigma, USA) for 1 hour at room temperature And washed 5 times with T-TBS. The membrane was treated with polyclonal antibody of phospho-STAT3 (1: 1000 dilution) at 4 ° C. for 12 hours as a primary antibody. After washing 5 times with T-TBS, HRP-binding anti-mouse antibody (1: 5000 dilution) was reacted with secondary antibody for 1 hour. After washing with T-TBS, the film was developed using an ECL kit (Amersham, USA) in the dark, and the results of the turmeric ground ethyl acetate fraction are shown in FIG. 3.

Figure 3 is a graph showing the IL-6 induced STAT3 phosphorylation inhibitory activity of turmeric ground ethyl acetate fraction. As shown in FIG. 3, when compared with the same amount of STAT3 protein, ethyl acetate fraction of turmeric induced similar phosphorylation as the positive control treated with IL-6 only at 10 μg / mL, but phosphorylation increased with increasing concentration. It was confirmed to be inhibited. In addition, it was confirmed that the extract and fraction of turmeric also inhibited the phosphorylation of STAT3 in a concentration-dependent manner (not shown).

These results show that ethylacetate fraction of turmeric inhibits the activity of STAT3 by inhibiting the phosphorylation of STAT3 induced by IL-6. This suggests that it has the effect of concentration dependently inhibiting the submechanisms mediated by the activity of STAT3.

< Example  5> extracts of the present invention and Fractions IL -6 induced phosphorylation STAT3 of Nucleus  Investigate impact on migration

In order to investigate the effects of the extracts and fractions of the present invention on the migration into the nucleus of the intracellular action of IL-6 induced phosphorylated STAT3 protein, the experiment was carried out as follows.

Hep3B cells were dispensed at 2 × 10 ⁴ cells / well in an 8 well plate and cultured 80% full in a culture dish, and then exchanged with a serum-free medium for an additional 12 hours, and the samples were treated for 60 minutes as follows.

1: negative control (non-treated);

2: positive control (IL-16 10 ng / mL);

3: fraction (30 μg / mL), and

4: Genestein treated group (60 μΜ).

After reacting for 10 hours with 10 ng / mL IL-6, the supernatant was removed, washed three times with PBS, and then treated with 200 μl of 4% paraformaldehyde to fix cells. After washing twice, cells were permeated with 100% methanol. Block with 1% BSA and react with STAT3 (1: 200 dilution) polyclonal antibody overnight at 4 ° C. overnight at 4 ° C., wash three times with PBS for 5 minutes, then use FITC-binding anti-rabbit antibody with secondary antibody. 1: 1000 dilution) for 1 hour. After rinsing three times with PBS for 5 minutes, the slides were fixed using a slowfade gold antifade reagent, and the change in the nuclear distribution of STAT3 was observed using a carl zeiss LSM 510 META confocal microscope. Results of the turmeric ground ethyl acetate fractions are shown in FIG.

Figure 4 is a photograph showing the effect of inhibiting migration in STAT3 nuclei phosphorylated by IL-6 of turmeric ground ethyl acetate fraction. As shown in FIG. 4, when ethyl acetate fraction of turmeric is treated at 30 μg / mL concentration, STAT3 is concentrated in the nucleus in the IL-6 treated control group, whereas turmeric ethyl acetate fraction is used. The treated group was found to be evenly distributed in the cytoplasm similar to the negative control. In addition, similar results were also observed in the treatment of extracts and fractions of turmeric (not shown).

These results show that ethylacetate fraction of turmeric inhibits the expression of genes expressed by activation of STAT3 by inhibiting the migration of IL-6 induced phosphorylated STAT3 into the nucleus. This indicates that they have the effect of inhibiting submechanisms mediated by the activity of STAT3.

< Example  6> extract of the present invention and Fractions STAT3  Induced SOCS Influence on -3 expression

In order to investigate the effect of the extracts and fractions of the present invention on the expression of SOCS-3 known to be induced by the activation of STAT3 protein, experiments were carried out as follows.

Hep3B cells were dispensed at 5 × 10 ⁴ cells / well in 6-well plates, cultured 80% full in a culture dish, exchanged with serum-free medium for 12 hours, and the samples were treated for 60 minutes as follows.

1: negative control (non-treated);

2: positive control (IL-16 10 ng / mL);

3: fractions (10, 30, 60 μg / mL) and,

8: Genestein treated group (60 μΜ).

After 20 ng / mL IL-6 treatment for 6 hours, the cells were collected in a tube and centrifuged to remove the medium, washed once with PBS, and then R & M Mini Elute Clean Up Kit (RNeasy Mini Elute RNA was extracted using a cleanup kit. The concentration and purity of RNA were measured by 2100 Bioanalyzer system (Agilent Technologies) and cDNA was synthesized using Maxim RT PreMix (Random primer; iNtRON Biotechnology, INC).

