Myonectin production promoter

Abstract

To provide a composition that can promote the production of myonectin and is suitable for oral ingestion.SOLUTION: A myonectin production promoter comprises one or more selected from Curcuma amada extract, extract from flower of Nelumbo nucifera, Uncaria tomentosa extract, and Tamarindus indica extract as an active ingredient.SELECTED DRAWING: Figure 1

Description

【Technical Field】 【0001】 The present invention relates to a myonectin production promoter and a composition for promoting myonectin production. 【Background Art】 【0002】 Myonectin was discovered as a kind 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 myokine functions variously in the skin and changes the expression of genes related to skin condition (Patent Document 1). In particular, since the amount of melanin production is suppressed in melanocytes to which myonectin is added, it has been proposed to use myonectin as an active ingredient in a whitening composition (Patent Document 2). In addition, it is known that in patients with type 2 diabetes and obesity, the amount of myonectin is lower than that in healthy subjects, or that when the amount of myonectin is high, obesity-related markers tend to be low (Non-Patent Document 2). 【Prior Art Documents】 【Patent Documents】 【0003】 【Patent Document 1】 Japanese Patent Application Laid-Open No. 2020-046195 【Patent Document 2】 Japanese Patent Application Laid-Open No. 2020-015692 【Non-Patent Documents】 【0004】 【Non-Patent Document 1】 M. M. Seldin, et al., J. Biol. Chem., 2012 Apr 6; 287(15): 11968-11980. 【Non-Patent Document 2】 Exp Clin Endocrinol Diabetes. 2019 Jul 24. [Overview of the Initiative] [Problems that the invention aims to solve] 【0005】 As mentioned above, it is becoming clear that myonectin is involved in keeping skin and the body healthy, and the inventors of this invention have focused on the usefulness of increasing its amount. However, myonectin secretion is usually stimulated by aerobic exercise, and until now there have been no other effective or efficient means to increase myonectin levels. In view of these circumstances, the object of the present invention is to provide a composition that can promote the production of myonectin and is suitable for oral intake. [Means for solving the problem] 【0006】 As a result of diligent research to solve the above problems, the inventors of this invention came to the realization that one or more of the following, selected from mango ginger extract, lotus flower extract, cat's claw extract, and Indian date extract, promote the production of myonectin in muscle cells, and thus completed the present invention. 【0007】 In other words, the present invention is as follows: [1] A myonectin production promoter containing one or more selected from mango ginger extract, lotus flower extract, cat's claw extract, and Indian date extract. [2] A myonectin production promoter as described in [1], which promotes myonectin production in muscle cells. [3] Mango ginger extract, lotus flower extract, cat's claw extract, and indigo An oral composition for myonectin production, containing one or more selected from diandrite extracts. [4] The composition described in [3], which is a food or beverage. [Effects of the Invention] 【0008】 The present invention provides a novel application for promoting myonectin production from specific plant extracts. Furthermore, a composition for myonectin production is provided. This composition can be in the form of food or beverages, allowing for easy and continuous incorporation into daily life. [Brief explanation of the drawing] 【0009】 [Figure 1] 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 2] 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 3] 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 4] 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】 The agents and compositions of the present invention contain one or more selected from mango ginger extract, lotus flower extract, cat's claw extract, and Indian date extract. Of these, mango ginger extract is particularly preferred from the viewpoint of myonectin production promoting effect. Mango ginger extract is an extract from mango ginger (Curcuma amada), a plant belonging to the ginger family (Zingiberaceae). Lotus flower extract is an extract of the flowers or flower buds of the lotus plant (Nelumbo nucifera), which belongs to the genus Nelumbo in the family Nelumbonaceae. Cat's claw extract is derived from Uncaria tomentosa, a species of cat's claw belonging to the Rubiaceae family. It is an extract of ). Tamarind extract is an extract of Tamarindus indica of the genus Tamarind in the subfamily Caesalpinioideae of the family Leguminosae. 【0011】 In the present invention, the above-mentioned extract shall mean not only the extract itself, but also the fractions of the extract, the purified fractions, the total of the solvent-removed products of the extract or fractions, and purified products. 【0012】 Also, as the extract, those extracted from the plant body by a conventional method can be used. In the extract, for example, in addition to using the whole plant (whole 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 extract of the flower of the lotus, 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. 