JP2024034009A - Dkk1 messenger rna expression inhibitor and white hair improver - Google Patents

Abstract

To identify components with DKK1 mRNA expression inhibitory action from naturally occurring substances known for high safety, and to provide a DKK1 mRNA expression inhibitor and a white hair improver comprising the identified component as an active ingredient.SOLUTION: A DKK1 mRNA expression inhibitor and a white hair improver each comprise at least one selected from the group consisting of Morinda citrifolia extract, Prunus mume Siebold et Zuccarini extract, Rhodomyrtus tomentosa (Ait.) Hassk. extract and Averrhoa carambola extract as an active ingredient.SELECTED DRAWING: None

Description

The present invention relates to a DKK1 mRNA expression inhibitor and a gray hair improving agent.

Conventionally, the production of melanin from melanocytes in hair follicles is promoted to increase the amount of melanin newly produced in hair, thereby preventing gray hair and improving hair color. For example, it is known that a melanocyte activator containing an extract of a plant belonging to the family Asteraceae, the genus Neclantia, as an active ingredient can be used as an agent for preventing gray hair (see Patent Document 1).

The WNT signal pathway is an intracellular signal pathway that is widely conserved from nematodes to mammals. In the WNT signal pathway, signals are transmitted when WNT, a secreted protein, binds to WNT receptors present on cell membranes. In the epidermis, activation of the WNT signal pathway is known to promote melanocyte differentiation and proliferation and melanin synthesis.

On the other hand, DKK1 (Dickkopf 1), a secreted protein that inhibits the binding between WNT and WNT receptor, is known as a factor that inhibits the WNT signal pathway. In the skin, DKK1 is secreted by dermal fibroblasts, which are mesenchymal cells in the dermis, and is known to suppress the differentiation and proliferation of melanocytes present in the epidermis, and suppress melanin synthesis (non-patent research). (See Reference 1). It is also known that DKK1 promotes the proliferation of epidermal keratinocytes (epidermal keratinocytes) and suppresses the uptake of melanin from melanocytes (see Non-Patent Document 2). Therefore, if the expression of DKK1 can be suppressed in dermal papilla cells, which are mesenchymal cells of the hair follicle, it will be possible to activate the WNT signal pathway in the melanocytes of the hair follicle, promoting melanin synthesis, and as a result, It is thought that it can improve gray hair.

Hair follicles are mainly composed of epithelial cells derived from the ectoderm and mesenchymal cells derived from the mesoderm, and are organs in which development and regeneration occur through the interaction of these cells. The process of involution repeats throughout life. The anagen phase begins when dormant hair follicle stem cells are activated. During the growth phase, mesenchymal dermal papilla cells and epithelial cells actively produce growth factors (VEGF, HGF, IGF-1, FGF7, BMP, WNT, Noggin, etc.) that signal hair growth. The division of epithelial cells such as hair matrix cells, which are the material for hair (hair shaft), becomes active and the hair elongates. At the end of the growth phase, mesenchymal cells such as the dermal papilla and subcutaneous fat actively produce growth factors (FGF5, TGF-β, etc.) that signal hair loss, and the hair follicle shifts to the catagen phase. . During the catagen phase, the hair matrix stops cell division and the number of cells decreases due to apoptosis. Thereafter, it passes through a telogen phase and enters a growth phase again (Non-Patent Document 3). In this way, in order to promote hair growth, it is necessary to directly activate the proliferation of epithelial cells (keratinocytes) in the hair follicle, which are the material for hair, and to increase the production of growth factors that serve as hair growth signals. It is important to induce and maintain the growth phase of hair follicles.

