Mitophagy activity enhancer

Abstract

To provide a novel composition that enhances mitophagy activity.SOLUTION: Provided is a mitophagy-enhancing agent that contains one or more selected from hypericum erectum extract, sage extract, pau d'arco extract, gardenia extract, Chinese tallow extract, soybean bud extract, pearl protein extract, white strawberry extract, royal jelly fermentation liquid, Salicornia europaea extract, daylily flower fermentation liquid, and chamomilla extract.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a composition for enhancing the activity of mitophagy, which is mitochondria-selective autophagy. [Background technology]

[0002] Within cells, there is a mechanism for breaking down intracellular proteins called autophagy, which breaks down abnormal proteins and proteins synthesized in excess, maintaining homeostasis in the body.

[0003] Mitophagy is a selective degradation mechanism of mitochondria via autophagy and is thought to be involved in mitochondrial metabolism. Damaged mitochondria produce reactive oxygen species, which accelerates cellular oxidation, but it is expected that enhancing mitophagy activity will have the effect of suppressing this.

[0004] For example, Patent Document 1 describes that an extract of lotus flowers belonging to the Nelumbo genus of the Nelumbo family has the effect of enhancing mitophagy activity. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] Japanese Patent Application Laid-Open No. 2017-178920 Summary of the Invention [Problem to be solved by the invention]

[0006] An objective of the present invention is to provide a novel composition that enhances mitophagy activity. [Means for solving the problem]

[0007] The present invention, which solves the above-mentioned problems, provides a mitophagy activity enhancer comprising one or more extracts selected from Hypericum perforatum extract, sage extract, pau d'arco extract, gardenia extract, Scutellaria root extract, soybean sprout extract, pearl protein extract, white strawberry extract, royal jelly fermented filtrate, Salicornia herb extract, daylily flower fermented filtrate, and chamomile extract. In a preferred embodiment of the present invention, the mitophagy activity enhancer contains at least a Hypericum perforatum extract. According to the present invention, mitophagy activity in cells can be enhanced.

[0008] In a preferred embodiment of the present invention, the mitophagy activity enhancer is used to enhance mitophagy activity in human skin fibroblasts and / or human epidermal keratinocytes. According to the present invention, by enhancing mitophagy activity in human skin fibroblasts and / or human epidermal keratinocytes, it is expected that aging conditions and the onset of diseases caused by mitochondria, particularly damaged mitochondria, can be prevented or ameliorated.

[0009] In a preferred embodiment of the present invention, the mitophagy activity enhancer is a cosmetic preparation for enhancing mitophagy activity. [Effects of the Invention]

[0010] According to the present invention, a novel composition that enhances mitophagy activity can be provided. [Brief explanation of the drawings]

