KR102037448B1 - Composition for preventing, improving or treating uterine cell hyperplasia disease comprising dehydrocostus lactone - Google Patents

Abstract

The present invention relates to a pharmaceutical composition and health functional food for preventing, ameliorating or treating uterine cell dysplasia, including dehydrocostus lactone or a salt thereof as an active ingredient. The dehydrocostus lactone of the present invention has an excellent effect of inducing apoptosis, inhibiting chemokine expression, and inhibiting expression of malignant factors on diseased cells or tissues such as VEGF, MMP-2 and MMP-9. It is effective in effectively preventing, ameliorating and treating uterine cell dysplasia including endometriosis. In addition, the dehydrocostus lactone of the present invention is a compound derived from natural, there is no side effect can be utilized in a variety of pharmaceutical compositions, health functional foods and the like.

Description

Composition for preventing, improving or treating uterine cell hyperplasia disease comprising dehydrocostus lactone

The present invention relates to a pharmaceutical composition and health functional food for preventing, improving or treating uterine cell dysplasia, including dehydrocostus lactone or a salt thereof as an active ingredient.

The uterus is an organ composed mainly of the fibrous muscle layer, which implants the embryo, attaches the placenta, and grows the fetus. The overall shape is the inverted western abdomen, and is divided into the upper uterine torso (uterine body) and the lower uterine neck (cervical neck). The cross section of the uterus can be divided into the endometrium where the embryo is implanted, the uterine muscular layer (uterine myometrium, uterine fascia) consisting of cells of smooth muscle (smooth muscle), and the outer uterine outer membrane (uterine envelope). The endometrium is the innermost part of the uterus and is a tissue in which the fertilized egg is implanted. The endometrium repeats proliferation and dropout according to the menstrual cycle. Dropped endometrial tissue corresponds to menstrual blood.

Endometriosis among uterine diseases is that endometrial tissue to be in the uterus exists in the abdominal cavity outside the uterus, and is known to be a common disease occurring in about 10 to 15% of women of childbearing age. Endometriosis can occur in women of all ages, from menstruation to menopause, with major symptoms associated with severe dysmenorrhea, lower abdominal pain and infertility. Endometriosis is a very frequent disease, but accurate diagnosis is often difficult before surgery, and it is known to be very difficult to treat due to its good recurrence and continuous progression. In this regard, studies on endometriosis, treatment methods, and therapeutic agents have been conducted (Korea Patent Publication No. 10-2006-0002708, 10-2006-0112709, etc.). There is still insufficient research and development on a therapeutic agent that guarantees stability.

Dehydrocostus lactone is a kind of sesquiterpene lactone and is known as a compound present in the root of Saussurea lappa Clarke, a perennial herbaceous herb. The efficacy of dehydrocostus lactone has been reported on the effect of promoting the production of collagen and hyaluronic acid (Korean Patent Publication No. 10-2013-0040262). Although there are reports, there is no known therapeutic effect of uterine related diseases of dehydrocostus lactone, and in particular, the efficacy of treating endometriosis has not been studied and reported at all.

Republic of Korea Patent Publication A No. 10-2006-0002708 Republic of Korea Patent Publication A 10-2006-0112709 Republic of Korea Patent Publication A 10-2013-0040262

An object of the present invention is to provide a pharmaceutical composition and health functional food for preventing, improving or treating uterine cell dysplasia, including dehydrocostus lactone or a salt thereof as an active ingredient.

The present invention provides a pharmaceutical composition for preventing or treating uterine cell dysplasia, comprising dehydrocostus lactone or a pharmaceutically acceptable salt thereof as an active ingredient.

Dehydrocostus lactone of the present invention is a kind of sesquiterpene lactone derived from nature, and is known as a compound present in the root of Saussurea lappa Clarke, a perennial herb. The specific structure of dehydrocostus lactone is represented by the following formula (1).

[Formula 1]

The dehydrocostose lactone of the present invention can be chemically synthesized or separated from natural substances, and may be purchased and used commercially available from home and abroad.

