IL-1α expression inhibitors

Myonectin is utilized as an IL-1α expression inhibitor, addressing its unknown physiological activity by suppressing IL-1α in keratinocytes, offering a new application in skin preparations and food/beverages for effective skin condition management.

JP7834457B2Active Publication Date: 2026-03-24POLA CHEMICAL INDUSTRIES INC
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Patent Information

Authority / Receiving Office
JP · JP
Patent Type
Patents
Current Assignee / Owner
Filing Date
2021-11-17
Publication Date
2026-03-24

AI Technical Summary

Technical Problem

The physiological activity of myonectin is largely unknown, and its potential to suppress IL-1α expression in keratinocytes has not been fully explored for skin conditions.

Method used

Myonectin is used as an IL-1α expression inhibitor, either alone or in combination with myonectin production promoters like plant extracts, to suppress IL-1α expression in keratinocytes, and can be incorporated into topical skin preparations, food, or beverages.

Benefits of technology

Myonectin effectively suppresses IL-1α expression in keratinocytes, providing a new application for skin condition management and can be easily integrated into daily life through various formulations.

✦ Generated by Eureka AI based on patent content.

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Abstract

To discover new functions of myonectin and to provide suitable uses thereof.SOLUTION: Myonectin is used as an active ingredient of an IL-1α expression inhibitor. In addition, a myonectin production promoter is included in a composition for IL-1α expression inhibition.SELECTED DRAWING: Figure 1
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Description

Technical Field

[0001] The present invention relates to a new use of myonectin, and specifically to an IL-1α expression inhibitor.

Background Art

[0002] Myonectin was discovered as a type of cytokine called myokine secreted from muscle (Non-Patent Document 1), but its physiological activity is still largely unknown and various studies have been conducted. So far, it has been found that myokines function in various ways in the skin and change the expression of genes involved in skin conditions (Patent Document 1). In particular, since the amount of melanin production is suppressed in melanocytes added with myonectin, it has been proposed to use myonectin as an active ingredient in a whitening composition (Patent Document 2).

Prior Art Documents

Patent Documents

[0003]

Patent Document 1

Patent Document 2

[0006] As a result of diligent research by the inventors, we conceived that myonectin suppresses IL-1α expression in keratinocytes, and thus completed the present invention.

[0007] In other words, the present invention is as follows: [1] An IL-1α expression inhibitor containing myonectin. [2] The agent described in [1] that suppresses IL-1α expression in keratinocytes. [3] The agent described in [1] or [2], which is contained in a topical skin preparation. [4] The agent described in [1] or [2], which is contained in food or beverages. [5] A composition for inhibiting IL-1α expression, containing a myonectin production promoter. [6] The composition described in [5], which is a topical skin preparation. [7] The composition described in [5], which is a food or beverage. [Effects of the Invention]

[0008] The present invention provides a new application for myonectin: the suppression of IL-1α expression. Furthermore, it provides a method for incorporating a myonectin production promoter into an IL-1α expression suppression composition. The agents and compositions of the present invention can be in the form of food or beverages or topical skin preparations, allowing for easy and continuous incorporation into daily life. [Brief explanation of the drawing]

[0009] [Figure 1] A graph showing the expression level of IL-1α in epidermal cells cultured in the presence of myonectin. [Figure 2] Graph showing the relative expression levels of myonectin gene mRNA in human skeletal muscle myoblasts treated with mango ginger extract, with the control level set to 1 (*p<0.05). [Figure 3]This graph shows the relative expression levels of myonectin gene mRNA in human skeletal muscle myoblasts treated with lotus flower extract, with the control level set to 1. [Figure 4] This graph shows the relative expression levels of myonectin gene mRNA in human skeletal muscle myoblasts treated with cat's claw extract, with the control level set to 1. [Figure 5] This graph shows the relative expression levels of myonectin gene mRNA in human skeletal muscle myoblasts treated with Indian date extract, with the control level set to 1. [Modes for carrying out the invention]

[0010] A first aspect of the present invention is an IL-1α expression inhibitor containing myonectin. The myonectin content in the IL-1α expression inhibitor of the present invention is preferably 0.01% by mass or more, more preferably 0.1% by mass or more, and even more preferably 1% by mass or more, based on the total amount of the agent. Myonectin is a protein secreted from muscles and present in the body in mammals, including humans, but the agent of the present invention is usually distinguishable from muscles and other materials containing myonectin in the manner described above.