[0011] [Figure 1] FIG. 1 shows, in the Examples, mitophagy activity in human skin fibroblasts and human epidermal keratinocytes cultured in an extract-free medium (negative control), and mitophagy activity in human skin fibroblasts and human epidermal keratinocytes cultured in a medium containing Hypericum perforatum extract. [Figure 2]FIG. 1 shows, in an example, mitophagy activity in human skin fibroblasts and human epidermal keratinocytes cultured in an extract-free medium (negative control), and mitophagy activity in human skin fibroblasts and human epidermal keratinocytes cultured in a medium containing sage extract. [Figure 3] FIG. 1 is a graph showing the mitophagy activity in human epidermal keratinocytes cultured in an extract-free medium (negative control) and the mitophagy activity in human epidermal keratinocytes cultured in a medium containing Pau d'Arco extract in an example. [Figure 4] FIG. 1 is a graph showing the mitophagy activity in human epidermal keratinocytes cultured in an extract-free medium (negative control) and the mitophagy activity in human epidermal keratinocytes cultured in a medium containing gardenia extract in an example. [Figure 5] FIG. 1 shows, in an example, mitophagy activity in human skin fibroblasts and human epidermal keratinocytes cultured in a medium containing no extract (negative control), and mitophagy activity in human skin fibroblasts and human epidermal keratinocytes cultured in a medium containing Scutellaria Baicalensis extract. [Figure 6] FIG. 1 shows, in an example, mitophagy activity in human skin fibroblasts and human epidermal keratinocytes cultured in an extract-free medium (negative control), and mitophagy activity in human skin fibroblasts and human epidermal keratinocytes cultured in a medium containing soybean germ extract. [Figure 7] In the Examples, this is a graph showing the mitophagy activity in human epidermal keratinocytes cultured in a medium containing no extract (negative control), and the mitophagy activity in human epidermal keratinocytes cultured in a medium containing pearl protein extract. [Figure 8] FIG. 1 shows, in an example, mitophagy activity in human skin fibroblasts and human epidermal keratinocytes cultured in an extract-free medium (negative control), and mitophagy activity in human skin fibroblasts and human epidermal keratinocytes cultured in a medium containing white strawberry extract. [Figure 9] FIG. 1 shows, in an example, mitophagy activity in human epidermal keratinocytes cultured in a medium containing no extract (negative control), and mitophagy activity in human epidermal keratinocytes cultured in a medium containing royal jelly fermentation solution. [Figure 10] FIG. 1 is a graph showing the mitophagy activity in human epidermal keratinocytes cultured in an extract-free medium (negative control) and in human epidermal keratinocytes cultured in a medium containing Salicornia herbacea extract in an example. [Figure 11] FIG. 1 shows, in an example, mitophagy activity in human epidermal keratinocytes cultured in a medium containing no extract (negative control), and mitophagy activity in human epidermal keratinocytes cultured in a medium containing daylily flower fermentation liquid. [Figure 12] FIG. 1 shows, in an example, mitophagy activity in human epidermal keratinocytes cultured in an extract-free medium (negative control), and mitophagy activity in human epidermal keratinocytes cultured in a medium containing chamomile extract. DETAILED DESCRIPTION OF THE INVENTION

[0012] The mitophagy activity enhancer according to the present invention comprises one or more extracts selected from Hypericum perforatum extract, sage extract, pau d'arco extract, gardenia extract, Scutellaria root extract, soybean sprout extract, pearl protein extract, white strawberry extract, royal jelly fermented filtrate, Salicornia herb extract, daylily flower fermented filtrate, and chamomile extract. In a preferred embodiment of the present invention, at least a Hypericum perforatum extract is contained. According to the present invention, mitophagy activity in cells can be enhanced.

[0013] Mitochondria produce reactive oxygen species (ROS) in conjunction with the production of ATP, but damaged mitochondria produce more ROS than normal (undamaged) mitochondria. ROS is known to cause lifestyle-related diseases such as stroke and skin aging. The present invention promotes the degradation of damaged mitochondria by enhancing mitophagy activity in cells, which is expected to prevent diseases and aging caused by reactive oxygen species produced by damaged mitochondria.

[0014] The terms "St. John's wort extract," "sage extract," "pau d'arco extract," "gardenia extract," "Scutellaria root extract," "soybean sprout extract," "pearl protein extract," "white strawberry extract," "Salvia officinalis extract," and "chamomile extract" used in the present invention refer not only to the extracts themselves derived from St. John's wort (Hypericum erectum), sage (Salvia officinalis), pau d'arco (Handroanthus impetiginosus), gardenia (Gardenia jasminoides), soybean (Glycine max), pearl, white strawberry (Fragaria x ananassa), Salvia (Salicornia europaea), or chamomile (Matricaria chamomilla), but also to fractions of these extracts, purified fractions, and products from which the solvent has been removed from the extracts, fractions, and purified products. In addition, extracts derived from St. John's wort, sage, pau d'arco, gardenia, soybean, pearl, white strawberry, Salicornia, and chamomile include extracts using wild-grown or cultivated plants, extracts using plants sold as raw materials for herbal medicines, and commercially available extracts. When extracting the above-mentioned extract from a plant, the extraction procedure can be performed using the whole plant or parts such as the plant itself, aboveground parts, rhizomes, trunks, leaves, stems, spikes, and flower buds, but it is preferable to crush or shred these beforehand to improve extraction efficiency. Suitable examples of the extraction solvent include one or more polar solvents selected from water, alcohols such as ethanol, isopropyl alcohol, and butanol, polyhydric alcohols such as 1,3-butanediol and polypropylene glycol, ketones such as acetone and methyl ethyl ketone, and ethers such as diethyl ether and tetrahydrofuran. The extraction solvent is preferably water, an alcohol, or a mixture of water and an alcohol.

