KR101582320B1 - Compositions for prevention or treatment of inflammatory disease comprising Acrosorium polyneurum extract - Google Patents

Abstract

The present invention relates to a pharmaceutical composition having an effect of preventing and treating an inflammatory disease comprising an extract of Acrosorium polyneurum as an active ingredient. The pinkish leaf extract of the present invention inhibits the production of inflammatory cytokines such as IL-12 p40, IL-6 and TNF-α and inhibits the phosphorylation of MAP kinase such as JNK and p38 and inhibits the degradation and phosphorylation of IκBα Inhibits NF-κB activation, inhibits NO production in macrophages, and can be used for the prevention and treatment of autoimmune diseases and sepsis shock.

Description

[0001] The present invention relates to a composition for preventing or treating an inflammatory disease,

The present invention relates to a pharmaceutical composition for preventing or treating an inflammatory disease comprising an extract of Acrosorium polyneurum Okamura as an active ingredient, and more particularly, to a pharmaceutical composition for preventing or treating an inflammatory disease comprising a pathogen-derived molecule pattern (PAMP) Inflammatory cytokine inhibition and MAP kinase inhibition induced by the binding of a macrophage to a macrophage cell line, inhibition of NO production in macrophage cells, and an agent for the prevention and treatment of sepsis shock.

Autoimmune disease is a disease caused by the immune function of our body attacking itself over a long period of time, symptoms are chronic persistent and usually cause permanent damage to organs, and there is little cure.

Examples of autoimmune diseases include: (i) Rheumatoid Arthritis, in which the immune system attacks the tissues of various joints, (ii) autoimmune diseases of the central nervous system induced by T cells, Multiple sclerosis (MP), which can lead to blindness, premature death, and (iii) insulin-producing cells of the pancreas are destroyed by immune cells and MHC (Major Histocompatibility Complex) Inflammatory Bowel Diseases, a disease in which the immune system attacks the intestines, (v) inducing thickening of the skin or blood vessels, Scleroderma, (vi) Systemic autoimmune disease which is accompanied by deep fatigue, rash, arthralgia, etc. In severe cases, , Brain, lung systemic lupus that can cause damage or the like and the like (Systemic Lupus Erythematosus, SLE).

Interleukin-12 (IL-12) is a kind of interleukin that is produced in antigen-presenting cells such as dendritic cells and macrophages by pathogen-derived molecular pattern stimulation. It stimulates T cells to induce type 1 helper T cells (Type 1 helper T cell, Th1), and plays an important role in the activity of NK (Natural Killer) cells and T lymphocytes. IL-12B (p40) is a heterodimer of IL-12A (p35) and IL-12B (p40), and the expression of IL-12A (p35) is always constitutive and thus the biological function of interleukin- Lt; / RTI > Studies have shown that such inhibition of interleukin-12 may be helpful in the treatment of autoimmune diseases, an over-immune response to cells in the body.

Innate immunity can be detected when pattern recognition receptors (PRRs), such as toll-like receptors (TLRs) in host cells, are recognized by the pathogen-derived molecular pattern (PAMP) shared by microbial pathogens . When PAMP binds to the TLRs, the NF-B and MAP kinase signaling pathways are stimulated, resulting in the production of inflammatory cytokines. Interleukin 12 is important for Type 1 helper T lymphocyte-mediated immunity and inflammation. Related inflammatory diseases include rheumatoid arthritis, asthma, psoriasis, and Crohns disease.

Sepsis is a condition in which microbes are infected and a serious inflammatory reaction occurs in the whole body. More specifically, hyperthermia with a body temperature of more than 38 ° C or hypothermia falling below 36 ° C, a respiratory rate of more than 24 times per minute, a heart rate of more than 90 beats per minute (tachycardia), an increase or a significant decrease in leukocyte count If you have symptoms that are more than a branch, it is called systemic inflammatory response syndrome (SIRS), which is called sepsis when the systemic inflammatory response syndrome is caused by infection of microorganisms.

