Agent for use in inhibiting expression of notch1 gene and use thereof

Abstract

To provide a novel agent or the like which is capable of inducing expression-inhibitory effects against the Notch1 gene or the like and is applicable to human skin.SOLUTION: The present invention discloses an agent for use in inhibiting expression of the Notch1 gene that comprises a flavonoid.SELECTED DRAWING: None

Description

Technical Field

[0001] The present disclosure relates to an agent for suppressing the expression of the Notch1 gene and its use.

Background Art

[0002] In order to solve problems related to the skin such as atopic dermatitis, dry skin in winter, melanin synthesis such as freckles and lentigines, and reduction of barrier function, various cosmetics and external preparations have been studied (Patent Document 1, Non-Patent Document 1).

Prior Art Documents

Patent Documents

[0003]

Patent Document 1

Non-Patent Documents

[0004]

Non-Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0005] Therefore, an object of the present disclosure is to provide a new agent that can induce an expression-suppressing effect on, for example, the Notch1 gene and is applicable to human skin.

Means for Solving the Problems

[0006] In order to achieve the above object, the present disclosure provides an agent or composition for suppressing the expression of the Notch1 gene, which contains flavonoids.

[0007] The present disclosure provides an agent or composition for suppressing the expression of the IL-6 gene, which contains flavonoids.

[0008] The present disclosure provides an agent or composition for suppressing the expression of the IL-8 gene, which contains flavonoids.

[0009] The present disclosure provides an agent or composition for suppressing the expression of the CYP1A1 gene, which contains flavonoids.

[0010] The present disclosure provides an agent or composition for suppressing the expression of the CYP1B1 gene, which contains flavonoids.

[0011] The present disclosure provides an agent or composition for maintaining the stemness of epidermal stem cells, which contains flavonoids.

[0012] The present disclosure provides an anti-inflammatory agent or anti-inflammatory composition, which contains flavonoids.

[0013] The present disclosure provides a melanin synthesis inhibitor or melanin synthesis inhibitory composition, which contains flavonoids.

[0014] According to the present disclosure, for example, an effect of suppressing the expression of the Notch1 gene or the like can be induced, and a new agent applicable to human skin can be provided.

Embodiments for Carrying Out the Invention

[0015] Hereinafter, the present disclosure will be specifically described with examples. Hereinafter, unless otherwise specified, each disclosure can incorporate the description of other disclosures.

[0016] <Agent or Composition for Suppressing the Expression of the Notch1 Gene> In one aspect, the present disclosure provides an agent or composition for use in suppressing the expression of the Notch1 gene. The agent for use in suppressing the expression of the Notch1 gene of the present disclosure contains flavonoids. Further, the composition for use in suppressing the expression of the Notch1 gene of the present disclosure contains flavonoids. In the following description, unless otherwise specified, the description of each agent of the present disclosure can be incorporated into the description of the corresponding composition.

[0017] As a result of intensive research, the present inventors have found that flavonoids exhibit an effect of suppressing the expression of the Notch1 gene in epidermal keratinocytes, and have thus established the present disclosure. Therefore, according to the agent or composition for use in suppressing the expression of the Notch1 gene of the present disclosure, for example, since the differentiation of epidermal stem cells into epidermal keratinocytes can be suppressed, it is expected that the stem cell property can be maintained.

[0018] In the present disclosure, "flavonoids" means a kind of polyphenol having a C6-C3-C6 structure (diphenylpropane structure, flavan skeleton) in which two benzene rings are bonded by three carbon atoms (the following formula (1)). The flavonoids include, for example, glycosides. Examples of the flavonoids include swertiajaponin (the following formula (2)), swertisin (the following formula (3)), Isovitexin (the following formula (4)), Isoorientin (the following formula (5)), and the like. Since the flavonoids can preferably suppress the expression of the Notch1 gene, they are swertiajaponin, swertisin, Isovitexin, and / or Isoorientin. The agent of the present disclosure may contain, for example, one kind of the flavonoids or a plurality of kinds. When the agent of the present disclosure contains a plurality of kinds of flavonoids, the agent of the present disclosure preferably contains, for example, swertiajaponin, swertisin, Isovitexin, and / or Isoorientin.

Chemical formula

[0019] When the agent of the present disclosure contains multiple types of flavonoids, the content and content ratio of each flavonoid in the agent may be, for example, within the range where the suppression of the expression of the Notch1 gene occurs. As a specific example, when the agent of the present disclosure contains swertiajaponin, swertisin, isovitexin, and isoorientin, the mass ratio (SJ:ST:I:IO) of the swertiajaponin (SJ), the swertisin (ST), the isovitexin (I), and the isoorientin (IO) is, for example, 1:1:0.1:1 to 10:10:5:1, 2:2:0.5:1 to 6:6:1.5:1, and preferably about 4:4:1:1.

[0020] The flavonoids may be, for example, isolated or purified compounds, artificially synthesized compounds, or compositions containing flavonoids. Also, the flavonoids may be, for example, self-prepared or commercially available products. Compositions containing the flavonoids include, for example, extracts containing flavonoids; crude purified products of the extracts, dried products of the extracts, freeze-dried products of the extracts, processed products of the extracts such as spray-dried products; and the like.

[0021] The extract containing the flavonoids may be, for example, a plant extract. The plant extract can be produced, for example, by subjecting a plant containing the flavonoids to solvent extraction. Examples of the plant containing the flavonoids include plants of the genus Zantedeschia of the family Araceae (e.g., Dutch calla (horticultural name: Color), Zantedeschia aethiopica). The plant may be, for example, one type or two or more types. The plant material to be subjected to the extraction may be, for example, a whole plant or a part of a plant. Examples of the part of the plant include flowers, spadices (inflorescences), spathes, or mixtures thereof. The material may be the collected plant itself or a processed product that has been dried and / or pulverized, etc.

[0022] The agent of the present disclosure preferably contains, as the flavonoids, an extract of a plant of the genus Zantedeschia. The extract of the plant of the genus Zantedeschia contains, for example, as the flavonoids, swertiajaponin, swertisin, isovitexin, and isoorientin. The mass ratio (SJ:ST:I:IO) of the swertiajaponin (SJ), the swertisin (ST), the isovitexin (I), and the isoorientin (IO) in the extract of the plant of the genus Zantedeschia is, for example, 1:1:0.1:1 to 10:10:5:1, 2:2:0.5:1 to 6:6:1.5:1, and preferably about 4:4:1:1.

[0023] The solvents used for the extraction of the flavonoids include, for example, aqueous solvents such as water and buffer solutions; lower alcohols or water-containing lower alcohols such as methanol, ethanol, propyl alcohol, isopropyl alcohol, butanol, isobutanol, etc.; polyhydric alcohols or water-containing polyhydric alcohols such as propylene glycol, 1,3-butylene glycol, 1,2-butylene glycol, 1,4-butylene glycol, 1,5-pentanediol, 1,2-pentanediol, 1,3-pentanediol, 1,4-pentanediol, 1,3,5-pentanetriol, glycerin, polyethylene glycol (for example, molecular weight 100 to 100,000), etc.; organic solvents such as acetone, ethyl acetate, diethyl ether, dimethyl ether, ethyl methyl ether, dioxane, hexane, acetonitrile, xylene, benzene, chloroform, carbon tetrachloride, phenol, toluene, etc.; acids (hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, formic acid, acetic acid, etc.) or alkalis (sodium hydroxide, potassium hydroxide, calcium hydroxide, ammonia, etc.) with appropriately regulated concentrations; and the like. The solvent is preferably ethanol or 1,3-butylene glycol, or a mixed solvent thereof. The solvent may be used, for example, singly or in combination of two or more. The extraction can be carried out, for example, by immersing the plant in the solvent at room temperature (about 25°C) for 1 to 7 days.

[0024] The treatments for the processed product include, for example, decomposition by adding an acid (hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, organic acid, etc.) or an alkali (sodium hydroxide, calcium hydroxide, ammonia, etc.); fermentation or metabolic conversion by microorganisms; component adsorption by ion exchange resins, activated carbon, diatomaceous earth, etc.; fractionation using chromatography having various separation modes (ion exchange, hydrophilic adsorption, hydrophobic adsorption, size exclusion, ligand exchange, affinity, etc.); filtration using filter paper, membrane filter, ultrafiltration membrane, etc.; pressurization or depressurization; heating or cooling; drying or freeze-drying; pH adjustment; deodorization; decolorization; long-term static storage; and the like. The treatment may be carried out singly or in combination of two or more.

[0025] The "epidermal keratinocytes" mean cells that constitute the epidermis and have the ability to differentiate into basal cells, spinous cells, granular cells, and keratinocytes. The epidermal keratinocytes finally differentiate into keratinocytes that form the stratum corneum through the above differentiation, and this process is called keratinization.

[0026] The "Notch1" is a kind of protein responsible for intercellular signal transduction. The Notch1 controls the Notch signaling system. The Notch signaling system is known to be involved in the control of cell differentiation and the like. As an example of the Notch1 gene, the mRNA encoded by the human Notch1 gene includes, for example, a polynucleotide consisting of the nucleotide sequence registered with the accession number: 4851 in Genbank. As the expression level of the Notch1 gene, the expression level of one or two or more isoforms of the Notch1 gene may be measured, or the expression levels of all isoforms may be measured.

[0027] In the present disclosure, "suppression of gene expression" means that the expression level of the target gene is suppressed or decreased, and may also mean that the expression of the target gene changes from a state with expression to a state without expression. The expression of the target gene can be evaluated, for example, by measuring the expression level of the mRNA of the target gene by quantitative PCR according to Example 1 described later. When the target gene has a plurality of isoforms, the expression level of the target gene may be measured for one or two or more isoforms of the target gene, or the expression levels of all isoforms may be measured, but preferably the latter.

[0028] The "gene" may exist in the form of RNA (for example, mRNA) or DNA (for example, cDNA or genomic DNA). The DNA may be double-stranded or single-stranded. In the present specification, the "gene" may include additional sequences such as the sequence of the untranslated region (UTR).

[0029] According to the agent for suppressing the expression of the Notch1 gene of the present disclosure, for example, the expression of the Notch1 gene can be suppressed. The suppression of the expression of the Notch1 gene can be evaluated, for example, by measuring the expression level of the mRNA of the Notch1 gene according to Example 1(1) described below.

[0030] The agent for suppressing the expression of the Notch1 gene of the present disclosure can, for example, suppress the differentiation of epidermal keratinocytes by being used for an administration subject. The usage conditions (administration conditions) of the agent for suppressing the expression of the Notch1 gene of the present disclosure are not particularly limited, and for example, the administration form, administration timing, dosage, etc. can be appropriately set according to the type of the administration subject, etc.