[0015] Specific extraction methods for the above-mentioned extract include, for example, a method in which 1 to 30 parts by mass of solvent is added to 1 mass of the part of the plant body or its dried material used for extraction, followed by immersion for several days at room temperature or for several hours at a temperature near the boiling point, cooling to room temperature, removing insoluble matter and / or solvent as desired, and fractionating and purifying by column chromatography or the like, but the extraction method is not limited to this.

[0016] The royal jelly fermented liquid may be one obtained by fermenting commercially available royal jelly by a known method, or a commercially available royal jelly fermented liquid may be used. The daylily flower fermented liquid is obtained by fermenting wild-grown or cultivated daylily flowers (preferably crushed or shredded in advance) with yeast, and commercially available daylily flower fermented liquid can also be used.

[0017] The mitophagy activity enhancer of the present invention can be appropriately combined with any component used in formulation to take any dosage form, and can be, for example, a topical agent for skin application, or, in the case of an edible extract, can be an oral agent. A preferred embodiment of the present invention is an external preparation for skin. Oral preparations or topical preparations for skin can be produced using known methods and equipment as appropriate.

[0018] When the mitophagy activity enhancer of the present invention is administered orally, it is preferably in the form of a food composition containing, as an active ingredient, one or more extracts selected from Hypericum perforatum extract, sage extract, Paul d'Arcossectus, gardenia extract, Scutellaria root extract, soybean sprout extract, pearl protein extract, white strawberry extract, royal jelly fermented filtrate, Salicornia herb extract, daylily flower fermented filtrate, and chamomile extract.Specifically, it is preferably in the form of a supplement in the dosage form of a general food, tablet, granule, drink, or the like.

[0019] The content of the extract in the oral preparation is, depending on the dosage form, 0.1 mg or more, preferably 1 mg or more, more preferably 10 mg or more, in terms of dry mass of the extract per dose. Also, it is usually 2000 mg or less, preferably 1000 mg or less, more preferably 500 mg or less. In addition, when the oral preparation contains two or more extracts selected from Hypericum perforatum extract, sage extract, pau d'arco extract, gardenia extract, Scutellaria root extract, soybean sprout extract, pearl protein extract, white strawberry extract, royal jelly fermented filtrate, Salicornia herb extract, daylily flower fermented filtrate, and chamomile extract, the total content of each extract may be within the above-mentioned numerical range.

[0020] When the mitophagy activity enhancer of the present invention is used as an external preparation for skin, examples of the form include cosmetics, quasi-drugs, external medicines for skin, etc. Although the dosage form is not particularly limited, it is more preferable that it be in the form of cosmetics. The cosmetic preparation is preferably in the form of a face wash, cleanser, lotion, serum, emulsion, cream, gel, sun care product, etc. It may also be in the form of a face pack. When the mitophagy activity enhancer of the present invention is in the form of an external preparation for skin, it may be in a form that does not need to be removed after application, or it may be in a form that can be removed by wiping or washing after a certain time (e.g., 5 to 10 minutes) has elapsed after application.

[0021] The content (dry weight) of the above extract in the topical skin preparation is 0.00001% by mass or more, preferably 0.0001% by mass or more, more preferably 0.001% by mass or more, even more preferably 0.01% by mass or more, and even more preferably 0.1% by mass or more. Also, it is usually 80% by mass or less, preferably 30% by mass or less, and more preferably 10% by mass or less. By setting the amount within the above range, mitophagy activity in cells can be enhanced. In addition, when the topical skin preparation contains two or more extracts selected from Hypericum extract, sage extract, pau d'arco extract, gardenia extract, Scutellaria root extract, soybean sprout extract, pearl protein extract, white strawberry extract, royal jelly fermented filtrate, Salicornia herb extract, daylily flower fermented filtrate, and chamomile extract, the total content of each extract may be within the above-mentioned numerical range.