As used herein, the term "MCP-1" is an abbreviation for "monocyte chemoattractant protein-1" and is one of monocyte chemotactic factors for producing monocytes, vascular endothelium, glioma cell lines and the like. MCP-1 is a type of C-C chemokine and has a molecular weight of about 8,000 to 18,000.

As used herein, the term "RANTES" is an abbreviation of "regulated on activation, normal T cell expressed and secreted", also called CCL5, and is a type of representative C-C chemokines with MCP-1. RANTES exhibits lactose activity against T cells, monocytes, basophils, eosinophils, and is known to play a role in moving leukocytes to inflammation sites.

As used herein, the term “VEGF” is an abbreviation of vascular endothelial growth factor, and means a glycoprotein that specifically acts on vascular endothelial cells to promote cell proliferation or angiogenesis.

As used herein, the term "MMP-2" is an abbreviation of "matrix metalloproteinase-2" and means a type of collagen type IV called gelatinase A.

As used herein, the term "MMP-9" is an abbreviation for "matrix metalloproteinase-9" and is also called gelatinase B. MMP-9 is a type IV collagenase and belongs to the family of zinc-metal proteolytic enzymes.

As used herein, the term "Trem-2" is an abbreviation for "triggering receptor expressed on myeloid cells 2" and corresponds to a marker that is increased when macrophages are polarized to M2.

The present inventors have found that the dehydrocostus lactone of the present invention induces apoptosis and inhibits the expression of chemokines such as MCP-1, RANTES, and the malignant factors of uterine disease cells or tissues such as VEGF, MMP-2, MMP-9. Inhibition of expression was first identified, and thus the first use of dehydrocostus lactone for the prevention, improvement or treatment of uterine cell dysplasia.

Specifically, in the embodiments of the present invention, when dehydrocostus lactone was treated to 12Z endometriosis cells, it was confirmed that apoptosis was induced to effectively inhibit the growth of endometriosis cells (FIG. 1), which is a kind of chemokine It was confirmed that the expression of MCP-1 and RANTES is effectively inhibited (FIG. 2), and it is confirmed that macrophage is inhibited from moving around endometriosis cells. In addition, in other embodiments, when dehydrocostus lactone is treated to endometriosis cells, M2 polarization of endometriosis-associated macrophage (EAM) is effectively inhibited (FIG. 3). It was confirmed that the suppression, the expression of VEGF, MMP-2 and MMP-9 corresponding to the endometriosis malignant factor is effectively suppressed to confirm that the malignancy of endometriosis is suppressed (Fig. 4). In addition, it was confirmed that the expression and secretion of brain-derived neurotrophic factor (BDNF) and NGF (Nerve Growth Factor), which are pain-associated neurotrophine secreted by endometriosis cells, were reduced (FIG. 5).

The disease to be prevented, improved or treated according to the present invention is not particularly limited as long as it falls within the scope of a disease related to cervical dysplasia, but in order to exhibit better efficacy, uterine myoma, uterine adenomyosis and endometriosis are preferred. , Uterine sarcoma, uterine fibrosis, uterine hypertrophy, cervicitis, cervical dysplasia, cervical epithelial tumor, cervical cancer, endometrial cancer and cervical cancer, more preferably endometriosis Can be.

As used herein, the term “pharmaceutically acceptable salts” refers to salts that can be used pharmaceutically, even among salts in which cations and anions are bonded by electrostatic attraction, and are commonly used as metal salts and organic salts. Salts with bases, salts with inorganic acids, salts with organic acids, salts with basic or acidic amino acids, and the like. For example, as a metal salt, alkali metal salts (sodium salt, potassium salt, etc.), alkaline earth metal salts (calcium salt, magnesium salt, barium salt, etc.), aluminum salt, etc .; Salts with organic bases include triethylamine, pyridine, picoline, 2,6-lutidine, ethanolamine, diethanolamine, triethanolamine, cyclohexylamine, dicyclohexylamine, N, N-dibenzylethylenediamine Salts and the like; Salts with inorganic acids include salts with hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid, and the like; Salts with organic acids include formic acid, acetic acid, trifluoroacetic acid, phthalic acid, fumaric acid, oxalic acid, tartaric acid, maleic acid, citric acid, succinic acid, methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid and the like; Salts with basic amino acids include salts with arginine, lysine, ornithine and the like; Salts with acidic amino acids can be salts with aspartic acid, glutamic acid and the like.