[0011] Myonectin can be obtained by any method; for example, it can be obtained by biosynthesizing the protein using the DNA of the gene encoding myonectin (CTRP15) using well-known genetic engineering techniques, followed by isolation and purification.

[0012] Furthermore, a component that promotes the production of myonectin in vivo, i.e., a myonectin production promoter, can also be used as an active ingredient for suppressing IL-1α expression. That is, the second aspect of the present invention is a composition for suppressing IL-1α expression containing a myonectin production promoter. The myonectin production promoter promotes the production of myonectin in muscle cells, and the produced myonectin suppresses the expression of IL-1α in keratinocytes.

[0013] The myonectin production promoter refers to a component that directly or indirectly enhances the expression of the myonectin gene (FAM132B) in muscle cells. Here, muscle cells include myoblasts and muscle fibers.

[0014] The myonectin production promoter is not particularly limited, such as plant extracts, compounds, etc. For example, plant extracts such as mangosteen ginger extract, lotus flower extract, cat's claw extract, and Indian date extract are preferably mentioned. Mangosteen ginger extract is an extract of Curcuma amada, a plant of the genus Curcuma in the family Zingiberaceae. Lotus flower extract is an extract of the flower or flower bud of Nelumbo nucifera, a plant of the genus Nelumbo in the family Nelumbonaceae. Cat's claw extract is from Uncaria tomentosa ), a plant of the genus Uncaria in the family Rubiaceae. Indian date extract is an extract of Tamarindus indica, a plant of the genus Tamarindus in the subfamily Caesalpinioideae of the family Fabaceae.

[0015] In the present invention, the above extract means not only the extract itself, but also the fraction of the extract, the purified fraction, the general name of the solvent-removed product of the extract or fraction, and the purified product.

[0016] Also, as the extract, those extracted from plants by conventional methods can be used. In the extract, for example, in addition to using the whole plant (herb), parts such as the plant body, aerial part, rhizome part, trunk part, leaf part, stem part, flower, flower bud, fruit, etc. are used for the extraction operation. However, in the lotus flower extract, the flower or flower bud is used for the extraction operation. As the extraction solvent, one or more selected from polar solvents such as water, alcohols such as ethanol, isopropyl alcohol, butanol, polyhydric alcohols such as 1,3-butanediol, polypropylene glycol, ketones such as acetone, methyl ethyl ketone, and ethers such as diethyl ether, tetrahydrofuran, etc. are preferably used.

[0017] Specific extraction methods include, for example, adding 1 to 30 parts by mass of solvent to 1 part by mass of the plant body or its dried product to be used for extraction, immersing it for several days at room temperature or for several hours at a temperature near its boiling point, cooling it to room temperature, removing insoluble matter and / or solvent as desired, and then fractionating and purifying it by column chromatography or the like.

[0018] The total content of mango ginger extract, lotus flower extract, cat's claw extract, and / or Indian date extract in the composition of the present invention is preferably 0.0001 to 50% by mass, more preferably 0.001 to 30% by mass, and even more preferably 0.001 to 10% by mass, based on solid matter, relative to the entire composition. By setting the content within the above range, the desired effect can be easily obtained, and flexibility in formulation design can be ensured. The above-mentioned content can be appropriately adjusted according to the administration route and the form of the composition to be contained, as described later.

[0019] As shown in the examples described later, IL-1α expression is suppressed in keratinocytes to which myonectin is added. In particular, IL-1α expression is normally increased in keratinocytes subjected to physical stimuli such as scratching, but this expression can be suppressed. Similar effects can also be expected in keratinocytes subjected to some kind of chemical or ultraviolet stimulation. Therefore, the agent of the present invention can be suitably used for suppressing IL-1α expression. Furthermore, the composition of the present invention promotes the production of myonectin in vivo, and as a result exerts an IL-1α expression suppression effect. Here, suppression of expression means that the expression level of the gene encoding IL-1α or the IL-1α protein is lower compared to when the agent or composition of the present invention is not applied.