[0031] The agent for suppressing the expression of the Notch1 gene of the present disclosure can, for example, in vivo be used in in vitro or be used in

[0032] The administration subject of the agent for suppressing the expression of the Notch1 gene of the present disclosure is not particularly limited. When using the agent for suppressing the expression of the Notch1 gene of the present disclosure in vivo in, for example, the administration subject includes, for example, humans or non-human animals excluding humans. Examples of the non-human animals include mammals such as mice, rats, rabbits, dogs, sheep, horses, cats, goats, monkeys, guinea pigs, etc., and birds, etc. When using the agent for suppressing the expression of the Notch1 gene of the present disclosure in vitro in, for example, the administration subject includes, for example, cells, tissues, organs, etc. Examples of the cells include cells collected from a living body, cultured cells, etc. Examples of the tissues or organs include tissues (biological tissues) or organs collected from a living body, etc.

[0033] In the following topical skin agent (for example, a transdermal administration agent or a composition for application to the skin) or the following oral administration agent or oral administration composition containing an agent for use in suppressing the expression of the Notch1 gene of the present disclosure, the compounding amount of the flavonoids may be in a range that exhibits an effect of suppressing the expression of the Notch1 gene, that is, any effective amount. The compounding amount may be the compounding amount of a single flavonoid or the total compounding amount of two or more flavonoids.

[0034] The dosage forms of the agent for use in suppressing the expression of the Notch1 gene of the present disclosure include oral administration and parenteral administration. Examples of the parenteral administration include transdermal administration, application (contact) to the skin, etc. The application to the skin may include application to the oral mucosa, that is, application or contact to epithelial cells in the oral cavity. In addition, the application to the skin may include, in addition to or instead of application to the skin surface, the meaning of administration or injection into or under the skin through the skin surface. The administration or injection into the skin through the skin surface can be carried out, for example, using microneedles.

[0035] The dosage form of the agent for use in suppressing the expression of the Notch1 gene of the present disclosure is not particularly limited and can be appropriately determined according to the dosage form, for example. Examples of the dosage form include liquid and solid. When the dosage form is oral administration, examples of the dosage form include tablets, pills, capsules, granules, powders, solutions, etc.

[0036] The agent for use in suppressing the expression of the Notch1 gene of the present disclosure may contain additives, for example, as necessary, and when used as a composition, the additives preferably contain pharmaceutically acceptable additives or pharmaceutically acceptable carriers. The additives are not particularly limited, and examples thereof include base raw materials, excipients, colorants, lubricants, binders, disintegrants, stabilizers, coating agents, preservatives, flavoring agents, and other flavor and odor correcting agents. In the present disclosure, the compounding amount of the additives is not particularly limited as long as it does not interfere with the effect of maintaining the structure of hyaluronic acid.

[0037] The excipients include, for example, sugar derivatives such as lactose, lactose hydrate, sucrose, glucose, mannitol, sorbitol, etc.; starch derivatives such as corn starch, potato starch, α-starch, dextrin, etc.; cellulose derivatives such as crystalline cellulose, etc.; gum arabic; dextran; organic excipients such as pullulan, etc.; silicate derivatives such as light anhydrous silicic acid, synthetic aluminum silicate, calcium silicate, magnesium aluminometasilicate, etc.; phosphates such as calcium hydrogen phosphate, etc.; carbonates such as calcium carbonate, etc.; and inorganic excipients such as calcium sulfate, etc. Examples of the coloring agent include, for example, yellow ferric oxide, etc. Examples of the lubricant include metal stearates such as stearic acid, calcium stearate, magnesium stearate, etc.; talc; polyethylene glycol; silica; hydrogenated vegetable oil, etc. Examples of the flavoring and odor-correcting agent include, for example, spices such as cocoa powder, peppermint oil, aromatic powder, peppermint oil, borneol, cinnamon powder, etc., sweeteners, acidulants, etc. Examples of the binder include, for example, hydroxypropyl cellulose, hydroxypropyl methylcellulose, polyvinyl pyrrolidone, macrogol, etc. Examples of the disintegrant include, for example, cellulose derivatives such as carboxymethyl cellulose, carboxymethyl cellulose calcium, etc.; chemically modified starches and chemically modified celluloses such as carboxymethyl starch, sodium carboxymethyl starch, cross-linked polyvinyl pyrrolidone, sodium starch glycolate, etc. Examples of the stabilizer include, for example, paraoxybenzoic acid esters such as methyl paraben, propyl paraben, etc.; alcohols such as chlorobutanol, benzyl alcohol, phenylethyl alcohol, etc.; benzalkonium chloride; phenols such as phenol, cresol, etc.; thimerosal; dehydroacetic acid; sorbic acid, etc. Examples of the coating agent include, for example, hypromellose, macrogols such as macrogol 6000, etc., talc, titanium oxide, etc.

[0038] When the composition for suppressing the expression of the Notch1 gene of the present disclosure is an oral administration composition, specific examples of the oral administration composition include, for example, beverages, foods, pharmaceuticals, quasi-drugs, etc.

[0039] When an agent or composition for suppressing the expression of the Notch1 gene of the present disclosure is used for transdermal administration or application to the skin (hereinafter, also referred to as "topical skin preparation"), the form of the topical skin preparation may be, depending on the form of use, ampoule, capsule, powder, granule, liquid, gel, foam, emulsion, sheet, mist, spray agent, etc. Examples of the form of use include pharmaceuticals; quasi-drugs; topical or systemic topical skin preparations; medicinal and / or cosmetic preparations (cosmetics) applied to the scalp and hair; bath agents used by adding them to bath water; other preparations; etc. Examples of the topical or systemic topical skin preparations include basic cosmetics such as lotion, emulsion, cream, ointment, lotion, oil, pack, etc., cleansing agents or skin cleansers such as solid soap, liquid soap, hand wash, etc., massage agents, cleansing agents, hair removal agents, depilatory agents, beard shaving agents, aftershave lotion, pre-shave lotion, shaving cream, foundation, lipstick, blush, eyeshadow, eyeliner, mascara, etc. Examples of the medicinal and / or cosmetic preparations applied to the scalp and hair include shampoo, conditioner, hair treatment agent, pre-hair treatment agent, permanent solution, hair dye, hair styling agent, hair tonic, hair growth and nourishing agent, pack, plaster, tape, sheet, aerosol, etc. Examples of the other preparations include antiperspirant or deodorant, antiperspirant, sanitary products, sanitary pads, wet tissues, etc.

[0040] The topical skin preparation can be optionally selected and / or used in combination with the components and / or additives exemplified below, as long as it does not interfere with the suppression of the expression of the Notch1 gene, as necessary.

[0041] (1) Various oils and fats Avocado oil, almond oil, perilla oil, perilla seed oil, olive oil, orange oil, orange raffia oil, sesame oil, cocoa butter, chamomile oil, carrot oil, cucumber oil, beef tallow fatty acid, kukui nut oil, safflower oil, shea butter, liquid shea butter, soybean oil, camellia oil, corn oil, rapeseed oil, peppermint oil, castor oil, cottonseed oil, peanut oil, turtle oil, mink oil, egg yolk oil, palm oil, palm kernel oil, beeswax, coconut oil, beef tallow, lard, squalene, squalane, pristane or hydrogenated products of these oils and fats (such as hardened oils), etc.

[0042] (2) Waxes Beeswax, carnauba wax, whale wax, lanolin, liquid lanolin, reduced lanolin, hard lanolin, candelilla wax, montan wax, shellac wax, rice wax, etc.

[0043] (3) Mineral oils Liquid paraffin, petrolatum, paraffin, ozokerite, ceresin, microcrystalline wax, etc.

[0044] (4) Fatty acids Lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, oleic acid, linoleic acid, linolenic acid, docosahexaenoic acid, eicosapentaenoic acid, 12 - hydroxystearic acid, undecylenic acid, tall oil, lanolin fatty acid and other natural fatty acids, isononanoic acid, caproic acid, 2 - ethylbutanoic acid, isopentanoic acid, 2 - methylpentanoic acid, 2 - ethylhexanoic acid, isopentanoic acid and other synthetic fatty acids.

[0045] (5) Alcohols Ethanol, isopropanol, lauryl alcohol, cetyl alcohol, stearyl alcohol, oleyl alcohol, lanolin alcohol, cholesterol, phytosterol, phenoxyethanol and other natural alcohols, 2 - hexyldecanol, isostearyl alcohol, 2 - octyldodecanol and other synthetic alcohols.

[0046] (6) Polyhydric alcohols Ethylene oxide, ethylene glycol, diethylene glycol, triethylene glycol, ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, polyethylene glycol, propylene oxide, propylene glycol, polypropylene glycol, 1,3-butylene glycol, pentyl glycol, glycerin, pentaerythritol, threitol, arabitol, xylitol, ribitol, galactitol, sorbitol, mannitol, lactitol, maltitol, etc.

[0047] (7) Esters Isopropyl myristate, isopropyl palmitate, butyl stearate, hexyl laurate, myristyl myristate, oleyl oleate, decyl oleate, octyldodecyl myristate, hexyldecyl dimethyloctanoate, cetyl lactate, myristyl lactate, diethyl phthalate, dibutyl phthalate, lanolin acetate, ethylene glycol monostearate, propylene glycol monostearate, propylene glycol dioleate, etc.

[0048] (8) Metal soaps Aluminum stearate, magnesium stearate, zinc stearate, calcium stearate, zinc palmitate, magnesium myristate, zinc laurate, zinc undecylenate, etc.

[0049] (9) Gums, sugars or water-soluble polymer compounds Arabic gum, benzoin gum, dammar gum, guaiac resin, Irish moss, karaya gum, tragacanth gum, carob gum, quince seed, agar, casein, lactose, fructose, sucrose or its esters, trehalose or its derivatives, dextrin, gelatin, pectin, starch, carrageenan, carboxymethyl chitin or chitosan, hydroxyalkyl (C2-C4) chitin or chitosan to which alkylene (C2-C4) oxides such as ethylene oxide are added, low molecular weight chitin or chitosan, chitosan salts, sulfated chitin or chitosan, phosphorylated chitin or chitosan, alginic acid or its salts, hyaluronic acid or its salts, chondroitin sulfate or its salts, heparin, ethyl cellulose, methyl cellulose, carboxymethyl cellulose, carboxyethyl cellulose, sodium carboxyethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, nitrocellulose, crystalline cellulose, polyvinyl alcohol, polyvinyl methyl ether, polyvinyl pyrrolidone, polyvinyl methacrylate, polyacrylate salts, polyalkylene oxides such as polyethylene oxide and polypropylene oxide or their cross-linked polymers, carboxyvinyl polymer, polyethyleneimine, etc.

