WO2008010335A1

WO2008010335A1 - Plant extract having arthritis-preventive effect

Info

Publication number: WO2008010335A1
Application number: PCT/JP2007/057108
Authority: WO
Inventors: Tetsuya Tomita; Osamu Masaki
Original assignee: Mmt Co., Ltd.
Priority date: 2006-07-21
Filing date: 2007-03-30
Publication date: 2008-01-24

Abstract

Disclosed is: an extract from a plant belonging to the family Compositae, preferably a plant Tanacetum parthenium, which contains a sesquiterpenelactone; or a beverage/food, quasi drug or pharmaceutical composition for prevention or treatment of a joint disease or a disease for which the inhibition of NFκB is effective, which comprises parthenolide. Also disclosed is a method for prevention or treatment of a joint disease or a disease for which the inhibition of NFκB is effective, which comprises feeding or administering an extract from a plant belonging to the family Compositae, preferably a plant Tanacetum parthenium, which contains a sesquiterpenelactone to a subject, or feeding or administering parthenolide to a subject.

Description

Specification

Plant extract with arthritis inhibitory action

Technical field

[0001] The present invention relates to a food and drink containing an Asteraceae plant extract, particularly a feverfew extract, or valthenolide, which is an active ingredient thereof, which has an effect of suppressing joint disease or a disease that is advantageous for suppressing NFκB. Products, supplements and medicines.

Background art

Many joint diseases such as arthritis and joint destruction are difficult to treat, and various drugs and treatment methods have been researched and developed so far. At present, methotrexate is widely used for the treatment of arthritis, but there are problems of side effects (especially the elderly), and there are not a few ineffective cases. In addition, there are quite a few patients who cannot suppress the progression of joint destruction with methotrexate alone.

[0003] In recent years, with the advent of biological preparations targeting TNFa, which play a major role in the development of arthritis, it has become possible to suppress the progression of joint destruction. Have been reported to have fatal side effects. Biological products are administered to patients by infusion or subcutaneous injection, and such administration modes are burdensome to the patient and are economically expensive.

[0004] In addition to chemical synthetic drugs such as methotrexate aspirin for the treatment of joint diseases, natural ingredients have also been studied. Supplements and health foods are considered to be effective for joint diseases, and have been frequently used (see Non-Patent Documents 1 and 2, etc.). However, these Kampo preparations, health foods, and supplements have the merit that they can be administered orally, but are often problematic in their effectiveness and are expensive.

Non-Patent Document 1: Merck Manual 16th Edition

Non-Patent Document 2: Japanese Medicinal Products Collection January 1997 edition

Disclosure of the invention

Problems to be solved by the invention [0005] A natural material that is effective for joint diseases or diseases that are advantageous to suppress NFκ, can be administered orally, has few side effects, and can be obtained in large quantities and at low cost. It was an object of the present invention to provide supplements and medicaments. Means for solving the problem

[0006] The present inventors have conducted intensive research and found that the above problems can be solved by using an Asteraceae plant extract containing sesquiterpene ratatones, particularly feverfew extract, or parthenolide which is an active ingredient thereof. The present invention has been completed.

The invention's effect

[0007] Extraction of Asteraceae plants, especially Nashirogiku, which is a natural material that is effective for joint diseases or diseases that are advantageous to suppress NFκΒ, and can be administered orally with few side effects and can be obtained in large quantities and at low cost. Foods and drinks, supplements, and medicines containing baltenolide are provided.

Brief Description of Drawings

[0008] FIG. 1 is a graph showing the time course of arthritis scores when feverfew extract or parthenolide is administered to mice. The black circle is the vehicle control group, the white square is the parthenolide 50 mg / kg / day administration group, and the black triangle is the feverfew extract 222 mg / kg / day administration group. Each data is the average soil standard deviation of 10 animals. Regarding the significant difference from the vehicle control group, the data for * is p 0.05 and the data for * is p 0.01.