The pharmaceutical composition of the present invention may further include a pharmaceutically acceptable carrier in addition to including dehydrocostus lactone or a pharmaceutically acceptable salt thereof as an active ingredient.

The kind of carrier that can be used in the present invention is not particularly limited and any carrier can be used as long as it is commonly used in the art. Non-limiting examples of the carrier include saline, sterile water, Ringer's solution, buffered saline, albumin injection solution, lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, maltodextrin, glycerol, ethanol, and the like. Can be. These may be used alone or in combination of two or more thereof.

In addition, the pharmaceutical composition of the present invention may be used, if necessary, by adding other pharmaceutically acceptable additives such as excipients, diluents, antioxidants, buffers or bacteriostatic agents, fillers, extenders, wetting agents, disintegrants, dispersants, surfactants , Binders or lubricants may be additionally added and used.

In the pharmaceutical composition of the present invention, dehydrocostus lactone or a pharmaceutically acceptable salt thereof may be included in an amount of 0.00001% to 99.99% by weight based on the total weight of the pharmaceutical composition, preferably 0.1% by weight. % To 90% by weight, more preferably 0.1% to 70% by weight, and more preferably 0.1% to 50% by weight, but is not limited thereto. It may be changed in various ways according to. If necessary, it may also be included in the total content of the pharmaceutical composition.

The pharmaceutical compositions of the present invention can be formulated and used in a variety of suitable formulations for oral or parenteral administration.

Non-limiting examples of oral formulations using the pharmaceutical compositions of the present invention include troches, lozenges, tablets, aqueous suspensions, oily suspensions, preparation powders, granules, emulsions, hard capsules, soft Capsules, syrups, or elixirs.

In order to formulate the pharmaceutical composition of the present invention for oral administration, a binder such as lactose, saccharose, sorbitol, mannitol, starch, amylopectin, cellulose or gelatin and the like; Excipients such as dicalcium phosphate and the like; Disintegrants such as corn starch or sweet potato starch; Lubricants such as magnesium stearate, calcium stearate, sodium stearyl fumarate or polyethylene glycol wax and the like can be used, and sweeteners, fragrances, syrups and the like can also be used. Furthermore, in the case of a capsule, a liquid carrier such as fatty oil may be additionally used in addition to the above-mentioned materials.

Non-limiting examples of parenteral preparations using the pharmaceutical composition of the present invention include injection solutions, suppositories, respiratory inhalation powders, spray aerosols, ointments, application powders, oils, creams and the like.

In order to formulate the pharmaceutical composition for parenteral administration, a sterile aqueous solution, a non-aqueous solvent, a suspension, an emulsion, a freeze-dried preparation, an external preparation, and the like may be used. The non-aqueous solvent and the suspension may be propylene glycol or polyethylene. Glycols, vegetable oils such as olive oil, injectable esters such as ethyloleate and the like can be used.

When formulating the pharmaceutical composition of the present invention into an injectable solution, the pharmaceutical composition of the present invention is mixed in water with a stabilizer or buffer to prepare a solution or suspension, which is intended for unit administration of ampoules or vials. It may be formulated.

When formulating the pharmaceutical composition of the present invention with an aerosol, a propellant or the like may be combined with the additive to disperse the dispersed dispersion or the wet powder.

When the pharmaceutical composition of the present invention is formulated into an ointment, a cream, a powder for application, an oil, an external skin preparation, etc., animal oil, vegetable oil, wax, paraffin, starch, tracant, cellulose derivative, polyethylene glycol, silicone, bentonite , Silica, talc, zinc oxide and the like can be formulated using a carrier.