[0050] (10) Surfactants Anionic surfactants (alkyl carboxylates, alkyl sulfonates, alkyl sulfate esters, alkyl phosphate esters), cationic surfactants (alkyl amine salts, alkyl quaternary ammonium salts), amphoteric surfactants: carboxylic acid type amphoteric surfactants (amino type, betaine type), sulfate ester type amphoteric surfactants, sulfonic acid type amphoteric surfactants, phosphate ester type amphoteric surfactants, nonionic surfactants (ether type nonionic surfactants, ether ester type nonionic surfactants, ester type nonionic surfactants, block polymer type nonionic surfactants, nitrogen-containing type nonionic surfactants), other surfactants (natural surfactants, derivatives of protein hydrolysates, polymer surfactants, surfactants containing titanium and silicon, fluorocarbon surfactants), etc.

[0051] (11) Various vitamins Group A vitamins: retinol, retinal (vitamin A1), dehydroretinal (vitamin A2), carotene, lycopene (provitamin A); Group B vitamins: thiamine hydrochloride, thiamine sulfate (vitamin B1), riboflavin (vitamin B2), pyridoxine (vitamin B6), cyanocobalamin (vitamin B12), folic acids, nicotinic acids, pantothenic acids, biotin, choline, inositols; Group C vitamins: ascorbic acid or its derivatives; Group D vitamins: ergocalciferol (vitamin D2), cholecalciferol (vitamin D3), dihydrotachysterol; Group E vitamins: vitamin E or its derivatives, ubiquinones; Group K vitamins: phylloquinone (vitamin K1), menaquinone (vitamin K2), menadione (vitamin K3), menadiol (vitamin K4); others, essential fatty acids (vitamin F), carnitine, ferulic acid, γ-oryzanol, orotic acid, Group P vitamins (rutin, eriocitrin, hesperidin), vitamin U, etc.

[0052] (12) Various amino acids Valine, leucine, isoleucine, threonine, methionine, phenylalanine, tryptophan, lysine, glycine, alanine, asparagine, glutamine, serine, cysteine, cystine, tyrosine, proline, hydroxyproline, aspartic acid, glutamic acid, hydroxylysine, arginine, ornithine, histidine, etc., and their sulfates, phosphates, nitrates, citrates, or amino acid derivatives such as pyrrolidonecarboxylic acid.

[0053] (13) Additives The topical skin preparation may further contain various additives derived from animals or plants. The additives can be arbitrarily selected from various materials and added after performing processing commonly carried out according to the type and form of the product to be added. The processing can be, for example, a treatment arbitrarily selecting and / or combining crushing, milling, washing, hydrolysis, fermentation, purification, pressing, extraction, fractionation, filtration, drying, powdering, granulation, dissolution, sterilization, pH adjustment, deodorization, decolorization, etc.

[0054] The solvent used for the extraction can be selected taking into consideration the purpose and type of the product to be used, or the subsequent processing. The extraction solvent is preferably one or a mixture of two or more selected from various organic solvents such as water, lower alcohols or water-containing lower alcohols such as water, methanol, ethanol, propyl alcohol, isopropyl alcohol, butanol, and isobutanol, polyhydric alcohols or water-containing polyhydric alcohols such as propylene glycol, 1,3-butylene glycol, and glycerin, acetone, and ethyl acetate. However, when the inclusion of an organic solvent is not preferable depending on the application, the extraction solvent may be water alone or ethanol, which is easy to remove after extraction, may be used alone or in any mixture with water, or may be extracted by squeezing.

[0055] When the additives derived from plant or animal raw materials are used in external preparations or cosmetics for systemic or local use, the external preparations for skin can be expected to have, for example, cosmetic effects such as protection of the skin and hair, moisturizing, improving feel and texture, imparting softness, easing irritation, relieving stress through fragrance, cell activation (preventing cell aging), suppressing inflammation, improving skin and hair quality, preventing and improving rough skin, hair growth, hair care, preventing hair loss, imparting shine, a cleansing effect, relieving fatigue, promoting blood flow, and a hot bath effect, as well as fragrance, deodorizing, thickening, preserving, buffering, and other effects.

[0056] The agent of the present disclosure can suppress, for example, the expression of the Notch1 gene. Therefore, the agent of the present disclosure can be said to be, for example, an agent for use in suppressing the expression of the Notch1 gene, or an agent for use in suppressing the differentiation of epidermal stem cells into epidermal cells by Notch1.

[0057] In addition to the above, the topical skin preparation can be made into a product that is expected to have various cosmetic and medicinal effects of each of the raw material materials that are known to date, and by combining these, it is possible to enhance the effect intended by this disclosure and create a product that is expected to have multifunctional effects.

[0058] <Agent or composition for use in suppressing the expression of the IL-6 gene> In another aspect, the present disclosure provides an agent or composition for use in suppressing the expression of the IL-6 gene. The agent for use in suppressing the expression of the IL-6 gene of the present disclosure contains flavonoids. The composition for use in suppressing the expression of the IL-6 gene of the present disclosure contains flavonoids. According to the agent or composition for use in suppressing the expression of the IL-6 gene of the present disclosure, an anti-inflammatory effect on epidermal keratinocytes can be obtained.

[0059] The "suppression of the expression of the IL-6 gene" means that the expression level of the IL-6 gene is suppressed or decreased, and may also mean that the expression of the IL-6 gene changes from a state of expression to a state of no expression. The expression of the IL-6 gene can be evaluated, for example, by measuring the expression level of the mRNA of the IL-6 gene according to Example 1(2) described below.

[0060] The agent for use in suppressing the expression of the IL-6 gene of the present disclosure can suppress the expression of the IL-6 gene, for example, by being used for an administration subject. Thereby, the agent for use in suppressing the expression of the IL-6 gene of the present disclosure can obtain, for example, an anti-inflammatory effect. The usage conditions (administration conditions) of the agent for use in suppressing the expression of the IL-6 gene of the present disclosure can refer to the description of the usage conditions of the agent for use in suppressing the expression of the Notch1 gene of the present disclosure.

[0061] <Agent or composition for use in suppressing the expression of the IL-8 gene> In another aspect, the present disclosure provides an agent or composition for use in suppressing the expression of the IL-8 gene. The agent for use in suppressing the expression of the IL-8 gene of the present disclosure contains flavonoids. The composition for use in suppressing the expression of the IL-8 gene of the present disclosure contains flavonoids. According to the agent or composition for use in suppressing the expression of the IL-8 gene of the present disclosure, an anti-inflammatory effect on epidermal keratinocytes can be obtained.

[0062] The "suppression of IL-8 gene expression" means that the expression level of the IL-8 gene is suppressed or decreased, and may also mean that the expression of the IL-8 gene changes from a state of expression to a state of no expression. The expression of the IL-8 gene can be evaluated, for example, by measuring the expression level of the mRNA of the IL-8 gene according to Example 1(2) described below.

[0063] The agent for use in suppressing the expression of the IL-8 gene of the present disclosure can suppress the expression of the IL-8 gene, for example, by being used for an administration subject. Thereby, the agent for use in suppressing the expression of the IL-8 gene of the present disclosure can obtain, for example, an anti-inflammatory effect. The usage conditions (administration conditions) of the agent for use in suppressing the expression of the IL-8 gene of the present disclosure can refer to the description of the usage conditions of the agent for use in suppressing the expression of the Notch1 gene of the present disclosure.

[0064] <Agent or composition for use in suppressing the expression of the CYP1A1 gene> In another aspect, the present disclosure provides an agent or composition for use in suppressing the expression of the CYP1A1 gene. The agent for use in suppressing the expression of the CYP1A1 gene of the present disclosure contains flavonoids. The composition for use in suppressing the expression of the CYP1A1 gene of the present disclosure contains flavonoids. According to the agent or composition for use in suppressing the expression of the CYP1A1 gene of the present disclosure, a melanin synthesis inhibitory effect can be obtained.

[0065] The "suppression of CYP1A1 gene expression" means that the expression level of the CYP1A1 gene is suppressed or decreased, and may also mean that the expression of the CYP1A1 gene changes from a state of expression to a state of no expression. The expression of the CYP1A1 gene can be evaluated, for example, by measuring the expression level of the mRNA of the CYP1A1 gene according to Example 1(3) described below and the like.

[0066] The agent for use in suppressing the expression of the CYP1A1 gene of the present disclosure can suppress the expression of the CYP1A1 gene, for example, by being used for an administration subject. Thereby, the agent for use in suppressing the expression of the CYP1A1 gene of the present disclosure can obtain, for example, a melanin synthesis inhibitory effect. The usage conditions (administration conditions) of the agent for use in suppressing the expression of the CYP1A1 gene of the present disclosure can refer to the description of the usage conditions of the agent for use in suppressing the expression of the Notch1 gene of the present disclosure.

[0067] <Agent or composition for use in suppressing the expression of the CYP1B1 gene> In another aspect, the present disclosure provides an agent or composition for use in suppressing the expression of the CYP1B1 gene. The agent for use in suppressing the expression of the CYP1B1 gene of the present disclosure contains flavonoids. The composition for use in suppressing the expression of the CYP1B1 gene of the present disclosure contains flavonoids. According to the agent or composition for use in suppressing the expression of the CYP1B1 gene of the present disclosure, a melanin synthesis inhibitory effect can be obtained.

[0068] The "suppression of the expression of the CYP1B1 gene" means that the expression level of the CYP1B1 gene is suppressed or decreased, and may also mean that the expression of the CYP1B1 gene changes from a state of having expression to a state of having no expression. The expression of the CYP1B1 gene can be evaluated, for example, by measuring the expression level of the mRNA of the CYP1B1 gene according to Example 1(3) etc. described later.

[0069] The agent for use in suppressing the expression of the CYP1B1 gene of the present disclosure can suppress the expression of the CYP1B1 gene, for example, by being used for an administration subject. Thereby, the agent for use in suppressing the expression of the CYP1B1 gene of the present disclosure can obtain, for example, a melanin synthesis inhibitory effect. The usage conditions (administration conditions) of the agent for use in suppressing the expression of the CYP1B1 gene of the present disclosure can refer to the description of the usage conditions of the agent for use in suppressing the expression of the Notch1 gene of the present disclosure.