Lipopolysaccharide (LPS) is a constituent of the cell wall of Gram negative bacteria. Excessive exposure to human body causes septic shock. This induces host-induced inflammation by stimulating antigen-presenting cells such as host macrophages and dendritic cells, where over-produced interleukin-6 and tumor necrosis factor (TNF-α) are the major causes of sepsis It is known to cause endotoxic shock. The mechanism by which bacterial endotoxin causes sepsis is as follows. LPS is a bacterially derived component that is a PAMP that stimulates TLR4 of antigen presenting cells such as host macrophages and dendritic cells. As a result, the inflammatory cytokines IL-6, TNF-a are overproduced, resulting in endotoxin shock.

Accordingly, an object of the present invention is to provide a pharmaceutical composition for preventing or treating an inflammatory disease which can be used for the treatment of the above-mentioned diseases, which comprises a residual pink leaf extract as an active ingredient.

It is another object of the present invention to provide a food composition for preventing or ameliorating an inflammatory disease containing an extract of a pinkish-leaf leaf as an active ingredient.

In order to accomplish the above object, the present invention provides a pharmaceutical composition for preventing or treating an inflammatory disease containing an extract of Panax notoginsensis as an active ingredient.

In one embodiment of the present invention, the leaf pink leaf extract may be extracted with water, a lower alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof.

In one embodiment of the invention, the inflammatory disease may be an autoimmune disease or a sepsis shock.

In one embodiment of the present invention, the Leaf Pink Leaf Extract may exhibit an inhibitory effect on the inflammatory response by inhibiting the production of inflammatory cytokines such as IL-12 p40, IL-6, and TNF-α.

In one embodiment of the present invention, the inhibition of said inflammatory cytokine may be induced through the signaling inhibition of NF-kB or MAP kinase.

In one embodiment of the present invention, the sepsis shock is characterized by being induced by NO overproduction.

In addition, the present invention provides a food composition for preventing or ameliorating an inflammatory disease containing an extract of a pinkish-leaf leaf as an active ingredient.

According to the present invention, the extract of the present invention is useful for the production of inflammatory cytokines such as IL-12, p40, IL-6 and TNF-a in dendritic cells and macrophages, the phosphorylation and activation of MAP kinases such as JNK, p38, And suppression of NF-κB activation and inhibition of NO production in macrophages, thereby preventing and treating septic shock induction. In addition, the present invention can be applied to the prevention and treatment of autoimmune diseases through the activity of the above-mentioned pink leaf extract.

FIG. 1 shows the results of measuring the effect of the leaf extract on the cell viability according to the present invention.
FIG. 2 shows the results of measuring the inhibitory effect of bone marrow-derived dendritic cells (BMDC) on the inflammatory cytokine production of the leaves of the leaves of the leaves of the present invention.
FIG. 3 shows the results of measuring the inhibitory effect of bone marrow-derived macrophages (BMDM) on the inflammatory cytokine production inhibition of the leaves of the leaves of the leaves of the present invention.
FIG. 4 shows the results of measuring the effect of the leaves of the leaves on leaves on the phosphorylation of MAP kinase according to the present invention.
FIG. 5 shows the results of measurement of the effect of the extract of P. falciparum on degradation and phosphorylation of IκBα according to the present invention.
FIG. 6 shows the results of measurement of the effect on the viability and NO production of RAW246.7 cells of the pinkish-leaf extract according to the present invention.

The present invention provides a pharmaceutical composition for preventing or treating an inflammatory disease containing an extract of Acrosorium polyneurum as an active ingredient.

The ' Acrosorium polyneurum ' used in the present invention is a kind of ferns growing on the coast of Jeju Island, and is mainly distributed on the coasts of Korea and Japan. The plant is reddish brown with a thin filmy shape, split at wide angle, prone to prone, branch is short, end of branch is wide, and it bends up or down. Microscopically, it has a lot of thin veins, it spreads in a net shape, and it can make many hapterons in various places in the plant, attach them to each other or attach them to other objects.

