TW201219360A - Heat shock protein expression inducer - Google Patents

Abstract

The purpose of the present invention is to provide: a heat shock protein expression inducer capable of inducing the in-vivo expression of HSP; food, drink, a pharmaceutical product, and a cosmetic containing the HSP expression inducer; and an HSP expression inducing method. Compounds derived from a specific plant such as Zerumbone or an analogue thereof exert an excellent action of inducing the expression of heat shock proteins in vivo, and can be used as the active ingredient for a heat shock protein expression inducer.

Description

201219360 VI. Description of the Invention: Technical Field of the Invention The present invention relates to a heat-induced protein expression inducer. More specifically, the present invention relates to a heat-induced protein expression inducer which induces heat-induced protein expression in a living body and can be effectively used to prevent or ameliorate various diseases and symptoms resulting from high-order structural abnormalities of proteins, Or various conditions and symptoms associated with heat-induced proteins. C Prior Art 3 Background of the Invention There are various anti-purple mechanisms in order to adapt to the growing environment. For example, a mechanism is known as follows: If the growth intensity is increased by 5 to 10 ° C, the steric structure of the cellular protein begins to change due to thermal denaturation, but is caused by a protein group called "ChaPeron". To fix it. The maintenance of the life or the life span of the protein is greatly affected by the "protein quality management" accompanying the protein. For example, 'Heterocephalus glaber is a rodent with a very long life of 30 years. Compared to mice (2 to 3 years of life), its protein quality management mechanism is meaningfully superior. Heat Shock Protein (hereinafter also referred to as hsp) is known as a representative protein that functions as a protein. At present, it is reported that HSp has more than ten species in mammals, and according to its molecular weight, it is classified into 11卯2〇 family, HSP40 family, HSP70 family, HSP90 family and the like. Hsp, also known as stress protein, reluctantly manifests itself in the body in response to environmental stress, pathological stress, psychological stress, etc. "The usual cells under non-stress also blame 201219360 for a certain amount of performance. In the body. The expressed HSP specifically binds to a multi-peptide that has just been synthesized but has not yet formed a high-order structure, or a protein that undergoes various pressures to change a part of the higher-order structure so that the original physiological function almost disappears, and utilizes ATP. The energy generated by the decomposition of water is used to restore the high-order structure of the protein of the binding object to restore the physiological function. Such HSP is helpful for the maintenance of the body and the maintenance of the body. It is effective to induce HSP in the living body, and it is effective for prevention or improvement of various diseases or symptoms caused by high-order structural abnormalities of proteins, or for various diseases or symptoms of HSP. The substance of the report, the report indicates: a specific structure of cholesterol glucoside (Patent Document 1), a disaccharide hyaluronic acid oligosaccharide ( Patent Document 2), tetramethyl-undecenetetraen-2-one (Patent Document 3), 2-cyclopenten-1-one (Patent Document 4), and hydroxylamine derivative having a specific structure (Patent Document 5) However, these substances are not natural compounds, but are chemically synthesized substances or substances obtained by decomposing natural substances. In the past, they have not been from natural compounds with high edible experience and high safety or the like. It is found that substances that induce HSP expression in the living body. Therefore, if a substance that induces HSP expression in the living body can be extracted from such natural compounds or their analogs, it can be highly useful and simple and safe. The method is to strengthen the maintenance of the biological defense function or the abnormality of the living body, and the prevention or improvement of various diseases or symptoms, and further achieve the maintenance or improvement of health such as prolonged life. On the other hand, it is known that the flower ginger contains Natural ingredient flower zingerone

4 201219360 (Zerumbone), its analog hop hop contains hops, carotene, lycopene, zeaxanthin, cryptoxanthin, lutein, phenylethyl isothiocyanate and ursolic acid There are compounds with high levels of experience and safety, but there is no report on the induction of HSP performance. CITATION LIST Patent Literature Patent Literature 1: Japanese Patent No. 4322329 Patent Document 2: Japanese Patent No. 4195107 Patent Document 3: Japanese Patent No. 4035591 Patent Document 4: Japanese Patent Laid-Open No. 2009-108048 SUMMARY OF THE INVENTION PROBLEMS TO BE SOLVED BY THE INVENTION An object of the present invention is to provide an HSP expression inducing agent capable of inducing Hsp expression in a living body. More specifically, it is an object of the present invention to provide a method for inducing HSP expression in a living body, for preventing or even improving various diseases and symptoms caused by abnormal structural abnormalities of proteins, or for various diseases and symptoms associated with HSP. The HSP expression inducer. Further, an object of the present invention is to provide a food and drink, a pharmaceutical, a cosmetic containing an HSP expression inducing agent, and to further provide a method for inducing HSP expression. Means for Solving the Problem In order to solve the above problems, the inventors of the present invention have intensively studied and found that specific plants such as Zermumone and its analogs are used to induce HSP expression in vivo in 201219360 source compounds. The action system is excellent and can be utilized as an active ingredient of an HSP expression inducer. The present invention has been completed on the basis of such knowledgeal knowledge. That is, the present invention has the following aspects: [Item 1] A heat-inducing protein expression inducer characterized by containing a pigment selected from the group consisting of zingerone and the like, carotenoid, and eggplant red At least a compound of the group consisting of zeaxanthin, zeaxanthin, cryptoxanthin, lutein, phenethyl isothiocyanate, ursolic acid and vitamin A is used as an active ingredient. [Claim 2] The heat-inducing protein expression inducer according to Item 1, which is selected from the group consisting of zingerone and its analogues, carotene, lycopene, zeaxanthin, cryptoxanthin, and chlorophyllin At least one compound selected from the group consisting of p-, ethyl isothiocyanate and ursolic acid is used as an active ingredient. [Item 3] The heat-inducing protein expression inducer according to Item (1), which is selected from the group consisting of Phyllostachys pubescens and its analogues, carotene, lycopene, zeaxanthin, lutein, At least one compound selected from the group consisting of phenethyl isothiocyanate and ursolic acid is used as an active ingredient. The heat-inducing protein expression inducer of any one of the items 1 to 3, which contains at least one compound selected from the group consisting of zingerone and the like as effective ingredient. [No. 5] The heat-inducing protein expression inducer according to any one of items 1 to 4, in JL; JI·Bahua _ and its analogs are not represented by the following formula (1) Saturated alicyclic compound: General formula (1) [Chemical 1] 201219360