[0020] The agents and compositions of the present invention can be suitably used for the prevention, improvement, and / or treatment of conditions and diseases caused by an increase in IL-1α levels, or conditions and diseases that improve with a decrease in IL-1α levels.

[0021] The administration route of the agents and compositions of the present invention is not particularly limited, including oral, transdermal, nasal, and intravenous injection, but oral or transdermal administration is preferred. Here, "administration" may be substituted with "ingestion".

[0022] When the agent or composition of the present invention is administered orally, it is preferable to provide it as food or beverage. When the agent of the present invention is provided in the form of a food or beverage, the myonectin content is preferably 0.01 to 20% by mass, more preferably 0.1 to 10% by mass, and even more preferably 1 to 5% by mass, relative to the total amount of the composition. This makes it easier to obtain the desired effect and ensures flexibility in formulation design. The preferred intake amount of the food and beverage containing myonectin of the present invention is not particularly limited, but for adults, a daily intake of 0.001 to 1000 mg / kg (body weight) in terms of myonectin content is preferred from the viewpoint of achieving sufficient efficacy, and more preferably 0.01 to 100 mg / kg (body weight), and especially 0.1 to 10 mg / kg (body weight). This daily amount can be taken all at once or divided into several doses. In addition to single-dose intake... It is preferable to take it continuously or intermittently for several weeks to several months.

[0023] When the composition of the present invention is provided in the form of food or beverage, the amount of myonectin production promoter contained therein can be appropriately adjusted depending on the promoter. For example, in the case of a plant extract having a myonectin production promoting effect, it is preferable to include an amount equivalent to 1 to 100 mg / day in solid matter terms, which is taken in one or several divided doses. In addition to single doses, it is also preferable to take it continuously or intermittently for several weeks to several months.

[0024] When the agent or composition of the present invention is made into a food or beverage, any ingredients commonly used in food and beverage manufacturing may be added during its production. Examples of such optional components include proteins, carbohydrates, fats, nutrients, seasonings, and flavorings. Examples of carbohydrates include monosaccharides such as glucose and fructose; disaccharides such as maltose, sucrose, and oligosaccharides; and polysaccharides such as dextrin and cyclodextrin, as well as sugar alcohols such as xylitol, sorbitol, and erythritol. Examples of flavorings include natural flavorings (thaumatin, stevia extract, etc.) and synthetic flavorings (saccharin, aspartame, etc.). In addition, additives used in the aforementioned pharmaceutical compositions and commonly added to food products may also be used.

[0025] The form of food and beverages can be liquid, paste, solid, powder, granules, etc. Furthermore, tablets, liquid foods, and animal feed are also included in the definition of food and beverages.

[0026] Furthermore, it may also be included in other general foods and beverages, for example, wheat flour products such as bread, macaroni, spaghetti, noodles, cake mix, fried chicken batter, and breadcrumbs; instant foods such as instant noodles, cup noodles, retort / prepared foods, canned prepared foods, microwaveable foods, instant soups / stews, instant miso soup / clear soup, canned soups, and freeze-dried foods; processed agricultural products such as canned agricultural products, canned fruit, jams / marmalades, pickles, boiled beans, dried agricultural products, and cereals (grain processed products); processed marine products such as canned seafood, fish ham / sausage, processed marine products, marine delicacies, and tsukudani; processed livestock products such as canned livestock / pastes and meat ham / sausage; milk and dairy products such as processed milk, milk beverages, yogurts, lactic acid bacteria beverages, cheese, ice cream, prepared milk powders, cream, and other dairy products; butter, ma - Fat and oil such as garine and vegetable oil; basic seasonings such as soy sauce, miso, sauces, tomato-based seasonings, mirin, and vinegar; compound seasonings and foods such as cooking mixes, curry bases, sauces, dressings, noodle soup bases, spices, and other compound seasonings; frozen foods such as raw frozen foods, semi-cooked frozen foods, and cooked frozen foods; confectionery such as caramel, candy, chewing gum, chocolate, cookies, biscuits, cakes, pies, snacks, crackers, Japanese sweets, rice sweets, bean sweets, and dessert sweets; beverages such as carbonated drinks, natural fruit juices, fruit juice drinks, fruit juice-containing soft drinks, fruit pulp drinks, fruit juice drinks with fruit pulp, vegetable drinks, soy milk, soy milk drinks, coffee drinks, tea drinks, powdered drinks, concentrated drinks, sports drinks, nutritional drinks, and alcoholic beverages; the agent or composition of the present invention may be added to foods other than those listed above.