[0022] When the above extracts are incorporated into cosmetics, whitening ingredients, wrinkle-reducing ingredients, anti-inflammatory ingredients, St. John's wort extract, sage extract, pau d'arco extract, gardenia extract, Scutellaria root extract, soybean sprout extract, pearl protein extract, white strawberry extract, royal jelly fermented filtrate, Salicornia herb extract, daylily flower fermented filtrate, and extracts derived from animals and plants other than chamomile extract, as well as ingredients normally used in cosmetics other than active ingredients, may be incorporated as optional ingredients, provided that the effect of enhancing mitophagy activity is not impaired. These optional ingredients may be commercially available and used, or may be synthesized by known methods and used. Each optional ingredient may have two or more effects (for example, a whitening effect and an anti-wrinkle effect).

[0023] As the whitening ingredient, ingredients generally used in cosmetics can be used without any particular restrictions. For example, 4-n-butylresorcinol, ascorbic acid glucoside, 3-O-ethyl ascorbic acid, tranexamic acid, arbutin, 1-triphenylmethylpiperidine, 1-triphenylmethylpyrrolidine, 2-(triphenylmethyloxy)ethanol, 2-(triphenylmethylamino)ethanol, 2-(triphenylmethyloxy)ethylamine, triphenylmethylamine, triphenylmethanol, triphenylmethane and aminodiphenylmethane, N-(o-toluoyl)cysteic acid, N-(m-toluoyl)cysteic acid, N-(p-toluoyl)cysteic acid, N-(p-methoxybenzoyl)cysteic acid, N-benzoylserine, N-(p-methylbenzoyl)cysteic acid N-benzoyl)serine, N-(p-ethylbenzoyl)serine, N-(p-methoxybenzoyl)serine, N-(p-fluorobenzoyl)serine, N-(p-trifluoromethylbenzoyl)serine, N-(2-naphthoyl)serine, N-(4-phenylbenzoyl)serine, N-(p-methylbenzoyl)serine methyl ester, N-(p-methylbenzoyl)serine ethyl ester, N-(2-naphthoyl)serine methyl ester, N-benzoyl-O-methylserine, N-(p-methylbenzoyl)-O-methylserine, N-(p-methylbenzoyl)-O-acetylserine, N-(2-naphthoyl)-O-methylserine, dexpanthenol W, and niacinamide.

[0024] The content of the whitening ingredient in the cosmetic is usually 0.0001 to 30% by mass, preferably 0.001 to 10% by mass, and more preferably 0.01 to 5% by mass (dry mass in the case of an extract).

[0025] As the wrinkle-reducing component, any component commonly used in cosmetics can be used without any particular limitation. Examples of vitamin A or its derivatives include retinol, retinal, retinoic acid, tretinoin, isotretinoin, tocopherol retinoate, retinol palmitate, and retinol acetate.Further examples include ursolic acid benzyl ester, ursolic acid phosphate, betulinic acid benzyl ester, benzilic acid phosphate, trifluoroisopropyloxopropylaminocarbonylpyrrolidinecarbonylmethylpropylaminocarbonylbenzoylaminoacetic acid sodium, and niacinamide.

[0026] The content of the wrinkle-reducing ingredient in the cosmetic is usually 0.0001 to 30% by mass, preferably 0.001 to 10% by mass, and more preferably 0.01 to 5% by mass (dry mass in the case of an extract).

[0027] Examples of anti-inflammatory ingredients include kurarinone, glabridin, glycyrrhizinic acid, glycyrrhetinic acid, pantothenyl alcohol, niacinamide, and tranexamic acid, and preferred examples include glycyrrhizinic acid and its salts, alkyl glycyrrhetinates and their salts, and glycyrrhetinic acid and its salts. The content of the anti-inflammatory component in the cosmetic is usually 0.01 to 30% by mass, preferably 0.1 to 10% by mass, and more preferably 1 to 5% by mass (dry mass in the case of an extract).