[In the formula (1), the cores ~1^4 are the same or different and represent a hydrogen atom or an alkyl group having 1 to 5 carbon atoms; and R15 and R16 are a hydrogen atom or a hydroxyl group, or collectively represent an oxygen atom]. [Item 6] The heat-inducing protein expression inducer according to Item 4, wherein 'R1, R7, Rii, and Ri2 in the formula (1) are a sulfhydryl group, Κ·2 to R6, and a size of 8 to Rio and Rl3. 〜Rl4 is a hydrogen atom; Rl5 and Rl6 are deuterium atoms or together form an oxygen atom. The heat-inducing protein expression inducer according to any one of items 1 to 6, which contains 1 to 1 mg of a substance selected from the group consisting of zingerone and the like At least one compound is used as a daily dose. The heat-inducing protein expression inducer according to any one of items 1 to 7, which contains 2 to 10% by weight selected from the group consisting of zingerone and the like At least one compound. The heat-inducing protein expression inducer according to any one of items 1 to 8, which comprises a plant extract comprising the aforementioned active ingredient. [10] The heat-inducing protein expression inducer according to Item 9, wherein the plant extract is selected from the group consisting of at least one plant consisting of a group consisting of ginger, medlar, hop, clove, and lavender. The extract. [11] The heat-inducing protein expression inducer according to Item 9 or 10, wherein the aforementioned plant extract contains at least one compound selected from the group consisting of zingerone and the like. After the ginger extract. [12] The heat-inducing protein expression inducer according to any one of the items of the present invention, wherein the aforementioned heat-trapping protein is a heat-trapping protein 7〇 family protein. The heat-inducing protein expression inducer according to any one of the items 12 to 12, which is suitable for preventing or restoring muscle atrophy, inhibiting muscle fatigue, anti-stress, preventing or ameliorating dementia, Prevent or improve depression, prevent or improve Mannatory Fatigue Syndrome, improve blood circulation, improve coldness of limbs, change edema, improve shoulder and neck stiffness, prevent or improve rheumatism, prevent or improve retinopathy, improve exercise capacity, and improve endurance , boosting immunity, or the use of anti-organic organ syndrome. [The item 14] The heat-inducing protein expression inducer according to any one of the items 1 to 13, which is suitable for preventing or restoring muscle atrophy, inhibiting muscle fatigue, resisting stress, preventing or improving chronic fatigue syndrome, Prevent or improve rheumatism, improve exercise capacity, enhance endurance, or use anti-organic organ syndrome. [Item 15] A food or drink, a pharmaceutical or a cosmetic comprising the heat-inducing protein expression inducer according to any one of items 1 to 14. [Item 16] A food or drink or a pharmaceutical preparation, which comprises the heat-inducing protein expression inducer according to any one of items 14 to 14. [Item 17] A method of inducing a heat-induced protein expression, which is characterized by using the heat-inducing protein expression inducer according to any one of items 1 to 14. [Embodiment 18] A method for inducing heat-induced protein expression, wherein the food or drink, the pharmaceutical or the cosmetic product according to item 15, or the food or drink or the pharmaceutical product according to item 16 is used. 201219360 [Item 19] Prevents or restores muscle atrophy, inhibits muscle fatigue, resists stress, prevents or improves dementia, prevents or improves depression, improves blood circulation, improves coldness of limbs, improves edema, and improves shoulder and neck stiffness , a method of preventing or improving rheumatism, preventing or ameliorating retinopathy, improving exercise capacity, improving endurance, enhancing immunity, or preventing or improving dysfunction of a motor organ, characterized in that the application is as described in any one of items 1-4 Heat-induced protein expression inducer. [Item 20] Preventing or restoring muscle atrophy, inhibiting muscle fatigue, resisting stress, preventing or ameliorating dementia, preventing or improving depression, improving blood circulation, improving coldness of limbs, improving edema, and improving shoulder and neck stiffness, A method for preventing or improving rheumatism, preventing or ameliorating retinopathy, improving exercise capacity, improving endurance, enhancing immunity, or preventing or improving dysmotility syndrome, characterized by using a food or beverage, a pharmaceutical or a cosmetic as described in claim 15. Or a food or drink or a pharmaceutical product as described in item 16. [Item 21] One selected from the group consisting of zingerone and its analogues, carotenoid lycopene, zeaxanthin, cryptoxanthin, lutein, phenethyl isothiocyanate, ursolic acid and vitamin A At least one of the constituent compounds in the group is used for the production of a heat-inducing protein expression inducer. [Item 22 contains a pigment selected from the group consisting of zingerone and its analogues, carotenoids, lycopene, zeaxanthin, cryptoxanthin, (tetra), phenethyl isothionate, ursolic acid and A plant extract of at least a compound of the group consisting of vitamin A is used for the production of a heat-inducing protein expression inducer. [Item 23] The use of the plant extract according to Item 22, wherein the plant extract is selected from the group consisting of at least one plant of 201219360 consisting of a group consisting of ginger, medlar, hop, clove, and lavender. . The use of the above-mentioned plant extracts each having a flowering ginger extract selected from the group consisting of at least an anthraquinone compound of the group consisting of zingiberone and the like. Item: a substance selected from the group consisting of flower tomb ketone and its analogues, carotene sulphate, auxin, zeaxanthin, cryptoxanthin, lutein, isothiocetic acid phenylacetic acid ursolic acid and The compounds of the group consisting of vitamins eight are used for the manufacture of food, drink, food or cosmetics having a heat-induced protein expression. [Item 26] A compound selected from the group consisting of zingerone and its analogues, carotenoids, lycopene, zeaxanthin, cryptoxanthin, lutein, isothiocyanate, and bearberry The acid and vitamins constitute a plant extract of at least a composition of the composition for use in the manufacture of a food or drink, a pharmaceutical or a cosmetic having a heat-induced protein expression. [27] The use according to Item 26, wherein the plant extract is selected from the group consisting of at least one plant selected from the group consisting of Ginger, IU1, hop, clove, and sylvestris. . The use of the plant extract according to Item 26 or 27, wherein the plant extract contains a flowering ginger extract selected from at least one compound selected from the group consisting of zingerone and the like. [Item 29] - a method for expressing a heat-inducing protein - a compound used in which the strain is selected from the group consisting of zingerone and its analogues, carotenoids, eggplant, corn, and corn At least a compound of the group consisting of flavin, lutein, phenethyl isothiocyanate, ursolic acid, and vitamin A.

