TW202000219A - Food material having rage signaling inhibitory effect - Google Patents

Abstract

To provide a novel RAGE signaling inhibitor. This RAGE signaling inhibitor contains, as an active ingredient, an extract from one or more plants selected from the plant group consisting of Geumjaponicum Thunb., Salvia sclarea, Boswellia serrata, Coleus forskohlii Briq., Fortunella species, Cinnamomum camphora, Salix alba, Ruscus aculeatus, Ficus pumila, Sassafras albidum, Hedychium coronarium, Claytonia perfoliata, Chenopodium album var. centrorubrum, and Carica papaya.

Description

Food material with RAGE message suppression effect

The invention relates to a RAGE (receptor for advanced glycation end products) message inhibitor.

The saccharification reaction is a series of reactions in which the amine group of a protein or amino acid and the carbonyl group of a reducing sugar are non-enzymatically bonded as a starting point, and the saccharification end product (AGE) is generated by the saccharification reaction. The generated AGE is the RAGE (Receptor for AGE) expressed in the cell membrane of monocytes/macrophages, T cells, endothelial cells, fibroblasts, smooth muscle cells, nerve cells, glial cells, chondrocytes, etc. The product receptor) binds to activate the RAGE signal, causing various aging-related diseases, diabetic complications, inflammation, etc. in the organism. If AGE binds to RAGE, the intracellular message pathway is activated. As one of the main message pathways, it induces the enhancement of intracellular oxidative stress and subsequent activation of the transcription factor NF-κB via the Ras/MAP kinase pathway. On the other hand, free RAGE that is not bound to the cell membrane is reported. As free RAGE, esRAGE (endogenous secretory RAGE) produced by selective splicing of RAGE gene transcription products is known. Product receptor), or sRAGE (soluble RAGE, soluble advanced glycation end-product receptor) formed by cutting the membrane-bound part on the cell membrane. It is believed that although esRAGE and sRAGE lack the membrane binding region, they retain the binding region with AGE, so they are released out of the cell and play the role of AGE scavenger, which has the function of inhibiting AGE or RAGE in the body (for example, refer to the patent Literature 1).

Furthermore, it is known that not only AGE, S100 protein, HMGB1 (High Mobility Group Box 1), amyloid and other factors are also combined with RAGE, and RAGE is reported to be involved in atherosclerosis and diabetic complications ( (E.g. diabetic nephropathy, diabetic retinopathy, diabetic neuropathy), hypertension, dementia, cancer, non-alcoholic steatohepatitis, infertility, obesity, male erectile dysfunction, periodontal disease, Alzheimer's Development of diseases, cataracts, osteoporosis, etc. (for example, refer to Patent Document 2 and Non-Patent Documents 1-8). [Prior Technical Literature] [Patent Literature]

[Patent Document 1] Japanese Patent No. 3837494 [Patent Document 2] Japanese Patent No. 4143716 [Non-patent literature]

[Non-Patent Literature 1] Japanese Journal of Pharmacology (Folia Pharmacol. Jpn.), 2014, Vol. 143, p. 10-13 [Non-Patent Document 2] Journal of Leukocyte Biology, 2013, Vol. 94, p. 55-68 [Non-Patent Document 3] MINERVA ENDOCRINOL, 2014, Vol. 39, p.167-74 [Non-Patent Document 4] Diabetes, 2014, Vol. 63, p. 1948-1965 [Non-Patent Literature 5] Clin Exp Med, 2011, Vol. 11, p.131-135 [Non-Patent Document 6] Japanese Journal of Periodontology, 2009, Vol. 51, No. 1, p. 7-18 [Non-Patent Document 7] Glycoconj J., 2016, Vol. 33, No. 4, p.631-643 [Non-Patent Document 8] Horm Metab Res., 2007, Vol.12, p.871-5

[Problems to be solved by the invention]

The main object of the present invention is to provide a novel RAGE message inhibitor that inhibits the RAGE message activated by the combination of AGE and RAGE generated by the saccharification reaction. [Technical means to solve the problem]

The present inventors have made intensive studies in order to solve the above problems, and found that Japanese curb green, sage, frankincense, coleus forsklar, kumquat, camphor tree, European white willow, false leaf tree, Ficus pumila, The plant extracts of sassafras, ginger flower, winter purslane, quinoa, or papaya have RAGE signal inhibitory effect, such as NF-κB activity inhibitory effect, RAGE-AGE binding inhibitory effect or RAGE shedding function, thus completing the present invention. In addition, the inventors of the present invention have found that the above plant extracts can be used as a preventive or therapeutic agent for vascular diseases, thereby completing the present invention.