In the pharmaceutical composition of the present invention, the above-mentioned residue of the pinkish-leaf leaf can be extracted according to a method known in the art, or commercially extracted and purified can be purchased and used. In addition, the pinkish leaves can be used without limitation such as cultivated or commercially available leaves, and can be cleaned and dried. The dried leaves are pulverized to an appropriate size, put into an extraction container, and put an appropriate amount of distilled water, alcohol or organic solvent. It is extracted for 24 hours or more at an appropriate temperature and then filtered to obtain a hot-water extract, an alcohol extract or an organic solvent extract according to the present invention.

As the hot-water extract, distilled water is preferably used as an extraction solvent, and it is more preferable to use tertiary distilled water. In the case of hot water extraction, it can be extracted by hot water heating at 65-80 ° C for 12-48 hours.

The alcohol extract may be extracted with, for example, a lower alcohol of C1-C4 as a solvent, and methanol, ethanol or a mixed solvent thereof may be preferably used.

The organic solvent extract may be ethyl ether, chloroform, ethyl acetate, or a mixed solvent thereof. The organic solvent extract may be extracted by hot water heating in the same manner as in the hot water extract.

In the embodiment of the present invention, a mixture of water and an alcohol is used as the residue of the pink leaf leaf extract, preferably 80% ethanol.

In the pharmaceutical composition of the present invention, the inflammatory disease means a disease having inflammation as a main lesion, and includes acute inflammatory diseases, inflammatory diseases caused by infection, and autoimmune diseases.

The acute inflammatory disease refers to diseases such as contact dermatitis, adult respiratory distress syndrome (ARDS), sepsis (including long-term disability caused by sepsis), and sepsis shock.

Inflammatory diseases caused by the infection include inflammatory diseases caused by infection such as endotoxin shock, AIDS, cachexia, other bacteria, viruses, mycoplasma, etc. (fever due to epidemic and non-infective cold, Long-term disability, etc.).

The autoimmune disease refers to diseases such as rheumatoid arthritis, multiple sclerosis, type I diabetes, inflammatory bowel disease, scleroderma, systemic lupus, and the like.

In a preferred embodiment of the present invention, the Leaf Pink Leaf Extract is an inflammatory disease and can be effectively used for the prevention and treatment of autoimmune diseases or sepsis shock.

According to an embodiment of the present invention, the Leaf Pink Leaf Extract inhibits the production of inflammatory cytokines such as IL-12 p40, IL-6 and TNF-α in dendritic cells and macrophages (see FIGS. 2 and 3) Inhibit phosphorylation and activation of MAP kinase such as JNK, p38 (see FIG. 4). In addition, the above-mentioned residue of pink leaf extract inhibits the degradation and phosphorylation of IκBα and the activation of NF-κB (see FIG. 5) and inhibits NO production in macrophages (see FIG. 6). Therefore, it can be effectively used for the prevention and treatment of autoimmune diseases and sepsis caused by excessive inflammation through the control of inflammation-related factors as described above.

In order to utilize the residue of the pink leaf extract of the present invention as a pharmaceutical composition, it can be formulated through pharmaceutical methods known in the art. For example, the pharmaceutical compositions of the present invention may further comprise suitable carriers, excipients or diluents according to conventional methods.

Examples of carriers, excipients and diluents that can be included in the pharmaceutical composition include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, mannitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose , Methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate or mineral oil.

The pharmaceutical composition may be administered orally or parenterally (for example, intravenously, subcutaneously, intraperitoneally or topically), preferably orally, depending on the intended method.

The composition of the present invention may be formulated into various formulations for administration. For example, it can be formulated into tablets, coated tablets, capsules, pills, granules, suppositories, solutions, suspensions, emulsions, pastes, ointments, gels, creams, lotions, have.