10 201219360 [Item 30] A plant extract for use in a method for expressing a heat-inducing protein, which comprises a flower selected from the group consisting of zingerone and its analogues, carotenes, lycopene, zeaxanthin , at least one of the group consisting of cryptoxanthin, lutein, phenethyl acetoacetate, ursolic acid, and vitamin A. [Item 31] Plant extraction as described in Item 30 The aforementioned plant extract is selected from the group consisting of extracts of at least one plant consisting of a group consisting of flower ginger, medlar, hop, clove, and lavender. [Claim 32] The plant extract according to Item 30, wherein the plant extract contains a flower ginger extract selected from at least one compound selected from the group consisting of zingerone and the like. Things. !"Into the six paste (10) milk, Mingluo_素, lycopene, zeaxanthin, cryptoxanthin, lutein, isothiocyanate, ethyl vinegar, canola acid and vitamin A At least a can compound, which is used to prevent muscle contraction or restore it, inhibit muscle fatigue, resist stress, prevent or ameliorate dementia, prevent or ameliorate anxiety, improve blood circulation, change limbs cold, improve edema, improve shoulder Use in a method of neck stiffness, prevention or improvement of wind/prevention or improvement of retinopathy, improvement of exercise capacity 'enhancement: immunization, or prevention or improvement of exercise' syndrome; [item 34] a substance selected from the group consisting of a hormone and a lip , zeaxanthin, barrier/de-Ming and "analogs, carrots, snails, ursolic acid and ... Λ, 、, lutein, sulphur, sulphur, sulphur, sulphur At least the shopping extract, which is attached to the preventive muscle (4). Planting, resisting stress, preventing or modifying or restoring, inhibiting muscle fatigue. Loss, prevent or improve worry, change 11 201219360 Good blood circulation, improve coldness of limbs, improve edema, improve shoulder and neck stiffness, prevent or improve rheumatism, prevent or improve retinopathy, improve exercise capacity, enhance endurance, enhance immunity Or a user in a method of preventing or ameliorating motility syndrome. The botanical extract according to the item 34, wherein the botanical extract is selected from the group consisting of at least one plant selected from the group consisting of sage ginger, medlar, hop, clove, and lavender. . The botanical extract according to the item 34 or claim 35, wherein the botanical extract contains a ginger extract selected from at least one compound selected from the group consisting of zingerone and the like. Things. [Claim 37] The food or drink according to Item 15, 'Pharmaceutical or Cosmetic, or the food or drink or the pharmaceutical according to Item 16, for use in a method for expressing a heat-induced protein. [Claim 38] The food or drink, the pharmaceutical or cosmetic according to Item 15, or the food or drink or the pharmaceutical according to Item 16, which is for preventing muscle atrophy or restoring, inhibiting muscle fatigue, and resisting Stress, prevent or improve dementia, prevent or improve depression, improve blood circulation, improve coldness of limbs, improve edema, improve (4) stiffness, prevent or improve rheumatism, prevent or improve retinopathy 'enhance exercise capacity, enhance endurance, enhance Used in methods of immunization, or prevention or improvement of dysarthon syndrome. [Item 39] - The food, the medicinal product or the cosmetic contains the heat-inducing protein expression inducer according to any one of items 1 to 14 such that the heat-induced protein expression-inducing function is such that the food or drink, the medicine The method of product or cosmetics. 12 • 'ί 201219360 EFFECTS OF THE INVENTION According to the present invention, it is possible to effectively induce HSP expression in a living body, thereby enhancing the maintenance of the biological defense function and the living body, and preventing or improving various diseases or symptoms. It is possible to further extend the life and other health = holding or improving. Further, the HSP performance material (4) of the present invention uses a natural compound having edible experience, such as flowers and the like, as an active ingredient, and has the advantage of high safety in use. Moreover, because of such high safety, the Hsp expression-inducing agent of the present invention can be continuously taken or administered over a long period of time, and the Hsp expression in the living body is maintained at a high state, which is accompanied by maintenance of the protein mechanism. It is also possible to activate the state. BRIEF DESCRIPTION OF THE DRAWINGS Fig. 1 is a view showing the results of measuring the amounts of HSP27, HSP40, HSP70, HSP90a and HSP90b in the presence of each concentration of zingerone in Example 1. In addition, in the first figure, rZER" means flower zingerone. Further, the vertical axis of Fig. 1 is a relative value of the amount of each HSP expression when the expression amount of each Hsp in the control group (flower zingerone 0 μΜ) is set to 1. Fig. 2 is a graph showing the results of HSP70 expression by measuring the culture of new mouse liver cells in 3.6 hours using a culture solution of cells treated with serotonin 〇 5〇μΜ in Example 3. In the second figure, "zer" is a flower zingerone. Further, the vertical axis of Fig. 2 is a relative value of the amount of HSP70 expression when the expression amount of each HSP in the control group (sedum ketone oxime) is set to 1. Fig. 3 is a graph showing the results of the effect of zingerone on the pressure in Example 4. 13 201219360 Figure 4-1 shows the results of reviewing the effect of zingerone on muscles in Example 5. The results shown in Fig. 4-1 are obtained by performing a tail suspension test after pre-administration of a test subject in a mouse. Fig. 4-2 is a graph showing the results of the effect of zingerone on the amount of mRNA expression of HSP72 in muscle in Example 5. Fig. 5-1 is a diagram showing the results of examining the effect of zingerone on muscles in Example 6. The results shown in Fig. 5-1 are obtained by administering a test substance to a mouse after performing a tail suspension test. Fig. 5-2 is a graph showing the results of the effect of zingerone on the amount of mRNA expression of HSP72 in muscle in Example 6. I. Embodiment 3 Mode for Carrying Out the Invention In the present specification, the term "~" indicating a limited value is used to mean a value including both sides of the symbol within the numerical range. The HSP expression inducing agent of the present invention contains a selected from the group consisting of zingerone and its analogues, carotene, lycopene, zeaxanthin, cryptoxanthin, lutein, phenylethyl isothiocyanate, bear At least one compound selected from the group consisting of fruit acid and vitamin A is characterized as an active ingredient. Two or more of these compounds may be contained or contained alone. The flower zingerone and its analog are unsaturated alicyclic compounds represented by the following formula (1). General formula (1) [Chemical 1]

14 201219360

In the formula (1), RcRm is a hydrogen atom which may be the same or different or a group having a carbon number of 1 to 5; and Ri 5 and Ri6 are a nitrogen atom, a trans group, or a combination thereof and are an oxygen atom. Specific examples of the alkyl group having 1 to 5 carbon atoms include methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, second butyl group, isobutyl group, tert-butyl group, and n-pentyl group. Base, isopentyl, second amyl, third amyl and the like. In the formula (1), RcRh can be exemplified by a hydrogen atom which may be the same or different or an alkyl group having 1 to 3 carbon atoms, more preferably a hydrogen atom of the same or different or a carbon number of 1 to 2. The alkyl group is preferred, and particularly preferably the same or different hydrogen atom or sulfhydryl group. Further, from the viewpoint of more effectively inducing HSP performance, in the formula (1), R丨, R7, R, 丨 and R12 are an alkyl group having 1 to 5 carbon atoms, and an alkyl group having 1 to 3 carbon atoms. The base is preferred, and the alkyl group having 1 to 2 carbon atoms is preferred, and the sulfhydryl group is preferred. Further, R2 to R~6 and R~8 to Rl. And Rl3 to Rl4 are preferably a hydrogen atom. In the formula (1), 'R1, Κ·7, R11 and Rl2 are an indenyl group, R2~6, R8~RlO and Rl3~Rl4 are a hydrogen atom, and Rl5 and Rl6 are taken together to form an unsaturated atom of an oxygen atom. The ring compound is a well-known compound called zingerone. Flower zingerone is a natural compound contained in the leaves or rhizome of Gingeraceae belonging to the genus Gingeraceae. It also has long-term edible experience and is a compound with high safety. In the general formula (1), 'R| R" Rl1 and Rl2 are methyl, r2~r6, r8~rI0 and R13 Ru are nitrogen atoms? RI5 and 1^16 are hydrogen atoms of an unsaturated alicyclic compound, which is called hop hemp. The olefinic compound is present in a secret plant, a pine plant, a hop, a clove oil, a lavender oil, etc. In the present invention, the unsaturated alicyclic compound represented by the formula (1) may also be pharmaceutically acceptable. Or edible salt (4). The formula (1) is not limited to the moon! The soil compound can be produced by a known method such as organic chemical synthesis, enzyme reaction synthesis, natural product extraction, etc. For example, '花姜_ can It can be obtained by extraction treatment with ginger, and it can be obtained by extracting from ginger, and the leaves, roots or whole plants of the flowering ginger can be subjected to steam distillation or solvent extraction, and the root portion is preferably used. In the solvent extraction, the extraction solvent can be carried out using ethanol. The extract obtained by steam distillation or solvent extraction is supplied to a purification step using a gas phase-water two-layer solvent phase flow distribution, gel chromatography or the like. Obtain high purity flower zingerone. Also, about from ginger A specific method for the extraction and purification of flower zingerone has been disclosed in Biosci, Biotechnol. Biochem., 63 (10), 1999, according to the well-known method. As carotene, lycopene, corn zeal , cryptoxanthin, lutein, phenylethyl isothiocyanate, ursolic acid and vitamin A ', for example, alpha carotene, beta carotene, gamma carotene, δ carotene, 8 carotene, stevia red , zeaxanthin, alpha cryptoxanthin, beta cryptoxanthin, lutein, phenylethyl isothiocyanate, ursolic acid and retinol. The HSP expression inducer of the present invention can be contained as needed Edible