[FIG. 2] FIG. 2 is a graph showing arthritis scores in the case of administration of parthenolide or feverfew extract on the same day as the onset of arthritis or 4 days after onset in mice. CAIA is the untreated arthritis group, vehicle (dO) is the group given methylcellulose on the same day as the onset of joint, PTL (dO) is the group given parthenolide on the same day as the onset of joint, PT L (d4) is Data for the group that received valtenolide 4 days after the onset of the joint, and feverfew (d4), for the group that received the feverfew extract 4 days after the onset of the joint.

[Fig. 3] Fig. 3 is a view showing the suppression of expression of NFκB lower layer gene in ankle joint when parthenolide is administered 4 days after the onset of arthritis in mice. Figure 3a shows IL-1β, Figure 3b shows TNF, Figure 3c shows MMP_9, and Figure 3d shows MIP_1 expression.

[Fig. 4] Fig. 4 shows parthenolide 3 hours after degeneration of normal human chondrocytes It is a figure which shows the expression suppression of the lower layer gene of NF (kappa) sputum when added. Fig. 4a shows IL 1 β Fig. 4b shows 、 -1, Fig. 4c shows MMP-3, and Fig. 4d shows TNF α expression.

FIG. 5 is a diagram showing suppression of expression of NFκNF lower layer genes when feverfew extract is added to synovial cells obtained from rheumatic patients. Fig. 5a shows IL-1 / 3, Fig. 5b shows TNF, Fig. 5c shows MMP_1, and Fig. 5d shows MMP-3 expression.

BEST MODE FOR CARRYING OUT THE INVENTION

The present invention provides the following:

(1) Foods and drinks for preventing or treating joint diseases, which contain extracts of Asteraceae plants;

(2) The food and drink according to (1), wherein the joint disease is selected from the group consisting of arthritis, osteoarthritis and joint destruction;

(3) Foods and drinks for preventing or treating a disease that is advantageous for suppressing NFκB, comprising an extract of an Asteraceae plant;

(4) The Asteraceae plant is feverfew, (1) Nile, (3) L, food or drink according to any of the above;

(5) The supplement (1) na la, shi (4) la, food or drink according to any of the above;

(6) A pharmaceutical composition for preventing or treating joint diseases, comprising an extract of Asteraceae or valthenolide;

(7) The pharmaceutical composition according to (6), wherein the joint disease is selected from the group consisting of arthritis, osteoarthritis and joint destruction;

(8) A pharmaceutical composition for preventing or treating a disease that is advantageous for inhibiting NFκB, comprising an extract of asteraceae or valthenolide;

(9) The pharmaceutical composition according to any one of (6) to (8), wherein the Asteraceae plant is feverfew.

(10) A method for preventing or treating a joint disease, characterized by feeding a subject with an extract of Asteraceae plants or administering an extract of Asteraceae plants or parthenolide to a subject;

(11) The method according to (10), wherein the joint disease is selected from the group consisting of arthritis, osteoarthritis and joint destruction; (12) Preventing a disease that is advantageous to suppress NFκB, characterized by feeding the subject with an extract of the asteraceae plant, or administering an extract of the asteraceae plant or parthenolide to the subject Or a method of treatment;

(13) The method according to any one of (10) to (12), wherein the Asteraceae plant is feverfew.

(14) Use of an extract of the Asteraceae plant for producing food and drink for preventing or treating joint diseases;

(15) Use of an extract of Asteraceae or barthenolide for the manufacture of a medicament for preventing or treating joint diseases;

(16) The use according to (14) or (15), wherein the joint disease is selected from the group consisting of arthritis, osteoarthritis and joint destruction;

(17) Use of NF _K B for the production of food for it to prevent or treat the advantageous diseases to suppress, extract of Asteraceae;

(18) use of an extract of Asteraceae or parthenolide for the manufacture of a medicament for preventing or treating a disease for which inhibition of NFκB is advantageous; and