Pharmaceutically effective amounts, effective dosages of the pharmaceutical compositions of the present invention may vary depending on the method of formulating the pharmaceutical composition, mode of administration, time of administration, and / or route of administration, and the type of reaction to be achieved by administration of the pharmaceutical composition. And the severity, type, age, weight, general state of health, general condition, condition or extent of the disease, sex, diet, excretion, and components of the drug or other composition used concurrently or simultaneously with the subject. It can be varied according to factors and analogous factors well known in the medicinal art, and one of ordinary skill in the art can easily determine and prescribe a dosage effective for the desired treatment.

Administration of the pharmaceutical composition of the present invention may be administered once a day, may be divided into several times. The pharmaceutical 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. All of the above factors can be considered and administered in an amount that can obtain the maximum effect in a minimum amount without side effects, which can be easily determined by those skilled in the art.

The dehydrocostus lactone of the present invention is a compound derived from natural products and has no toxicity and side effects, and thus can be safely used even for long-term administration for the purpose of preventing, improving or treating a disease.

The route of administration and mode of administration of the pharmaceutical compositions of the present invention may be independent of each other, and may be any route of administration and mode of administration without particular limitation, so long as the pharmaceutical composition can reach the desired site of interest. The pharmaceutical composition may be administered by oral or parenteral administration.

As a parenteral administration method of the pharmaceutical composition of the present invention, intravenous administration, intraperitoneal administration, intramuscular administration, transdermal administration or subcutaneous administration can be used, and the method of applying, spraying, or inhaling the composition to a diseased site. It may also be used but is not limited thereto.

The pharmaceutical composition of the present invention may exert an excellent effect even when used alone, but may be used in combination with various treatment methods such as hormonal therapy, chemotherapy, and other drug combination therapy to increase the treatment efficiency.

The present invention provides a health functional food for the prevention or improvement of uterine cell dysplasia, comprising dehydrocostus lactone or a food acceptable salt thereof as an active ingredient.

As used herein, the term “food acceptable salt” refers to a salt in a form that can be used in foodstuffs, among salts in which cations and anions are bound by electrostatic attraction. Specific examples include examples of the "pharmaceutically acceptable salts" described above.

As used herein, the term "health food" refers to a food having an active health maintenance or promotion effect compared to a general food, and a health supplement food means a food for health supplement purposes. In some cases, the terms functional food, health food, health supplement food are used in. The food may be prepared in various forms such as tablets, capsules, powders, granules, liquids, pills, etc. in order to obtain useful effects.

The term “functional food” used in the present invention is the same term as food for special health use (FOSHU), and is processed to efficiently display bioregulatory functions in addition to nutrition and medicine. Means foods that are highly effective.

The present inventors have found that the dehydrocostus lactone of the present invention induces apoptosis and inhibits the expression of chemokines such as MCP-1, RANTES, and also inhibits M2 polarization of endometriosis related macrophages, VEGF, MMP-2, In addition to inhibiting the expression of malignant factors in uterine disease cells or tissues such as MMP-9, the brain-derived neurotrophic factor (BDNF) and the Nerve Growth Factor (NGF), a pain-associated neurotrophic hormone secreted by endometriosis cells The first to identify the decrease in the expression and secretion of a) was identified, thereby the first use of dehydrocostus lactone for the prevention, improvement or treatment of uterine cell dysplasia.

The disease to be prevented or improved in the health functional food of the present invention is not specifically limited as long as it falls within the category of diseases related to abnormal uterine cell proliferation, but in order to exhibit better efficacy, preferably, uterine myoma, uterine adenomyosis, Endometriosis, uterine sarcoma, uterine fibrosis, uterine hypertrophy, cervicitis, cervical dysplasia, cervical epithelial tumor, cervical cancer, endometrial cancer and cervical cancer, more preferably Endometriosis.

