JP2023021890A - Anti-aging gene expression promoter - Google Patents

Abstract

To provide a material that promotes the expression of LINC00942, particularly in lip-derived fibroblasts.SOLUTION: One or two or more Lamiales plant extracts selected from sage extract, perilla extract, lavender extract, rosemary extract, and common verbena extract, and Lagerstroemia speciosa extract are used as active ingredients of a LINC00942 expression promoter. The LINC00942 expression promoter can be blended in a composition for suppressing skin aging. In addition, one or two or more Lamiales plant extracts selected from sage extract, perilla extract, lavender extract, rosemary extract, and common verbena extract, and Lagerstroemia speciosa extract are contained in a lip cosmetic. The cosmetics are expected to be able to increase myofiber-constituting proteins of lips, and to realize lips that are three-dimensional, thick, and substantial.SELECTED DRAWING: Figure 1

Description

TECHNICAL FIELD The present invention relates to an anti-aging gene expression promoter, a composition for suppressing skin aging containing the expression promoter, and a lip cosmetic containing the anti-aging gene expression promoter.

Cells that make up living organisms age with age. Cells are responsible for biological reactions and form and maintain tissues and organs that are responsible for life activities, and aging of cells also leads to aging of individuals.
In addition, senescent cells release factors that induce senescent cell-like reactions to surrounding cells, accelerating the aging of tissues and organs. For this reason, it has been suggested that removal of senescent cells can delay the aging of individuals and tissues, and improve symptoms of aging that have already occurred (see, for example, Non-Patent Document 1).

Therefore, senescent cells are expected as anti-aging targets (see, for example, Non-Patent Document 2). However, there is a problem that it is difficult to remove senescent cells non-invasively.

On the other hand, in recent years, non-coding RNAs (ncRNAs), which are RNAs that do not encode proteins, have been reported as biological components that control cellular senescence (e.g., Non-Patent Document 3
reference). Among these ncRNAs, long-chain ncRNAs (LncRNAs), which are RNAs having 200 bases or more, are known, and it is estimated that there are about 8,200 types of LncRNAs (see, for example, Non-Patent Document 4). With respect to lncRNAs, it has recently been reported that skin samples were collected from young and old donors, the expression levels were compared, and the amounts of some lncRNAs changed with aging (see, for example, Non-Patent Document 5). ).

LncRNAs of NESPAS, FLJ46906, and HOTAIR, whose expression increases with age, and LncRNAs of SNHG5, LOC100292680 (also known as 'LINC00942', which represent the same LncRNA), and IPW, whose expression decreases with age, were found particularly in cells. The LncRNA is a powerful indicator for judging the inhibitory effect of aging.
It is reported that the effect of suppressing skin aging can be determined using as an index (see, for example, Patent Documents 1 and 2).
In addition, a component that promotes the expression of LINC00942 as an anti-aging gene has been found, and an anti-aging cosmetic containing such a component has been proposed (Patent Document 3).

JP 2015-130857 A JP 2017-112892 A Patent application 2020-012419

Baker DJ. et al., Nature. (2011), 479, 232-236 Naylor RM. et al., Clin Pharmacol Ther. (2013) 93, 105-116 Abdelmohsen K. et al., Wiley Interdiscip Rev RNA. (2015) 6, 615-629 Cabili MN. et al., Genes Dev. (2011), 25, 1915-1927 Chang ALS. et al., J Invest Dermatol. (2012), 133, 394-402

An object of the present invention is to provide a material that promotes the expression of LINC00942, particularly in lip-derived fibroblasts.

The present inventors have investigated various materials in search of a new material for suppressing skin aging, and found that the expression of LncRNA LINC00942 is promoted when an extract of lamiaceous plants such as sage is combined with Lagerstroemia myrtle extract. (or enhanced) and found to be effective as a material for suppressing skin aging.In addition, such enhancement of expression is observed in fibroblasts derived from the lips, and it is useful as a component to be added to lip cosmetics for suppressing skin aging. The present invention was completed based on the discovery of the property.
Furthermore, the present inventors have found that lip-derived fibroblasts increase the expression of muscle fiber-constituting proteins in adjacent skeletal muscle cells. It was also found to increase muscle fiber constituent proteins. Based on these findings, we conceived that a combination of lamiaceous plant extracts such as sage, which can increase the expression of LINC00942 in lip-derived fibroblasts, and Lagerstroemia myrtle extract can increase proteins constituting lip muscle fibers. Completed the invention of a new lip cosmetic.