(19) The use according to any one of (14) to (18), wherein the Asteraceae plant is feverfew. The present invention relates to the prevention or treatment of joint diseases, comprising an extract of a plant containing sesquiterpene ratatones. It is related to food and drink to do. If the plant extract used in the food or drink of the present invention is a plant extract containing sesquiterpene ratatones, the type of plant is not particularly limited. Examples of plants containing a large amount of sesquiterpene ratatones include asteraceae plants, such as plants of the genus Artemisia and dandelions. Accordingly, in one aspect, the present invention provides a food and drink for preventing or treating joint diseases, which contains an extract of a asteraceae plant. Among the sesquiterpene ratatones, parthenolide is a substance that has been reported to have various physiological activities so far. As shown in the examples, the arthritis inhibitory effect in the present invention is mainly derived from parthenolide. available. Therefore, it is preferable to use a plant having a high parthenolide content. Such plants include Asteraceae plants, preferably plants belonging to the genus Artemisia, particularly preferably feverfew. (Tanacetum parthenium) (also called Fever-Fu). Therefore, a particularly preferred plant extract used in the present invention is feverfew extract. Feverfew plants, especially leaves, usually contain about 0.2-0.9% parthenolide. Surprisingly, it has been found that when feverfew extract is orally administered to animals, the same effect as with parthenolide alone can be obtained even if only a very small amount of bartenolide is administered in terms of bartenolide. (See Examples).

[0011] The plant extract can be obtained by a general method. The extraction site may be any site as long as it is an aerial part of the plant, but in the case of an Asteraceae plant such as feverfew, a preferable extraction site is a leaf. Extracts can be obtained by immersing the plant in a solvent as it is, but extraction efficiency is higher by crushing and extracting the contents. Plants can be raw or dried. For drying, a known drying method such as warm air drying or air drying can be used. Various plant crushing means can be used. For example, hand grinders, homogenizers such as potter-no-lene gem homogenizers, blenders such as Waring blenders, crushers such as dyno mills, French presses, mortars and pestles, rabies, freezing and crushing with liquid nitrogen, Plants can be crushed by means such as sonication. The plant crushed material is suspended in an appropriate medium, and the contents are extracted. If desired, stirring may be performed during extraction. Suspension / extraction media include ether, methanol, ethanol, or a mixture of ethanol and water. Suspension media should be less toxic or non-toxic. From the standpoint of strength, ethanol or a mixture of ethanol and water is particularly preferable as a suspension / extraction medium. Extraction conditions such as temperature and time during suspension 'extraction can be selected according to the type and amount of plants. Usually, it is extracted at room temperature and normal pressure for several hours to several days. In addition, the above-ground parts of plants, for example, leaf candy and the like, are dried by a known drying method such as warm air drying or air drying, and pulverized to obtain a food or drink or pharmaceutical composition of the present invention. May be used for things

[0012] If necessary, the obtained extract can be subjected to decantation, filtration, centrifugation, or the like to remove solids and particulate matter. The obtained extract may be concentrated by a known method such as evaporation. In addition, the obtained extract is known It may be used after further purification by methods such as various chromatographic and precipitation methods.

[0013] The plant extract used in the food and drink of the present invention can be obtained as described above, but the nashirogiku extract is also sold and can be used. These extracts can be made into various forms according to usage forms, purposes, etc., and can be prepared into liquids, semi-solids, powders (for example, freeze-dried powders, etc.).

[0014] An Asteraceae plant extract, particularly a feverfew extract, can be blended with various foods to obtain the foods and drinks of the present invention. These asteraceae plant extracts are of low toxicity or non-toxic because they are derived from natural products, and can be incorporated into any food or drink. For example, the extract may be blended in juices or herbal seasonings. The food and drink of the present invention can be a health food, a functional nutritional food, or a food for specified health use (so-called “tokuho”).