The composition may be formulated into liquid preparations such as solid preparations such as tablets, pills, powders, granules or capsules for oral administration or suspensions, solutions, emulsions or syrups. Alternatively, the composition may be formulated into sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations or suppositories for parenteral administration.

The composition of the present invention may be formulated into sustained release or immediate release formulations using carriers, diluents, dispersants, surfactants, binders, lubricants and additives. For example, the active ingredient of the pharmaceutical composition according to the present invention may be formulated into a sustained or immediate release formulation so as to release it to a specific site.

When the composition of the present invention is formulated into a sustained release preparation, it can be formulated into a sustained release form using a polymerizable substance such as an enteric polymer, a water-insoluble polymer, a hydrophobic compound or a hydrophilic polymer, or a wax-like composition. For example, when the pharmaceutical composition is formulated into tablets, capsules, pills or granules, a coating film may be formed on the outside to form a sustained release formulation.

In the formulation of the composition, the content of excipients such as carriers, fillers, weighing agents, binders, wetting agents, disintegrants, dispersants, surfactants or diluents, and additives is not particularly limited and is generally used for formulation The content can be appropriately adjusted within the range of the content.

The dosage of the pharmaceutical composition according to the present invention may vary depending on the patient's body weight, age, sex, health condition, diet, administration time, administration method, administration period or interval, excretion rate, sickness specificity, The range varies. For example, the pharmaceutical composition of the present invention may be administered in an amount of about 0.001 to 10 g / kg, preferably 0.1 to 5 g / Kg, based on the mixed pulverized product before the mixed extract is extracted, It can be administered once to several times a day.

The pharmaceutical composition according to the present invention can be administered by various routes. The route of administration is not particularly limited, and can be administered, for example, by oral, rectal or intravenous, muscular, subcutaneous injection.

The pinkish leaf extract contained in the pharmaceutical composition of the present invention has little toxicity and side effects, so that it can be safely used for prolonged use even for prophylactic purposes.

In addition, the present invention provides a food composition for preventing or ameliorating an inflammatory disease containing an extract of a pinkish-leaf leaf as an active ingredient.

The food is a food which can be expected to have a certain level of pharmacological efficacy by containing a residual pink leaf extract having excellent anti-inflammatory activity of the present invention, and is not limited to health supplements, health functional foods, functional foods and the like, Food, processed foods, and general food ingredients, which are added to the composition for preventing and improving inflammatory diseases according to the present invention.

The food composition for preventing or ameliorating the inflammatory disease of the present invention may be used as it is, or may be used together with other food or food composition, and suitably used according to a conventional method. The amount of the active ingredient to be mixed can be suitably determined according to its intended use (prevention, health or therapeutic treatment). In general, the food composition for inflammatory prevention and improvement of the present invention may be added in an amount of 0.1 to 70 parts by weight, preferably 2 to 50 parts by weight, based on 100 parts by weight of the raw material for food or beverage in the production of food or beverage. The effective dose of the composition for preventing and / or ameliorating the inflammatory disease can be used in accordance with the effective dose of the pharmaceutical composition. However, in the case of long-term intake for health and hygiene purposes or for health control purposes, And the active ingredient can be used in an amount of more than the above range since there is no problem in terms of safety.

There is no particular limitation on the kind of the food. The food composition for the prevention or amelioration of the inflammatory disease can be used in the form of tablets, hard or soft capsules, liquids, suspensions, and the like, and these preparations can be administered orally or parenterally, In the case of a pharmaceutical preparation, it can be prepared using excipients, binders, disintegrants, lubricants, solubilizers, suspending agents, preservatives or extenders.

Examples of foods to which the food composition for preventing or ameliorating the inflammatory disease can be added include meat products such as sausages, breads, chocolates, candies, snacks, confectionery, pizza, ramen noodles, other noodles, gums, dairy products including ice cream, Soups, drinks, tea, drinks, alcoholic beverages and vitamin complexes, but not limited to these kinds of foods.