[0027] Examples of the food and beverages of the present invention include ordinary foods, beverages, foods with functional claims, health functional foods such as foods for specified health uses, and supplements, with foods with functional claims being particularly preferred. When the food or beverage of the present invention is used for the purpose of suppressing IL-1α expression, a label indicating its usefulness and functionality may be attached to the product during commercialization. Such "display" acts include all acts that inform consumers of the aforementioned use, and any expression that can evoke or infer the use of "suppressing the expression of IL-1α" falls under the "display" acts of the present invention, regardless of the purpose of the display, the content of the display, or the object or medium to which it is displayed. Furthermore, the "display" will be made using language that allows consumers to directly recognize the above-mentioned uses. This is preferable. Specifically, examples include transferring, delivering, displaying for transfer or delivery, or importing food and beverage products or their packaging, containers, etc., on which the above-mentioned uses are described; displaying or distributing advertisements, price lists, catalogs, brochures, POP displays, or other promotional materials at sales sites or transaction documents on which the above-mentioned uses are described; or providing information containing these materials by electromagnetic means (such as the Internet). Furthermore, if the food and beverage products of the present invention are approved under various systems established by the government, such as health functional foods, and are implemented under such approval, it is preferable to display them in a manner based on said approval.

[0028] Preferred forms of transdermal administration of the agent or composition of the present invention include topical skin preparations such as cosmetics, quasi-drugs, and pharmaceuticals. The dosage form of the topical skin composition is not particularly limited and includes, for example, lotion, emulsifiers such as emulsions and creams, oil, gel, and pack forms.

[0029] When the agent of the present invention is provided in the form of a topical skin preparation, the myonectin content is preferably 0.01 to 20% by mass, more preferably 0.1 to 10% by mass, and even more preferably 1 to 5% by mass, relative to the total amount of the composition. This makes it easier to obtain the desired effect and ensures flexibility in formulation design. When the composition of the present invention is provided as a topical skin preparation, the amount of myonectin production promoter contained therein can be appropriately adjusted depending on the myonectin production promoter. For example, in the case of a plant extract having a myonectin production promoting effect, the total amount is preferably 0.01 to 20% by mass, more preferably 0.1 to 10% by mass, and even more preferably 1 to 5% by mass, relative to the total amount of the composition, which makes it easier to obtain the desired effect and ensures flexibility in formulation design.