[0015] In particular, supplements are mentioned as a preferred form of the food and drink of the present invention. The supplement may be in any shape that can be taken orally, such as tablets, capsules, granules, and powders (e.g., freeze-dried powder). Etc.), suspensions, drinks, IJs, elixirs, tiable forms, jelly forms, etc. These supplements can be produced according to processes used in the food and pharmaceutical fields. For example, when manufacturing a tablet-shaped supplement, a general process such as mixing, drying, and tableting used in the pharmaceutical field can be used. For example, in the case of a capsule form, a general process such as mixing and encapsulation can be used. Soft capsules and hard capsules can also be appropriately selected according to the purpose. To produce a liquid supplement, the extract can be dissolved or suspended in a less toxic medium such as ethanol. To produce powder and granule supplements, it is still possible to use conventional processes such as mixing, drying, grinding and sieving. When a carrier or excipient is used in the production of supplements, the type and amount can be selected according to the practice in the pharmaceutical field. Examples of solid carriers or excipients include talc, carboxymethylcellulose, sucrose, and wheat flour. Examples of the liquid carrier include water, ethanol, and edible fats and oils. [0016] The food and drink of the present invention is effective in the treatment and prevention of all joint diseases. In particular, arthritis such as infectious arthritis due to viral infection of bacteria, rheumatoid arthritis, arthritis due to gout, psoriatic arthritis, etc. It is effective for the treatment and prevention of osteoarthritis and joint destruction. In addition, since the food and drink of the present invention, particularly those containing feverfew extract, are considered to have a function of controlling NF / c B, feverfew extract, in addition to the above diseases, glomerulonephritis, arteries It is effective in the treatment and prevention of diseases such as sclerosis, atopy and asthma.

[0017] The intake of Asteraceae extract per day depends on the amount of sesquiterpene ratatones contained, particularly parthenolide. In the case of feverfew extract, it is common to take about 0.05g to 50g per day for adults (body weight 70kg), and it is appropriate to take about 0.15g to 15g.

[0018] In the food and drink or supplement of the present invention, not only asteraceae plant extracts but also one or more other active ingredients may be mixed. For example, the food and drink of the present invention may be used in combination with other ingredients effective for joint diseases such as dalcosamine, chondroitin, and calcium. It is also possible for a person who has already been treated for a joint disease to promote the therapeutic effect by eating the food or drink of the present invention. In particular, feverfew extract is thought to regulate NF / c B and may act by a mechanism different from conventional arthritis therapeutics, so the pharmaceutical composition of the present invention synergizes with these drugs there is a possibility.

[0019] In another embodiment, the present invention provides a pharmaceutical composition for treating a joint disease, comprising an extract of an Asteraceae plant. The active ingredient in the pharmaceutical composition of the present invention is the above-mentioned Asteraceae plant extract, preferably feverfew extract. Further, as the active ingredient, those obtained by purifying these extracts to increase the parthenolide content may be used. In addition, sesquiterpene ratatones, preferably panoretenolide (for example, isolated from the above extract or chemically synthesized product) may be used as an active ingredient of the pharmaceutical composition of the present invention. As used herein, “noretenolide” includes parthenolide and analogs and derivatives thereof.

[0020] The pharmaceutical composition of the present invention can be formulated into various dosage forms. When using an extract of Asteraceae such as feverfew extract as an active ingredient, the pharmaceutical composition of the present invention is For example, tablets, capsules, granules, powders, drinks and the like are preferable to have a dosage form suitable for oral administration. When sesquiterpene ratatones such as parthenolide are used as the active ingredient, the pharmaceutical composition of the present invention is preferably in a dosage form suitable for oral administration and topical administration, but administration by other administration routes. Is also possible. These dosage forms can be produced by methods known in the pharmaceutical field.

[0021] The pharmaceutical composition of the present invention is effective in the treatment and prevention of all joint diseases, particularly infectious arthritis due to viral or bacterial infection, rheumatoid arthritis, arthritis due to gout, psoriatic arthritis, etc. It is effective in the treatment and prevention of arthritis, osteoarthritis and joint destruction. In addition, it is considered that parthenolide in an Asteraceae plant, especially feverfew extract, has an action of controlling NFκB. Therefore, the pharmaceutical composition of the present invention is beneficial to control NFicB in addition to the above diseases. It is effective in the treatment and prevention of various diseases such as glomerulonephritis, arteriosclerosis, atopy and asthma.