[0028] Examples of extracts derived from plants and animals include akebia extract, asparagus extract, avocado extract, hydrangea extract, almond extract, arnica extract, aronia extract, apricot extract, ginkgo extract, fennel extract, udo extract, Siberian ginseng extract, emmeiso extract, phellodendron bark extract, Panax ginseng extract, white nettle extract, kakyō extract, pueraria root extract, carrot extract, artemisia capillaris extract, licorice extract, kiwi extract, cucumber extract, and guava extract. , Kumazasa extract, Walnut extract, Black rice extract, Chlorella extract, Mulberry extract, Kaneko extract, Alpinia zerumbet extract, Gentian extract, Rice extract, Fermented rice extract, Fermented rice bran extract, Rice germ oil, Salvia extract, Soapwort extract, Sasa extract, Sandalwood extract, Japanese pepper extract, Shiitake mushroom extract, Rehmannia root extract, Lithospermum root extract, Perilla extract, Tilia extract, Meadowsweet extract, Ginger extract, Calamus root extract, Horsetail extract, Stevia extract, Fermented stevia, European Kojiro extract, peppermint extract, mallow extract, cnidium extract, swertia bristle extract, mulberry bark extract, rhubarb extract, soybean extract, tallow extract, dandelion extract, clove extract, chili pepper extract, angelica extract, calendula extract, peach kernel extract, houttuynia cordata extract, tomato extract, natto extract, carrot extract, garlic extract, hibiscus extract, burdock extract, lotus extract, parsley extract, birch extract, witch hazel extract, sedge extract, Japanese cypress extract, Japanese cypress Preferred examples of extracts include Japanese whiting, loquat extract, coltsfoot extract, butterbur extract, poria extract, loofah extract, peppermint extract, linden extract, pine extract, skunk cabbage extract, melissa extract, mozuku extract, peach extract, cornflower extract, lily extract, coix seed extract, mugwort extract, lavender extract, apple extract, rooibos tea extract, lychee extract, lettuce extract, forsythia extract, astragalus extract, rosemary extract, and burnet extract.

[0029] The content (dry mass) of the optional animal and plant-derived extract in the cosmetic is usually 0.01 to 30 mass %, preferably 0.1 to 10 mass %, more preferably 0.3 to 3 mass %.

[0030] In addition to the active ingredients, ingredients commonly used in cosmetics include polyethylene glycol, glycerin, 1,3-butylene glycol, erythritol, sorbitol, xylitol, lucitol, propylene glycol, dipropylene glycol, diglycerin, isoprene glycol, polyols such as 1,2-pentanediol, 2,4-hexylene glycol, 1,2-hexanediol, and 1,2-octanediol, fatty acid soaps (sodium laurate, sodium palmitate, etc.), potassium lauryl sulfate, and triethanolamine alkyl sulfate. anionic surfactants such as esters, cationic surfactants such as stearyltrimethylammonium chloride, benzalkonium chloride, laurylamine oxide, imidazoline-based amphoteric surfactants (2-cocoyl-2-imidazolinium hydroxide-1-carboxyethyloxy disodium salt, etc.), betaine-based surfactants (alkyl betaine, amido betaine, sulfobetaine, etc.), amphoteric surfactants such as acyl methyl taurine, sorbitan fatty acid esters (sorbitan monostearate, sorbitan sesquioleate, etc.), glycerin fatty acids (monostearate, Glycerin phosphate, 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 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 alkyl phenyl ethers (POE nonylphenyl ether, etc.), Pluronic (registered trademark) types, POE·POP alkyl ethers (POE·POP 2-decyltetradecyl ether, etc.), Tetronics, POE castor oil·hydrogenated castor oil derivatives (POE castor oil, POE hydrogenated castor oil, etc.), sucrose fatty acid esters, nonionic surfactants such as alkyl glucosides, moisturizing ingredients such as sodium pyrrolidone carboxylate, lactic acid, sodium lactate, which may be surface-treated,Powders such as mica, talc, kaolin, synthetic mica, calcium carbonate, magnesium carbonate, silicic anhydride (silica), aluminum oxide, and barium sulfate; inorganic pigments such as cobalt oxide, ultramarine, Prussian blue, and zinc oxide, which may be surface-treated; composite pigments such as sintered iron oxide and titanium dioxide, which may be surface-treated; pearling agents such as titanium dioxide, fish phosphate foil, and bismuth oxychloride, which may be surface-treated; and laked pigments such as Red 202, Red 228, Red 226, Yellow 4, Blue 404, Yellow 5, Red 505, Red 230, Red 223, Orange 201, Red 213, Yellow 204, Yellow 203, Blue 1, Green 201, and Purple 20. Examples of suitable organic pigments include organic dyes such as Red No. 1 and Red No. 204; organic powders such as polyethylene powder, polymethyl methacrylate, nylon powder, and organopolysiloxane elastomer; lower alcohols such as ethanol and isopropanol; vitamin A or a derivative thereof; vitamin B6 hydrochloride, vitamin B6 tripalmitate, vitamin B6 dioctanoate, vitamin B2 or a derivative thereof, vitamin B12, and vitamin B15 or a derivative thereof; vitamin E such as α-tocopherol, β-tocopherol, γ-tocopherol, and vitamin E acetate; vitamin D, vitamin H, pantothenic acid, pantethine, and pyrroloquinoline quinone.