That is, the present invention is as follows.
[1] A LINC00942 expression promoter containing one or more lamiaceae plant extracts selected from sage extract, perilla extract, lavender extract, rosemary extract and vervain extract, and Lagerstroemia myrtle extract.
[2] The expression promoter of [1], which promotes the expression of LINC00942 in lip-derived fibroblasts.
[3] The expression promoter according to [1] or [2], wherein the dry weight ratio of the contents of the Lamiaceae plant extract and Lagerstroemia myrtle extract is 20:1 to 100:1.
[4] A composition for suppressing skin aging, containing one or more lamiaceae plant extracts selected from sage extract, perilla extract, lavender extract, rosemary extract and vervain extract, and Lagerstroemia myrtle extract.
[5] The composition according to [4], wherein the anti-skin aging is one or more selected from the group consisting of prevention of skin elasticity reduction, wrinkle prevention, sagging prevention, stain formation prevention, dullness prevention and pore enlargement prevention.
[6] The composition according to [4] or [5], which is a lip cosmetic.
[7] A lip cosmetic containing one or more Labiatae plant extracts selected from sage extract, perilla extract, lavender extract, rosemary extract and vervain extract, and Lagerstroemia gossamer extract.
[8] The cosmetic according to [7], which is used to increase muscle fiber-constituting proteins of the lips.

INDUSTRIAL APPLICABILITY According to the present invention, it is possible to provide a new material for suppressing skin aging that has the effect of promoting the expression of the anti-aging gene LINC00942.
In addition, according to the present invention, due to the increased expression of LINC00942 in lip-derived fibroblasts, muscle fiber-constituting proteins in adjacent skeletal muscle cells increase, resulting in a three-dimensional, thick and voluminous feeling. It is expected to provide a lip cosmetic that can make the lips look fuller or more attractive.

Graph showing the expression level of LINC00942 in lip-derived fibroblasts cultured with test samples added. Fluorescence-staining photograph of myofibre-constituting protein (MYH2) in skeletal muscle cells to which the culture supernatant of lip-derived fibroblasts was added (green: myofibre-constituting protein, blue: cell nucleus). Fluorescence-staining photograph of myofiber-constituting protein (MYH7) in skeletal muscle cells to which culture supernatant of lip-derived fibroblasts was added (green: myofiber-constituting protein, blue: cell nucleus). Graph showing the expression level of muscle fiber constituent protein (MYH2) gene in skeletal muscle cells to which the culture supernatant of lip-derived fibroblasts was added. Graph showing the expression level of myofiber-constituting protein (MYH7) gene in skeletal muscle cells to which the culture supernatant of lip-derived fibroblasts was added. Graph showing the expression level of myofiber-constituting protein (MYH2) gene in skeletal muscle cells to which the culture supernatant of lip-derived fibroblasts with enhanced LINC00942 expression was added. Graph showing the expression level of muscle fiber constituent protein (MYH7) gene in skeletal muscle cells to which the culture supernatant of lip-derived fibroblasts in which LINC00942 expression was enhanced. A photograph of the lip of a subject who continuously used a lip cosmetic containing a sage extract and Lagerstroemia myrtle extract.

One aspect of the present invention is a LINC00942 expression promoter containing one or more Labiatae plant extracts selected from sage extract, perilla extract, lavender extract, rosemary extract, and vervain extract, and Lagerstroemia myrtle extract. (hereinafter also referred to as "expression promoter of the present invention"). The Lamiaceae plant extract is not particularly limited, but is more preferably a sage extract. That is, a more preferable combination of extracts in the present invention is a combination of sage extract and Lagerstroemia gossamer extract.
The inventors of the present invention investigated various materials in search of new materials for suppressing skin aging, and found that rosmanol and analogs thereof contained in lamiaceae plant extracts have the effect of promoting the expression of LINC00942. and also found that the effect of promoting the expression of LINC00942 in lip-derived fibroblasts by the Labiatae plant extract tends to be further enhanced by the combination with Lagerstroemia gossamer extract.

Rosmanol and its analogues are rosmanol and rosmanol-related compounds contained in plants of the order Lamiales, such as sage, perilla, lavender, rosemary, and vervain. The labiatae plant extract used in the present invention usually contains one or more of rosmanol and its analogues.

Rosmanol and its analogues include, for example, compounds represented by the following formula (I).

In the formula, R ¹ and R ² are each independently hydrogen, oxygen, hydroxy, or alkyloxy having 1 to 6 carbon atoms (preferably 1 to 3 carbon atoms, more preferably 1 to 2 carbon atoms). ^R1 and
^R2 is preferably hydroxy or alkyloxy.
Examples of alkyloxy having 1 to 6 carbon atoms include methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, n-pentoxy and n-hexoxy.