16 201219360 Or an optional ingredient such as a pharmaceutically or cosmetically acceptable carrier or additive. Examples of such a carrier or additive include, for example, an aqueous vehicle, a shaped agent, a binder, a disintegrant 'lubricant, a tackifier, a surfactant, a permeation regulator, a wetting agent, a pH adjuster, Sweeteners, flavors, colorants, etc. The above is well known to those skilled in the art and can be suitably selected for use. As long as it is a person in the industry, these ingredients can be appropriately selected. Further, the HSP expression inducing agent of the present invention may also contain, in addition to the aforementioned flower zingerone and its analogs, carotene, lycopene, zeaxanthin, cryptoxanthin, lutein, stupid ethyl isothiocyanate, bear A substance other than fruit acid and vitamin A having an induction effect of HSP or other physiologically active substance. The applicable form (dosing route) of the HSP expression-inducing agent of the present invention may be, for example, oral ingestion or transdermal, transmucosal, intravenous, subcutaneous, intramuscular, intra-articular, enteral administration, etc., depending on the induced HSp. The body parts of the performance are appropriately set. As a suitable form of the Hsp expression-inducing agent of the present invention, it is preferably used orally or transdermally, and more preferably, it can be administered orally. The form of the HSP expression inducing agent of the present invention is not limited, and examples thereof include a solid form such as a powder, a tablet, a granule, and a pill; a semi-solid form such as a cream, an ointment, a curtain, or a gel; A liquid form such as a dose, a suspension, an emulsion, or a sugar polymerization agent. Further, these forms may be filled in a microcapsule, a soft capsule, a hard capsule or the like to form a capsule. Further, the HSP expression inducing agent of the present invention can also be in the form of a foaming preparation. The production method of the material form can be carried out according to the method known in the art, and the form of the material can be suitably determined according to the applicable form of the HSP expression inducer of the present invention. Moreover, it can be added to various beverage types and food forms. 17 201219360 The amount of the HSP expression-inducing agent to be used in the present invention may be appropriately determined depending on the purpose of use (the type of the subject's disease or the type of the symptoms, etc.), the sex of the user, the age, etc., and the amount of use per adult per day is as usual. The foregoing is selected from the group consisting of zingerone and its analogues, carotenoids, ruthenium, cryptoxanthin, lutein, isothiocyanate, ursolic acid and vitamin A. At least one compound in the group is preferably from 1 to 100 mg in total, and preferably from 2 to 50 mg, more preferably from 3 to 2 mg, particularly preferably from 5 to 1. The HSP expression inducing agent of the present invention uses the above-mentioned amount to be used in the target site by using -1 or 2 to 5 times, and is limited to a person, for example, a light animal other than a human or a so-called peeping object. Various animals such as poultry. In the HSP expression inducer of the present invention, the above-mentioned one selected from the group consisting of squid _ and its analogues, carotenoid, lycopene, zeaxanthin, cryptoxanthin, lutein, phenyl isothiocyanate (5) The mixing ratio of at least one compound in the group consisting of ursolic acid and vitamin A may be appropriately set within the range in which the amount of the above-mentioned use can be administered or ingested. For example, the aforementioned Hsp expression inducing agent of the present invention is selected from the group consisting of zingerone and its analogues, carrot =, lycopene, zeaxanthin, cryptoxanthin, lutein, phenyl isothiocyanate. The ratio of the mixed 5 of at least the compound of the group consisting of samarium, ursolic acid and vitamin A is 2 〇 to 1 〇〇 by weight in total, and 4 〇 to 1 〇〇 by weight. Further, it is preferably 60 to 100% by weight. Further, the active ingredients can be obtained by plant extraction and purification treatment, and the extract obtained by the process itself can also be used as the HSP expression inducer of the present invention. For example, the aforementioned flower zingerone and the like may be extracted by Hua Jiang, zedoary, hop, clove, lavender, etc., and purified by 201219360. The material obtained by the process (4) itself may also be used as the HSP expression inducer of the present invention. Further, the extract may be mixed with the optional components as the HSp expression inducer of the present invention. The blending amount of the above optional components which can be contained in accordance with the requirements can be suitably adjusted to suit the effect of the present invention, and can be suitably used as a target form or a preference. The HSP expression-inducing agent of the present invention itself may be in the form of a food or drink, a medicine (including a quasi-drug) or a cosmetic. Preferred examples thereof include pharmaceuticals (including quasi-drugs taken internally) and foods and drinks. When the HSP expression inducing agent of the present invention is prepared as a food product, in addition to the above-mentioned active ingredients, a mixed sweetener, a coloring agent, a preservative, a tackifier, a stabilizer, a gelling agent, a paste, an antioxidant, and a Coloring agent, bleaching agent, antifungal agent (mold inhibitor), yeast nutrient, gum base, flavor, sour agent, seasoning, emulsifier, pH adjuster, alkaline water, expansion agent, nutritional supplement, other food and beverage The material can be modulated into a desired form. When the HSP expression-inducing agent of the present invention is in the form of a food or drink, the form is not particularly limited. Examples thereof include foods in the form of supplements such as gelatinous preparations, granules, fine granules, capsules, troches, powders, liquid preparations, and semi-solid preparations; carbonated drinks, refreshing drinks, milk drinks, alcoholic drinks, and fruit drinks. , tea, nutritious drinks and other beverages; powdered drinks such as powdered juices and powder soups; chewing gums, ingots, candies, biscuits, fondants, scallops, biscuits, jellies and other snacks; bread, noodles, valleys Slices, jams, seasonings, etc. These foods are used as foods and drinks for the induction of HSP expression, and are used, for example, as general foods, and as food supplements such as nutritional supplements, functional foods, 19 201219360 specific health foods, and patient foods. When the H S P expression inducing agent of the present invention is prepared as a pharmaceutical product (including a quasi-drug), other medicinal ingredients, pharmaceutically acceptable carriers or additives may be optionally mixed in addition to the above-mentioned active ingredients. Specific examples of the pharmaceutically acceptable carrier or additive include a binder, a disintegrator, a lubricant, a wetting agent, a buffer, a preservative, a perfume, and the like. When the preparation of the HSP expression-inducing agent of the present invention is prepared as a pharmaceutical, the form thereof is not particularly limited, and examples thereof include an injection, an external preparation, an inhalant, a suppository, a tablet, a buccal, a liquid, a powder, and a lozenge. , granules, capsules, syrups, eye drops, eye washes, nose drops, and the like. Among them, a form suitable for oral administration (that is, an internal administration of a pharmaceutical) is preferred, and examples of the form include a buccal preparation, a liquid preparation, a powder, a lozenge, a granule, a capsule, a syrup, and the like. . These pharmaceutical products (including quasi-drugs) are used as a medicine for inducing Hsp expression. When the HSP expression inducing agent of the present invention is prepared as a cosmetic (including a functional cosmetic) or a topical quasi-drug, a pharmaceutically or cosmetically acceptable carrier (water, oily component, etc.) may be mixed in addition to the above-mentioned active ingredient. In order to make the desired form. The above-mentioned cosmetics are not particularly limited as long as they can be used on the skin. Examples thereof include a liquid form, an emulsion form, a powder form, a solid form, a suspension form, a cream form, a cream form, a curtain form, a granule form, a tablet form, a gel form, a jelly form, and a paste form. It is in the form of a gel, an aerosol, a spray, an elixir, or a film-forming agent. These cosmetics are used as cosmetics having an effect of inducing HSP expression. Further, the HSP expression-inducing agent of the present invention may be used as a food or drink or a pharmaceutical containing the HSP expression-inducing agent of the present invention as an additive to a food or drink, a pharmaceutical product (including a quasi-drug) or a cosmetic as 20 201219360. (Containing quasi-drugs) 'Cosmetic, the effect of the HSP expression inducer caused by the present invention can be obtained. In other words, the HSP expression inducing function can be imparted thereto by using the HSP expression inducing agent of the present invention in a food or drink, a pharmaceutical product (including a quasi drug) or a cosmetic. Among them, the HSP expression-inducing agent of the present invention is suitable for use in a pharmaceutical product (including a quasi-drug for internal administration) and a food or drink which are administered to the inside of the HSP expression-inducing function. When the HSP expression-inducing agent of the present invention is used as an additive, it is not limited to the form of foods and drinks, pharmaceuticals (including quasi-drugs), and cosmetics. The foods and drinks and pharmaceuticals (including quasi-drugs) ), the form of cosmetics. In the cosmetics, pharmaceuticals (including quasi-drugs), the amount of the HSP expression-inducing agent of the present invention is not limited, and may be used depending on the purpose of use (the type of the disease or the symptom of the subject), the target site, and the use. The gender and age, food and beverage, pharmaceutical products (including quasi-drugs) or the form of cosmetics, and their secrets of drug administration are eliminated. Therefore, the HSP expression inducing agent of the present invention is limited to a mixed shirt in a food or beverage, a pharmaceutical product (including a quasi-drug) or a cosmetic, and can be exemplified as follows: the coffee table of the present invention _ guides the secret person to produce a daily amount of The foregoing is at least i selected from the group consisting of zingerone and its analogues, (tetra) vasopressin, vasopressin, zeaxanthin, cryptoxanthin, lutein, isothiocyanate W, and bear pure silk biotin A. The total amount of the compound is called (10), and it is preferably 2 to 50 mg, more preferably 3 to 2%, and particularly ^^ wrist ^ is preferred. Further, 21 201219360 As described above, the aforementioned flower zingerone and the like can be obtained by extracting and purifying the flower ginger, medlar, hop, clove, lavender, etc., and the components can be extracted and purified by plants. The extract obtained by the process itself may be used as the HSP expression inducer of the present invention, and the extract itself may be used as the HSP expression inducer of the present invention, as compared with foods and drinks, pharmaceuticals (including quasi-drugs). And cosmetics, as the amount of use per day for an adult, the extract is preferably mixed in the range of 0.05 to lg, and preferably mixed in the range of 0.1 to 0.6 g. In the HSP expression-inducing agent of the present invention, any of the HSP lines which are targets for expression induction are included: HSP20 family proteins such as HSP20, HSP27, and HSP28; HSP40 family proteins such as HSP40 and HSP47; HSP70 and HSP72. HSP70 family proteins such as HSP73; HSP90 family proteins such as HSP90a and HSP90b. Among them, HSP27, HSP4, HSP70, HSP72, HSP90a, and HSP90b are suitable expression-inducing agents of the HSP expression-inducing agent of the present invention. Further, it has been reported that HSP70 family proteins, which are representative examples of HSP, particularly various physiological functions of HSP7〇 and HSP72, play an important role in the defense of the body or the maintenance of the body constant, and therefore belong to the present invention. HSP exhibits a particularly suitable expression-inducing agent for the inducer. Furthermore, HSP72 is secreted outside the cell and also exhibits a cytotoxic effect. It can widely produce NK (natural killer) cells, NKT (external thymus) cells, activated tau cells, and specific antibodies. Natural immunity and acquired immunological activation are therefore suitable expression-inducing subjects belonging to the HSP expression-inducing agent of the present invention. The HSP expression inducer of the present invention can be inhibited by inducing HSP expression