Japanese Patent Application Publication No. 2002-114700

J. Cell Biol., 2004, vol.165, no.2, pp.275-285 FASEB J., 2008, vol.22, issue 4, pp.1009-1020 Seiji Arase et al., “Anti-Aging Series 1: The Reality of Gray Hair, Hair Loss, and Hair Growth,” NTS, July 4, 2005, p.1-34, 65-77

An object of the present invention is to find a substance having a DKK1 mRNA expression suppressing effect among highly safe natural product-derived ingredients, and to provide a DKK1 mRNA expression suppressant and a gray hair improving agent containing the same as an active ingredient. .

In order to solve the above-mentioned problems, the DKK1 mRNA expression inhibitor and gray hair improving agent of the present invention contain at least one active ingredient selected from the group consisting of noni extract, plum extract, chinensis extract, and star fruit extract. Contained as.

According to the present invention, it is possible to provide a DKK1 mRNA expression inhibitor and a gray hair improving agent that have an excellent DKK1 mRNA expression inhibitory effect and are highly safe.

Embodiments of the present invention will be described in detail.
The DKK1 mRNA expression inhibitor, gray hair improving agent, and hair growth agent according to the present embodiment all contain at least one selected from the group consisting of noni extract, plum extract, chinensis extract, and star fruit extract. Contained as an ingredient.

The extraction raw materials used to obtain various extracts as active ingredients in the present embodiment include noni (scientific name: Morinda citrifolia), plum (scientific name: Prunus mume Siebold et Zuccarini), and rhododendron (scientific name: Rhodomyrtus tomentosa (Ait. ) Hassk.) and star fruit (scientific name: Averrhoa carambola).

Noni (Morinda citrifolia) is a small evergreen tree belonging to the family Rubiaceae, and is also called Morinda citrifolia. It is distributed in Okinawa, the Ogasawara Islands, Taiwan, China, India, etc., and can be easily obtained from these areas. The constituent parts of noni that can be used as extraction raw materials can be selected as appropriate depending on the purpose, such as leaves, stems, flowers, buds, fruits, pericarp, seeds, seed coats, Examples include fruit juice obtained by natural fermentation of the bark part, aerial part, root part, or a mixture thereof, or fruit part, but the above-mentioned fruit juice is preferable.

Prunus mume (Prunus mume Siebold et Zuccarini) is a small deciduous tree belonging to the Rosaceae family, and has been cultivated in China and Japan since ancient times, and can be easily obtained from these regions. Constituent parts of plum that can be used as extraction raw materials include, for example, leaves, branches, bark, trunks, stems, flowers, buds, fruits, pulp, pericarp, roots, or any of these parts. Examples include mixtures, but preferably the fruit part or the pulp part.

Rhodomyrtus tomentosa (Ait.) Hassk. is an evergreen shrub belonging to the Myrtaceae family that is distributed in tropical to subtropical regions of Southeast Asia. It can be easily obtained. Tenninka fruit is eaten raw and is also used as an ingredient in juice and jam. In China, it is also called Taojinniang, and the fruit is folkly used as an anemia and hemostatic agent for pregnant women, and the leaves and roots are also folkly used to treat headaches, abdominal pain, etc. Examples of the constituent parts of A. chinensis that can be used as extraction raw materials include leaves, branches, bark, trunks, stems, fruits, flowers, and other aerial parts, roots, and mixtures of these parts. However, preferably the fruit part.

Starfruit (Averrhoa carambola) belongs to the genus Carambola in the family Oxalis, and the fresh fruit is edible. Star fruit is cultivated in Okinawa, southeastern China, Yunnan, and other tropical regions, and can be easily obtained from these regions. Constituent parts of star fruit that can be used as extraction raw materials include, for example, leaves, trunks, flowers, buds, fruits, seeds, roots, and mixtures of these parts, but preferably leaves. It is.

Although the details of the substance that has the inhibitory effect on DKK1 mRNA expression contained in the extract from the above-mentioned extraction raw material are unknown, the inhibitory effect on DKK1 mRNA expression can be obtained from the above-mentioned extraction raw material using an extraction method commonly used for plant extraction. It is possible to obtain an extract having Note that extracts include extracts obtained from extraction raw materials through extraction processing, diluted or concentrated extracts, dried products obtained by drying extracts, or crude or purified products thereof. is included.