[0070] <Agent or composition for maintaining the stem cell property of epidermal stem cells> In another aspect, the present disclosure provides an agent or composition capable of maintaining the stem cell property of epidermal stem cells. The agent for maintaining the stem cell property of epidermal stem cells of the present disclosure contains flavonoids. The composition for maintaining the stem cell property of epidermal stem cells of the present disclosure contains flavonoids. According to the agent or composition for maintaining the stem cell property of epidermal stem cells of the present disclosure, since the expression of the Notch1 gene can be suppressed, it is expected that the stem cell property of epidermal stem cells can be maintained. Therefore, according to the agent or composition for maintaining the stem cell property of epidermal stem cells of the present disclosure, it is expected that effects such as enhancing the moisture retention of the skin can be obtained.

[0071] The above-mentioned "maintaining stem cell property" means that the differentiation ability is maintained or does not decrease during cell proliferation. The maintenance of the stem cells may, for example, mean that the differentiation into differentiated cells differentiated from the stem cells is suppressed. When the stem cells are epidermal stem cells, the maintenance of the differentiation ability can be evaluated, for example, by measuring the expression level of the mRNA of the MCSP (Melanoma-associated chondroitin sulfate proteoglycan) gene, which is an epidermal stem cell marker.

[0072] The agent for maintaining the stem cell property of epidermal stem cells of the present disclosure can, for example, maintain the stem cell property of epidermal stem cells by being used for an administration subject. The usage conditions (administration conditions) of the agent for maintaining the stem cell property of epidermal stem cells of the present disclosure can refer to the description of the usage conditions of the agent for suppressing the expression of the Notch1 gene of the present disclosure.

[0073] <Anti-inflammatory agent or composition> In another aspect, the present disclosure provides an agent or composition capable of suppressing the inflammation of epidermal keratinocytes. The anti-inflammatory agent of the present disclosure contains flavonoids. The composition for anti-inflammation of the present disclosure contains flavonoids. According to the anti-inflammatory agent or composition of the present disclosure, the inflammation of epidermal keratinocytes can be suppressed.

[0074] The anti-inflammatory agent of the present disclosure can suppress the inflammation of epidermal keratinocytes, for example, by being used for an administration subject. The usage conditions (administration conditions) of the anti-inflammatory agent of the present disclosure can refer to the description of the usage conditions of the agent for suppressing the expression of the Notch1 gene of the present disclosure.

[0075] <Melanin synthesis inhibitor or composition> In another aspect, the present disclosure provides an agent or composition capable of suppressing the melanin synthesis of epidermal keratinocytes. The melanin synthesis inhibitor of the present disclosure contains flavonoids. The composition for suppressing melanin synthesis of the present disclosure contains flavonoids. According to the melanin synthesis inhibitor or composition of the present disclosure, since the melanin synthesis of epidermal keratinocytes can be suppressed, a whitening effect can be obtained.

[0076] The melanin synthesis inhibitor of the present disclosure can suppress the melanin synthesis of epidermal keratinocytes, for example, by being used for an administration subject. The usage conditions (administration conditions) of the melanin synthesis inhibitor of the present disclosure can refer to the description of the usage conditions of the agent for suppressing the expression of the Notch1 gene of the present disclosure.

[0077] <Method for suppressing the expression of Notch1 gene> In another aspect, the present disclosure discloses a method capable of suppressing the expression of the Notch1 gene. The method for suppressing the expression of the Notch1 gene of the present disclosure uses the agent and / or composition for suppressing the expression of the Notch1 gene of the present disclosure. According to the method for suppressing the expression of the Notch1 gene of the present disclosure, for example, along with the maintenance of the stem cell property of epidermal stem cells, the supply of epidermal keratinocytes from the epidermal stem cells can be maintained, so that an effect of enhancing the moisture retention of the skin is expected to be obtained.

[0078] The method for suppressing the expression of the Notch1 gene of the present disclosure includes a usage step of using, for a subject, the agent and / or composition for suppressing the expression of the Notch1 gene of the present disclosure. The usage may be, for example, contact with the skin or the like, or administration.

[0079] In the method for suppressing the expression of the Notch1 gene of the present disclosure, the use step is, for example, in vitro or in vivo and may be performed. The subject (administration subject) and administration conditions of the method for suppressing the expression of the Notch1 gene of the present disclosure can, for example, refer to the description of the administration subject and administration conditions in the agent and / or composition used for suppressing the expression of the Notch1 gene of the present disclosure.

[0080] <Method for suppressing the expression of the IL-6 gene> In another aspect, the present disclosure discloses a method capable of suppressing the expression of the IL-6 gene. The method for suppressing the expression of the IL-6 gene of the present disclosure uses the agent and / or composition used for suppressing the expression of the IL-6 gene of the present disclosure. According to the method for suppressing the expression of the IL-6 gene of the present disclosure, for example, it is expected to obtain an anti-inflammatory effect on epidermal keratinocytes.

[0081] The method for suppressing the expression of the IL-6 gene of the present disclosure includes a use step of using, for a subject, the agent and / or composition used for suppressing the expression of the IL-6 gene of the present disclosure. The use may be, for example, contact with the skin or the like, or administration.

[0082] In the method for suppressing the expression of the IL-6 gene of the present disclosure, the use step is, for example, in vitro or in vivo and may be performed. The subject (administration subject) and administration conditions of the method for suppressing the expression of the IL-6 gene of the present disclosure can, for example, refer to the description of the administration subject and administration conditions in the agent and / or composition used for suppressing the expression of the Notch1 gene of the present disclosure.

[0083] <Method for suppressing the expression of the IL-8 gene> In another aspect, the present disclosure discloses a method capable of suppressing the expression of the IL-8 gene. The method for suppressing the expression of the IL-8 gene of the present disclosure uses an agent and / or composition for use in suppressing the expression of the IL-8 gene of the present disclosure. According to the method for suppressing the expression of the IL-8 gene of the present disclosure, for example, an inflammation-suppressing effect on epidermal keratinocytes is expected to be obtained.

[0084] The method for suppressing the expression of the IL-8 gene of the present disclosure includes a step of using, on a subject, an agent and / or composition for use in suppressing the expression of the IL-8 gene of the present disclosure. The use may be, for example, by contact with the skin or the like, or by administration.

[0085] In the method for suppressing the expression of the IL-8 gene of the present disclosure, the step of using may be, for example, in vitro or in vivo It may also be carried out in. The subject (administration subject) and administration conditions of the method for suppressing the expression of the IL-8 gene of the present disclosure can, for example, refer to the description of the administration subject and administration conditions in the agent and / or composition for use in suppressing the expression of the Notch1 gene of the present disclosure.

[0086] <Method for Suppressing the Expression of the CYP1A1 Gene> In another aspect, the present disclosure discloses a method capable of suppressing the expression of the CYP1A1 gene. The method for suppressing the expression of the CYP1A1 gene of the present disclosure uses an agent and / or composition for use in suppressing the expression of the CYP1A1 gene of the present disclosure. According to the method for suppressing the expression of the CYP1A1 gene of the present disclosure, for example, an effect of suppressing melanin synthesis is expected to be obtained.

[0087] The method for suppressing the expression of the CYP1A1 gene of the present disclosure includes a step of using, on a subject, an agent and / or composition for use in suppressing the expression of the CYP1A1 gene of the present disclosure. The use may be, for example, by contact with the skin or the like, or by administration.

[0088] In the method for suppressing the expression of the CYP1A1 gene of the present disclosure, the step of using may be, for example, invitro or in vivo It may also be carried out with vivo . The subject (administration subject) and administration conditions of the method for suppressing the expression of the CYP1A1 gene of the present disclosure can, for example, refer to the description of the administration subject and administration conditions in the agent and / or composition for suppressing the expression of the Notch1 gene of the present disclosure.

[0089] <Method for Suppressing the Expression of CYP1B1 Gene> In another aspect, the present disclosure discloses a method capable of suppressing the expression of the CYP1B1 gene. The method for suppressing the expression of the CYP1B1 gene of the present disclosure uses the agent and / or composition for suppressing the expression of the CYP1B1 gene of the present disclosure. According to the method for suppressing the expression of the CYP1B1 gene of the present disclosure, for example, an effect of suppressing the synthesis of melanin is expected to be obtained.

[0090] The method for suppressing the expression of the CYP1B1 gene of the present disclosure includes a use step of using, for a subject, the agent and / or composition for suppressing the expression of the CYP1B1 gene of the present disclosure. The use may be, for example, contact with the skin or the like, or administration.

[0091] In the method for suppressing the expression of the CYP1B1 gene of the present disclosure, the use step is, for example, in vitro or in vivo It may also be carried out with vivo . The subject (administration subject) and administration conditions of the method for suppressing the expression of the CYP1B1 gene of the present disclosure can, for example, refer to the description of the administration subject and administration conditions in the agent and / or composition for suppressing the expression of the Notch1 gene of the present disclosure.

[0092] <Method for Maintaining Stem Cell Property of Epidermal Stem Cells> In another aspect, the present disclosure discloses a method capable of maintaining the stem cell property of epidermal stem cells. The method for maintaining the stem cell property of the epidermal stem cells of the present disclosure uses the agent for maintaining the stem cell property of the epidermal stem cells of the present disclosure and / or the composition for maintaining the stem cell property of epidermal stem cells. According to the method for maintaining the stem cell property of the epidermal stem cells of the present disclosure, since the expression of the Notch1 gene can be suppressed, it is expected that the stem cell property of epidermal stem cells can be maintained. Therefore, according to the method for maintaining the stem cell property of the epidermal stem cells of the present disclosure, it is expected that effects such as enhancing the moisture retention of the skin can be obtained.

[0093] The method for maintaining the stem cell property of the epidermal stem cells of the present disclosure includes a use step of using the agent for maintaining the stem cell property of the epidermal stem cells of the present disclosure and / or the composition for a subject. The use may be, for example, contact with the skin or the like, or administration.

[0094] In the method for maintaining the stem cell property of the epidermal stem cells of the present disclosure, the use step may be, for example, in vitro or in vivo and may be carried out. The subject (administration subject) and administration conditions of the method for maintaining the stem cell property of the epidermal stem cells of the present disclosure can refer to the description of the administration subject and administration conditions in the agent and / or composition for suppressing the expression of the Notch1 gene of the present disclosure.

[0095] <Method for suppressing inflammation> In another aspect, the present disclosure discloses a method capable of suppressing inflammation. The method for suppressing inflammation of the present disclosure uses the anti-inflammatory agent of the present disclosure and / or the anti-inflammatory composition. According to the method for suppressing inflammation of the present disclosure, inflammation of epidermal keratinocytes, particularly inflammation of epidermal keratinocytes caused by IL-6 or IL-8, can be suppressed.