As the present invention, for example, the following can be mentioned. (1) An inhibitor of RAGE message, which is selected from the group consisting of Japanese roadside green, clary sage, frankincense, coleus fortunei, kumquat, camphor tree, European white willow, false leaf tree, Ficus pumila, sassafras, Extracts of one or more plants in the flora consisting of ginger flower, winter purslane, quinoa and papaya as active ingredients. (2) An NF-κB activity inhibitor containing the plant extract as described in (1) above as an active ingredient. (3) A type of hypertension, dementia, cancer, non-alcoholic steatohepatitis, infertility, obesity, male erectile dysfunction, periodontal disease, Alzheimer's disease, cataract or osteoporosis prevention, improvement or The therapeutic composition contains the plant extract as described in (1) above as an active ingredient. (4) A composition for preventing, ameliorating or treating vascular diseases, which contains the plant extract as described in (1) above. (5) The composition for prevention, improvement or treatment of vascular diseases as described in (4) above, wherein the vascular diseases are inflammation of blood vessels, arteriosclerosis or vascular endothelial dysfunction. [Effect of invention]

The RAGE message inhibitor of the present invention inhibits the RAGE message activated by the saccharification reaction. In addition, the RAGE message inhibitor of the present invention contains an extract of a plant with edible experience and few side effects as an effective ingredient, and has high safety.

Plant extracts The plant extracts of the present invention are selected from the group consisting of Japanese roadside green, clary sage, frankincense, coleus fortunei, kumquat, camphor tree, white willow, false leaf tree, Ficus pumila, sassafras, Extracts of one or more plants in the flora consisting of ginger flower, winter purslane, quinoa and papaya. The Japanese roadside green is a plant belonging to the genus Rosaceae, and its scientific name is Geum japonicum Thunb. The alias is also known as Japanese avens or swell. Happy Sage is a plant belonging to the genus Salvia of the Labiatae family. Its scientific name is Salvia sclarea L., and its alias is also known as clary, clary sage, clary wort, muscatel sage, or sage. Boswellia serrata belongs to the Boswellia serrata Roxb. (ex colebr). The alias is also known as Indian olibanum, Indian frankincense, frankincense or Indian frankincense, frankincense.

Coleus Forskohlii Briq. is a plant belonging to the genus Fragaria of the Labiatae family. The alias is also known as Coleus forskohlii auct., Plectranthus barbatus Andrews, Coleus barbatus (Andrews) Benth. or forskohlii. Kumquat is a plant belonging to the genus Kumquat in the Rutaceae family. Its scientific name is Fortunella japonica (Thunb) Swingle. The alias is also called Fortunella Swingle, Fortunella margarita (Lour.) Swingle, kumquat, round kumquat or kumquat. The camphor tree belongs to the genus Cinnamomum, and the scientific name is Cinnamomum camphora (L.) J. Presl. The alias is also called Camphora camphora (L.) H. Karst., nom. Illeg., Camphora officinalis Nees, Laurus camphora L., camphor tree, camphor tree or camphor tree leaf.

The European white willow belongs to the Salix genus of Salicaceae, and its scientific name is Salix alba L. The alias is also called Salix aurea Salisb., golden willow, white willow, European willow, goat willow, common willow or white willow. The false-leaf tree family belongs to the genus Falseleaf of the Asparagaceae subfamily, and the scientific name is Ruscus aculeatus L. The alias is also called butcher's broom, box holly, or Jew's myrtle. Ficus pumila is a plant belonging to the genus Ficus genus, and its scientific name is Ficus pumila L. The alias is also known as Ficus repense hort. Non Willd. Nec Rottl., creeping fig, climbing fig, creeping rubber plant, Wang Buluhang, Dao Shrub or Manglietia.