[0030] When the agent or composition of the present invention is in the form of a topical skin preparation, it may optionally contain components commonly used in topical skin compositions other than myonectin or myonectin-producing agents, as long as they do not impair the effects of the present invention. Such ingredients include, for example, oils and waxes such as macadamia nut oil, avocado oil, corn oil, olive oil, rapeseed oil, sesame oil, castor oil, safflower oil, cottonseed oil, jojoba oil, coconut oil, palm oil, liquid lanolin, hydrogenated coconut oil, hydrogenated oil, Japanese wax, hydrogenated castor oil, beeswax, candelilla wax, carnauba wax, privet wax, lanolin, reduced lanolin, hard lanolin, jojoba wax, liquid paraffin, squalane, pristane, ozokerite, paraffin, Hydrocarbons such as ceresin, petrolatum, and microcrystalline wax; higher fatty acids such as oleic acid, isostearic acid, lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, and undecylenic acid; higher alcohols such as cetyl alcohol, stearyl alcohol, isostearyl alcohol, behenyl alcohol, octyldodecanol, myristyl alcohol, and cetostearyl alcohol; cetyl isooctanoate, isopropyl myristate, hexyldecyl isostearate, diisopropyl adipate, di-2-ethylhexyl sebatate, cetyl lactate, diisostearyl malate, ethylene glycol di-2-ethylhexanoate, neopentyl glycol dicaprate, glycerin di-2-heptylundecanoate, glycerin tri-2-ethylhexanoate, trimethylolpropane tri-2-ethylhexanoate, trimethylolpropane triisostearate, pentane tetra-2-ethylhexanoate Synthetic ester oils such as lit; linear polysiloxanes such as dimethylpolysiloxane, methylphenylpolysiloxane, and diphenylpolysiloxane; cyclic polysiloxanes such as octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane, and dodecamethylcyclohexanesiloxane; modified polysiloxanes such as amino-modified polysiloxane, polyether-modified polysiloxane, alkyl-modified polysiloxane, and fluorine-modified polysiloxane; and other oils such as silicone oils.

[0031] Fatty acid soaps (sodium laurate, sodium palmitate, etc.), sodium lauryl sulfate Anionic surfactants such as potassium and alkyl sulfate triethanolamine ether; cationic surfactants such as stearyltrimethylammonium chloride, benzalkonium chloride, and laurylamine oxide; amphoteric surfactants such as imidazoline-based surfactants (2-cocoyl-2-imidazolinium hydroxide-1-carboxyethyloxy disodium salt, etc.), betaine-based surfactants (alkyl betaine, amide betaine, sulfobetaine, etc.), and amphoteric surfactants such as acylmethyl taurine; sorbitan fatty acid esters (sorbitan monostearate, sorbitan sesquioleate, etc.), glycerin fatty acid esters (glyceryl monostearate, etc.), propylene glycol fatty acid esters (propylene glycol monostearate, etc.), hydrogenated castor oil derivatives, glycerin alkyl ether, POE sorbitan fatty acid esters (POE sorbitan monooleate, polyoxyethylene sorbitan monostearate, etc.), POE sorbitan fatty acid esters (POE-sorbitan monolaurate, etc.), POE Ricelin fatty acid esters (e.g., POE-glycerin monoisostearate), POE fatty acid esters (e.g., polyethylene glycol monooleate, POE distearate), POE alkyl ethers (e.g., POE 2-octyldodecyl ether), POE alkylphenyl ethers (e.g., POE nonylphenyl ether), Pluronic® type, POE-POP alkyl ethers (e.g., POE-POP 2-decyltetradecyl ether), Tetronic, POE castor oil, hydrogenated castor oil Nonionic surfactants such as castor oil derivatives (POE castor oil, POE hydrogenated castor oil, etc.), sucrose fatty acid esters, and alkyl glucosides; polyhydric alcohols such as polyethylene glycol, glycerin, 1,3-butylene glycol, erythritol, sorbitol, xylitol, maltitol, propylene glycol, dipropylene glycol, diglycerin, isoprene glycol, 1,2-pentanediol, 2,4-hexanediol, 1,2-hexanediol, and 1,2-octanediol;

[0032] Moisturizing ingredients such as sodium pyrrolidone carboxylate, lactic acid, and sodium lactate; powders such as mica, talc, kaolin, synthetic mica, calcium carbonate, magnesium carbonate, anhydrous silicic acid (silica), aluminum oxide, and barium sulfate, which may be surface-treated; inorganic pigments such as red iron oxide, yellow iron oxide, black iron oxide, cobalt oxide, ultramarine, Prussian blue, titanium dioxide, and zinc oxide, which may be surface-treated; pearl agents such as titanium mica, fish scale foil, and bismuth oxychloride, which may be surface-treated; and Red No. 202, Red No. 228, Red No. 226, Yellow No. 4, and Blue No. 404, which may be lakeped. Organic dyes such as Yellow 5, Red 505, Red 230, Red 223, Orange 201, Red 213, Yellow 204, Yellow 203, Blue 1, Green 201, Violet 201, Red 204; Organic powders such as polyethylene powder, polymethyl methacrylate, nylon powder, organopolysiloxane elastomer; Para-aminobenzoic acid-based UV absorbers; Anthranilic acid-based UV absorbers; Salicylic acid-based UV absorbers; Cinnamic acid-based UV absorbers; Benzophenone-based UV absorbers; Sugar-based UV absorbers; 2-(2'-hydroxy-5'-t-octylphenyl)benzotriazole, 4-methoxy UV absorbers such as C-4'-t-butyldibenzoylmethane;