Hereinafter, the present invention will be described in detail with reference to examples. However, these examples are intended to further illustrate the present invention, and the scope of the present invention is not limited to these examples.

Example 1 Preparation of a Leaf Pink Leaf Extract

Acrosorium polyneurum samples were collected from Cheju Island, Korea. The sample of evidence was deposited with Jeju Biodiversity Research Institute (JBRI) and received JBRI 20052.

The leaves were collected in Jeju Island, Korea in April 2009 and shaded. Then, 100 g of the dried leaf residue was extracted with 2 L of 80% ethanol (EtOH, 2 L) for 24 hours at room temperature, filtered and concentrated under reduced pressure using a rotary evaporator to obtain an ethanol-soluble fraction of the leaves.

Experimental animal

Wild type C57BL / 6 mice were purchased from Orient Bio Inc (Seongnam, South Korea). It was raised in an aseptic place according to the guidelines of the National Institutes of Health. All experiments using mice were carried out according to the regulations of the Experimental Animals Ethics Committee of Jeju University (# 2010-0028).

Example 2. Mouse macrophage-derived macrophage and dendritic cell preparation.

Bone marrow-derived dendritic cells (BMDC) and macrophages (BMDM) were obtained from wild-type C57BL / 6 mice. Bone marrow cells were obtained by flushing the shinbone and femur of a mouse in DMEM (Dulbeccos modified Eagles medium) medium. The obtained bone marrow cells were supplemented with 3% J558L hybridoma cell culture supernatant containing granulocyte-macrophage colony-stimulating factor (GM-CSF), supplemented with 10% heat-inactivated FBS (Gibco, NY, USA), 50 [mu] M [beta] -mercaptoethanol, 2 mM glutamine.

In addition, the obtained bone marrow cells were cultured in DMEM medium containing 30% L929 cell culture medium and 1% penicillin-streptomycin, containing 20% heat-treated FBS and macrophage colony stimulating factor for macrophage culture.

Example 3. Measurement of cell survival ability of leaves of pink leaf extract

(3-1) Experimental method

It was experimentally determined whether the leaf extract of Leucocephalus according to the present invention is cytotoxic to cells. To this end, the macrophage and dendritic cells cultured in Example 2 were treated with 6.25, 12.5, 25, and 50 μg / ml of ground leaf extract, respectively. After 18 hours, MTT (Sigma-Aldrich, USA) Cell viability was measured using Assay assay kit. The macrophages and dendritic cells obtained from the mouse bone marrow were divided into 96 well plates at a concentration of 5 x 10 ⁴ cells / ml and cultured for 1 hour. Then, the leaves of the leaves were adjusted to 6.25, 12.5, 25 and 50 μg / ml Followed by further culturing for 18 hours. Each cell was treated with 0.2 mg of MTT reagent and incubated at 37 ° C for 4 hours. The cultured cells were collected, dissolved in 250 μl of dimethyl sulfoxide (DMSO), and then the cell viability was measured by measuring the absorbance at 540 nm. The measurement results represent the mean ± SD of three independent experiments.

(3-2) Experimental result: Toxicity test of the extract of pink leaf

FIG. 1 shows that the leaves of the leaves are not cytotoxic. It can be confirmed that the bone marrow-derived macrophages and the bone marrow-derived dendritic cells do not significantly affect the cell survival (%) before and after the treatment of the residual pink leaf extract (Fig. 1, A and B). Therefore, the extract according to the present invention is not cytotoxic.