The yellow sassafras belongs to the genus Sassafras, and the scientific name is Sassafras albidum (Nutt.) Nees. The alias is also called Sassafras officinale T. Nees et C.H. Eberm., Sassafras variifolium O. Kuntze, Laurus sassafras L., sassafras, common sassafras or file. Zingiberaceae belongs to the genus Zingiberaceae, and the scientific name is Hedychium coronarium J. König. The alias is also called white garland-lily, garland flower, ginger lily, common ginger lily, butterfly ginger, butterfly lily, cinnamon jasmine or ginger orchid. Winter Purslane is a plant belonging to the genus Purslane in the Purslane family. Its scientific name is Montia perfoliata (Donn. ex Willd.) Howell. The alias is also known as the leaf spring grass.

Chenopodiaceae belongs to the Chenopodiaceae plant, the scientific name is Chenopodium album L.. The alias is also known as Chenopodium album L. var. centrorubrum Makino or Chenopodium centrorubrum (Makino) Nakai. Papaya is a plant belonging to the genus Papaya of the papaya family, and its scientific name is CaricapapayaL. The alias is also known as papaya, pawpaw, papaw, melon tree, common papaw, papaya, papaya, marigold, marigold, milk melon or papaya.

The parts of the plant used in the production of the plant extract of the present invention are not particularly limited, and various parts of the above plants can be used. For example, flowers, spikes, peels, fruits, stems, leaves, leaves, branches, twigs, branches and leaves, stems, bark, resin, rhizomes, root barks, roots, seeds, galls, heartwood, aerial parts, aerial parts Or whole grass. The production method of the plant extract of the present invention is not particularly limited, and can be produced by a commonly used method. For example, it can be manufactured by directly or cutting each part of the plant to an appropriate size for juice extraction or extraction with a solvent. As the extraction solvent, for example, water, various organic solvents, or a mixed solvent of these can be used. Examples of organic solvents used for extraction include lower alcohols (methanol, ethanol, etc.), chloroform, ethyl acetate, and n-hexane. Among the extraction solvents, water, methanol and ethanol are particularly preferred. In addition, these solvents may be used alone or in combination of two or more. The use amount of the extraction solvent varies according to the plant raw material or extraction solvent used, and is preferably within a range of 1:2 to 1:30 (plant raw material: extraction solvent) in terms of weight ratio, preferably 1:3 to Within the range of 1:20, it is more preferably within the range of 1:5 to 1:10. The extraction time is suitably in the range of 1 hour to 15 days. The extraction temperature is suitably in the range of 5 to 100°C. The extraction method is not particularly limited, and any method such as batch extraction and continuous extraction using a column can be applied.

The obtained plant extract can also be used in its original state, and can be further refined within a range that does not affect its activity if necessary. Such refining treatment may be carried out by a usual method, for example, it can be carried out by filtering plant extracts by a conventional method. Thereafter, the obtained filtrate can be concentrated under reduced pressure and freeze-dried to prepare the plant extract of the present invention.

Composition of the present invention RAGE message inhibitor, NF-κB activity inhibitor of the present invention, or hypertension, dementia, cancer, non-alcoholic steatohepatitis, infertility, obesity, male erectile dysfunction, periodontal disease, Al The composition for prevention, improvement or treatment of Alzheimer's disease, cataract, osteoporosis or vascular disease (hereinafter, collectively referred to as "the composition of the present invention") contains one or two or more plants obtained as described above Extractor. The composition of the present invention can be produced, for example, by directly using the plant extract obtained as described above or mixing it with a material that can be used as a carrier, and then processing it into various forms such as powder, block, and liquid by conventional methods. .

In the composition of the present invention, additives acceptable in medicine, cosmetics or food can be arbitrarily formulated. Examples of such additives include binders, disintegrants, lubricants, dispersants, suspending agents, emulsifiers, buffers, antioxidants, excipients, surfactants, ultraviolet inhibitors, and metal ion blockers. One, two or more of these may be used in appropriate amounts for agents, tackifiers, preservatives, antibacterial agents, moisturizers, and pigments. The formulation amount of the plant extract in the composition of the present invention is not particularly limited, and it is preferably 0.0001% by weight (hereinafter, abbreviated as "%") in terms of solids in the total weight of the composition of the present invention, preferably It is 0.01% or more, and more preferably 0.05 to 50%. The composition of the present invention can be suitably prepared into tablets, powders, granules, capsules, liquids, syrups, drops, conditioning liquids, lotions, ointments, creams, injections, patches, etc. by conventional methods. Dosage form. The intake amount of the composition of the present invention varies according to the type, dosage form, administration method, age, body weight, symptoms, etc. of the plant extracts contained in it. Usually, adults take the weight of plant extracts per day, and it is suitable to set It is in the range of 0.1 to 100 g, preferably in the range of 1 to 60 g, but it is not necessarily limited to this range. This daily intake can be taken once, or it can be divided into multiple intakes. The use form of the composition of the present invention is not particularly limited, and as a pharmaceutical composition, food composition, cosmetic composition, etc., for example, it can be used in the form of oral preparations, food and drink, and external preparations.