【0013】 As a specific extraction method, for example, 1 to 30 parts by mass of a solvent is added to 1 part by mass of the part used for extraction of the plant body or its dried product, immersed at room temperature for several days or at a temperature near the boiling point for several hours, cooled to room temperature, and then, if desired, the insoluble matter and / or the solvent are removed, and fractionation and purification are carried out by column chromatography or the like can be mentioned. 【0014】 The total content of mangosteen ginger extract, lotus flower extract, cat's claw extract, and / or tamarind 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 in terms of solids based on the whole composition. By setting the content within the above range, the desired effect can be easily obtained, and the freedom 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. 【0015】 Mango ginger extract, lotus flower extract, cat's claw extract, and Indian date extract each enhance the expression of the myonectin gene (FAM132B) in muscle cells, as shown in the examples described below. Here, muscle cells include myoblasts and muscle fibers. Since the enhancement of myonectin gene expression promotes myonectin production, these plant extracts are active ingredients in myonectin production promoters. 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 a decrease in myonectin levels, or conditions and diseases that improve with an increase in myonectin levels, as they promote the production of myonectin. 【0016】 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". While there are no particular limitations on the dosage, considering the desired effect and safety, it is preferable to take 1 to 100 mg / day of the total amount of mango ginger extract, lotus flower extract, cat's claw extract, and / or Indian date extract in solid matter equivalent, 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. 【0017】 When the agent or composition of the present invention is administered orally, it is preferable to provide it as a food or beverage. 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. 【0018】 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. 【0019】 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 marine products, fish ham / sausage, processed marine products, marine delicacies, and tsukudani; and processed livestock products such as canned livestock / pastes and livestock ham / sausage. Processed dairy products; processed milk, milk beverages, yogurts, lactic acid bacteria beverages, cheeses, ice creams, powdered milk, creams, and other dairy products; fats and oils such as butter, margarines, and vegetable oils; basic seasonings such as soy sauce, miso, sauces, tomato-based seasonings, mirin, and vinegars; 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. The agent or composition of the present invention may be added to the following foods, etc.: caramel, candy, chewing gum, chocolate, cookies, biscuits, cakes, pies, snacks, crackers, Japanese sweets, rice sweets, bean sweets, dessert sweets, and other confectionery; carbonated drinks, natural fruit juice, 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, alcoholic beverages, and other foods, etc. 【0020】 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 to promote myonectin production, 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 uses, and any expression that can evoke or infer uses such as "increase myokines" or "obtain the effects of myokines" 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 on which it is displayed. Furthermore, the "display" should preferably be made in a manner that allows consumers to directly recognize the above-mentioned use. 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 use is written; displaying or distributing advertisements, price lists, catalogs, brochures, POPs, and other promotional materials at sales sites or in transaction documents that include the above-mentioned use; or providing information containing the above-mentioned use by electromagnetic means (such as the Internet). 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. 【0021】 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. 【0022】 When the agent or composition of the present invention is in the form of a topical skin preparation, the content of mango ginger extract, lotus flower extract, cat's claw extract, and / or Indian date extract 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, making it easier to obtain the desired effect and ensuring freedom in formulation design. 【0023】 When the agent or composition of the present invention is in the form of a topical skin preparation, it may optionally contain, in addition to one or more extracts selected from mango ginger extract, lotus flower extract, cat's claw extract, and Indian date extract, other components commonly used in topical skin compositions, 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, and ozoke. Hydrocarbons such as lye, paraffin, 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, and neopentyl glycoside dicaprate. Synthetic ester oils such as glyceryl di-2-heptylundecanoate, glyceryl tri-2-ethylhexanoate, trimethylolpropane tri-2-ethylhexanoate, trimethylolpropane triisostearate, pentane erythritol tetra-2-ethylhexanoate; 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. 