The dietary supplement of the present invention may include additional ingredients that are commonly used in food compositions to improve odor, taste, visual acuity, and the like. For example, it may include vitamins A, C, D, E, B1, B2, B6, B12, niacin, biotin, folate, panthotenic acid, and the like. In addition, it may include minerals such as zinc (Zn), iron (Fe), calcium (Ca), chromium (Cr), magnesium (Mg), manganese (Mn), copper (Cu). It may also contain amino acids such as lysine, tryptophan, cysteine, valine and the like. Also preservatives (potassium sorbate, sodium benzoate, salicylic acid, sodium dihydroacetate, etc.), fungicides (bleaching powder and highly bleaching powder, sodium hypochlorite, etc.), antioxidants (butylhydroxyanisol (BHA), butylhydroxytoluene (BHT) ), Colorants (such as tar pigments), colorants (such as sodium nitrite, sodium nitrite), bleach (sodium sulfite), seasonings (such as MSG glutamate), sweeteners (ducin, cyclate, saccharin, sodium, etc.), Food additives such as fragrances (vanillin, lactones, etc.), swelling agents (alum, potassium D-tartrate, etc.), reinforcing agents, emulsifiers, thickeners (pigments), coatings, gum herbicides, foam inhibitors, solvents, and improving agents Can be added. The additive may be selected according to the type of food and used in an appropriate amount.

When the health functional food of the present invention is used as a food additive, it may be added as it is or used with other food or food ingredients, and may be appropriately used according to a conventional method.

In the health functional food of the present invention, the content of dehydrocostus lactone or a food-acceptable salt thereof is not particularly limited, and may be variously changed depending on the state of administration, the type of specific disease, the degree of progress, and the like. If necessary, it may also be included in the total content of the food.

The dehydrocostus lactone of the present invention is excellent in inducing apoptosis and inhibiting the expression of chemokines and inhibiting the expression of malignant factors on diseased cells or tissues such as VEGF, MMP-2 and MMP-9. It is effective in effectively preventing, ameliorating and treating uterine cell dysplasia including endometriosis.

In addition, the dehydrocostus lactone of the present invention is a compound derived from natural, there is no side effect can be utilized in a variety of pharmaceutical compositions, health functional foods and the like.

Figure 1 is a graph confirming the efficacy of apoptosis (apoptosis) of 12Z cells according to the treatment of dehydrocostus lactone (dehydrocostus lactone).
Figure 2 is a graph confirming the inhibitory effect of MCP-1 and RANTES expression of 12Z cells following the treatment of dehydrocostus lactone.
Figure 3 is a graph confirming the inhibition of CD206 and Trem-2 expression in THP-1 macrophages following the treatment of dehydrocostus lactone.
Figure 4 is a graph confirming the effect of inhibiting the expression of VEGF, MMP-2 and MMP-9 in THP-1 macrophages following the treatment of dehydrocostus lactone.
5 is a graph confirming the effect of reducing the BDNF and NGF expression and secretion in 12Z cells following the treatment of dehydrocostus lactone.

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 Confirmation of Apoptosis Induction Efficacy According to Dehydrocostus Lactone Treatment

Dehydrocostus lactone was treated on 12Z endometriosis cells to harvest cells that had inhibited cell viability and washed twice with ice-cooled phosphate buffered saline (PBS). Annexin V and PI double staining for apoptosis analysis was performed in the following manner.

For Annexin V and PI double staining, cells are suspended with 100 μL of binding buffer (10 mM HEPES / NaOH, 140 mM NaCl, 2.5 mM CaCl 2, pH 7.4) and 1.25 μL of FITC-bound Annexin V and PI (50 mg / ml). The mixture was incubated in the dark for 15 minutes at room temperature and analyzed with a FACS Carter-Plus flow cytometer.

As a result, when the endometriosis cells were treated with dehydrocostus lactone, it was confirmed that apoptosis was induced to effectively inhibit the growth of endometriosis cells (FIG. 1).

Example 2: Confirmation of chemokine (chemokine) expression inhibition effect by dehydrocostus lactone treatment

RNA isolation and real-time RT-PCR analysis were performed in the following manner.

RNA of 12Z cells treated with dehydrocostus lactone was extracted using the Easy Blue ^® kit (Intron Biotechnology, Seoul, Korea) according to the manufacturer's instructions. Total RNA was reverse transcribed into the first strand cDNA (Amersham Pharmacia Biotech, Oakville, Ontario, Canada) following the manufacturer's procedure. The synthesized cDNA was used as a template for polymerase chain reaction (PCR) amplification. Real time PCR was performed using a Thermo Cycler Dice Real Time PCR System (Takara, Tokyo, Japan). Primers used for SYBR Green real-time RT-PCR are shown in Table 1 below:

TABLE 1

Dissociation curve analysis showed a single peak and PCR was performed 50 times using the conditions shown in Table 2 below:

TABLE 2

The mean cycle threshold (Ct) of the gene of interest was calculated from three measurements and normalized to the mean Ct of GAPDH, the control gene.