The above extract can be obtained by directly subjecting the extraction raw material to extraction with an extraction solvent, or by drying the extraction raw material and then pulverizing it as it is or using a coarse pulverizer and subjecting it to extraction with an extraction solvent. The extraction raw material may be dried in the sun or may be dried using a commonly used dryer. Alternatively, it may be used as an extraction raw material after being subjected to pretreatment such as degreasing with a nonpolar solvent such as hexane. By performing pre-treatment such as degreasing, extraction treatment of plants with a polar solvent can be efficiently performed.

Examples of the solvent used for extraction include water, a hydrophilic organic solvent, or a mixture thereof, and it is preferable to use it at room temperature or at a temperature below the boiling point of the solvent. A component having an effect of suppressing DKK1 mRNA expression contained in the extraction raw material can be easily extracted by an extraction process using a polar solvent as an extraction solvent.

Examples of water that can be used as an extraction solvent include pure water, tap water, well water, mineral spring water, mineral water, hot spring water, spring water, fresh water, and those obtained by subjecting these to various treatments. Examples of treatments applied to water include purification, heating, sterilization, filtration, ion exchange, adjustment of osmotic pressure, buffering, and the like. Therefore, water that can be used as an extraction solvent in the present invention includes purified water, hot water, ion exchange water, physiological saline, phosphate buffer, phosphate buffered saline, and the like.

Examples of hydrophilic organic solvents that can be used as extraction solvents include lower aliphatic alcohols having 1 to 5 carbon atoms such as methanol, ethanol, propyl alcohol, and isopropyl alcohol; lower aliphatic ketones such as acetone and methyl ethyl ketone; - Polyhydric alcohols having 2 to 5 carbon atoms, such as butylene glycol, propylene glycol, and glycerin.

When a mixture of two or more polar solvents is used as an extraction solvent, the mixing ratio can be adjusted as appropriate. For example, when using a mixed solution of water and lower aliphatic alcohol, it is preferable to mix 1 to 90 parts by volume of the lower aliphatic alcohol to 10 parts by volume of water. When using a mixed solution of water and a lower aliphatic ketone, it is preferable to mix 1 to 40 parts by volume of the lower aliphatic ketone to 10 parts by volume of water. When using a mixed solution of water and polyhydric alcohol, it is preferable to mix 1 to 90 parts by volume of polyhydric alcohol to 10 parts by volume of water.

In the extraction process, there is no need to employ a special extraction method as long as the soluble components contained in the extraction raw material can be eluted into the extraction solvent, and extraction can be performed at room temperature or under reflux heating. For example, by putting the extraction raw material into a processing tank filled with an extraction solvent, stirring if necessary, leaving it to stand for 30 minutes to 4 hours to elute the soluble components, and then filtering to remove solids. Extracts can be obtained. A paste-like concentrate is obtained by distilling off the extraction solvent from the obtained extract, and a dry product is obtained by further drying this concentrate. Extraction conditions may be as long as about 1 to 4 hours at 50 to 95° C. when water is used as the extraction solvent. Further, when a mixed solvent of water and ethanol is used as the extraction solvent, the temperature may be about 30 minutes to 4 hours at 40 to 80°C.

The extract obtained as described above is diluted, concentrated, It may be subjected to treatments such as drying and purification.

The obtained extract can be used as it is as an active ingredient of a DKK1 mRNA expression inhibitor, a gray hair improver, and a hair growth agent, but it is preferable to use it as a concentrated solution or a dried product. When obtaining a dried product, a carrier such as dextrin or cyclodextrin may be added to improve hygroscopicity.