The expression level of SOCS-3 was measured by real-time PCR using a Taqman PCR master mix kit (Applied Biosystem). Shown in

5 is a graph showing SOCS-3 expression inhibitory activity induced by STAT3 of turmeric ground ethyl acetate fraction. As shown in Figure 5, when treated with ethyl acetate fraction of turmeric at concentrations of 10, 30 and 60 μg / mL, the expression level of about 50, 30, 10, respectively, showed more than 90 of the positive control treated with IL-6 It was confirmed that the expression is low depending on the concentration compared to the degree of expression. In addition, similar results were also observed in the treatment of extracts and fractions of turmeric (not shown).

These results indicate that the ethyl acetate fraction of turmeric has the effect of inhibiting the expression of SOCS-3 induced by phosphorylated STAT3.

Putting together the results of the above examples, the turmeric or turmeric extract and nonpolar organic solvent fractions thereof according to the present invention are used for cancer and rheumatoid arthritis, osteoporosis, plasmacytosis, hyperimmunoglobulinemia caused by excessive activity of IL-6 induced STAT3. , Anemia, nephritis, cachexia, pastoral disease, vasculitis, multiple sclerosis, uveitis, chronic thyroiditis, hypersensitivity, contact dermatitis, atopic dermatitis, systemic erythematosus, Crohn's disease, pancreatitis, psoriasis, combustive idiopathic atrophy, diabetes and It can be effectively used for the prevention and treatment of inflammatory diseases such as Alzheimer's disease.

Examples of formulations for the composition of the present invention are illustrated below.

Preparation Example 1 Preparation of Pharmaceutical Formulation

Pharmaceutical formulations comprising turmeric or turmeric extract of turmeric or turmeric according to the present invention as non-polar organic solvent fractions thereof as an active ingredient were prepared as follows.

<1-1> Preparation of powder

2 g of turmeric or turmeric extract, non-polar organic solvent fractions thereof

Lactose 1 g

After mixing the above components, the airtight cloth was filled to prepare a powder.

<1-2> Preparation of tablets

100 mg of turmeric or turmeric extract, nonpolar organic solvent fractions thereof

Corn starch 100 mg

Lactose 100 mg

2 mg magnesium stearate

After mixing the above components, tablets were prepared by tableting according to a conventional tablet production method.

&Lt; 1-3 > Preparation of capsules

100 mg of turmeric or turmeric extract, nonpolar organic solvent fractions thereof

Corn starch 100 mg

Lactose 100 mg

2 mg magnesium stearate

After mixing the above components, the capsule was prepared by filling in gelatin capsules according to the conventional capsule preparation method.

<1-4> Preparation of Injection Solution

10 μg / ml ground extract of turmeric or turmeric, its nonpolar organic solvent fraction

Dilute hydrochloric acid BP until pH 3.5

Injectable sodium chloride BP up to 1 ml

Dissolve the coriander seed extract, its nonpolar organic solvent fraction, or the linarol compound isolated therefrom in an appropriate volume of sodium chloride BP for injection, and adjust the pH of the resulting solution to pH 3.5 using dilute hydrochloric acid BP. Afterwards, the volume was adjusted using sodium chloride BP for injection and mixed well. The solution was filled into a 5 ml Type I ampoule of clear glass, encapsulated under an upper grid of air by dissolving the glass, and sterilized by autoclave at 120 ° C. for at least 15 minutes to prepare an injection solution.

Preparation Example 2 Preparation of Food

Food products containing the extract of turmeric or turmeric according to the present invention and its non-polar organic solvent fractions were prepared as follows.

<2-1> Production of flour food

Turmeric or turmeric extract according to the present invention, 0.1 to 10.0 parts by weight of nonpolar organic solvent fractions thereof is added to flour, and the bread, cake, cookies, crackers and noodles are prepared by conventional methods using this mixture for health promotion. Food was prepared.

<2-2> Production of soups and gravies

The ground extract of turmeric or turmeric according to the present invention, 0.1 to 1.0 parts by weight of a nonpolar organic solvent fraction thereof was added to soups and broth to prepare meat products for health promotion, soups and broths in a conventional manner.

<2-3> Preparation of ground beef

Ground beef extract of turmeric or turmeric according to the present invention, 10 parts by weight of the non-polar organic solvent fraction thereof was added to the ground beef to prepare a ground beef for health promotion in a conventional manner.

<2-4> Production of Dairy Products

The ground extract of turmeric or turmeric according to the present invention, 0.1 to 1.0 parts by weight of a nonpolar organic solvent fraction thereof was added to milk, and various dairy products such as butter and ice cream were prepared in a conventional manner using the milk.