In the case of using the composition of the present invention in the form of oral preparations, the plant extract of the present invention can be used directly or as required by appropriate preparation of the pharmaceutical or food additives used in the preparation of oral preparations and then used It is obtained by conventional formulation. Examples of such additives include excipients, fillers, extenders, binders, disintegrants, surfactants, seasonings, fragrances, and lubricants. In the preparation of oral preparations, materials with other physiological functions can also be formulated. The oral dosage form is not particularly limited, and examples include tablets, powders, granules, capsules, liquids, syrups, and drops. The content of the plant extract in the oral preparation may be appropriately prepared according to the type and dosage form of the plant extract, for example, as long as it is in the total amount of the preparation, calculated as solid content, it is preferably 0.5 to 60%. The plant extract can be formulated within a range of 3-50%, particularly preferably 5-10%.

When the composition of the present invention is used in the form of an external preparation, the plant extract of the present invention can be directly or as needed in appropriate amounts by blending the pharmaceutically or cosmetically acceptable additives used in the manufacture of the external preparation and then using the conventional Obtained by the method of preparation. Examples of such additives include base materials for ointments, alcohols, polyols, water-soluble polymers, antioxidants, pH adjusters, ultraviolet inhibitors, metal ion blocking agents, tackifiers, surfactants, and purifications. Water, preservatives, antibacterial agents, oils, higher fatty acids, fatty acid esters, humectants, pigments, vitamins, amino acids, etc. Furthermore, the composition of the present invention can be used in the form of external preparations in known quasi-drugs and cosmetics. In the external preparation, in addition to the composition of the present invention, a component for enhancing the RAGE inhibitory effect may be further formulated, or a material having other physiological functions may also be formulated. Examples of such components include ultraviolet inhibitors, antioxidants, humectants, cell activators, and blood flow promoters. One or more of these may be used in appropriate amounts. The specific use of the external preparation is not particularly limited, and examples thereof include lotions, emulsions, creams, ointments, lotions, oils, and compresses. The content of the plant extract in the external preparation may be appropriately prepared according to the type and dosage form of the plant extract of the present invention contained, for example, as long as it is in the total amount of the preparation, calculated in terms of solid content, from 0.0001 to 30 %, preferably 0.001 to 25%, and particularly preferably 0.5 to 20%.

When the composition of the present invention is used in the form of food and drink, it can be obtained by mixing the plant extract of the present invention with a well-known food material or food and drink and processing it into food by a conventional method. The form of such food and drink is not particularly limited, and examples thereof include powder, block, liquid, syrup, and jelly. In food and beverage, other ingredients allowed in food can be blended. Examples of such components include nutrients, excipients, bulking agents, sweeteners, flavors, colorants, preservatives, emulsifiers, cosolvents, polyols, organic acids, inorganic acids, and high water solubility. molecular. One or more of these may be used in appropriate amounts. Examples of the types of food and drink include beverages, powdered beverages, home-cooked dishes, noodles, toasted bread, bread, snacks, and seasonings. The amount of the plant extract added to the food and drink varies according to the presence or absence of additives or the type of food. Based on the conversion of the solid content of the plant extract contained, it is preferably set within the range of 0.01 to 50%, preferably It is set within the range of 0.1 to 30%, but it is not necessarily limited to this range.