In addition, since the above extract has a unique odor and taste, it is possible to purify it for purposes such as decolorization and deodorization as long as it does not reduce its physiological activity. When added, since it is not used in large quantities, there is no practical problem even if it is unrefined. Purification can be performed, for example, by activated carbon treatment, adsorption resin treatment, ion exchange resin treatment, etc.

Since the noni extract, plum extract, chinensis extract, and star fruit extract obtained as described above have an effect of suppressing DKK1 mRNA expression, this effect can be used to improve the effectiveness of the DKK1 mRNA expression inhibitor Can be used as an ingredient.

In addition, since noni extract, plum extract, apricot extract, and star fruit extract have a gray hair-improving effect, they can be used as active ingredients of a gray hair-improving agent by utilizing this effect. The gray hair-improving effect of noni extract, plum extract, Japanese apricot extract, and star fruit extract is exerted, for example, based on the effect of suppressing DKK1 mRNA expression. However, the gray hair improving effect of the noni extract, plum extract, blackberry extract, and star fruit extract is not limited to the gray hair improving effect exerted based on the above-mentioned DKK1 mRNA expression suppressing effect.

Furthermore, since noni extract, plum extract, chinensis extract, and star fruit extract have a hair-growth effect, they can be used as active ingredients in hair-growth agents by utilizing this effect. The hair growth effect of noni extract, plum extract, chinensis extract, and star fruit extract is exerted, for example, based on the effect of suppressing DKK1 mRNA expression. However, the hair-growth effect of the noni extract, plum extract, Japanese apricot extract, and star fruit extract is not limited to the hair-growth effect exerted based on the above-mentioned DKK1 mRNA expression suppressing effect.

Here, it has been elucidated that WNT signals are involved in the activation of hair follicle stem cells. WNT signals are in-vivo signals produced by the WNT group, which are secreted proteins, and are known to play an important role in a wide variety of biological processes during development. Cells are activated when WNT, which is a ligand, binds to WNT receptors (LPR, FZD, etc.) on the cell membrane. WNT signals are broadly classified into three known routes: WNT/β-catenin pathway (classical WNT pathway), PCP pathway, and Wnt/Ca ²⁺ pathway. In signal transduction of the WNT/β-catenin pathway, when the ligand WNT binds to a receptor, β-catenin is stabilized and accumulated within the cell and translocated to the nucleus. In the nucleus, β-catenin binds to the TCF/LEF family and transcriptional activation of target genes occurs.

During the resting phase of hair follicles, when WNT ligand is expressed and WNT/β-catenin signals are activated, hair follicle stem cells are activated, the hair follicle shifts to the growth phase, and hair elongation begins. That is, activating WNT signals is important for hair growth.

DKK1 (Dickkopf-related protein 1) is an example of a protein that inhibits WNT signals. If DKK1 production can be suppressed, WNT signals can be activated and keratinocyte proliferation can be promoted.

The DKK1 mRNA expression inhibitor according to the present embodiment is capable of preventing or improving gray hair etc. through the DKK1 mRNA expression suppressing effect of the active ingredients of noni extract, plum extract, blackberry extract, and star fruit extract. can. In addition, the DKK1 mRNA expression inhibitor according to the present embodiment activates WNT signals through the DKK1 mRNA expression suppressing effect possessed by the active ingredients of noni extract, plum extract, chinensis extract, and star fruit extract, and suppresses keratinocytes. can promote the proliferation of. Therefore, the DKK1 mRNA expression inhibitor according to the present embodiment can prevent, treat, or improve alopecia such as androgenetic alopecia, alopecia areata, and trichotillomania. Furthermore, the DKK1 mRNA expression inhibitor according to the present embodiment inhibits bone formation in osteoblasts through the DKK1 mRNA expression suppressing effect of the active ingredients of noni extract, plum extract, chinensis extract, and star fruit extract. can be promoted. Therefore, according to the DKK1 mRNA expression inhibitor according to the present embodiment, osteoporosis and the like can be prevented, treated, or improved.