[0031] In a preferred embodiment of the present invention, the mitophagy activity enhancer is a composition for enhancing mitophagy activity in human skin fibroblasts and / or human epidermal keratinocytes. In a more preferred embodiment of the present invention, the mitophagy activity enhancer is a composition for enhancing mitophagy activity in human skin fibroblasts and human epidermal keratinocytes. Human dermal fibroblasts are prone to revealing signs of skin aging (e.g., age spots, wrinkles, sagging, etc.). It is also known that reactive oxygen species are one of the causes of the appearance of skin aging in human dermal fibroblasts. According to the present invention, mitophagy activity in human dermal fibroblasts is enhanced, promoting the degradation of damaged mitochondria. This suppresses the production of reactive oxygen species by damaged mitochondria, and the present invention is therefore expected to be able to suppress and / or improve the appearance of the aforementioned signs of skin aging. Furthermore, human epidermal keratinocytes are prone to milder aging conditions, such as dryness and disrupted cell turnover, than the aging conditions manifested in human skin fibroblasts with aging. It is known that the generation of reactive oxygen species is also one of the causes of these mild aging conditions. According to the present invention, mitophagy activity in human epidermal keratinocytes is enhanced, promoting the degradation of damaged mitochondria. This suppresses the production of reactive oxygen species, and the present invention is expected to be able to suppress and / or ameliorate the onset of the mild aging conditions. [Example]

[0032] The present invention will be described in more detail below with reference to examples, but the technical scope of the present invention is not limited to the following examples.

[0033] Using a mitophagy detection kit (Dojin Chemical Co., Ltd.), mitophagy was detected in human epidermal keratinocytes (NHEK) and / or human dermal fibroblasts (NHDF) cultured in medium containing each extract and in medium without the extract.

[0034] <Test Method> (1) Human epidermal keratinocytes and human skin fibroblasts were cultured in a medium appropriate for each cell type at 4 × 10 4 The cells were seeded at 1000 cells / well and cultured at 37°C for 24 hours. (2) After removing the medium from each sample, the plate was washed twice with 500 μL / well of PBS(-). (3) 150 μL / well of 100 nM Mtphagy Dye working solution, prepared freshly according to the kit instructions, was added and incubated at 37°C for 30 minutes. (4) After removing the supernatant, the plate was washed twice with 500 μL / well of PBS(-). (5) Hypericum perforatum extract, sage extract, pau d'arco extract, gardenia extract, Scutellaria root extract, soybean sprout extract, pearl protein extract, white strawberry extract, royal jelly fermented solution, Salicornia herbacea extract, daylily flower fermented solution, or chamomile extract was added to a medium appropriate for each cell type to a final concentration of 0.1%, and the medium containing each extract was added to the cells washed in (4) above. Additionally, medium without the extract was added to the cells washed in (4) above as a negative control. Each cell type was cultured at 37°C for 24 hours. (6) To confirm the colocalization of the Mtphagy Dye added in (3) above with lysosomes, 1 μM Lyso Dye DMSO stock solution, prepared according to the kit instructions, was added to each sample at 150 μL / well and incubated at 37°C for 30 minutes. (7) After removing the supernatant, the cells were washed once with 500 μL / well of PBS(-), and an equal volume of PBS(-) was added again. The degree of staining of each cell was observed under a fluorescence microscope (KEYENCE BZ-X800) at 10x20x magnification (objective lens).