As a result, when endometriosis cells were treated with dehydrocostus lactone, it was confirmed that the expression of MCP-1 and RANTES, which is a kind of chemokine, was effectively suppressed (FIG. 2). This means that the expression of chemokines can be inhibited by the treatment of dehydrocostus lactone and consequently the macrophage can be inhibited from moving around the endometriosis cells.

Example 3 Confirmation of M2 Polarization Inhibitory Effect of Endometriosis-Related Macrophages (EAM) Following Dehydrocostus Lactone Treatment

RNA was extracted according to the manufacturer's instructions using Easy Blue Kit E from THP-1 macrophages (12Z-associated macrophages: 12Z-AM) stimulated with media containing dehydrocostus lactone and 12Z endometriosis cells. . Detailed experimental method is the same as in Example 2, the primers used in RT-PCR are shown in Table 3 below:

TABLE 3

As a result of the experiment, when endometriosis cells were treated with dehydrocostus lactone, it can be seen that CD206 and Trem-2 were inhibited (FIG. 3). CD206 and Trem-2 are markers that increase expression when macrophages are polarized to M2, and thus M2 polarization of EAM is inhibited by dehydrocostus lactone. This means that the malignation of endometriosis can be suppressed by the treatment of dehydrocostus lactone.

Example 4: Confirmation of the expression inhibitory effect of VEGF, MMP-2 and MMP-9 following dehydrocostus lactone treatment

RNA was extracted from THP-1 macrophages (12Z-associated macrophages: 12Z-AM) stimulated with medium containing dehydrocostus lactone and 12Z endometriosis cells using the Easy Blue Kit according to the manufacturer's instructions. Detailed experimental methods are the same as in Example 2, and the primers used in RT-PCR are shown in the following [Table 4]:

TABLE 4

As a result, when endometriosis cells were treated with dehydrocostus lactone, it was confirmed that the expression of VEGF, MMP-2 and MMP-9 was effectively suppressed (FIG. 4). VEGF, MMP-2 and MMP-9 are endometriosis malignant factors, and the results indicate that malignancy of endometriosis can be suppressed by the treatment of dehydrocostus lactone.

Example 5 Confirmation of Pain-Related Brain Stimulating Hormone (neurotrophine) Reduction by Dehydrocostus Lactone Treatment

RNA of 12Z cells treated with dehydrocostus lactone was extracted using the manufacturer's instructions. Detailed experimental methods are the same as in Example 2, and the primers used in RT-PCR are shown in the following [Table 5]:

TABLE 5

Secretion of BDNF and NGF are dehydroepiandrosterone courses tooth in the media raised the endometriosis cells treated with the lactone human multi-neutroavidin pin Rapids ^{(Human Multi-Neurotrophin Rapid TM)} ELISA kit (Bio-Line System (biosensis ^®)) to the manufacturer's instructions It was measured according to. Specifically, 100 μl of standard (BDNF and NGF) and samples were dispensed into the coated 96 wells, incubated at room temperature for 90 minutes, and washed five times. Detection antibodies (BDNF and NGF) were dispensed in 100 μl into each well, incubated for 30 minutes at room temperature, and washed five times. 1 × streptavidin-HRP conjugate was dispensed in 100 μl into each well, incubated for 30 minutes at room temperature, and washed again. 100 µl of TMB (3,3 ', 5,5'-Tetramethylbenzidine) substrate was dispensed into each well and incubated for 10 minutes with light blocking, and then 100 µl of TMB stopper was dispensed. The secretion of BDNF and NGF was measured at 450 nm using a microplate spectrophotometer (Spectra Max; Molecular Devices, Sunnyvale, Calif., USA).