The gray hair improving agent according to the present embodiment can prevent or improve gray hair etc. through the DKK1 mRNA expression suppressing effect of the active ingredients of noni extract, plum extract, chinensis extract, and star fruit extract.

The hair growth agent according to the present embodiment activates WNT signals and promotes the proliferation of keratinocytes through the DKK1 mRNA expression suppressing effect of the active ingredients of noni extract, plum extract, chinensis extract, and star fruit extract. be able to. Therefore, the hair growth agent according to the present embodiment can prevent, treat, or improve alopecia such as androgenic alopecia, alopecia areata, and trichotillomania.

In addition, in the DKK1 mRNA expression inhibitor, gray hair improving agent, and hair growth agent according to the present embodiment, any one of noni extract, plum extract, chinensis extract, and star fruit extract is used as the above-mentioned active ingredient. They may be used, or two or more of them may be mixed and used as the above-mentioned active ingredient. When two or more of the above extracts are mixed and used as an active ingredient, the blending ratio may be appropriately determined depending on the degree of their effects.

The DKK1 mRNA expression inhibitor, gray hair improving agent, and hair growth agent according to the present embodiment are prepared by formulating at least one selected from the group consisting of noni extract, plum extract, chinensis extract, and star fruit extract. It may be.

The above extract, etc. can be formulated into any desired dosage form, such as powder, granules, or liquid, according to a conventional method using a pharmaceutically acceptable carrier such as dextrin or cyclodextrin, or any other auxiliary agent. Can be done. In this case, as the auxiliary agent, for example, an excipient, a stabilizer, a flavoring agent, etc. can be used. Forms of the DKK1 mRNA expression inhibitor, gray hair improving agent, and hair growth agent formulated from the above-mentioned extracts include, for example, ointments, external liquids, and the like.

In addition, the DKK1 mRNA expression inhibitor, gray hair improving agent, and hair growth agent according to the present embodiment can be used as an active ingredient by blending other natural extracts having a DKK1 mRNA expression inhibiting effect, if necessary.

The method of administering the DKK1 mRNA expression inhibitor, gray hair improving agent, or hair growth agent according to the present embodiment generally includes transdermal administration, oral administration, etc., but depending on the type of disease, it is suitable for prevention, treatment, etc. You can select the appropriate method. Further, the dosage of the DKK1 mRNA expression inhibitor, gray hair improving agent, or hair growth agent according to the present embodiment may be appropriately increased or decreased depending on the type of disease, severity, individual differences among patients, administration method, administration period, etc.

The gray hair improving agent according to the present embodiment can prevent or improve gray hair etc. through the DKK1 mRNA expression suppressing effect of the above-mentioned active ingredient. However, the gray hair improving agent according to the present embodiment can be used for all other uses in which it is meaningful to exert the DKK1 mRNA expression suppressing effect in addition to these uses.

The hair growth agent according to the present embodiment can prevent, treat, or improve alopecia such as androgenetic alopecia, alopecia areata, and trichotillomania through the DKK1 mRNA expression suppressing effect of the above-mentioned active ingredient, and in particular, Androgenetic alopecia can be suitably prevented, treated or improved. However, the hair growth agent according to the present embodiment can be used for all other uses in which it is meaningful to exert the effect of suppressing DKK1 mRNA expression.

The DKK1 mRNA expression inhibitor according to the present embodiment prevents, treats, or improves alopecia such as androgenetic alopecia, alopecia areata, and trichotillomania, osteoporosis, etc. through the DKK1 mRNA expression suppressing effect of the above-mentioned active ingredient. It is possible to prevent or improve gray hair and the like. However, the DKK1 mRNA expression inhibitor according to the present embodiment can be used in any other applications in which it is meaningful to exert the DKK1 mRNA expression suppressing effect in addition to these applications.