In this specification, "RAGE message inhibitor" is a composition with RAGE message inhibitory effect, and "RAGE signal inhibitory effect" is an inhibitory effect on the transmission of messages via RAGE. The RAGE message inhibitory effect includes, for example, the effect of inhibiting the binding of RAGE and AGE (hereinafter, referred to as "RAGE-AGE binding inhibitory effect"), and the effect of inhibiting the activity of NF-κB as a vehicle for RAGE messages (hereinafter, referred to as " NF-κB activity inhibitory effect"), the effect of cutting off cell membrane-bound RAGE, and increasing the production of soluble RAGE (sRAGE) (RAGE cutting effect). The composition of the present invention is useful for inhibiting RAGE messages, preventing, improving or treating various symptoms caused by glycation, so it can be used, for example, to reduce the elasticity of cartilage, the aging of skin (collagen which causes the reduction of elasticity of the skin, wrinkles or sagging) Formation of protein crosslinks, pigmentation that causes dullness of the skin, etc.), arteriosclerosis, diabetic complications (such as myocardial infarction, diabetic nephropathy, diabetic retinopathy, diabetic neuropathy), inflammation, cancer metastasis , Hypertension, dementia, cancer, non-alcoholic steatohepatitis, infertility, obesity, male erectile dysfunction, periodontal disease, Alzheimer's disease, cataract, osteoporosis, or vascular disease (such as inflammation of blood vessels , Atherosclerosis, diabetic vascular complications, vascular endothelial dysfunction) prevention, improvement or treatment. [Example]

Hereinafter, Examples, Test Examples, and Production Examples will be disclosed to further detail the present invention. However, the present invention is not limited to the scope shown in the following examples.

Example 1 Manufacture of plant extracts After the plants of No. 1 to No. 9 and No. 11 to No. 14 described in Table 1 were air-dried, they were dried overnight at 60°C. After pulverized by a blender, 100 g of the obtained pulverized product was immersed in 500 mL of methanol, and allowed to stand at room temperature for one week. Filtration of the obtained extract was carried out by distilling off the methanol with a rotary evaporator and drying, and dissolved in dimethyl sulfoxide (DMSO) in the manner of 50 mg/mL to obtain Nos. 1-9 And 11-14 plant extracts. The plant of No. 10 described in Table 1 was extracted with 35% of 85% ethanol of the dried resin. The filtrate obtained by filtering the obtained extract was dried to obtain a plant extract. The obtained plant extract was dissolved in DMSO so as to become 50 mg/mL, and the plant extract No. 10 was obtained.

[Table 1]

Test Example 1 Inhibition analysis of NF-κB activity (1) Test method In the test, a large gene that stably expresses the human RAGE gene and introduced the firefly luciferase (Luciferase) gene downstream of the promoter region of NF-κB was used. Mouse C6 glioma cells (hereinafter, referred to as "C6 cells for analysis") (refer to Food Funct., 2013, Vol. 4, p. 1835-1842). The C6 cell line for analysis was dispersed in a low-glucose DMEM (Dalberg Modified Eagle) containing 10% FBS (Fetal Bovine Serum, manufactured by Gibco) and 100 μg/mL geneticin (manufactured by Roche). In a culture medium (Dulbecco's Modified Eagle Medium), manufactured by Nacalai Tesque (hereinafter referred to as "10% FBS/DMEM medium"), a cell culture flask (bottom area 150 cm ² , manufactured by Japan Bio Science) (hereinafter, 1.0×10 ⁶ inoculated into “flask”). A CO ₂ incubator (manufactured by Sanyo Electric Biomedical; CO ₂ concentration 5%, humidity 90%) was cultured at 37° C. for 3 days, and 80% fusion of C6 cells for analysis was confirmed by a microscope, and used for the experiment. Using trypsin-EDTA (manufactured by Gibco), 80% of the fused C6 cells for analysis were peeled from the flask and recovered. The recovered C6 cells for analysis were suspended in 10% FBS/DMEM medium, and seeded in 96-well plates (made by Corning) at a cell density of 4.0×10 ⁵ cells/mL per 100 μL/well. After incubating for 12 hours at 37°C and 5% CO ₂ , the medium was removed by an aspirator and replaced with 50 μL/well containing 0.1% FBS (fetal bovine serum, manufactured by Gibco), 100 μg/mL geneticin The low-glucose DMEM (made by Roche) (Dalburk modified Eagle medium, manufactured by Nacalai Tesque) (hereinafter referred to as "0.1% FBS/DMEM medium") was cultured for 4 hours. After 4 hours, bovine serum albumin (BSA) prepared by 0.1% FBS/DMEM (manufactured by Sigma Aldrich, the same below) and AGE derived from glyceraldehyde (manufactured by Nacalai Tesque, added below) were added at 50 μL/well Same) or specimen (samples 1 to 14 in Table 1). BSA (final concentration 100 μg/mL) was added to the control group, and AGE derived from glyceraldehyde (final concentration 100 μg/mL) was added to the AGE alone treatment group. In addition, AGE (final concentration 100 μg/mL) derived from glyceraldehyde and specimen (final concentration 10 μg/mL) were added to the specimen treatment group. After the specimen was processed for 4 hours, the medium was removed with an aspirator, washed with PBS (phosphate buffered saline), and then added with 25 μL/well of Lysis Buffer (produced by Promega). Thereafter, it was shaken for 10 minutes to prepare a cell lysate. Transfer the obtained cell lysate at 20 μL/well to a white plate for luminescence measurement, add a Reporter Substrate Reagent (manufactured by Promega), and use GloMax with dual injectors and pump station The Navigator System (GloMax Navigator System with Dual Injector and Pump Station) (manufactured by Promega) measures the luminescence amount at 560 nm. In addition, 20 μL/well of ultrapure water (MilliQ (registered trademark) water) was added to 5 μL of the cell lysate remaining in the 96-well plate, and BCA Protein Assay Kit (Thermo Fisher Scientific) was used. ) Determine the amount of protein. The value obtained by dividing the amount of light emission by the amount of protein (hereinafter, referred to as "corrected amount of light emission") was defined as NF-κB activity, and the inhibition rate of each sample was investigated. The difference between the corrected luminescence amount of the AGE alone treatment group and the control group was set to 100%, and the difference between the corrected luminescence amount of the AGE alone treatment group and the sample added group was relatively converted to calculate the inhibition rate of NF-κB activity (% ). The greater the inhibition rate, the greater the inhibition of NF-κB activity. The results are shown in Table 2.