[0033] Lower alcohols such as ethanol and isopropanol; vitamin A or its derivatives, vitamin B6 hydrochloride, vitamin B6 tripalmitate, vitamin B6 dioctanoate, vitamin B2 or its derivatives, vitamin B 12 Vitamin B 15Vitamin B compounds or their derivatives; vitamin E compounds such as α-tocopherol, β-tocopherol, γ-tocopherol, vitamin E acetate, vitamin D compounds, vitamin H, pantothenic acid, pantethine, pyrroloquinoline quinone, and other vitamins; antibacterial agents (preservatives) such as methylparaben, ethylparaben, butylparaben, and phenoxyethanol; anti-inflammatory agents such as glycyrrhizic acid derivatives, glycyrrhetinic acid derivatives, salicylic acid derivatives, hinokitiol, zinc oxide, and allantoin; wrinkle-improving agents such as retinol, ascorbic acid, tocopherol, or farnesyl acetate; various extracts (e.g., Phellodendron amurense, Coptis japonica, Lithospermum erythrorhizon, Paeonia lactiflora, Swertia japonica, Birch, Sage, Loquat, Carrot, Aloe vera, Malva sylvestris, Iris ensata, Grape, Coix lacryma-jobi). Examples include loofah, lily, saffron, Cnidium officinale, ginger, St. John's wort, ononis, garlic, chili pepper, dried tangerine peel, angelica root, seaweed, etc.; activators such as royal jelly, photosensitizer, and cholesterol derivatives; blood circulation promoters such as nonylic acid vanenylamide, capsaicin, gingerol, and tannic acid; anti-seborrheic agents such as sulfur and thianthol; anti-inflammatory agents such as tranexamic acid, thiotaurine, and hypotaurine; and water-soluble polymers such as collagen and hyaluronic acid. [Examples]

[0034] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to the following examples unless it exceeds the essence of the invention.

[0035] <Example> Investigation of the effect of myonectin on IL-1α expression levels The following procedure was used to measure IL-1α expression levels in keratinocytes treated with myonectin. Each well of the 12-well plate contains basal culture medium (HUMedia-KG2 medium, manufactured by Kurabo Industries Ltd.) Add 0.5 mL each, and then add human keratinocyte (Kurabo Industries Ltd., Lot #06445). Spread 0.5 mL of the suspension (6.0 × 10 4Cells were cultured in 1.0 mL / well at 37°C under 5% CO2 conditions for 48 hours. After culturing, to simulate physical stimulation, a microspatula (specific method) was used to scratch the well in a straight line across the diameter, and myonectin-containing medium (myonectin concentration 100 ng / mL, HUMedia-KG2 medium name, ( The cells were replaced with 0.5 mL / well of Kurabo stock and cultured at 37°C under 5% CO2 conditions for 24 hours. After culturing, the cells were washed with PBS and harvested, then metabolized using QIAcube (QIAGEN). RNA was extracted. RT-qPCR was performed using Fast SYBR Green Master Mix 5ml (Applied Biosystems), Superscript VILO cDNA Synthesis kit 250T (Invitrogen), and Hs_IL1A_1_SG QuantiTect Primer Assay (QIAGEN, QT00001127, Cat.249900) to identify IL-1α. We analyzed the expression levels of [the substance].

[0036] Figure 1 shows the mRNA expression level of the IL-1α gene in keratinocytes, expressed as a relative value with the mRNA expression level of the IL-1α gene in keratinocytes without physical stimulation set to 1. In keratinocytes treated with myonectin, the mRNA expression level of the IL-1α gene was significantly lower than in cells without myonectin, indicating that myonectin suppresses IL-1α expression.