The DKK1 mRNA expression inhibitor, gray hair improving agent, and hair growth agent according to the present embodiment have excellent DKK1 mRNA expression suppressing effect, gray hair improving effect, and hair growth effect, and therefore are suitable for being incorporated into external skin preparations, etc. be. In this case, the above-mentioned extract may be blended as it is, or a DKK1 mRNA expression inhibitor, a gray hair improving agent, and a hair growth agent prepared from the above-mentioned extract or the like may be blended.

Here, the topical skin preparations are not limited in their classification and include a wide range of skin cosmetics, which will be described later, as well as quasi-drugs and pharmaceuticals used transdermally.

In addition, the DKK1 mRNA expression inhibitor, gray hair improving agent, and hair growth agent according to the present embodiment have excellent DKK1 mRNA expression suppressing effect, gray hair improving effect, and hair growth effect, and therefore can be used as a reagent for research on the mechanism of action of these agents. can also be suitably used.

Although the DKK1 mRNA expression inhibitor, gray hair improving agent, and hair growth agent according to the present embodiment are preferably applied to humans, they may also be applied to animals other than humans as long as the respective effects are achieved. It is also possible to apply it.

The DKK1 mRNA expression inhibitor, gray hair improving agent, and hair growth agent according to the present embodiment described above have the effect of suppressing DKK1 mRNA expression and improving gray hair due to the noni extract, plum extract, chinensis extract, and star fruit extract contained therein. It can be suitably blended into skin cosmetics or hair cosmetics since it exhibits the action and hair growth effect. In this case, the skin cosmetic or hair cosmetic may contain the above-mentioned extract, etc. as is, or may contain a DKK1 mRNA expression inhibitor, a gray hair improving agent, and a hair growth agent formulated from the above-mentioned extract, etc. You may.

By blending the above-mentioned extract, etc., or the above-mentioned DKK1 mRNA expression inhibitor, gray hair improving agent, or hair growth agent, a DKK1 mRNA expression suppressing effect, a gray hair improving agent effect, and a hair growth effect can be imparted to a skin cosmetic or hair cosmetic. Can be done.

All of these effects exert favorable effects when added to skin cosmetics or hair cosmetics, but among them, the DKK1 mRNA expression suppressing effect, gray hair improving effect, and hair growth effect are effective when added to skin cosmetics or hair cosmetics. When added to cosmetics, these effects are likely to be exerted, so it is particularly suitable.

Examples of skin cosmetics that may contain the above extracts, etc., or DKK1 mRNA expression inhibitors, gray hair improvers, or hair growth agents include ointments, creams, milky lotions, lotions, packs, foundations, etc.; Examples of the hair tonic include hair tonic, hair cream, hair liquid, shampoo, pomade, conditioner, and the like.

When the above-mentioned extracts, etc., DKK1 mRNA expression inhibitor, gray hair improving agent, or hair growth agent are added to skin cosmetics or hair cosmetics, the amount to be added may be adjusted as appropriate depending on the type of skin cosmetics or hair cosmetics. However, a suitable blending ratio is about 0.0001 to 10% by weight, and a particularly preferred blending ratio is about 0.001 to 1% by weight.

The skin cosmetic or hair cosmetic according to the present embodiment contains main ingredients and auxiliary agents that are used in the production of ordinary cosmetics, as long as they do not interfere with the DKK1 mRNA expression suppressing effect, gray hair improving effect, and hair growth effect of the above-mentioned extract, etc. or other ingredients, such as astringents, bactericidal/antibacterial agents, whitening agents, ultraviolet absorbers, humectants, cell activators, anti-inflammatory/anti-allergic agents, antioxidants/active oxygen scavengers, oils and fats, waxes, carbonization Hydrogens, fatty acids, alcohols, esters, surfactants, fragrances, etc. can be used in combination. By using them in combination in this way, the product becomes more general in use, and the synergistic effect with other active ingredients used in combination may bring about better effects than would normally be expected.