[0096] The method for suppressing inflammation of the present disclosure includes a use step of using the anti-inflammatory agent of the present disclosure and / or the composition for a subject. The use may be, for example, contact with the skin or the like, or administration.

[0097] In the method for suppressing inflammation of the present disclosure, the use step may be, for example,in vitro or in vivo It may also be performed in this manner. Regarding the subject (administration subject) and administration conditions of the inflammation suppression method of the present disclosure, for example, the descriptions of the administration subject and administration conditions in the agent and / or composition used for suppressing the expression of the Notch1 gene of the present disclosure can be incorporated.

[0098] <Melanin synthesis suppression method> In another aspect, the present disclosure discloses a method capable of suppressing melanin synthesis. The melanin synthesis suppression method of the present disclosure uses the melanin synthesis inhibitor and / or melanin synthesis suppression composition of the present disclosure. According to the melanin synthesis suppression method of the present disclosure, for example, it is expected that the synthesis of melanin can be suppressed.

[0099] The melanin synthesis suppression method of the present disclosure includes a use step of using the melanin synthesis inhibitor and / or composition of the present disclosure for a subject. The use may be, for example, contact with the skin or the like, or administration.

[0100] In the melanin synthesis suppression method of the present disclosure, the use step is, for example, in vitro or in vivo It may also be performed in this manner. Regarding the subject (administration subject) and administration conditions of the melanin synthesis suppression method of the present disclosure, for example, the descriptions of the administration subject and administration conditions in the agent and / or composition used for suppressing the expression of the Notch1 gene of the present disclosure can be incorporated.

[0101] <Use> In another aspect, the present disclosure is an agent and / or composition for use in suppressing the expression of the Notch1 gene and / or its use for suppressing the expression of the Notch1 gene. The present disclosure is an agent and / or composition for use in suppressing the expression of the IL-6 gene and / or its use for suppressing the expression of the IL-6 gene. The present disclosure is an agent and / or composition for use in suppressing the expression of the IL-8 gene and / or its use for suppressing the expression of the IL-8 gene. The present disclosure is an agent and / or composition for use in suppressing the expression of the CYP1A1 gene and / or its use for suppressing the expression of the CYP1A1 gene. The present disclosure is an agent and / or composition for use in suppressing the expression of the CYP1B1 gene and / or its use for suppressing the expression of the CYP1B1 gene. The present disclosure is an agent and / or composition for use in maintaining the stem cell properties of epidermal stem cells and / or its use for maintaining the stem cell properties of stem cells. The present disclosure is an anti-inflammatory agent and / or composition and / or its use for suppressing inflammation. The present disclosure is a melanin synthesis inhibitor and / or composition and / or its use for suppressing melanin synthesis.

[0102] The present disclosure is for the use of an agent and / or composition for suppressing the expression of the Notch1 gene to produce an agent and / or composition for suppressing the expression of the Notch1 gene. The present disclosure is for the use of an agent and / or composition for suppressing the expression of the IL-6 gene to produce an agent and / or composition for suppressing the expression of the IL-6 gene. The present disclosure is for the use of an agent and / or composition for suppressing the expression of the IL-8 gene to produce an agent and / or composition for suppressing the expression of the IL-8 gene. The present disclosure is for the use of an agent and / or composition for suppressing the expression of the CYP1A1 gene to produce an agent and / or composition for suppressing the expression of the CYP1A1 gene. The present disclosure is for the use of an agent and / or composition for suppressing the expression of the CYP1B1 gene to produce an agent and / or composition for suppressing the expression of the CYP1B1 gene. The present disclosure is for the use of an agent and / or composition for maintaining the stemness of stem cells to produce an agent and / or composition for maintaining the stemness of stem cells. The present disclosure is for the use of an anti-inflammatory agent and / or composition to produce an anti-inflammatory agent and / or composition. The present disclosure is for the use of a melanin synthesis inhibitor and / or composition to produce a melanin synthesis inhibitor and / or composition.

Example

[0103] Next, examples of the present invention will be described. However, the present invention is not limited by the following examples. Commercially available reagents were used based on their protocols unless otherwise indicated. Note that "mol / l" may also be denoted as "M".

[0104] [Example 1] It was confirmed that the flavonoids of the present disclosure exhibit an effect of suppressing the expression of the Notch1 gene and the like.

[0105] (1) Test of Notch1 gene expression level The Dutch iris extract was prepared by extracting the flowers of Dutch iris with 50% butylene glycol (BG). NHEK cells, which are human epidermal keratinocytes (purchased from Kurabo Industries Ltd.), were seeded in 35 mm dishes at a density of 6×10 4 cells / dish. The culture medium used was HuMedia KG2 (manufactured by Kurabo Industries Ltd.) containing 10 μg / ml insulin, 0.1 ng / ml human epidermal growth factor (hEGF), 0.67 μg / ml hydrocortisone hemisuccinate, 50 μg / ml gentamicin, 50 ng / ml amphotericin, 0.4% bovine pituitary extract (BPE), and 0.6 mmol / l calcium chloride. After seeding, the cells were cultured under conditions of 5% CO2 and 37 °C until they became confluent. After the culture, the Dutch iris extract was added to the dishes and cultured for 24 hours. After the culture, the culture supernatant was collected, and mRNA was purified using the RNeasy Mini Kit (manufactured by QIAGEN) according to the attached protocol. After the purification, a reverse transcription reaction was performed using PrimeScript Master Mix (manufactured by TaKaRa). Next, qRT-PCR was performed using the primer set for the Notch1 gene shown in Table 1 below according to the method described in TB Green Master Mix (manufactured by TaKaRa). A LightCycler (registered trademark) 96 (manufactured by Roche) was used as the PCR device. The ΔΔCT method was used to compare the mRNA expression between different experimental groups. Note that the control was performed in the same manner except that the Dutch iris extract was not added. These results are shown in Table 2 below.

[0106]

Table 1

[0107]

Table 2

[0108] Table 2 shows the values when the control value is 1. In Table 2, * indicates a significant difference (p < 0.01) compared to the control value in the Dunnett test. The expression level of Notch1 mRNA was 0.8 in the group supplemented with 0.05% Dutch kale extract and 0.5 in the group supplemented with 0.2% Dutch kale extract. From these results, it was found that in epidermal keratinocytes, the gene expression of Notch1 was suppressed in a concentration-dependent manner by Dutch kale extract. Also, in epidermal keratinocytes, it was suggested that Dutch kale extract can maintain the stem cell properties of epidermal stem cells.

[0109] (2) Test of the expression levels of IL-6 gene and IL-8 gene The Dutch kale extract was obtained by extracting the flowers of Dutch kale with 50% butylene glycol (BG). NHEK cells, which are human epidermal keratinocytes (purchased from Kuraray Co., Ltd.), were seeded in a 35 mm dish at a density of 6×10 4 cells / dish. As the medium, HuMedia KG2 (manufactured by Kuraray Co., Ltd.) containing 10 μg / ml of insulin, 0.1 ng / ml of human epidermal growth factor (hEGF), 0.67 μg / ml of hydrocortisone hemisuccinate, 50 μg / ml of gentamicin, 50 ng / ml of amphotericin, 0.4% of bovine pituitary extract (BPE), and 0.6 mmol / l of calcium chloride was used. After the seeding, the cells were cultured under the conditions of 5% CO2 and 37 °C until they became confluent. After the culture, the cells were washed with PBS and irradiated with UVB (10 mJ / cm 2) was irradiated onto the dish. After the irradiation, the Dutch kale extract was added to the dish and cultured for 24 hours. After the culture, the culture supernatant was collected, and mRNA was purified using the RNeasy Mini Kit (manufactured by QIAGEN) according to the attached protocol. After the purification, a reverse transcription reaction was performed using PrimeScript Master Mix (manufactured by TaKaRa). Next, qRT-PCR was performed using the primer set for the IL-6 gene or the primer set for the IL-8 gene shown in Table 3 below according to the method described in TB Green Master Mix (manufactured by TaKaRa). As the PCR apparatus, LightCycler (registered trademark) 96 (manufactured by Roche) was used. The ΔΔCT method was used to compare the mRNA expression between different experimental groups. Note that Control 1 was performed in the same manner except that the UV was not irradiated and the Dutch kale extract was not added. Also, Control 2 was performed in the same manner except that the Dutch kale extract was not added. These results are shown in Tables 4 and 5 below.

[0110]

Table 3

[0111]

Table 4

[0112] Table 4 shows the values when the value of Control 1 is set to 1. In Table 4, *** indicates a significant difference (p < 0.001) by comparison with the value of Control 2 in the Dunnett test. As shown in Table 4, the expression level of IL-6 mRNA was 5.2 in Control 2 and 2.3 in the group to which 0.1% Dutch kale extract was added. From these results, it was found that in epidermal keratinocytes in which inflammation was induced by UV, the gene expression of IL-6 was suppressed by the Dutch kale extract, that is, the inflammation was suppressed.

[0113]

Table 5

[0114] The above Table 5 shows the values when the value of Control 1 is set to 1. In the above Table 5, * indicates a significant difference (p < 0.05) by comparison with the value of Control 2 in the Dunnett test, and *** indicates a significant difference (p < 0.001) by comparison with the value of Control 2 in the Dunnett test. In the above Table 5, the expression level of IL-8 mRNA was 9.5 in Control 2 and 6.2 in the group supplemented with 0.1% Dutch sea buckthorn extract. From these results, it was found that in epidermal keratinocytes in which inflammation was induced by UV, the gene expression of IL-8 was suppressed by Dutch sea buckthorn extract, that is, inflammation was suppressed.