[0035] The observation results are shown in FIGS. The degree of staining was visually confirmed, and if the fluorescence intensity of the cells cultured in the medium containing each extract was stronger than that of the cells cultured in the medium without the extract (negative control), it was evaluated that the mitophagy activity of the cells had been enhanced.

[0036] As shown in Figures 1, 2, 5, 6, 7, and 8, cells cultured in medium supplemented with Hypericum perforatum extract, sage extract, Scutellaria root extract, soybean sprout extract, or white strawberry extract had stronger fluorescence intensity than cells cultured in extract-free medium (negative control). This suggests that mitophagy activity was enhanced in human skin fibroblasts and human epidermal keratinocytes cultured in medium supplemented with Hypericum perforatum extract, sage extract, Scutellaria root extract, soybean sprout extract, or white strawberry extract.

[0037] Furthermore, as shown in Figures 3, 4, 7, 9, 10, 11, and 12, human epidermal keratinocytes cultured in media supplemented with Pau d'Arco extract, gardenia extract, pearl protein extract, royal jelly fermentation filtrate, Salicornia extract, daylily flower fermentation filtrate, or chamomile extract had stronger fluorescence intensity than human epidermal keratinocytes cultured in extract-free media (negative control). This suggests that mitophagy activity was enhanced in human epidermal keratinocytes cultured in media supplemented with Pau d'Arco extract, gardenia extract, pearl protein extract, royal jelly fermentation filtrate, Salicornia extract, daylily flower fermentation filtrate, or chamomile extract.

[0038] Furthermore, as mentioned above, damaged mitochondria produce reactive oxygen species, which are known to be one of the causes of the appearance of age-related skin aging conditions (e.g., age spots, wrinkles, sagging, etc.) in human skin fibroblasts and mild aging conditions (e.g., dryness and disrupted cell turnover) in human epidermal keratinocytes. Therefore, it is expected that a composition containing at least any of the above extracts will enhance mitophagy activity in human skin fibroblasts and / or human skin epidermal keratinocytes, thereby suppressing the production of reactive oxygen species by damaged mitochondria and thereby suppressing and / or preventing the onset of skin aging and / or mild aging. In other words, it has been suggested that the mitophagy activity enhancer according to the present invention can be used as an agent (including cosmetics) for suppressing and / or preventing the onset of skin aging and / or mild aging.

[0039] A production example of the mitophagy activity enhancer according to the present invention will be shown below, with units being % by mass.

[0040] [Table 1]

[0041] <Example of manufacturing method> 1. Preparation of Each Phase (A) Phase: After dissolving ethanol in water, add St. John's wort extract to make a uniform solution. Phase (B): Heat to 80°C or higher and dissolve uniformly. Phase C: Xanthan gum is dispersed in BG. (D) Phase: After dissolving glycerin in water, citric acid and sodium citrate are dissolved to prepare a pH buffer solution. 2. Preparation method (1) Add heated (B) to (A) and stir for a few minutes, then cool to 30°C. (2) (D) is mixed with (C) while stirring until it is uniformly dissolved. (3) Slowly add the mixture of (A) and (B) to the mixture of (C) and (D). [Industrial Applicability]

[0042] According to the present invention, a composition capable of enhancing mitophagy activity in cells can be provided.

Claims

1. A mitophagy activity enhancer comprising one or more extracts selected from Hypericum perforatum extract, soybean sprout extract, and white strawberry extract as an active ingredient, and used to enhance mitophagy activity in human skin fibroblasts and human epidermal keratinocytes.

2. The mitophagy activity enhancer according to claim 1 , comprising at least a St. John's wort extract.

3. A mitophagy activity enhancer according to claim 1 or 2, which is a cosmetic for enhancing mitophagy activity.

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