The skin cosmetic or hair cosmetic of the present embodiment can be used for preventing or improving gray hair etc. through the DKK1 mRNA expression suppressing effect and gray hair improving effect that the extract and the like have. In addition, the skin cosmetic or hair cosmetic of the present embodiment prevents alopecia such as androgenetic alopecia, alopecia areata, and trichotillomania through the DKK1 mRNA expression suppressing effect and hair growth effect of the above-mentioned extract. It can be used for purposes such as treatment or improvement.

[Food and beverages]
The food/beverage product according to this embodiment is one in which the above-mentioned extract and the like are blended. The food/beverage products according to the present embodiment may contain the above extracts as they are, or may contain DKK1 mRNA expression inhibitors, gray hair improvers, and hair restorers prepared from the extracts.

Here, food and drink refers to foods that have little risk of harming human health and are ingested orally or through gastrointestinal administration in normal social life, such as foods, drugs, and quasi-drugs according to administrative classifications. It is not limited to the following categories. Therefore, the "food and drink" according to the present embodiment includes general food that is orally ingested, health food (functional food and drink), food with health claims (food for specified health uses, food with nutritional function claims, food with functional claims), It includes a wide range of compositions that constitute quasi-drugs, pharmaceuticals, etc. The food/beverage product according to the present embodiment may be one in which the desirable effects of the extract, etc. (DKK1 mRNA expression suppression effect, gray hair improvement effect, hair growth effect) are displayed on the food/beverage product or its packaging; The food or drink may be a food with health claims (food for specified health uses, food with functional claims, food with nutritional claims), a quasi-drug, or a pharmaceutical.

When the above-mentioned extracts, etc., or DKK1 mRNA expression inhibitors, gray hair improvers, and hair growth agents formulated from the above-mentioned extracts, etc. are added to foods and drinks, the amount of active ingredients in them should be determined based on the purpose of use, symptoms, gender, etc. However, it is recommended that the intake amount of the extract be approximately 1 to 1000 mg per day for an adult, taking into consideration the general intake of the food and drink to which it is added. preferable. In addition, when the food or drink to be added is in the form of granules, tablets, or capsules, the amount of the above-mentioned extract, etc., or the DKK1 mRNA expression inhibitor, gray hair improving agent, or hair growth agent formulated from the above-mentioned extract, etc. is usually 0.1 to 100% by mass, preferably 5 to 100% by mass, based on the food or beverage to which it is added.

The food/beverage product according to this embodiment can be added to any food/beverage product that does not interfere with the activity of the extract, etc., or a DKK1 mRNA expression inhibitor, a gray hair improving agent, or a drug formulated from the extract, etc. It may be a product containing a hair growth agent, or it may be a nutritional supplement containing the above-mentioned extract or the like as a main ingredient.

When producing the food and drink products according to the present embodiment, for example, sugars such as dextrin and starch; proteins such as gelatin, soybean protein, and corn protein; amino acids such as alanine, glutamine, and isoleucine; Polysaccharides; optional auxiliaries such as oils and fats such as soybean oil and medium-chain fatty acid triglycerides can be added to produce food and drink products of any shape.

There are no particular restrictions on the food and drink products that can contain the above extracts, but specific examples include beverages such as soft drinks, carbonated drinks, nutritional drinks, fruit drinks, and lactic acid drinks (concentrated stock solutions and powders for preparation of these drinks). Frozen desserts such as ice cream, ice sorbet, and shaved ice; Noodles such as soba, udon, harusame, gyoza skin, shumai skin, Chinese noodles, and instant noodles; candy, chewing gum, candies, chewing gum, chocolate, and tablets Confectionery such as snacks, biscuits, jellies, jams, creams, and baked goods; Fishery and livestock processed foods such as kamaboko, ham, and sausage; Dairy products such as processed milk and fermented milk; Salad oil, tempura oil, margarine, mayonnaise, Fats and oil-processed foods such as shortening, whipped cream, and dressings; Seasonings such as sauces and sauces; Soups, stews, salads, side dishes, and pickles; Other health and nutritional supplements in various forms; tablets, capsules, and drinks. etc. When blending the above-mentioned extracts and the like into these foods and drinks, commonly used auxiliary raw materials and additives can be used in combination.