[0115] (3) Test of the expression level of CYP1A1 gene or CYP1B1 gene in melanocytes (pigment cells) The Dutch sea buckthorn extract was prepared by extracting the flowers of Dutch sea buckthorn with 50% butylene glycol (BG). 6 × 10 were placed in a 35 mm dish 4Normal human epidermal melanocytes (NHEM, purchased from Lonza) were seeded to form cell / dish. Melanocyte basal medium (MBM-4, manufactured by Lonza) was used. After the seeding, the cells were cultured under the conditions of 5% CO2 and 37 °C. Then, the Dutch sea buckthorn extract was added to the dish and cultured for 24 hours. After the culture, the cells were exposed to 50 μg / ml of PM2.5 (particulate matter, manufactured by National Institute of Standards & Technology) for 4 hours. After the exposure, the culture supernatant was collected, and mRNA was purified using the RNeasy Mini Kit (manufactured by QIAGEN) according to the attached protocol. After the purification, a reverse transcription reaction was performed using PrimeScript Master Mix (manufactured by TaKaRa). Next, qRT-PCR was performed using the primer set for CYP1A1 gene or the primer set for CYP1B1 gene shown in Table 6 below according to the method described in TB Green Master Mix (manufactured by TaKaRa). A LightCycler (registered trademark) 96 (manufactured by Roche) was used as the PCR device. The ΔΔCT method was used to compare the mRNA expression between different experimental groups. Note that Control 1 was performed in the same manner except that it was not exposed to the PM2.5 and the Dutch sea buckthorn extract was not added. Also, Control 2 was performed in the same manner except that the Dutch sea buckthorn extract was not added. Note that exposure to PM2.5 is known to cause pigmentation and melanin production in melanocytes due to an increase in the expression of AhR (aryl hydrocarbon receptor). CYP1A1 and CYP1B1 are markers of the AhR activation and indicators of melanin synthesis. These results are shown in Tables 7 and 8 below.

[0116]

Table 6

[0117]

Table 7

[0118] Table 7 shows the values when the value of Control 1 is set to 1. In Table 7, the expression level of CYP1A1 mRNA was 1.5 in Control 2 and 1 in the group to which 0.5% Dutch sea buckthorn extract was added. From these results, it was found that in melanocytes, the gene expression of CYP1A1 was suppressed by Dutch sea buckthorn extract. Also, it was suggested that in melanocytes, Dutch sea buckthorn extract exhibits a melanin synthesis inhibitory effect.

[0119]

Table 8

[0120] Table 8 shows the values when the value of Control 1 is set to 1. In Table 8, the expression level of CYP1B1 mRNA was 2.5 in Control 2 and 2.1 in the group to which 0.5% Dutch sea buckthorn extract was added. From these results, it was found that in melanocytes, the gene expression of CYP1B1 was suppressed by Dutch sea buckthorn extract. Also, it was suggested that in melanocytes, Dutch sea buckthorn extract exhibits a melanin synthesis inhibitory effect.

[0121] (4) Test of the expression level of CYP1A1 gene or CYP1B1 gene in epidermal keratinocytes Dutch sea buckthorn extract was obtained by extracting the flowers of Dutch sea buckthorn with 50% butylene glycol (BG). 6×10 were placed in a 35 mm dish 4NHEK cells, which are human epidermal keratinocytes (purchased from Kurabo Industries Ltd.), were seeded so as to become cells / dishes. As the medium, HuMedia KG2 (manufactured by Kurabo Industries Ltd.) containing 10 μg / ml of insulin, 0.1 ng / ml of human epidermal growth factor (hEGF), 0.67 μg / ml of hydrocortisone hemisuccinate, 50 μg / ml of gentamicin, 50 ng / ml of amphotericin, 0.4% of bovine pituitary extract (BPE), and 0.6 mmol / l of calcium chloride was used. After the seeding, the cells were cultured under the conditions of 5% CO2 and 37 °C until they became confluent. After the culture, the Dutch sea buckthorn extract was added to the dish and cultured for 24 hours. After the culture, the cells were exposed to PM2.5 (50 μg / ml) for 4 hours. After the exposure, the culture supernatant was collected, and mRNA was purified using the RNeasy Mini Kit (manufactured by QIAGEN) according to the attached protocol. After the purification, a reverse transcription reaction was performed using PrimeScript Master Mix (manufactured by TaKaRa). Next, qRT-PCR was performed using the primer set for the CYP1A1 gene or the primer set for the CYP1B1 gene shown in Table 6 above according to the method described in TB Green Master Mix (manufactured by TaKaRa). As the PCR apparatus, LightCycler (registered trademark) 96 (manufactured by Roche) was used. The ΔΔCT method was used to compare the mRNA expression between different experimental groups. Note that Control 1 was performed in the same manner except that it was not exposed to the PM2.5 and the Dutch sea buckthorn extract was not added. Also, Control 2 was performed in the same manner except that the Dutch sea buckthorn extract was not added. These results are shown in Tables 9 and 10 below.

[0122]

Table 9

[0123] Table 9 shows the values when the value of Control 1 is set to 1. In Table 9, the expression level of CYP1A1 mRNA was 93.6 in Control 2 and 77.6 in the group to which 0.5% Dutch kale extract was added. From these results, it was found that in epidermal keratinocytes, the gene expression of CYP1A1 was suppressed by Dutch kale extract. Also, it was suggested that Dutch kale extract exhibits a melanin synthesis inhibitory effect in epidermal keratinocytes.

[0124]

Table 10

[0125] Table 10 shows the values when the value of Control 1 is set to 1. In Table 10, the expression level of CYP1B1 mRNA was 61.8 in Control 2 and 59.3 in the group to which 0.5% Dutch kale extract was added. From these results, it was found that in epidermal keratinocytes, the gene expression of CYP1B1 was suppressed by Dutch kale extract. Also, it was suggested that Dutch kale extract exhibits a melanin synthesis inhibitory effect in epidermal keratinocytes.

[0126] Although the present disclosure has been described with reference to the embodiments and examples above, the present disclosure is not limited to the above embodiments and examples. Various changes that can be understood by those skilled in the art can be made to the configuration and details of the present disclosure within the scope of the present disclosure.