S 22 201219360 Cytopathic (cell degeneration, cell damage, etc.) or cell death caused by environmental stress, pathological stress, psychological stress, etc., can prevent or ameliorate the condition or symptom caused by the cytopathic or cell death. Further, the Hsp expression inducing agent of the present invention is effective for preventing or improving various diseases or symptoms caused by high-order structural abnormalities of proteins or for various diseases or symptoms of HSP. For example, HSP70 family proteins are known to prevent or improve blood circulation, protect various organs or tissues, protect against oxygen, enhance oxygen carrying capacity, restore nervous function, improve exercise capacity, enhance immunity, and resist inflammation. Other health effects, etc. Therefore, the HSP expression inducer of the present invention is based on the effect of preventing or improving blood circulation disorder by the Hsp70 family protein, for skin beauty, whitening, maintaining mucosa, improving limb cold, improving edema, preventing thrombosis, and improving shoulder and neck stiffness. Improve low back pain, enhance wound healing, enhance natural healing power, improve constipation, promote digestion, prevent or improve myocardial infarction / cardiac insufficiency, prevent or improve myocardial infarction, prevent or improve ischemia/reperfusion injury, hair growth, prevention The use of hair is effective. Further, the HSP of the present invention exhibits the protective effects of various organs or tissues caused by the inducer-based mHSP70 family protein, that is, the protective effects on livers, digestive organs, kidneys, retinas and the like, and prevents hangovers and prevention. It is also effective to improve liver function, enhance liver function, protect gastrointestinal mucosa, prevent or improve renal insufficiency, prevent or improve retinopathy, prevent or ameliorate multiple sclerosis, and prevent or improve cystic fibrosis. Further, the HSP expression-inducing agent of the present invention is effective in the anti-oxidation effect of 23 201219360 based on the HSP70 family protein, and is also effective for anti-aging, prevention or improvement of diabetes, improvement of insulin resistance and the like. Further, the HSP performance inducing agent of the present invention is effective for enhancing the oxygen carrying ability by the HSP70 family protein, and is also effective for improving the stamina and improving the exercise ability. The HSP expression-inducing agent of the present invention is based on the recovery effect of the nervous system function caused by the HSP70 family of proteins' for preventing or improving dementia, preventing or improving mental deterioration, preventing or improving depression, preventing or improving Alzheimer's disease, and anti- Stress, increased desire, sleep, and induced sleep are also effective. The HSP expression inducer of the present invention is based on the effect of improving exercise ability caused by the HSP70 family protein, for preventing or improving muscle pain, inhibiting muscle damage during exercise, inhibiting muscle fatigue, preventing or improving muscle atrophy (for example, muscles when plaster bandage is fixed) It is also effective for use in atrophy, life extension, and anti-organic organ syndrome. Further, the HSP expression-inducing agent of the present invention is based on an anti-inflammatory effect by a HSP70 family protein, and is also effective for preventing or improving acute pancreatitis, inflammatory bowel disease, rheumatism, and prevention or improvement of arthritis. The HSP expression-inducing agent of the present invention is effective in preventing or improving cancer, preventing or ameliorating infectious diseases, etc. based on an enhanced immune effect by the HSP70 family protein. Further, the HSP expression inducer of the present invention is based on other health effects of the HSP70 family protein, for preventing or improving infectious diseases, anti-metabolic syndrome, anti-obesity, preventing or improving hyperlipemia, detoxification, improving body odor/age age Stinky and other uses are also effective. Among the above uses, 'to prevent or improve muscle atrophy, inhibit muscle fatigue, resist stress' prevent or improve dementia, prevent or improve depression, prevent or improve chronic fatigue syndrome, improve blood circulation, improve limbs and ice 24 201219360 cold It is suitable to improve edema, improve shoulder and neck stiffness, prevent or improve rheumatism, prevent or improve retinopathy, improve exercise capacity, enhance endurance, enhance immunity, and resist organ syndrome. In addition, the foods and drinks, pharmaceuticals (including quasi-drugs), and cosmetics are all based on the HSP expression-inducing agent of the present invention, and are based on the above-mentioned effects selected from the group consisting of zingerone and the like. At least one compound of the group consisting of carotene, lycopene, zeaxanthin, cryptoxanthin, lutein, phenylethyl thiocyanate, ursolic acid, and vitamin A has the above-described effects. Further, the HSP expression inducing method of the present invention is thus provided. The induction of HSP expression of the present invention is carried out by using the HSp expression inducing agent of the present invention or the aforementioned food, medicine, pharmaceutical (including quasi-drug) or cosmetic. For example, the HSP expression inducing method of the present invention can be carried out by administering an animal which induces HSP expression induction or ingesting the HSP expression inducer of the present invention or a food or drink, a pharmaceutical product (including a quasi drug) or a cosmetic. . In the HSP expression-inducing method of the present invention, the administration amount of the hSp expression inducer or the above-mentioned food, medicine (including quasi-drug) or cosmetic of the present invention, the administration number, the administration method, the administration site, and the like are as described above. Further, the present invention provides a food or drink, a pharmaceutical product (including a quasi-drug) or a cosmetic containing the HS p expression inducing agent of the present invention, thereby imparting an induction function to a food or drink, a pharmaceutical product (including a quasi-drug) or a cosmetic HSP. method. The method can also be carried out as described above. EXAMPLES Hereinafter, the present invention will be described by way of examples, but the present invention is not limited to 25 201219360. In addition, "%" stands for "% by weight" unless otherwise mentioned. Example 1: Review of HSP profile induced by flowering zingerone 1. Experimental method Mouse liver cell Hepalclc7 (manufactured by Dainippon Sumitomo Pharma Co., Ltd.) was added to a 24-well plate at a density of lxl05 cells/ml (24-well) Plate, IWAKI company, pre-cultured for one night at 37 ° C, 5% C 〇 2 in DMEM (manufactured by GIBCO) containing 1% by volume of FBS (manufactured by BIOLOGICAL INDUSTRIES). After washing the cells with PBS, the cells were exchanged in serum-free DMEM medium, and the geranone dissolved in diterpenoid (DMSO) was added at a final concentration of 10, 25, 50 μM (the final concentration of DMSO was 0.5%). The culture was carried out for 3 hours at 37 ° C under 5% CO 2 . Three hours after the addition of the flower zingerone, the cells were washed with PB S, and the whole RNA was recovered with the RNeasy kit (manufactured by QIAGEN). A total RNA solution equivalent to 500 ng was reverse transcribed by reverse transcriptase (TAKARA) to obtain cDNA. This was amplified by a real-time polymerase chain reaction (Real Time PCR) apparatus (manufactured by APPLIED BIOSYSTEMS) to quantify the expression amounts of HSP27, HSP40, HSP70, HSP90a, and HSP90b mRNA. Further, hypoxanthine guanine phosphate ribose transfer plum (HPRT) was used as an internal standard. The primers and PCR conditions used in the instant polymerase chain reaction are as follows. <introduction sequence>