Hereinafter, the present invention will be explained in more detail with reference to test examples and the like, but the present invention is not limited to the following test examples and the like. In addition, each of the extracts obtained in Production Examples 1 to 4 was used as the samples in the following test examples, such as noni extract, plum extract, blackberry extract, and star fruit extract.

[Production Example 1] Production of Noni Extract Butylene glycol and purified water were added to 100 g of Noni juice to prepare a Noni juice-containing liquid. The obtained noni juice-containing liquid was dried to obtain a noni extract (5 g, sample 1).

[Production Example 2] Production of plum extract 50% by volume butylene glycol was added to 100 g of pulp obtained from plum fruit, mixed, and filtered. The obtained extract was dried to obtain a plum extract (4 g, sample 2).

[Production Example 3] Manufacture of extract of A. chinensis 1500 mL of 80% by volume ethanol was added to 100 g of dried fruit part of a. The obtained extract was dried to obtain an extract (2 g, sample 3) of A. chinensis.

[Production Example 4] Production of star fruit extract 1500 mL of 80% ethanol by volume was added to 100 g of dried star fruit leaves, extracted at 80 to 90°C for 2 hours using a reflux extractor, and filtered while hot. . The obtained extract was dried to obtain a star fruit extract (10 g, sample 4).

[Test Example 1] DKK1 mRNA expression suppression effect test Normal human dermal papilla cells (derived from the top of HFDPC head) were seeded in a 60 mm Petri dish and cultured using a dermal papilla cell growth medium. After culturing, 3 mL of samples (samples 1 to 4) dissolved in dermal papilla cell basal medium was added to each petri dish and cultured for 2 hours, and then total RNA was prepared by a conventional method. Furthermore, total RNA was prepared in the same manner for cells cultured without the addition of a sample. The amount of each RNA was measured using a spectrophotometer, and total RNA was prepared at 200 ng/μL.

Using total RNA as a template, the expression levels of hair cycle-related genes and GAPDH mRNA, which was an internal standard, were measured. Detection was performed using a real-time PCR device (Thermal Cycler Dice (registered trademark) Real Time System III, manufactured by Takara Bio Inc.) using PrimeScript ^TM RT Master Mix (Perfect Real Time, manufactured by Takara Bio Inc.) and TB Green. (Registered trademark) A two-step real-time RT-PCR reaction was performed using Fast qPCR Mix (manufactured by Takara Bio Inc.). The expression level of DKK1 mRNA was corrected by the expression level of GAPDH mRNA, and a correction value was calculated.

From the obtained correction value, the DKK1 mRNA expression suppression rate (%) was calculated using the following formula.
DKK1 mRNA expression suppression rate (%) = {1-(A/B)}×100
In the formula, A represents the "correction value when adding the sample" and B represents the "correction value when the sample is not added."
The results are shown in Table 1.

As shown in Table 1, it was confirmed that the noni extract, the plum extract, the chinensis extract, and the star fruit extract had an excellent effect of suppressing DKK1 mRNA expression.

The DKK1 mRNA expression inhibitor, gray hair improving agent, and hair growth agent according to the present embodiment can be used to prevent or improve gray hair, prevent alopecia such as androgenetic alopecia, alopecia areata, and trichotillomania, and prevent osteoporosis. It can greatly contribute to treatment or improvement.

Claims (2)

A DKK1 mRNA expression inhibitor characterized by containing as an active ingredient at least one selected from the group consisting of noni extract, plum extract, chinensis extract, and star fruit extract. A gray hair improving agent characterized by containing as an active ingredient at least one member selected from the group consisting of noni extract, plum extract, blackberry extract, and star fruit extract.