&Lt; 2-5 >

Brown rice, barley, glutinous rice, and yulmu were dried by a known method and dried, and the mixture was granulated to a powder having a particle size of 60 mesh. Black soybeans, black sesame seeds, and perilla seeds were steamed and dried by a conventional method, and then they were prepared into powder having a particle size of 60 mesh by a pulverizer. The ground extract of turmeric or turmeric and the nonpolar organic solvent fraction thereof according to the present invention were decompressed and concentrated in a vacuum concentrator, and dried by spraying and drying with a hot air dryer to pulverize the dried product to a particle size of 60 mesh to obtain a dry powder.

The grains, seeds, and ground powder extracts of turmeric or turmeric according to the present invention, and dry powders of the nonpolar organic solvent fractions thereof prepared in the following ratio, were prepared in a conventional manner.

Cereals (30 parts by weight brown rice, 15 parts by weight barley, 20 parts by weight of barley)

Seeds (7 parts by weight perilla, 8 parts by weight black beans, 7 parts by weight black sesame)

Ground powder extract of turmeric or turmeric, dry powder of nonpolar organic solvent fractions (1 part by weight)

Manor (0.5 parts by weight)

(0.5 parts by weight)

Preparation Example 3 Preparation of Beverage

A beverage comprising a turmeric or turmeric extract of turmeric or turmeric according to the present invention and a nonpolar organic solvent fraction thereof was prepared as follows.

<3-1> Preparation of health drink

Substances such as liquid fructose (0.5%), oligosaccharides (2%), sugars (2%), salts (0.5%), water (75%) and ground extracts of turmeric or turmeric according to the present invention, nonpolar organic solvent fractions thereof After homogeneous mixing and sterilization, it was packaged in small packaging containers such as glass bottles and plastic bottles to prepare a healthy beverage.

<3-2> Preparation of Vegetable Juice

0.5 g of turmeric or turmeric ground extract according to the present invention and 0.5 g of nonpolar organic solvent fractions thereof were added to 1,000 ml of a vegetable juice such as tomato or carrot to prepare vegetable juice for health promotion in a conventional manner.

<3-3> Preparation of Fruit Juice

0.1 g of turmeric or turmeric extract of turmeric or turmeric according to the present invention and a nonpolar organic solvent fraction thereof were added to 1,000 ml of a fruit juice such as apple or grape to prepare fruit juice for health promotion in a conventional manner.

Claims (9)

A composition for the treatment of IL-6 induced STAT3-mediated diseases comprising extracts of turmeric or turmeric ground, or nonpolar organic solvent fractions thereof as an active ingredient.
The method of claim 1,
The extract is a composition extracted from the ground portion of turmeric or turmeric using water, an organic solvent or a mixed solvent thereof.
The method of claim 2,
The organic solvent is methanol, ethanol, isopropanol, butanol, ethylene, acetone, hexane, ether, chloroform, ethyl acetate, butyl acetate, dichloromethane, N, N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO ), 1,3-butylene glycol, propylene glycol and mixed solvents thereof.
The method of claim 1,
Wherein the non-polar organic solvent fraction is the extract is extracted with a non-polar organic solvent selected from the group consisting of hexane, ether, dichloromethane, chloroform, ethyl acetate and a mixed solvent thereof.
The method of claim 1,
A pharmaceutical composition characterized in that the IL-6 induced STAT3-mediated disease is cancer or an inflammatory disease.
The method of claim 5,
The cancer includes pancreatic cancer, breast cancer, prostate cancer, brain tumor, head and neck carcinoma, melanoma, myeloma, leukemia, lymphoma, liver cancer, gastric cancer, colon cancer, bone cancer, uterine cancer, ovarian cancer, rectal cancer, esophageal cancer, small intestine cancer, anal muscle cancer, colon cancer, Pharmaceutical composition selected from the group consisting of fallopian tube carcinoma, endometrial carcinoma, cervical carcinoma, vaginal carcinoma, vulvar carcinoma, Hodgkin's disease, bladder cancer, kidney cancer, ureter cancer, renal cell carcinoma, renal pelvic carcinoma and central nervous system tumor Composition.
The method of claim 5,
The inflammatory diseases include rheumatoid arthritis, osteoporosis, plasmacytosis, hyperimmunoglobulinemia, anemia, nephritis, cachexia, pastoral disease, vasculitis, multiple sclerosis, uveitis, chronic thyroiditis, delayed hypersensitivity, contact dermatitis, atopic dermatitis, systemic The pharmaceutical composition is selected from the group consisting of erythematoses, Crohn's disease, pancreatitis, psoriasis, combustive idiopathic atrophy, diabetes and Alzheimer's.
Functional food for improving IL-6-induced STAT3-mediated disease, comprising extracts of turmeric or turmeric ground, or nonpolar organic solvent fractions thereof.
A method for treating IL-6 induced STAT3-mediated disease in an animal other than a human, comprising administering the therapeutic composition according to any one of claims 1 to 7 to an individual in need thereof.

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