[0022] When the active ingredient in the pharmaceutical composition of the present invention is an Asteraceae plant extract, taking a feverfew extract as an example, the daily dosage is 0 per day for an adult (body weight 70 kg). It is common to take about 05g to 5Og, and it is appropriate to take about 0.15g to 15g. In addition, when using parthenolide (single product without extract), the daily dose (oral administration) is generally 0.45 mg to 450 mg per day for adults (70 kg body weight). 1. 35mg ~: About 135mg is appropriate.

[0023] In the pharmaceutical composition of the present invention, not only asteraceae plant extracts and parthenolides but also one or more other active ingredients may be mixed. For example, other components effective for joint diseases such as known anti-inflammatory drugs such as steroids and non-steroids, darcosamine, chondroitin, and calcium may be contained in the pharmaceutical composition of the present invention. For example, a person who has already been treated for arthritis can promote the therapeutic effect by using the pharmaceutical composition of the present invention in combination. Parthenolides in the Asteraceae plants, especially feverfew extract, are thought to regulate NFκB and may act by a mechanism different from conventional arthritis therapeutic agents. There is a possibility of synergistic effects.

[0024] In a further aspect, the present invention provides an extract of Asteraceae plant, preferably feverfew extract. Provided is a method for preventing or treating joint diseases such as arthritis, osteoarthritis, and joint destruction characterized by feeding an object to a subject. Furthermore, the present invention also relates to a method for preventing or treating joint diseases such as arthritis, osteoarthritis and joint destruction, characterized by administering to the subject a asteraceae plant extract, preferably feverfew extract or parthenolide. provide. In this method, the Asteraceae plant extract may be consumed as food or drink. In this method, the asteraceae plant extract or valenolide may be administered as a pharmaceutical composition. You can combine power and treatment with other joint disease treatments. Since parthenolide and extracts of Asteraceae, especially feverfew, which contain it, are thought to regulate NFκB and may act by a mechanism different from conventional arthritis therapeutic agents, the treatment or prevention method of the present invention May have a synergistic effect with the treatment or prevention methods using these drugs. In addition, from the viewpoint of the control action of NFκB, the present invention is beneficial to control NFκB, which is characterized by feeding a compositae plant extract, preferably a feverfew extract, to a subject. Provided is a method for preventing or treating diseases such as glomerulonephritis, arteriosclerosis, atopy and asthma. Furthermore, the present invention relates to a disease beneficial to control NFκB, such as glomerulonephritis, arteriosclerosis, atopy, characterized by administration of an Asteraceae plant extract, preferably a feverfew extract, or parthenolide. Also provided are methods for preventing or treating diseases such as asthma.

In yet another embodiment, the present invention provides an extract of Asteraceae plant, preferably feverfew extract, for the production of food and drink for preventing or treating joint diseases such as arthritis, osteoarthritis and joint destruction. Provide the use of things. Furthermore, the present invention relates to an extract of a asteraceae plant extract, preferably feverfew extract, or baltenolide for the manufacture of a pharmaceutical composition for preventing or treating joint diseases such as arthritis, osteoarthritis and joint destruction. Also provides use. In aggressive use, other joint disease treatments may be used in combination. Parthenolide and extracts from the family Asteraceae, especially feverfew, are considered to regulate NFκB and may act by a mechanism different from conventional therapeutic agents for joint diseases. The composition may produce a synergistic effect with these drugs. In addition, from the viewpoint of the control action of NFκB, the present invention provides a disease in which it is beneficial to control NFκB, such as glomerulonephritis, arteriosclerosis, atopy, asthma. The use of an Asteraceae plant extract, preferably a feverfew extract, for the manufacture of food and drink for the prevention or treatment of diseases such as Furthermore, the present invention relates to a chrysanthemum preparation for the production of a pharmaceutical composition for the prevention or treatment of diseases for which NFκB is beneficially controlled, for example, glomerulonephritis, arteriosclerosis, atopy, asthma and the like. Also provided is the use of a family plant extract, preferably feverfew extract, or valenolide.