(2) Results According to Table 2, it can be seen that the plant extract of the present invention inhibits the RAGE message activated by AGE and inhibits the activity of NF-κB.

[Table 2]

Test Example 2 AGE-RAGE binding inhibition analysis (1) Test method Dilute glyceraldehyde-derived AGE to 3 μg/mL with phosphate buffer and add 100 μL/well to ELISA (enzyme linked immunosorbent assay). Adsorption analysis) plate, solid phase overnight at 4°C. After solid phase, wash, add blocking solution (20 mM Tris-HCl, 0.15 M NaCl, 1% BSA) at 200 μL/well, block for 1 hour at room temperature, and wash. A mixed liquid of esRAGE and specimens Nos. 1-10 described in Table 2 was prepared, and the mixed liquid was added to an ELISA culture plate (manufactured by PerkinElmer Japan) at 100 μL/well. The esRAGE is obtained by affinity purification from the culture supernatant of 293T cells into which the human esRAGE gene has been introduced. The final concentrations of esRAGE and samples Nos. 1-10 described in Table 2 were 2.0 μg/mL and 1000 μg/mL, respectively. After culturing for 1 hour, it was washed, anti-RAGE antibody (manufactured by Iwai Chemicals Co., Ltd.) was added at 100 μL/well, and cultured at room temperature for 1 hour. Then, after washing, TMB solution (manufactured by Nacalai Tesque) was added at 100 μL/well, and 2 N of H ₂ SO _{4 was} added at 100 μL/well after a certain period of time, by a microdisk reader (CORONA ELECTRIC) Manufacturing, MTP-300) The absorbance at 450 nm was measured. The AGE-RAGE binding rate when no sample was added was set to 100%, and the inhibition rate (%) of AGE-RAGE binding caused by the added sample was calculated. The results are shown in Table 3.

(2) Results According to Table 3, it can be seen that the plant extract of the present invention inhibits the binding of AGE and RAGE.