HPRT F: 5'-GTAATGATCAGTCAACGGGGAC-3' (SEQ ID NO: 1) R: 5'-CCAGCAAGCTTGCAACCTTAACCA-3 (Sequence to Tiger 2)

26 201219360 HSP27 F: 5'-TGCTTCACCCGGAAATACAC-3' (SEQ ID NO: 3) R: 5'-CTCGAAAGTAACCGGAATGG-3 (SEQ ID NO: 4) HSP40 F: 5 '-TTAC A AGGCG AGGAG A AG AC-3 '(SEQ ID NO: 5 R: 5'-TTGACAATCTGACCTGGATG-3, (SEQ ID NO: 6) HSP70 F: 5'-TGGTGCTGACGAAGATGAAG-3' (SEQ ID NO: 7) R: 5'-AGGTCGAAGATGAGCACGTT-3' (SEQ ID NO: 8) HSP90a F: 5 ' - AA AGGC AG AGGCTG AC A AG A-3 '(SEQ ID NO: 9) R: 5 '-AGGGGAGGCATTTCTTCAGT-3 '(SEQ ID NO: 1) HSP90b F: 5'-GCGGCAAAGACAAGAAAAG-3' (SEQ ID NO: 11) R: 5 ' -GAAGTGGTCCTCCCAGTCAT-3 '(SEQ ID NO: 12) <PCR conditions> 95〇C -3 min [95°C-10sec/60°C-lmin] x 99 cycle 2. Experimental results The control group (DMSO concentration 0.5%) The expression amount of each HSP in the flower zingerone ΟμΜ) was set to 1'. The result of calculating the relative value of the HSP expression amount under each condition is shown in Fig. 1. According to the results, it was confirmed that the performance of HSP90a, HSP90b, HSP70, HSP40, and HSP27 was significantly increased in the presence of S. glabra. Especially for HSP90b, HSP70, HSP40, in the presence of 50μΜ花姜27 201219360 ketone, it was confirmed that the engraving was much more than 5 times higher than that of the control group. Example 2: Review of HSp expression induction of plant-derived components or other components other than squid S. 1. Experimental method Based on the method of the method described in Example 1, the source other than zingerone was reviewed. HSP70 expression induction of plant components, vitamins or trace metals. The final wave degree of each component is shown in Table 1. 2. Experimental results As shown in Table 1, it was confirmed that HSP70-inducing ability was as follows: as a plant-derived component, there were β-carotenoid, α-carotene, lycopene, zeaxanthin, β-cryptoxanthin, and scutellarin. , hops, phenylethyl acetoacetate and ursolic acid; as a vitamin 'has vitamin A; as a metal' has zinc. [Table 1] Ingredients (final concentration) HSP induction (HSP70/HPRT) Isothiocyanate (2μΜ) + ursolic acid (50μΜ) + α-carotene (50μΜ) + β-carotene (50μΜ) + lycopene (50μΜ) + zeaxanthin (5〇μΜ) + β cryptoxanthin (50μΜ) + lutein (50μΜ) + quercetin (5〇μΜ) — epigallocatechin Acid ester (5〇μΜ) — hopsene* (25μΜ) + vitamin Α (50μΜ) + zinc (50μΜ) + vitamin Ε (50μΜ) — meaning of the mark—no HSP70 induction + ; HSP70 induction & * hop numbness; an analog of zingerone, which is a genus of zingerone. 28 201219360 From this result, it is also expected that phytonutrients such as carotenoids, terpenes, flavonoids, etc., which are called phytochemicals other than the above, can be expected. The organic sulfides such as sulfur, propyl or isothiocyanate, the long-chain alkyl derivatives or polysaccharides represented by capsaicin or ginger oil have the same effect. Example 3: Review of induction of expression by 113]?7 细胞 cell culture solution which has been treated with zingerone 1. Experimental method Mouse liver cell Hepalclc7 (manufactured by Dainippon Sumitomo Pharma Co., Ltd.) at a density of lxl05 cells/ml It was added to a 24-well plate (manufactured by IWAKI Co., Ltd.) in a DMEM (manufactured by GIBCO Co., Ltd.) containing 10 volumes of 〇/grab 8 (manufactured by BIOLOGICAL INDUSTRIES) under conditions of 37 ° C and 5% c〇2. Pre-trained for one night. After washing the cells with PBS, the cells were exchanged in serum-free DMEM medium. The zingiberone was added at a final concentration of 5 μM, and cultured at 37 ° C under 5% C 2 for 14 hours. After the cells were cultured for 14 hours, the cells were washed with PBS, and then 3 mL of the medium was added and added to a mouse culture cell Hepalclc7 which was pre-cultured for one night in a membrane culture insert (available at a pressure of 0·45 μm, manufactured by FALCON). (Xlxl 〇 5 cells/ml manufactured by Dainippon Sumitomo Pharmaceutical Co., Ltd.), cultured at 37 ° C, 5 ° / 〇 C 〇 2 for 3 or 6 hours. The cells on the membrane culture cup were recovered after the respective hours of culture, and the amount of HSP70 mRNA expression was measured in the same manner as in the above Example. 2. Experimental results The results obtained are shown in Figure 2. From the results, it was revealed that even if the cell supernatant of the chemotherapone treated with 29 201219360 was added to the liver cells of the mouse which was pre-cultured for one night, the expression of HSP70 was also induced. That is, the results revealed that the substance which induces the expression of HSp7〇 is released to the outside of the cell by treating the zingerone in the cells. From the above results, it can be expected that the amount of HSP70 induced by the flower zingerone (that is, the accompanying protein enhancement effect) can be expected to be immediate and delayed, so that its long-term effect can be considered to diffuse through the circulator system. whole body. Example 4: Review of the effect of zingerone on the pressure 1. Experimental method Seven-year-old SD male rats (manufactured by Charles River, Japan) were grouped so that the average values of body weight and swimming time were equal. After grouping, the immersion pressure experiment was started, and the subjects were orally administered to each group every 12 hours. The swimming time was measured 1 hour after the administration of the test body on the 2nd and 5th day of the water immersion pressure test. After the end of the swimming experiment, whole blood was taken and the concentration of HSP70 (HSP72) in the sputum was measured using an HSP70 high-sensitivity enzyme immunoassay kit (EIA kit, manufactured by Enzo Life Sciences). The measurements were carried out in accordance with the attached sequence. Further, the concentration of monoamine in plasma as a pressure index was measured using a commercially available enzyme immunoassay kit (ELISA kit). In addition, as a subject to be administered, the "pressure group" of the load water immersion pressure is a 0.25% preparation liquid of carboxymethyl cellulose (CMC) (manufactured by Wako Pure Chemical Industries, Ltd.), and the water immersion pressure is applied to the flower zingerone. In the "pressure + flower gingerone group" which was administered by the method, a medicinal preparation of a flower squid (manufactured by Wako Pure Chemical Industries, Ltd.) having the same final concentration as that of the above was used. The dosage of the flower zingerone was set to 50 mg/kg per time. 30 .-·〇201219360 Determination of swimming time In a container with a water depth of 4〇Cm from the bottom, the rats were allowed to swim in the following state and measured until the nose was flooded for more than 1 second: The rat tail clamp RTC2 〇〇 9 and the load (manufactured by Yamashita Techno Co., Ltd.) were attached to the forcible swimming, and the weight was loaded to a weight equivalent to 8 〇/〇 of the body weight. Immersion pressure test Rats were subjected to a pressure load by placing water in a cage 2 ml higher than the bottom and cultivating them in a state of continuous water immersion. Determination of monoamine concentration in plasma As a concentration of monoamine in plasma, acetylcholine (ACTH) and corticosteroid (CORT) were measured. The measurement was carried out using an acetylcholine enzyme immunoassay kit (manufactured by mdbioproducts) and an AssayMax corticosteroid immunoassay kit (manufactured by ASSAYPRO) and in accordance with the attached sequence. 2. Experimental Results The results obtained are shown in Figure 3 and Table 2. In the swimming time shown in Fig. 3, the "pressure group" was confirmed to have a significant decrease in the "control group" in which the water immersion pressure was not applied. However, the "pressure + flower gingerone group" was meaningfully suppressed. In addition, as for the concentration of Hsp7(Hsp72) in the plasma shown in Table 2, it was confirmed that there was a significant increase in the concentration of HSP70 (HSP72) in the "pressure group" and "pressure group" compared with the "control group" and "pressure group". , showing meaningful gaps between groups. In addition, the swimming time of the "control group" and the concentration of Hsp7 in the plasma were revealed before the start of the experiment in which the "water force group" and "pressure + seam_" immersion experiments began (Fig. 3 and Table 2, For the "pre-experiment"). 31 201219360 Experiment 7