[0026] The present invention will be described more specifically and in detail below with reference to examples, but the present invention is not limited to the examples.

Example 1

[0027] Experimental methods and materials

Feverfew Extract (batch number: 051016-107) manufactured by HANDA FINE CHEMICALS was used as the feverfew extract. The content of parthenolide in this extract was about 0.9%. Parthenolide manufactured by sigma (purity of 90% or more) was used. The feverfew extract and parthenolide were dissolved in 0.5 w / v% aqueous methylcellulose solution and orally administered to the animals using a metal sonde (twice a day, dose volume 10 mL / kg / dose). The doses of feverfew extract were 222 mg / kg / day and 888 mg / kg / day, and the dose of parthenolide was 50 mgZkg / day. The vehicle control group received 0.5 w / v% methylcellulose aqueous solution. The number of animals per experiment was 10.

[0028] The animals used were male BALB / Cr Slc (SPF) mice, which were 6 weeks old and weighed 19-24g, and were used for the experiment after acclimatization for 7 days.

[0029] Arthritis in animals was induced as follows. On day 0 of the experiment, 2 mg / mouse of an arthritis-inducing monoclonal cocktail (Chondrex, lot numbers OK-514 and OJ-428) were injected intravenously, and 3 days later, lipopolysaccharide (included in the cocktail) 30 μm g / animal was injected intraperitoneally.

[0030] The inflammation score was scored by observing the joints. The scoring criteria are as follows: 0: Normal joint.

1: Mild inflammation and redness are observed.

2: Severe erythema and swelling affecting the entire leg are observed. Animals hesitate to use their legs. 3: Leg or joint deformation is recognized. With stiffness, joint stiffness, and loss of joint function.

[0031] ¾ Test Results

Figure 1 shows the experimental results. In both the parthenolide administration group and the feverfew extract administration group, an arthritis inhibitory effect was observed. Indicated. If the parthenolide content in feverfew extract is 0.9%, the dosage of feverfew extract 222 mgZkgZ days corresponds to parthenolide 2. Omg / mg / day. It is surprising that such a high arthritis inhibitory effect was obtained by oral administration. The reason may be a synergistic effect of other components contained in the feverfew extract.

[0032] The safety of the feverfew extract used in the above experiment was examined. The test method was a fixed dose method based on the E CD Chemical Test Guideline (TG420), and Sic: ICR female mice were used. As a result, there was no animal death in the feverfew extract 2000 mg / kg dose, no abnormalities were observed in the general condition, and the weight gain was also steady. Based on these results, it was estimated that the LD value of pear extract was over 2000 mg / kg.

50

[0033] Further, the mutagenicity of the feverfew extract used in the above experiments was determined using Salmonell atyphimurium TA100, TA1535, TA98, TA1537 and Escherichia coli WP2 uvrA as test bacteria in the absence and presence of S9mix. Examined. As a result, mutagenicity was not observed even at a dose of 5000 _μ§ / plate. From these results, it was found that feverfew extract is extremely safe and high.

Example 2

[0034] In the above experiment, administration of parthenolide and feverfew extract was started at the same time as the arthritis induction procedure for animals. In this experiment, a system for administering force parthenolide 4 days after the onset of arthritis in animals was included.