【0024】 Anionic surfactants such as fatty acid soaps (sodium laurate, sodium palmitate, etc.), potassium lauryl sulfate, and alkyl sulfate triethanolamine ether; cationic surfactants such as stearyltrimethylammonium chloride, benzalkonium chloride, and laurylamine oxide; imidazoline-based amphoteric surfactants (2-cocoyl-2-imidazolinium hydroxide-1-carboxyethyloxy disodium salt, etc.), betaine-based surfactants (alkyl betaine, amide betaine, sulfobetaine, etc.), Amphoteric surfactants such as acylmethyl taurine; sorbitan fatty acid esters (sorbitan monostearate, sorbitan sesquioleate, etc.), glycerin fatty acids (glyceryl monostearate, etc.), propylene glycol fatty acid esters (propylene glycol monostearate, etc.), hydrogenated castor oil derivatives, glycerin alkyl ethers, POE sorbitan fatty acid esters (POE sorbitan monooleate, polyoxyethylene sorbitan monostearate, etc.), POE sorbitan fatty acid esters (POE -Sorbit monolaurate, etc.), POE glycerin fatty acid esters (POE-glycerin monoisostearate, etc.), POE fatty acid esters (polyethylene glycol monooleate, POE distearate, etc.), POE alkyl ethers (POE 2-octyldodecyl ether, etc.), POE alkylphenyl ethers (POE nonylphenyl ether, etc.), Pluronic® type, POE·POP alkyl ethers (POE·POP 2-decyltetradecyl ether, etc.), Tetronic, PO Nonionic surfactants such as E castor oil, hydrogenated castor oil derivatives (POE castor oil, POE hydrogenated castor oil, etc.), sucrose fatty acid esters, and alkyl glucosides; 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; 【0025】 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, Blue No. 404, Yellow No. 5, Red No. 505, Red No. 230, Red No. 223, Orange No. 201, Red No. 213, Yellow No. 204, Yellow No. 203, and Blue No. 1, which may be laked. Organic dyes such as Green No. 201, Violet No. 201, Red No. 204; organic powders such as polyethylene powder, polymethyl methacrylate, nylon powder, organopolysiloxane elastomers; 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; 【0026】 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, etc.; antibacterial agents (preservatives) such as methylparaben, ethylparaben, butylparaben, phenoxyethanol; anti-inflammatory agents such as glycyrrhizic acid derivatives, glycyrrhetinic acid derivatives, salicylic acid derivatives, hinokitiol, zinc oxide, allantoin; wrinkle-improving agents such as retinol, ascorbic acid, tocopherol, or farnesyl acetate; various extracts (for example, Examples include: Phellodendron amurense, Coptis japonica, Lithospermum erythrorhizon, Paeonia lactiflora, Swertia japonica, Birch, Sage, Loquat, Carrot, Aloe vera, Malva sylvestris, Iris ensata, Grape, Coix lacryma-jobi, Luffa gourd, Lily, Saffron, Cnidium officinale, Zingiber officinale, St. John's wort, Ononis scutellaria, Garlic, Chili pepper, Citrus unshiu peel, Angelica acutiloba, Seaweed, etc.; activators such as royal jelly, photosensitizers, and cholesterol derivatives; blood circulation promoters such as nonylic acid valenylamide, 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] 【0027】 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. 【0028】 <Reference example> Various extracts were prepared using the following procedure. 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 flowers and flower buds of the Nelumbo nucifera (family Nelumbonaceae) were mixed with a 10-fold volume of 30% aqueous ethanol 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. 【0029】 <Example of test> Examination of the effect of various extracts on the mRNA expression level of the myonectin gene. 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 BulletKit (Lonza: CC-3245)) at 37°C under 5% CO2 conditions for 24 hours. After culturing, remove the basal medium and wash with PBS, then add differentiation medium (DMEM:F-12 (Lonza:12-719F) + 2% Horse Serum (Gibco:16050-130) + 1% aa (Gibco:15240062)) 1.0 mL / 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. The test extract used was the one prepared in the reference example. 【0030】 Figures 1-4 show the mRNA expression levels of the myonectin gene in muscle cells, expressed as relative values ​​with the mRNA expression level of the myonectin gene in solvent-controlled muscle cells set to 1. 【0031】 In muscle cells treated with each extract, an increasing trend in myonectin gene mRNA expression was observed compared to the control group. In particular, muscle cells treated with mango ginger extract showed a significant increase in myonectin gene mRNA expression compared to the control group. [Industrial applicability] 【0032】 This invention provides a novel application for promoting myonectin production from specific plant extracts. Furthermore, since it provides a myonectin-producing composition that can be in the form of food or beverages and can be easily and continuously incorporated into daily life, it is highly useful industrially.

Claims

[Claim 1] Contains mango ginger extract, The aforementioned mango ginger extract is a polar solvent extract of mango ginger, a member of the ginger family (Zingiberaceae), and is a myonectin production promoter. [Claim 2] A myonectin production promoter according to claim 1, which promotes myonectin production in muscle cells. [Claim 3] Contains mango ginger extract, The aforementioned mango ginger extract is a polar solvent extract of mango ginger, a member of the ginger family (Zingiberaceae), and is an oral composition for myonectin production. [Claim 4] The composition according to claim 3, which is a food or beverage.

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