Example 4. Measurement of inhibitory effect of IL-12 p40, IL-6 and TNF-

(4-1) Experimental method

The following experiment was carried out in order to confirm the activity of inhibiting the production of inflammatory cytokine that induces inflammation in the leaves of the leaves of Leucocephalus. The dendritic cells derived from the bone marrow of the mouse prepared in Example 2 were suspended in 1 x 10 < ⁵ > cells / 0.5 ml of cells were added to a 48-well plate, and the leaves were treated with a concentration of 6.25, 12.5, 25, and 50 μg / ml. As a control group, a group not treated with the leaf extract of Leucocephalus was used. The expression level of IL-12 p40, IL-6 and TNF-α was measured by ELISA (BD PharMingen, CA, USA, R & D system, MN, USA ) (A, B and C in Fig. 2). Results represent the mean ± SD of three independent experiments.

(4-2) Experimental result 1: Inhibition of inflammatory cytokine production of bone marrow-derived dendritic cells

FIG. 2 shows that the leaf extract of Leucocephalum has an inhibitory effect on inflammatory cytokine production. IL-12 p40, IL-6, and TNF-α were reduced after treatment than before treatment of pink leaf extract (FIGS. 2A, B and C). In particular, the production of IL-12 p40 (A) was significantly reduced even after a small amount of the extract was treated. Therefore, the extract of the present invention has an effect of inhibiting the production of inflammatory cytokines.

(4-3) Experimental Result 2: Inhibition of inflammatory cytokine production of bone marrow-derived macrophages

The above experiment was carried out in the same manner on bone marrow-derived macrophages, and the results are shown in Fig. In bone marrow-derived macrophages, the production of inflammatory cytokines was markedly reduced even when a small amount of the extract was added.

Example 5. Measurement of MAP Kinase Phosphorylation and NF-κB Activity of Pink Leaf Extract of Leaves

(5-1) Experimental method

As shown in Example 4 above, it was confirmed that the pinkish-leaf leaf extract had an activity of inhibiting the production of inflammatory cytokine induced by LPS. Thus, the activity of MAP kinase and NF-κB, which are upper signal transduction systems for producing inflammatory cytokines, Were confirmed by western blotting to determine if the residue was controllable by the pink leaf extract.

For this purpose, the bone marrow-derived macrophages obtained in Example 2 were first divided into 5 × 10 ⁶ cells in a 60-mm dish, and cultured at 37 ° C. for 24 hours. After incubation, the cells were treated with 25 μg / ml of leaf extract and 10 ng / ml of LPS. As a control group, a group not treated with the leaf extract of Leucocephalus was used. After the cells were collected, the cells were lysed using an elution buffer (PRO-PREP Lysis buffer, iNtRON Biotechnology), and protein samples were electrophoresed on 10% SDS PAGE. (P-ERK1 / 2), p44 / 42 MAPK, phospho-p38, and the like, which are primary antibodies diluted 1/1000 times and then transferred to a polyvinylidene fluoride membrane. p38 MAPK, phospho-SAPK / JNK, SAPK / JNK, phospho-IκBα, and IκBα (Cell Signaling Technology, MA, USA). The membranes were washed and reacted with horseradish peroxidase-linked anti-rabbit IgG (Cell Signaling Technology) by reacting with Horseradish peroxidase-linked anti-rabbit IgG (WEST-ZOL plus Western blot detection system -ZOL plus western blot detection system, iNtRON Biotechnology). ERK p44 and p42 were used as loading controls. The experimental results are representative of three independent experiments.

(5-2) Experimental result 1: inhibition of phosphorylation of MAP kinase

Fig. 4 shows that the extract of Panax notoginseng has a phosphorylation inhibitory effect of MAP kinase. As a result of western blotting, the amount of phosphorylated JNK and p38 in LPS - stimulated cells treated with Leaf Pink Leaf Extract was small. Therefore, the extract according to the present invention has an effect of inhibiting the phosphorylation of MAP kinase (JNK, p38), which is an upper signal transduction system for producing inflammatory cytokines, and thus inhibits the production of immune-related inflammatory cytokines It can be judged.