[0035] The animals used were male BALB / c Cr Sic (SPF) mice, which were 6 weeks old and acclimated to a body weight of 19 24 g for 7 days before use in the experiment (n = 10). Arthritis in animals was induced as follows. On day 0 of the experiment, a monoclonal antibody cocktail for inducing arthritis (Chond rex) 2 mg / animal was injected intravenously, 3 days later, lipopolysaccharide (included in the cocktail) 30 / g The animals were injected intraperitoneally. Starting 4 days after the start of the experiment (onset of arthritis), parthenolide (Sigma) was dissolved in a 0.5 w / v% methylcellulose aqueous solution and orally administered to animals using a plastic sonde (1 day). 2 times 25mg / kg / time). In the feverfew extract extract group, feverfew extract (Fever few Extract batch number 609M907-235, manufactured by Handa Fine Chemicals) was dissolved in 0.5 wZv% methylcellulose aqueous solution and orally administered to animals using a plastic sonde. (220mg / kgZ twice a day). The vehicle control group was given a 0.5 wZv% methylcellulose solution. In addition to observing joint score data over time, the redness and swelling of the ankle joint were observed after 7 and 14 days.

[0036] Fig. 2 shows changes in joint scores over time. Compared to the vehicle group, the progression of arthritis was suppressed in the parthenolide administration group and feverfew extract extract administration group. In addition, there was no difference between the administration of parthenolide at the same time as the onset of arthritis (valtenolide d0) and the administration of parthenolide and feverfew extract 4 days after the onset of arthritis (parthenolide d4, feverfew extract d4). It was a result.

[0037] The observation results on the redness and expansion of the ankle joint will be described. Seven days later, the vehicle control group administered with methinoreser mouth showed redness and swelling in the ankle joint, whereas both the parthenolide administration group and the feverfew extract administration group were compared with the vehicle control group. The swelling and redness of the part were suppressed. After 14 days, the vehicle control group was further reddened and expanded, and the joint was not bent due to the expansion. On the other hand, in the group treated with bartenolide and the feverfew extract, redness and swelling were observed compared to mice that did not develop the disease, but redness was suppressed and swelling of the joints was observed compared to the vehicle control group. The few joints were as mobile as the mice that did not develop the disease.

[0038] From these results, it was revealed that administration of parthenolide and feverfew extract has not only a preventive effect on the onset of illness but also a therapeutic effect.

Example 3

[0039] Subsequent experiments were to investigate the effects of parthenolide administration on arthritic animals on the expression of genes underneath NFκB. [0040] The animals used were male BALB / cCr Slc (SPF) mice, which were 6 weeks old and acclimated to a body weight of 19 24g for 7 days before use in the experiment. (N = 7). Arthritis in animals was induced as follows. On day 0 of the experiment, 2 mg / mouse of arthritis-inducing monoclonal antibody cocktail (Chond rex) was injected intravenously, and 3 days later, lipopolysaccharide (attached to the cocktail) was injected intraperitoneally. Four days after the start of the experiment (onset of arthritis), parthenolide (manufactured by sigma) was dissolved in an aqueous 0.5 wZv% methylcellulose solution and orally administered to the animals using a plastic sonde. (Twice a day, 25 mgZkg / dose) A 0.5 wZv% methylcellulose solution was given to the vehicle group. After 14 days of slaughter, tota 1 RNA was extracted from the ankle joint, and the effect of suppressing the progression of arthritis was examined at the gene level. Gene expression was examined by real-time PCR (RT_PCR).

[0041] The results are shown in FIG. IL-1 / 3, TNF, MMP_9, MIP by administration of parthenolide

1. The increase of each gene was suppressed. In other words, it was revealed that mice that developed rheumatoid arthritis to which parthenolide was administered suppressed the expression of these genes locally in the joint. Since these underlying genes of NFκB were suppressed by parthenolide, it was considered that the expression of NFκB was suppressed by parthenolide.

Example 4

[0042] After collecting chondrocytes of normal humans, IL-l j3 was added to cause degeneration. After 3 hours from the start of denaturation, vartenolide (manufactured by Sigma) was added, and the effect of suppressing gene expression was examined. (N = 3). The concentration of parthenolide was examined at 20 zg / ml (final concentration) (experiment with ⁵ × 10 ⁵ cells per ml). Gene expression was examined by RT-PCR.