[0127] <Supplementary Note> Some or all of the above embodiments and examples can be described as follows, but are not limited thereto. <Agent for use in suppressing the expression of Notch1 gene> (Supplementary Note 1) An agent for use in suppressing the expression of Notch1 gene, comprising flavonoids. (Supplementary Note 2) The flavonoids are the agent described in Supplementary Note 1, which is swertiajaponin, swertisin, Isovitexin, and / or Isoorientin. (Supplementary Note 3) The flavonoids are the agent described in Supplementary Note 1 or 2, which is the aforementioned swertiajaponin, swertisin, Isovitexin, and Isoorientin. (Supplementary Note 4) The mass ratio (SJ:ST:I:IO) of the aforementioned swertiajaponin (SJ), swertisin (ST), Isovitexin (I), and Isoorientin (IO) is 2:2:0.5:1 to 6:6:1.5:1, which is the agent described in Supplementary Note 3. (Supplementary Note 5) The agent described in any one of Supplementary Notes 1 to 4, which contains a plant extract. (Supplementary Note 6) The plant is a plant of the genus Centaurium, which is the agent described in Supplementary Note 5. (Supplementary Note 7) An agent for topical application to the skin, which contains the agent described in any one of Supplementary Notes 1 to 6. <Composition for use in suppressing the expression of the Notch1 gene> (Supplementary Note 8) A composition for use in suppressing the expression of the Notch1 gene, which contains the agent described in any one of Supplementary Notes 1 to 7. (Supplementary Note 9) The composition described in Supplementary Note 8, which is a cosmetic. <Agent for use in suppressing the expression of the IL-6 gene> (Supplementary Note 10) An agent for use in suppressing the expression of the IL-6 gene, which contains flavonoids. (Supplementary Note 11) The flavonoids are the agent described in Supplementary Note 10, which is swertiajaponin, swertisin, Isovitexin, and / or Isoorientin. (Supplementary Note 12) The flavonoids are the agent described in Supplementary Note 10 or 11, which is swertiajaponin, swertisin, isovitexin, and isoorientin. (Supplementary Note 13) The agent described in Supplementary Note 12, wherein the mass ratio of the swertiajaponin (SJ), swertisin (ST), isovitexin (I), and isoorientin (IO) (SJ:ST:I:IO) is 2:2:0.5:1 to 6:6:1.5:1. (Supplementary Note 14) The agent described in any one of Supplementary Notes 10 to 13, which contains a plant extract. (Supplementary Note 15) The agent described in Supplementary Note 14, wherein the plant is a plant of the genus Swertia. (Supplementary Note 16) An agent for topical application to the skin, which contains the agent described in any one of Supplementary Notes 10 to 15. <Composition for use in suppressing the expression of the IL-6 gene> (Supplementary Note 17) A composition for use in suppressing the expression of the IL-6 gene, which contains the agent described in any one of Supplementary Notes 10 to 16. (Supplementary Note 18) The composition described in Supplementary Note 17, which is a cosmetic. <Agent for use in suppressing the expression of the IL-8 gene> (Supplementary Note 19) An agent for use in suppressing the expression of the IL-8 gene, which contains flavonoids. (Supplementary Note 20) The agent described in Supplementary Note 19, wherein the flavonoids are swertiajaponin, swertisin, Isovitexin, and / or Isoorientin. (Supplementary Note 21) The agent described in Supplementary Note 19 or 20, wherein the flavonoids are the swertiajaponin, swertisin, isovitexin, and isoorientin. (Supplementary Note 22) The agent according to Supplementary Note 21, wherein the mass ratio of the swertiajaponin (SJ), the swertisin (ST), the isovitexin (I), and the isoorientin (IO) (SJ:ST:I:IO) is 2:2:0.5:1 to 6:6:1.5:1. (Supplementary Note 23) The agent according to any one of Supplementary Notes 19 to 22, containing a plant extract. (Supplementary Note 24) The agent according to Supplementary Note 23, wherein the plant is a plant of the genus Swertia. (Supplementary Note 25) An agent for application to the skin, containing the agent according to any one of Supplementary Notes 19 to 24. <Composition for use in suppressing the expression of the IL-8 gene> (Supplementary Note 26) A composition for use in suppressing the expression of the IL-8 gene, containing the agent according to any one of Supplementary Notes 19 to 25. (Supplementary Note 27) The composition according to Supplementary Note 26, which is a cosmetic. <Agent for use in suppressing the expression of the CYP1A1 gene> (Supplementary Note 28) An agent for use in suppressing the expression of the CYP1A1 gene, containing flavonoids. (Supplementary Note 29) The agent according to Supplementary Note 28, wherein the flavonoids are swertiajaponin, swertisin, Isovitexin, and / or Isoorientin. (Supplementary Note 30) The agent according to Supplementary Note 28 or 29, wherein the flavonoids are the swertiajaponin, the swertisin, the isovitexin, and the isoorientin. (Supplementary Note 31) The agent according to Supplementary Note 30, wherein the mass ratio of the swertiajaponin (SJ), the swertisin (ST), the isovitexin (I), and the isoorientin (IO) (SJ:ST:I:IO) is 2:2:0.5:1 to 6:6:1.5:1. (Supplementary Note 32) An agent according to any one of Appendices 28 to 31, containing a plant extract. (Appendix 33) An agent according to Appendix 32, wherein the plant is a plant of the genus Swertia. (Appendix 34) An agent for applying to the skin, containing an agent according to any one of Appendices 28 to 33. <Composition for use in suppressing the expression of the CYP1A1 gene> (Appendix 35) A composition for use in suppressing the expression of the CYP1A1 gene, containing an agent according to any one of Appendices 28 to 34. (Appendix 36) The composition according to claim 35, which is a cosmetic. <Agent for use in suppressing the expression of the CYP1B1 gene> (Appendix 37) An agent for use in suppressing the expression of the CYP1B1 gene, containing flavonoids. (Appendix 38) The agent according to Appendix 37, wherein the flavonoids are swertiajaponin, swertisin, Isovitexin, and / or Isoorientin. (Appendix 39) The agent according to Appendix 37 or 38, wherein the flavonoids are the swertiajaponin, the swertisin, the Isovitexin, and the Isoorientin. (Appendix 40) The agent according to Appendix 39, wherein the mass ratio (SJ:ST:I:IO) of the swertiajaponin (SJ), the swertisin (ST), the Isovitexin (I), and the Isoorientin (IO) is 2:2:0.5:1 to 6:6:1.5:1. (Appendix 41) An agent according to any one of Appendices 37 to 40, containing a plant extract. (Appendix 42) The agent according to Appendix 41, wherein the plant is a plant of the genus Swertia. (Appendix 43) An agent for application to the skin, comprising the agent described in any one of Appendices 37 to 42. <Composition for use in suppressing the expression of the CYP1B1 gene> (Appendix 44) A composition for use in suppressing the expression of the CYP1B1 gene, comprising the agent described in any one of Appendices 37 to 43. (Appendix 45) The composition described in Appendix 44, which is a cosmetic. <Agent for use in maintaining the stem cell property of epidermal stem cells> (Appendix 46) An agent for use in maintaining the stem cell property of epidermal stem cells, comprising flavonoids. (Appendix 47) The agent described in Appendix 46, wherein the flavonoids are swertiajaponin, swertisin, Isovitexin, and / or Isoorientin. (Appendix 48) The agent described in Appendix 46 or 47, wherein the flavonoids are the swertiajaponin, the swertisin, the Isovitexin, and the Isoorientin. (Appendix 49) The agent described in Appendix 48, wherein the mass ratio of the swertiajaponin (SJ), the swertisin (ST), the Isovitexin (I), and the Isoorientin (IO) (SJ:ST:I:IO) is 2:2:0.5:1 to 6:6:1.5:1. (Appendix 50) The agent described in any one of Appendices 46 to 49, containing a plant extract. (Appendix 51) The agent described in Appendix 50, wherein the plant is a plant of the genus Swertia. (Appendix 52) An agent for application to the skin, comprising the agent described in any one of Appendices 46 to 51. <Composition for use in maintaining the stem cell property of epidermal stem cells> (Appendix 53) A composition for maintaining the stem cell property of epidermal stem cells, comprising the agent described in any one of Supplementary Notes 46 to 52. (Supplementary Note 54) A cosmetic composition according to Supplementary Note 53. <Anti-inflammatory agent> (Supplementary Note 55) An anti-inflammatory agent containing flavonoids. (Supplementary Note 56) The flavonoids in the agent described in Supplementary Note 55 are swertiajaponin, swertisin, Isovitexin, and / or Isoorientin. (Supplementary Note 57) The flavonoids in the agent described in Supplementary Note 55 or 56 are the swertiajaponin, the swertisin, the Isovitexin, and the Isoorientin. (Supplementary Note 58) The mass ratio (SJ:ST:I:IO) of the swertiajaponin (SJ), the swertisin (ST), the Isovitexin (I), and the Isoorientin (IO) in the agent described in Supplementary Note 57 is 2:2:0.5:1 to 6:6:1.5:1. (Supplementary Note 59) An agent according to any one of Supplementary Notes 55 to 58, containing a plant extract. (Supplementary Note 60) The plant in the agent described in Supplementary Note 59 is a plant of the genus Swertia. (Supplementary Note 61) An agent for applying to the skin, comprising the agent described in any one of Supplementary Notes 55 to 60. <Anti-inflammatory composition> (Supplementary Note 62) An anti-inflammatory composition, comprising the agent described in any one of Supplementary Notes 55 to 61. (Supplementary Note 63) A cosmetic composition according to Supplementary Note 62. <Melanin synthesis inhibitor> (Supplementary Note 64) A melanin synthesis inhibitor containing flavonoids. (Supplementary Note 65) The agent according to Supplementary Note 64, wherein the flavonoids are swertiajaponin, swertisin, Isovitexin, and / or Isoorientin. (Supplementary Note 66) The agent according to Supplementary Note 64 or 65, wherein the flavonoids are the swertiajaponin, the swertisin, the Isovitexin, and the Isoorientin. (Supplementary Note 67) The agent according to Supplementary Note 66, wherein the mass ratio (SJ:ST:I:IO) of the swertiajaponin (SJ), the swertisin (ST), the Isovitexin (I), and the Isoorientin (IO) is 2:2:0.5:1 to 6:6:1.5:1. (Supplementary Note 68) The agent according to any one of Supplementary Notes 64 to 67, containing a plant extract. (Supplementary Note 69) The agent according to claim 68, wherein the plant is a plant of the genus Swertia. (Supplementary Note 70) An agent for topical application to the skin, containing the agent according to any one of Supplementary Notes 64 to 69. <Melanin synthesis inhibitory composition> (Supplementary Note 71) A melanin synthesis inhibitory composition containing the agent according to any one of Supplementary Notes 64 to 70. (Supplementary Note 72) The composition according to Supplementary Note 71, which is a cosmetic. <Method for suppressing the expression of Notch1 gene> (Supplementary Note 73) A method for suppressing the expression of Notch1 gene, which uses the agent for suppressing the expression of Notch1 gene according to any one of Supplementary Notes 1 to 7 and / or the composition for suppressing the expression of Notch1 gene according to Supplementary Note 8 or 9. (Supplementary Note 74) The suppression method according to Supplementary Note 73, comprising a step of using an agent for suppressing the expression of the Notch1 gene and / or a composition for suppressing the expression of the Notch1 gene for a subject. (Supplementary Note 75) in vitro Or in vivo The suppression method according to Supplementary Note 73 or 74, which is used in... <Method for Suppressing the Expression of the IL-6 Gene> (Supplementary Note 76) A method for suppressing the expression of the IL-6 gene, which uses an agent for suppressing the expression of the IL-6 gene according to any one of Supplementary Notes 10 to 16 and / or a composition for suppressing the expression of the IL-6 gene according to Supplementary Note 17 or 18. (Supplementary Note 77) The suppression method according to Supplementary Note 76, comprising a step of using an agent for suppressing the expression of the IL-6 gene and / or a composition for suppressing the expression of the IL-6 gene for a subject. (Supplementary Note 78) in vitro Or in vivo The suppression method according to Supplementary Note 76 or 77, which is used in... <Method for Suppressing the Expression of the IL-8 Gene> (Supplementary Note 79) A method for suppressing the expression of the IL-8 gene, which uses an agent for suppressing the expression of the IL-8 gene according to any one of Supplementary Notes 19 to 25 and / or a composition for suppressing the expression of the IL-8 gene according to Supplementary Note 26 or 27. (Supplementary Note 80) The suppression method according to Supplementary Note 79, comprising a step of using an agent for suppressing the expression of the IL-8 gene and / or a composition for suppressing the expression of the IL-8 gene for a subject. (Supplementary Note 81) in vitro Or in vivo The suppression method according to Supplementary Note 79 or 80, which is used in... <Method for Suppressing Expression of CYP1A1 Gene> (Appendix 82) A method for suppressing the expression of the CYP1A1 gene, which uses an agent for suppressing the expression of the CYP1A1 gene described in any one of Appendices 28 to 34 and / or a composition for suppressing the expression of the CYP1A1 gene described in Appendix 35 or 36. (Appendix 83) The suppression method according to Appendix 82, which includes a step of using, for a subject, an agent for suppressing the expression of the CYP1A1 gene and / or a composition for suppressing the expression of the CYP1A1 gene. (Appendix 84) in vitro Or in vivo The suppression method according to Appendix 82 or 83, which is used in... <Method for Suppressing Expression of CYP1B1 Gene> (Appendix 85) A method for suppressing the expression of the CYP1B1 gene, which uses an agent for suppressing the expression of the CYP1B1 gene described in any one of Appendices 37 to 43 and / or a composition for suppressing the expression of the CYP1B1 gene described in Appendix 44 or 45. (Appendix 86) The suppression method according to Appendix 85, which includes a step of using, for a subject, an agent for suppressing the expression of the CYP1B1 gene and / or a composition for suppressing the expression of the CYP1B1 gene. (Appendix 87) in vitro Or in vivo The suppression method according to Appendix 85 or 86, which is used in... <Method for Maintaining Stemness of Epidermal Stem Cells> (Appendix 88) A method for maintaining the stemness of epidermal stem cells, which uses an agent for maintaining the stemness of epidermal stem cells described in any one of Appendices 46 to 52 and / or a composition for maintaining the stemness of epidermal stem cells described in Claim 53 or 54. (Appendix 89) The suppression method according to Supplementary Note 88, including a step of using, for a subject, an agent for maintaining the stem cell property of the epidermal stem cells and / or a composition for maintaining the stem cell property of the epidermal stem cells. (Supplementary Note 90) in vitro Or in vivo The suppression method according to Supplementary Note 88 or 90, for use in <Inflammation suppression method> (Supplementary Note 91) An inflammation suppression method of using an inflammation suppressant according to any one of Supplementary Notes 55 to 61 and / or an inflammation suppression composition according to Supplementary Note 62 or 63. (Supplementary Note 92) The suppression method according to Supplementary Note 91, including a step of using, for a subject, the inflammation suppressant and / or the inflammation suppression composition. (Supplementary Note 93) in vitro Or in vivo The suppression method according to Supplementary Note 91 or 92, for use in <Melanin synthesis suppression method> (Supplementary Note 94) A melanin synthesis suppression method of using a melanin synthesis inhibitor according to any one of Supplementary Notes 64 to 70 and / or a melanin synthesis suppression composition according to Supplementary Note 71 or 72. (Supplementary Note 95) The suppression method according to Supplementary Note 94, including a step of using, for a subject, the melanin synthesis inhibitor and / or the melanin synthesis suppression composition. (Supplementary Note 96) in vitro Or in vivo The suppression method according to Supplementary Note 94 or 95, for use in <Use> (Supplementary Note 97) Use of an agent for suppressing the expression of the Notch1 gene according to any one of Supplementary Notes 1 to 7 and / or a composition for suppressing the expression of the Notch1 gene according to Supplementary Note 8 or 9 for suppressing the expression of the Notch1 gene. (Appended Note 98) Use of the agent for suppressing the expression of the IL-6 gene described in any one of Appended Notes 10 to 16 and / or the composition for suppressing the expression of the IL-6 gene described in Appended Note 17 or 18, for use in suppressing the expression of the IL-6 gene. (Appended Note 99) Use of the agent for suppressing the expression of the IL-8 gene described in any one of Appended Notes 19 to 25 and / or the composition for suppressing the expression of the IL-8 gene described in Appended Note 26 or 27, for use in suppressing the expression of the IL-8 gene. (Appended Note 100) Use of the agent for suppressing the expression of the CYP1A1 gene described in any one of Appended Notes 28 to 34 and / or the composition for suppressing the expression of the CYP1A1 gene described in Appended Note 35 or 36, for use in suppressing the expression of the CYP1A1 gene. (Appended Note 101) Use of the agent for suppressing the expression of the CYP1B1 gene described in any one of Appended Notes 37 to 43 and / or the composition for suppressing the expression of the CYP1B1 gene described in Appended Note 44 or 45, for use in suppressing the expression of the CYP1B1 gene. (Appended Note 102) Use of the agent for maintaining the stemness of epidermal stem cells described in any one of Appended Notes 46 to 52 and / or the composition for maintaining the stemness of epidermal stem cells described in Appended Note 53 or 54, for use in maintaining the stemness of epidermal stem cells. (Appended Note 103) Use of the anti-inflammatory agent described in any one of Appended Notes 55 to 61 and / or the anti-inflammatory composition described in Appended Note 62 or 63, for use in suppressing inflammation. (Appended Note 104) Use of the melanin synthesis inhibitor described in any one of Appended Notes 64 to 70 and / or the melanin synthesis inhibitor composition described in Appended Note 71 or 72, for use in suppressing melanin synthesis.