As a result, when the endometriosis cells were treated with dehydrocostus lactone, it was confirmed that the expression and secretion of the pain-related brain stimulating hormones BDNF and NGF secreted by the endometriosis cells were reduced (FIG. 5).

In the present specification, those skilled in the art of the present invention can fully recognize and infer the details that have been omitted, and the technical spirit or essential configuration of the present invention in addition to the specific examples described in this specification are changed. Many more variations are possible without departing. Therefore, the present invention may be implemented in a manner different from that specifically described and illustrated herein, which can be understood by those skilled in the art.

<110> UNIVERSITY-INDUSTRY COOPERATION GROUP OF KYUNG HEE UNIVERSITY <120> Composition for preventing, improving or treating uterine cell          hyperplasia disease comprising dehydrocostus lactone <130> P17-153-KHU <160> 20 <170> KoPatentIn 3.0 <210> 1 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> sense primer of MCP-1 <400> 1 gctcatagca gccaccttca 20 <210> 2 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> antisense primer of MCP-1 <400> 2 ggacacttgc tgctggtgat 20 <210> 3 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> sense primer of RANTES <400> 3 cctcattgct aggccctct 19 <210> 4 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> antisense primer of RANTES <400> 4 ggtgtggtgt cccgaggaat 20 <210> 5 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> sense primer of GAPDH <400> 5 gagtcaacgg atttggtcgt 20 <210> 6 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> antisense primer of GAPDH <400> 6 ttgattttgg agggatctcg 20 <210> 7 <211> 23 <212> DNA <213> Artificial Sequence <220> <223> sense primer of CD206 <400> 7 acctcacaag tatccacacc atc 23 <210> 8 <211> 22 <212> DNA <213> Artificial Sequence <220> <223> antisense primer of CD206 <400> 8 ctttcatcac cacacaatcc tc 22 <210> 9 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> sense primer of Trem-2 <400> 9 ttgcccctat gactccatga 20 <210> 10 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> antisense primer of Trem-2 <400> 10 cgcagcgtaa tggtgagagt 20 <210> 11 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> sense primer of MMP-2 <400> 11 accgcgacaa gaagtatggc 20 <210> 12 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> antisense primer of MMP-2 <400> 12 ccacttgcgg tcatcatcgt 20 <210> 13 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> sense primer of MMP-9 <400> 13 cgatgacgag ttgtggtccc 20 <210> 14 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> antisense primer of MMP-9 <400> 14 tcgtagttgg ccgtggtact 20 <210> 15 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> sense primer of VEGF <400> 15 atggcagaag gaggagggca 20 <210> 16 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> antisense primer of VEGF <400> 16 atcgcatcag gggcacacag 20 <210> 17 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> sense primer of BDNF <400> 17 tgccttgctc aatggaagag 20 <210> 18 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> antisense primer of BDNF <400> 18 ggggatccat ttttccaaga 20 <210> 19 <211> 32 <212> DNA <213> Artificial Sequence <220> <223> sense primer of NGF <400> 19 acattaacaa cagtgtattc aaacagtast tt 32 <210> 20 <211> 15 <212> DNA <213> Artificial Sequence <220> <223> antisense primer of NGF <400> 20 cggcacccgc tgtca 15

Claims (10)

A pharmaceutical composition for preventing or treating endometriosis comprising dehydrocostus lactone or a pharmaceutically acceptable salt thereof as an active ingredient. The pharmaceutical composition of claim 1, wherein the dehydrocostus lactone has an effect of inhibiting the expression of MCP-1 or RANTES. The pharmaceutical composition of claim 1, wherein the dehydrocostus lactone has the effect of inhibiting the expression of VEGF, MMP-2 or MMP-9. delete delete Health functional food for the prevention or improvement of endometriosis comprising dehydrocostus lactone or a food-acceptable salt thereof as an active ingredient. The dietary supplement according to claim 6, wherein the dehydrocostus lactone has an effect of inhibiting the expression of MCP-1 or RANTES. The dietary supplement according to claim 6, wherein the dehydrocostus lactone has an effect of inhibiting the expression of VEGF, MMP-2 or MMP-9. delete delete

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