[0043] The results are shown in FIG. The expression of IL-1 j3, MMP_1, and TNF_a genes was clearly repressed compared to those with the addition of bartenolide. Although MMP-3 was not statistically significant, it showed a tendency to suppress gene expression when compared with those that did not receive parthenolide. Since these underlying genes of NFκB were suppressed by parthenolide, it was considered that the expression of NFκB was suppressed by parthenolide.

Example 5 [0044] After collecting synovial cells from a rheumatic patient, stimulation was performed by adding 10 μg / ml of TNFa. Three hours after the start of stimulation, feverfew extract (feverfew extract batch number 609M907-235 manufactured by Handa Fine Chemicals was used for feverfew extract) was added and the inhibitory effect on gene expression was examined (n = 3) . Feverfew extract (were experiments in 5XL 0 ⁵ cells per lml) to 0. 2ng / ml, 2ng / ml , 20ng / ml 3 kinds discussed in (both final concentration). Gene expression was examined by RT-PCR.

The results are shown in FIG. There was a tendency for the expression of IL_1j3, TNF, and MMP_3 genes to be suppressed, and there was also a dose-dependent tendency for IL-1 / 3 gene expression. MMP-1 also showed a tendency to be suppressed Although it was not significant in statistical statistics. This is probably because MMP-1 is greatly influenced not only by NF / c B but also by other transcription factors. Since the genes underneath these NFκB were suppressed by the feverfew extract, it was considered that the expression of NFκB was suppressed by the feverfew extract.

Industrial applicability

[0046] The present invention is useful in the fields of health foods, functional foods and pharmaceuticals.

Claims

The scope of the claims

[I] A food and drink for preventing or treating joint diseases, comprising an extract of a asteraceae plant.

[2] The food or drink according to claim 1, wherein the joint disease is selected from the group consisting of arthritis, osteoarthritis and joint destruction.

[3] A food and drink for preventing or treating a disease for which suppression of NFκB is advantageous, comprising an extract of an Asteraceae plant.

[4] The food or drink according to any one of claims 1 to 3, wherein the Asteraceae plant is feverfew.

[5] The food or drink according to any one of claims 1 to 4, which is a supplement.

[6] A pharmaceutical composition for preventing or treating joint diseases, comprising an extract of Asteraceae plants or parthenolide.

[7] The pharmaceutical composition according to claim 6, wherein the joint disease is selected from the group consisting of arthritis, osteoarthritis and joint destruction.

[8] A pharmaceutical composition for preventing or treating a disease that is capable of inhibiting NFκB, comprising an extract of Asteraceae or parthenolide.

[9] The pharmaceutical composition according to any one of claims 6 to 8, wherein the Asteraceae plant is feverfew.

[10] A method for preventing or treating a joint disease, characterized by feeding an extract of an Asteraceae plant to a subject or administering an extract of an Asteraceae plant or parthenolide to a subject.

[II] The method according to claim 10, wherein the joint disease is selected from the group consisting of arthritis, osteoarthritis and joint destruction.

[12] A disease advantageous for suppressing NFκB, characterized by feeding a subject with an extract of an Asteraceae plant, or administering an extract of a compositae plant or parthenolide to a subject. How to prevent or treat.

[13] The method according to any one of claims 10 to 12, wherein the Asteraceae plant is feverfew.

[14] Use of extracts from Asteraceae plants to produce food and drink for the prevention or treatment of joint diseases.

[15] Extract of asteraceae plants for the manufacture of a medicament for preventing or treating joint diseases Products or parthenolides.

[16] The use according to claim 14 or 15, wherein the joint disease is selected from the group consisting of arthritis, osteoarthritis and joint destruction.

[17] Use of an extract of an Asteraceae plant for producing a food or drink for preventing or treating a disease for which suppression of NFκB is advantageous.

[18] Use of an extract of Asteraceae or parthenolide for the manufacture of a medicament for preventing or treating a disease for which inhibition of NFκB is advantageous.

[19] The use according to any one of claims 14 to 18, wherein the Asteraceae plant is feverfew.