Industrial Applicability

[0128] As described above, according to the present disclosure, it is possible to provide an agent, a composition, and the like for use in suppressing the expression of the Notch1 gene. Therefore, the present invention can be said to be extremely useful, for example, in the fields of cosmetics, external skin preparations, and the like.

Claims

1. An agent for suppressing the expression of Notch1 gene, which contains flavonoids.

2. The agent according to Claim 1, wherein the flavonoids are swertiajaponin, swertisin, Isovitexin, and / or Isoorientin.

3. The agent according to Claim 1 or 2, wherein the flavonoids are the swertiajaponin, the swertisin, the Isovitexin, and the Isoorientin.

4. The agent according to Claim 3, wherein the mass ratio (SJ:ST:I:IO) of the swertiajaponin (SJ), the swertisin (ST), the Isovitexin (I), and the Isoorientin (IO) is 2:2:0.5:1 to 6:6:1.5:

1.

5. The agent according to any one of Claims 1 to 4, which contains a plant extract.

6. The agent according to Claim 5, wherein the plant is a plant of the genus Swertia.

7. An agent for topical application to the skin, which contains the agent according to any one of Claims 1 to 6.

8. A composition for suppressing the expression of Notch1 gene, which contains the agent according to any one of Claims 1 to 7.

9. The composition according to Claim 8, which is a cosmetic.

10. An agent for suppressing the expression of IL-6 gene, which contains flavonoids.

11. The agent according to Claim 10, wherein the flavonoids are swertiajaponin, swertisin, Isovitexin, and / or Isoorientin.

12. The agent according to Claim 10 or 11, wherein the flavonoids are the swertiajaponin, the swertisin, the Isovitexin, and the Isoorientin.

13. The agent according to Claim 12, wherein the mass ratio (SJ:ST:I:IO) of the swertiajaponin (SJ), the swertisin (ST), the Isovitexin (I), and the Isoorientin (IO) is 2:2:0.5:1 to 6:6:1.5:

1.

14. The agent according to any one of Claims 10 to 13, which contains a plant extract.

15. The agent according to claim 14, wherein the plant is a plant of the genus Swertia.

16. An agent for topical application to the skin, comprising the agent according to any one of claims 10 to 15.

17. A composition for use in suppressing the expression of the IL-6 gene, comprising the agent according to any one of claims 10 to 16.

18. The composition according to claim 17, which is a cosmetic.

19. An agent for use in suppressing the expression of the IL-8 gene, comprising flavonoids.

20. The agent according to claim 19, wherein the flavonoids are swertiajaponin, swertisin, Isovitexin, and / or Isoorientin.

21. The agent according to claim 19 or 20, wherein the flavonoids are the swertiajaponin, the swertisin, the Isovitexin, and the Isoorientin.

22. The agent according to claim 21, wherein the mass ratio (SJ:ST:I:IO) of the swertiajaponin (SJ), the swertisin (ST), the Isovitexin (I), and the Isoorientin (IO) is 2:2:0.5:1 to 6:6:1.5:

1.

23. The agent according to any one of claims 19 to 22, containing a plant extract.

24. The agent according to claim 23, wherein the plant is a plant of the genus Swertia.

25. An agent for topical application to the skin, comprising the agent according to any one of claims 19 to 24.

26. A composition for use in suppressing the expression of the IL-8 gene, comprising the agent according to any one of claims 19 to 25.

27. The composition according to claim 26, which is a cosmetic.

28. An agent for use in suppressing the expression of the CYP1A1 gene, comprising flavonoids.

29. The agent according to claim 28, wherein the flavonoids are swertiajaponin, swertisin, Isovitexin, and / or Isoorientin.

30. The agent according to claim 28 or 29, wherein the flavonoids are the swertiajaponin, the swertisin, the Isovitexin, and the Isoorientin.

31. The mass ratio (SJ:ST:I:IO) of the said swertiajaponin (SJ), the said swertisin (ST), the said isovitexin (I), and the said isoorientin (IO) is 2:2:0.5:1 to 6:6:1.5:1, the agent according to claim 30.

32. The agent according to any one of claims 28 to 31, containing a plant extract.

33. The plant is a plant of the genus Swertia, the agent according to claim 32.

34. An agent for applying to the skin, containing the agent according to any one of claims 28 to 33.

35. A composition for use in suppressing the expression of the CYP1A1 gene, containing the agent according to any one of claims 28 to 34.

36. The composition according to claim 35, which is a cosmetic.

37. An agent for use in suppressing the expression of the CYP1B1 gene, containing flavonoids.

38. The flavonoids are swertiajaponin, swertisin, Isovitexin, and / or Isoorientin, the agent according to claim 37.

39. The flavonoids are the said swertiajaponin, the said swertisin, the said isovitexin, and the said isoorientin, the agent according to claim 37 or 38.

40. The mass ratio (SJ:ST:I:IO) of the said swertiajaponin (SJ), the said swertisin (ST), the said isovitexin (I), and the said isoorientin (IO) is 2:2:0.5:1 to 6:6:1.5:1, the agent according to claim 39.

41. The agent according to any one of claims 37 to 40, containing a plant extract.

42. The plant is a plant of the genus Swertia, the agent according to claim 41.

43. An agent for applying to the skin, containing the agent according to any one of claims 37 to 42.

44. A composition for use in suppressing the expression of the CYP1B1 gene, containing the agent according to any one of claims 37 to 43.

45. The composition according to claim 44, which is a cosmetic.

46. An agent for use in maintaining the stem cell property of epidermal stem cells, containing flavonoids.

47. The agent according to claim 46, wherein the flavonoids are swertiajaponin, swertisin, Isovitexin, and / or Isoorientin.

48. The agent according to claim 46 or 47, wherein the flavonoids are the swertiajaponin, the swertisin, the Isovitexin, and the Isoorientin.

49. The agent according to claim 48, wherein the mass ratio (SJ:ST:I:IO) of the swertiajaponin (SJ), the swertisin (ST), the Isovitexin (I), and the Isoorientin (IO) is 2:2:0.5:1 to 6:6:1.5:

1.

50. The agent according to any one of claims 46 to 49, which contains a plant extract.

51. The agent according to claim 50, wherein the plant is a plant of the genus Swertia.

52. An agent for topical application to the skin, which contains the agent according to any one of claims 46 to 51.

53. A composition for use in maintaining the stemness of epidermal stem cells, which contains the agent according to any one of claims 46 to 52.

54. The composition according to claim 53, which is a cosmetic.

55. An anti-inflammatory agent containing flavonoids.

56. The agent according to claim 55, wherein the flavonoids are swertiajaponin, swertisin, Isovitexin, and / or Isoorientin.

57. The agent according to claim 55 or 56, wherein the flavonoids are the swertiajaponin, the swertisin, the Isovitexin, and the Isoorientin.

58. The agent according to claim 57, wherein the mass ratio (SJ:ST:I:IO) of the swertiajaponin (SJ), the swertisin (ST), the Isovitexin (I), and the Isoorientin (IO) is 2:2:0.5:1 to 6:6:1.5:

1.

59. The agent according to any one of claims 55 to 58, which contains a plant extract.

60. The agent according to claim 59, wherein the plant is a plant of the genus Swertia.

61. An agent for topical application to the skin, comprising the agent according to any one of claims 55 to 60.

62. An anti-inflammatory composition, comprising the agent according to any one of claims 55 to 61.

63. The composition according to claim 62, which is a cosmetic.

64. A melanin synthesis inhibitor comprising flavonoids.

65. The agent according to claim 64, wherein the flavonoids are swertiajaponin, swertisin, Isovitexin, and / or Isoorientin.

66. The agent according to claim 64 or 65, wherein the flavonoids are the swertiajaponin, the swertisin, the Isovitexin, and the Isoorientin.

67. The agent according to claim 66, wherein the mass ratio (SJ:ST:I:IO) of the swertiajaponin (SJ), the swertisin (ST), the Isovitexin (I), and the Isoorientin (IO) is 2:2:0.5:1 to 6:6:1.5:

1.

68. The agent according to any one of claims 64 to 67, containing a plant extract.

69. The agent according to claim 68, wherein the plant is a plant of the genus Swertia.

70. An agent for topical application to the skin, comprising the agent according to any one of claims 64 to 69.

71. A melanin synthesis inhibitory composition, comprising the agent according to any one of claims 64 to 70.

72. The composition according to claim 71, which is a cosmetic.

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