(5-3) Experimental Result 2: Decomposition of IκBα and inhibition of phosphorylation and inhibition of NF-κB activation

TLR4 stimulation by LPS induces phosphorylation of IκBα by IκB kinase and induces NF-κB activation following ubiquitination and degradation of IκBα (Bao L, et al., Brain Pathol. 12: 420-429 )). Thus, activation of NF-κB was indirectly analyzed by degradation and phosphorylation of IκBα.

FIG. 5 shows that the extract of the leaves of the pinkish leaves has an effect of inhibiting the degradation and phosphorylation of IκBα. As a result of western blotting, IκBα was degraded by LPS stimulation and its amount was decreased. On the other hand, the amount of phosphorylated IκBα was almost not obtained after the treatment of the extract. Therefore, the extract according to the present invention has an effect of inhibiting degradation and phosphorylation of IκBα and thus inhibiting NF-κB activation.

Example 6. Measurement of cell survival and nitric oxide production effect of RAW246.7 cells from leaves of pink leaf extract

(6-1) Experimental method

Mouse macrophage RAW246.7 cells were seeded in 24-well plates at a density of 1 × 10 ⁵ cells / 0.5 ml and cultured for 18 hours. Then, the leaves of the leaves of pinkish brown were treated at concentrations of 6.25, 12.5, 25 and 50 μg / ml Respectively. After 1 hour, the cells were stimulated with 10 ng / ml of LPS, and 18 hours later, cell culture was obtained. Thereafter, the amount of nitrogen monoxide contained in the cell culture medium was measured using a grease reagent (Griess regent, Promega). The experimental results represent the mean ± SD of three independent experiments.

(6-2) Experimental result: Decrease in NO production

As can be seen from the graph in FIG. 6, it can be seen that RAW246.7 cells did not significantly affect cell survival (%) before and after treatment of the residual pink leaf extract. Therefore, the extract according to the present invention is not cytotoxic. The graph below shows that the extract has NO production inhibitory effect. As can be seen from the lower graph of FIG. 6, the amount of NO produced in the leaves of the leaves was reduced, and the amount of NO produced decreased as the amount of the extract increased. Therefore, the extract of the present invention has an effect of inhibiting NO production. Since excessive production of NO may cause sepsis shock, the extract according to the present invention is effective in preventing sepsis shock.

The present invention has been described above with reference to preferred embodiments thereof. It will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention as defined by the appended claims. Therefore, the disclosed embodiments should be considered in an illustrative rather than a restrictive sense. The scope of the present invention is defined by the appended claims rather than by the foregoing description, and all differences within the scope of equivalents thereof should be construed as being included in the present invention.

Claims (8)

A pharmaceutical composition for preventing or treating an inflammatory disease containing an extract of Acrosorium polyneurum as an active ingredient. [Claim 2] The pharmaceutical composition according to claim 1, wherein the leaf extract is extracted with water, a lower alcohol having 1-4 carbon atoms, or a mixed solvent thereof. 2. The pharmaceutical composition according to claim 1, wherein the inflammatory disease is an autoimmune disease or a sepsis shock. 4. The pharmaceutical composition according to claim 3, wherein said autoimmune disease is selected from the group consisting of rheumatoid arthritis, multiple sclerosis, type I diabetes, inflammatory bowel disease, scleroderma and systemic lupus. The pharmaceutical composition according to claim 1, wherein the leaf extract has an inhibitory effect on the inflammatory reaction by inhibiting the production of inflammatory cytokines such as IL-12 p40, IL-6 and TNF-α. The pharmaceutical composition according to claim 5, wherein the inhibition of the production of the inflammatory cytokine is induced through signaling inhibition of NF-kB or MAP kinase. 4. The pharmaceutical composition according to claim 3, wherein the sepsis shock is induced by excessive NO production. Food composition for prevention or improvement of inflammatory diseases containing extract of pink leaf as an active ingredient

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