Mean±standard error, ^HSP70 (HSP72) concentration in plasma (Pg/mL) Control group--------- Pressure group pressure + flower gingerone group __J76+62 — — 220±58 423±138 — 90±27 513+159 :7 ～10 As the concentration of monoamine in blood coagulation, in the fifth experiment of the experiment, it was confirmed that the plasma was in the “pressure group” compared to “Yes, Zhao Zao r, and f J ' in the pressure group”. In contrast, the two concentrations of ACTH and CORT are relative to this, and the increase in the "pressure + flower gingerone group" is suppressed. From & 1 it appears that the HSP-inducing agent of the present invention is effective not only for stress but also expected to be effective for sorrow and chronic fatigue syndrome. Further, it has been confirmed that the Hsp-inducing agent of the present invention is able to pass through the blood and contribute to the prevention of the disease in the brain, the eye, and the skin where the symptoms of stress are easily exhibited. Example 5: Review of the effect of zingerone on muscle production i. Experimental method SD male rats of 12 years old (manufactured by Charles River, Japan) were grouped so that the average body weight was averaged. After grouping, paper-weeks will be administered orally to each group twice a week for every 12 hours. Thereafter, the tail suspension test was carried out for 5 or 8 days. The administration of the subject is also continued during the tail suspension. On the 5th or 8th day of the tail suspension experiment, the specific muscles of the sole weight were measured from the rats under anesthesia. Next, the amount of Hsp mRNA in the soleus muscle on the fifth day was measured for the purpose of reviewing the change in HSP in the soleus muscle. As the subject to be administered, the "control group" which did not carry out the tail suspension experiment and the "tail suspension group" which carried out the tail suspension experiment used corn oil.

32 201219360 (manufactured by Sigma-Aldrich Co., Ltd.), and the "tail suspension + flower gingerone group" which was subjected to the tail suspension test and administered with zingiberone was used to dissolve the flower vine steel with corn oil. The amount of zingerone was 5 〇mg/kg per dose. Tail suspension experiment A 75 mm x 5 m kinesiology tape (manufactured by DOME Co., Ltd.) was wound around the tail of the rat and the patch was attached to the upper part of the breeding box so that the hind limb could not be contacted anywhere, thereby causing muscle atrophy of the hind limb. One part of the muscle was cut out, and RNA was stabilized using RNAlater (manufactured by QIAGEN). Thereafter, whole RNA was recovered using an RNeasy Fibrous Tissue Mini Kit (manufactured by QIAGEN). The whole RNA solution adjusted to 〇.2pg/pL was subjected to reverse transcription by a high-capacity cDNA reverse transcription kit containing a RNase inhibitor (High Capacity cDNA Reverse Transcription Kit with RNase Inhibitor 5 Life Technologies) to obtain cDNA. Thereafter, TaqMan Gene Expression Assays (manufactured by Life Technologies) was used, and an instant polymerase chain reaction was carried out in iCycler IQ (manufactured by BIO-RAD) to measure the mRNA expression amount of HSP72. Further, HPRT was used as an internal standard, and each experiment was carried out in accordance with the sequence attached to the product, and the mRNA expression amount of HSP72 was corrected using the amount of mRNA of HPRT. The use of the instant polymerase chain reaction

Rn01525688_sl and Rn01527840_ml (made by Life Technologies). 2. Experimental Results The results obtained are shown in Figures 4-1 and 4-2. As shown in Figure 4-1, the number of the soleus muscle weight of the unit weight before and after the experiment is not confirmed; in contrast, the "tail suspension group" is light to a meaningful single weight. The soleus muscle weight decreases. On the other hand, regarding the "tail wag + gingerone group", the decrease in the soleus muscle weight is suppressed compared to the "tail dangling group". Further, as is clear from Fig. 4-2, it has been confirmed that the HSP72 expression of the "tail core dripping ginger ketone group" is higher than that of the "tail suspension group". From this point of view, flower zingerone inhibits or prevents muscle atrophy caused by not using muscle. Example 6: Review of the effect of zingerone on muscle production 2 1. Experimental method 12-year-old SD male rats (manufactured by Sakamoto Charles Co., Ltd.) were grouped so that the average body weight was averaged, and the tail (4) was implemented. Experiment 1 the next day. Thereafter, the tail suspension is suspended and returned to normal breeding, and the subject is orally administered to each group every 12 hours. After the test body was administered for 3 or 7 days, the soleus muscle was taken from the rats under anesthesia, and the weight of the target fish muscle was measured. Next, the amount of HSP mRNA in the soleus muscle of the third sputum was measured by the aforementioned method. As the subject to be administered, the "control group" which did not carry out the tail suspension test and the "tail suspension group" which carried out the tail suspension test were corn oil (manufactured by Sigma-Aldrich Co., Ltd.), and the tail suspension experiment was carried out and the ginger was carried out. The "tail suspension + flower ginger ketone group" of the ketone administration uses a substance in which corn olein is dissolved by corn oil. The dosage of zingerone was 5 〇mg/kg per time. 2. Experimental results The results obtained are shown in Figures 5-1 and 5-2. As shown in Figure 5, the weight of the soleus muscle weight per unit weight after hanging is significantly reduced compared to the "Control 34 201219360 Group". Further, it can be seen from Fig. 5-2 that the performance of HSP72 has been confirmed to be high. From this point of view, it is shown that the performance of HSP72 is increased in the muscles of the same flower that is already atrophy. The flower zingerone can improve the recovery effect of the atrophied muscle. From the above results, it has been confirmed that the plant-derived component that induces HSP is caused by the expression of various HSps, which are caused by the HSP70 family in the living body, and is caused by dysfunction of organs such as stress or muscle weakness. It is useful to strengthen the maintenance of the body's constantity, prevent or improve various diseases or symptoms, and prolong life. I: BRIEF DESCRIPTION OF THE DRAWINGS 2 Fig. 1 is a graph showing the results of measuring the expression amounts of HSP27, HSP40, HSP70, HSP90a, and HSP90b in the presence of each of the concentrations of zingerone in Example 1. Further, "ZER" in Fig. 1 indicates flower zingerone. Further, the vertical axis of Fig. 1 is a relative value of the amount of each HSP expression when the amount of expression of each HSP in the control group (flowered ketone ketone) is set to 1. Fig. 2 is a graph showing the results of measuring the amount of HSP70 expression by performing the culture of fresh mouse liver cells for 3.6 hours in a culture medium of cells treated with serotonin 〇5〇μΜ in Example 3. In the second figure, "ZER" is a flower zingerone. Further, the vertical axis of Fig. 2 is a relative value of the amount of HSP70 expression when the expression amount of each HSP in the control group (sedum ketone oxime) is set to 1. Fig. 3 is a view showing the results of the effect of the ginger _ on the pressure in Example 4. Fig. 4-1 is a view showing the results of the effect of the ginger _ on the muscles in Example 5. The results shown in Fig. 4-1 are obtained by performing a tail suspension experiment after pre-administration of the test subject of mouse 35 201219360. Fig. 4-2 is a graph showing the results of the effect of zingerone on the amount of mRNA expression of HSP72 in muscle in Example 5. Fig. 5-1 is a diagram showing the results of examining the effect of zingerone on muscles in Example 6. The results shown in Fig. 5-1 are obtained by administering a test substance to a mouse after performing a tail suspension test. Fig. 5-2 is a graph showing the results of the effect of zingerone on the amount of mRNA expression of HSP72 in muscle in Example 6. [Main component symbol description] (none) 36 201219360 Sequence Listing