[0037] <Example> Confirmation of myonectin production promoting effect of various extracts Various extracts were prepared using the following procedure and used as test extracts. Mango Ginger Extract: The whole plant of dried mango ginger (Turmeric genus, Zingiberaceae family) is mixed with 10 times the volume of a 30% ethanol aqueous solution, refluxed, and extracted. The resulting liquid is then freeze-dried to produce a powder. Lotus flower extract: Dried lotus flowers and flower buds of the Nelumbonaceae family, genus Nelumbo, were mixed with 10 times the volume of a 30% ethanol aqueous solution, refluxed, and extracted. The resulting liquid was then freeze-dried to produce a powder. Cat's Claw Extract: The whole plant of the dried cat's claw (Uncaria rhynchophylla), a member of the Rubiaceae family, is mixed with a 30% aqueous solution of ethanol (10 times the volume), refluxed, and extracted. The resulting liquid is then freeze-dried to produce a powder. Indian Date Extract: Dried tamarind fruit (Tamarindaceae family, Caesalpinioideae subfamily) is mixed with 10 times the volume of a 30% ethanol aqueous solution, refluxed, and extracted. The resulting liquid is then freeze-dried to produce a powder.

[0038] The myonectin gene expression level in muscle cells treated with the test extract was measured using the following procedure. Human skeletal muscle myoblasts Lonza CC-2580 (Lonza, Lot #29715) were seeded in a 24-well plate (4 × 10⁶). 4 Cells were divided into wells and incubated in 0.5 mL / well of basal medium (SkGM-2 Bullet Kit (Lonza: CC-3245)) at 37°C under 5% CO2 conditions for 24 hours. After incubation, the basal medium was removed and washed with PBS, then incubated in 1.0 mL / well of differentiation medium (DMEM: F-12 (Lonza: 12-719F) + 2% Horse Serum (Gibco: 16050-130) + 1% aa (Gibco: 15240062)). The cells were added to the wells and cultured at 37°C under 5% CO2 conditions for 72 hours. After culturing, the differentiation medium was removed, and differentiation medium containing the test extract to the specified solid content was added at 1.0 mL / well, and cultured at 37°C under 5% CO2 conditions for 72 hours. After culturing, the cells were washed with PBS and tested for Fast SYBR Green Master Mix (Termo Fisher Scientific) and Hs_FAM132B_4_SG QuantiTect Primer Assay (QIAGEN, for myonectin FAM132B gene measurement). , and using Hs_TBP_1_SG QuantiTect Primer Assay (manufactured by QIAGEN, endogenous control) Then, qRT-PCR was performed to analyze the expression level of the myonectin gene (FAM132B). did.

[0039] Figures 2-5 show the mRNA expression levels of the myonectin gene in muscle cells, expressed as relative values ​​with the myonectin gene mRNA expression level in solvent-controlled muscle cells set to 1.

[0040] In muscle cells treated with each extract, an increasing trend in myonectin gene mRNA expression was observed compared to the control. In particular, in muscle cells treated with mango ginger extract, myonectin gene mRNA expression significantly increased compared to the control. Therefore, it can be understood that these plant extracts can act as myonectin production promoters and, due to their myonectin production-promoting effect, can be active ingredients in compositions for inhibiting IL-1α expression. [Industrial applicability]

[0041] This invention provides a new application for myonectin: the suppression of IL-1α expression. Furthermore, an embodiment is provided in which a myonectin production promoter is used as the active ingredient in an IL-1α expression suppression composition. These agents and compositions can be in the form of food or beverages or topical skin preparations, and are highly industrially useful because they can be easily and continuously incorporated into daily life.

Claims

1. An IL-1α expression inhibitor containing myonectin.

2. The agent according to claim 1, which suppresses IL-1α expression in keratinocytes.

3. The agent according to claim 1 or 2, which is an embodiment of a topical skin preparation.

4. The agent according to claim 1 or 2, in the form of a food or beverage.

Citation Information

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