[table 3]

Test Example 3 RAGE cut-off analysis (1) Test method The same analytical C6 cells as Test Example 1 were used to inoculate a 24-well plate (manufactured by Corning) at a cell density of 1.5×10 ⁵ cells/mL at 1 mL/well. . Twelve hours after the inoculation, specimens No. 11-14 described in Table 3 prepared at 10 times the final concentration (10 μg/mL) with 10% FBS/DMEM at 10 times the final concentration (10 μg/mL) were added at 110 μL/well. In addition, the control group was diluted with 10% FBS/DMEM so that the DMSO concentration was the same as the sample addition group, and added at 110 μL/well in the same manner as the sample addition group. 24 hours after the sample was added, the culture solution was recovered at 120 μL/well, and sRAGE was measured by ELISA. Human RAGE Capture Antibody (manufactured by R&D SYSTEMS) was prepared with phosphate buffer (PBS) at 1.0 μg/mL, added to ELISA culture plate at 100 μL/well, and incubated overnight at room temperature . After washing, a blocking solution (manufactured by R&D Systems) was added at 100 μL/well, and incubated at room temperature for 1 hour. After washing, the recovered culture solution or standard (Recombinant Human RAGE (Recombinant human RAGE), manufactured by R&D Systems) was added at 100 μL/well, and cultured at room temperature for 2 hours. After washing, detection antibody (Detection Antibody) (manufactured by R&D SYSTEMS) was added at 100 μL/well, and incubated at room temperature for 2 hours. Furthermore, after washing, streptavidin-HRP (Streptavidin-HRP) (manufactured by R&D SYSTEM) was added at 100 μL/well, and cultured at room temperature under shading for 20 minutes. After washing, a Substrate Solution (manufactured by R&D SYSTEMS) was added at 100 μL/well, and incubated at room temperature under shading for 20 minutes. After incubation, 50 μL/well of 2 NH ₂ SO _{4 was added} , and the absorbance at 450 nm was measured by a microdisk reader (manufactured by CORONA ELECTRIC, MTP-300). The results are expressed as the relative value (%) of the amount of sRAGE in the culture supernatant of the specimen-added group relative to the amount of sRAGE in the culture supernatant of the control group. The results are shown in Table 4.

(2) Results According to Table 4, it can be seen that the plant extract of the present invention exhibits higher RAGE shedding activity than the control group.

[Table 4]

Next, examples of production of oral preparations, external preparations, foods and beverages containing the inhibitor of the present invention are shown. Production Example 1 Preparation of oral preparations (lozenges) The ingredients are mixed according to the following mixing ratio, and tablets are manufactured according to a conventional method.

[table 5]

Production Example 2 Preparation of oral preparations (granules) The ingredients are mixed according to the following mixing ratio, and granules are manufactured according to a conventional method.

[Table 6]

Production Example 3 Preparation of oral preparation (soft capsule) The ingredients are mixed according to the following mixing ratio, and a soft capsule is manufactured according to a conventional method.

[Table 7]

Production Example 4 Preparation of external preparation (cream) The ingredients are mixed according to the following mixing ratio, and a cream is manufactured according to a conventional method.

[Table 8]

Production Example 5 Preparation of external preparation (lotion) The ingredients are mixed according to the following mixing ratio, and a lotion is manufactured according to a conventional method.

[Table 9]

Production Example 6 Preparation of Food and Beverage (Beverage) The ingredients are mixed according to the following mixing ratio, and the beverage is manufactured according to a conventional method.

[Table 10]

Production Example 7 Preparation of Food and Drink (Candy) The ingredients are mixed according to the following mixing ratio, and the candy is manufactured according to the conventional method.

[Table 11]

Claims (5)

A RAGE message inhibitor, which is selected from the group consisting of Japanese roadside green, clary sage, frankincense, coleus fortunei, kumquat, camphor tree, European white willow, false leaf tree, Ficus pumila, yellow camphor, ginger flower, The extracts of one or more plants in the flora composed of winter purslane, quinoa and papaya are used as active ingredients. An NF-κB activity inhibitor containing the plant extract as claimed in claim 1 as an active ingredient. A composition for the prevention, improvement or treatment of dementia, cancer, non-alcoholic fatty hepatitis, infertility, obesity, male erectile dysfunction, periodontal disease, Alzheimer's disease, cataract or osteoporosis, which contains The plant extract as claimed in claim 1 is used as the active ingredient. A composition for the prevention, improvement or treatment of vascular diseases, which contains the extract of plants as claimed in claim 1. The composition for prevention, improvement or treatment of vascular disease according to claim 4, wherein the vascular disease is inflammation of blood vessels, arteriosclerosis or vascular endothelial dysfunction.