<110> Otsuka Pharmaceutical Co., Ltd. <120> HSP performance introduction <130> 201177TW <150> JP 2010-224306 <151>2010-10-01 <150> JP 2011-057762 <151> 2011-03-16 <160> 12 <170> Patentln Version 3.4 <210> 1 <211> 22 <212> DNA <213> Artificial <220><223> HPRT To the primer <400> 1 gtaatgatca gtcaacgggg ac 22 <210> 2 <211> 24 <212> DNA <213> artificial <220><223> HPRT reverse primer <400> Ccagcaagct tgcaacctta acca 24 <210> 3 <211> 20 1 201219360 <212> DNA <213>manual <220><223> HSP27 forward index <400> 3 tgcttcaccc ggaaatacac 20 <210> 4 <211> 20 <212> DNA <213> Artificial <220><223> HSP27 reverse primer <400> 4 ctcgaaagta accggaatgg 20 <210> 5 <211><212> DNA <213> Artificial <220><223> HSP40 forward introduction <400> 5 ttacaaggcg aggagaa Gac 20 <210> 6 <211> 20 <212> DNA <213>manual <220><223> HSP40 reverse introduction 2 201219360 <400> 6 ttgacaatct gacctggatg <210><211> 20 <212> DNA <213> Artificial <220><223> HSP70 forward index <400> 7 tggtgctgac gaagatgaag <210> 8 <211> 20 <212> DNA <213> Artificial <220><223> Reverse Inversion of HSP70 <400> 8 aggtcgaaga tgagcacgtt <210> 9 <211> 20 <212> DNA <213> Artificial <220><223> HSP90a forward index <400> 9 aaaggcagag gctgacaaga

<210> 10 <211> 20 <212> DNA 201219360 <213>manual <220><223>HSP90a reverse introduction <400> 10 aggggaggca tttcttcagt 20 <210> 11 < 211> 19 <212> DNA <213> Artificial <220><223> HSP90b forward index <400> 11 gcggcaaaga caagaaaag 19 <210> 12 <211> 20 <212> DNA <213> Manual <220><223> Reverse Inversion of HSP90b <400> 12 gaagtggtcc tcccagtcat 20 4

Claims (1)

201219360 VII. Patent application scope: 1. An inducer of heat-induced protein expression, characterized by containing a selected from the group consisting of ketones and their analogues, carotene, orysin, zeaxanthin, cryptoxanthin, and leaves At least one compound selected from the group consisting of flavin, phenylethyl isothiocyanate, and ursolic acid is used as an active ingredient. 2. The heat-inducing protein expression inducer according to item 1 of the patent application, characterized in that the flower zingerone and the analogue thereof are unsaturated alicyclic compounds represented by the following formula (1): general formula (1) [ 1] [In the formula (1), RcR, 4 is the same or different and represents a hydrogen atom or an alkyl group having 1 to 5 carbon atoms; and a core 5 and a core 6 represent a hydrogen atom or a hydroxyl group, or a hydrogen atom; 3. The heat-inducing protein expression inducer according to item 2 of the patent application, wherein in the formula (1), R, R7, R丨丨 and R12 are a methyl group; &~, R8~Ri〇 and shame~Ru It is a hydrogen atom; ~ and ~ are respectively hydrogen atoms, or together they become oxygen atoms. 4 'As claimed in the scope of claim (1), the heat-inducing protein exhibits 1 201219360. The above-mentioned heat-trapping protein is a heat-trapping protein 7〇 family protein. 5. The inducer of heat-induced protein expression according to any one of claims 4 to 4, which is suitable for: preventing or restoring muscle atrophy, inhibiting muscle fatigue, resisting stress, preventing or improving dementia, prevention Or improve sorrow, prevent or improve chronic fatigue, improve blood circulation, improve coldness of limbs, improve edema, improve shoulder and neck stiffness, prevent or improve rheumatism, prevent or improve retinopathy, improve exercise capacity, enhance endurance, strengthen immunity or Use of anti-organic organ syndrome. 6. The heat-inducing protein expression inducer according to any one of claims 1 to 5, which is suitable for: preventing or restoring muscle atrophy, inhibiting muscle fatigue, resisting stress, preventing or improving chronic fatigue syndrome, and preventing Or use to improve rheumatism, improve exercise capacity, enhance endurance or fight organ syndrome. 7. A food or drink, a pharmaceutical or a cosmetic comprising the heat-inducing protein expression inducer according to any one of claims 1 to 6. A method for inducing heat-induced protein expression, which is characterized by using the heat-inducing protein expression inducer according to any one of claims 1 to 6. A method for inducing heat-induced protein expression, which is characterized by using a food or drink, a pharmaceutical or a cosmetic as claimed in claim 7 of the patent application. 10. Prevent muscle atrophy or restore it, inhibit muscle fatigue, resist stress, prevent or improve dementia, prevent or improve depression, improve blood circulation, improve limb cold, improve edema, improve shoulder and neck stiffness, prevent or The 201219360 method for improving rheumatism, preventing or improving retinopathy, improving exercise capacity, improving endurance, enhancing immunity, or preventing or improving dysarthon syndrome, is characterized by using any one of claims 1 to 6 of the patent application scope. Heat-induced protein expression inducer. 11. Prevention of muscle atrophy or recovery, inhibition of muscle fatigue, stress resistance 'Prevention or improvement of dementia, prevention or improvement of depression, improvement of blood circulation, improvement of limb cold, improvement of edema, improvement of neck and neck stiffness, prevention or improvement A method of preventing rheumatism, preventing or improving retinopathy, improving exercise capacity, improving endurance, enhancing immunity, or preventing or improving dysfunction of a dysarthic organ, and is characterized by using a food or drink, a pharmaceutical or a cosmetic as claimed in claim 7.