R ³ is carboxy or alkoxycarbonyl of 1 to 6 carbon atoms (preferably 1 to 3 carbon atoms, more preferably 1 to 2 carbon atoms), or together with R ⁴ or R ⁵ —CO -O-. ^R3 is preferably carboxy, or together with ^R4 or ^R5 is -CO-O-. ^{When R3} together with ^R4 or ^R5 is -CO-O-, ^R4 or ^R5 not bound to R3 is preferably other than hydrogen.
Examples of alkoxycarbonyl having 1 to 6 carbon atoms include methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, sec-butoxycarbonyl, tert-butoxycarbonyl, n-
Examples include pentoxycarbonyl, n-hexoxycarbonyl and the like.

R ⁴ and R ⁵ are each independently hydrogen, oxygen, hydroxy, or alkyloxy having 1 to 6 carbon atoms (preferably 1 to 3 carbon atoms, more preferably 1 to 2 carbon atoms). Specific examples of alkyloxy are the same as above. ^R4 and ^R5 are preferably hydrogen, hydroxy or alkyloxy.

The hydrogen atoms attached to the ring are each independently oxygen, linear, branched or cyclic alkyl having 1 to 6 carbon atoms, linear or branched alkenyl or alkynyl having 2 to 6 carbon atoms, or It may be substituted with alkyloxy having 1 to 6 carbon atoms.
Alkyl includes, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, n-hexyl, cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl, and the like. .
Alkenyl is a straight-chain or branched-chain alkenyl having 2 to 6 carbon atoms and having a carbon-carbon double bond at one or more positions of the above alkyl. For example vinyl, 1-propenyl, allyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl and the like.
Alkynyl is a straight-chain or branched-chain alkynyl having 2 to 6 carbon atoms and having a carbon-carbon triple bond at one or more positions of the above alkyl. Examples include ethynyl, 1-propynyl, propargyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-pentynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, 1-hexynyl and the like.
Specific examples of alkyloxy are the same as above.

Rosmanol and its analogues are preferably, but not limited to, carnosic acid, rosmanol, isolosmanol, 11,12-di-O-methylisorosmanol, 12-O-carnosic acid, rosmanol-9-ethyl ether, epiros Manol, 7-methyl-epirosmanol, more preferably carnosic acid, rosmanol or isolosmanol.

One or two or more kinds of Lamiaceae plant extracts selected from sage extract, perilla extract, lavender extract, rosemary extract and vervain extract used in the present invention are whole plants, fruits, leaves, stems, and It can be obtained by extracting selected parts from the root with water and/or an organic solvent.
The Lagerstroemia speciosa extract used in the present invention can be obtained by extracting parts selected from the whole plant, fruit, leaves, stems, and roots of Lagerstroemia speciosa with water and/or an organic solvent. can be done.
Organic solvents that can be used for extraction include aliphatic alcohols such as methanol and ethanol, aliphatic ketones such as acetone, aliphatic ethers such as dioxane and ethyl ether, halogenated hydrocarbons such as methylene chloride and chloroform, and ethyl acetate. , fatty acid esters such as butyl acetate and isobutyl acetate, hydrocarbons such as hexane and benzene, and mixtures of two or more of these solvents.

In the present invention, the weight ratio of the total content of Lamiaceae plant extracts to the content of Lagerstroemia gossips extract is preferably 20:1 to 100:1, more preferably 45:1 to 100, in terms of dry weight. :1 is more preferred.

Lamiaceae plant extracts promote the expression of LINC00942 in cells as previously found (Patent Document 3). tend to increase. Therefore, the combination of these extracts is the active ingredient of the LINC00942 expression promoter.
As the cells in which the expression of LINC00942 is promoted, fibroblasts are more preferable, and lip-derived fibroblasts are particularly preferable.
In addition, "promoting expression" refers to increasing the expression level or expression rate of LINC00942 compared to when the agent for promoting expression of the present invention is not applied. The degree of such increase is not particularly limited.

As disclosed in Patent Document 1, there is a correlation between the expression-promoting action of LINC00942 and the skin aging-suppressing action. Therefore, the expression promoter of the present invention can exhibit skin aging inhibitory action.
Based on this, another aspect of the present invention contains one or two or more Labiatae plant extracts selected from sage extract, perilla extract, lavender extract, rosemary extract and vervain extract, and lagerstroemia Lagerstroemia extract, It is a composition for suppressing skin aging.
Here, the term "skin aging inhibition" refers to one or more selected from the following: prevention of skin elasticity loss, wrinkle prevention, sagging prevention, stain formation prevention, dullness prevention, and pore enlargement prevention.

The composition for suppressing skin aging of the present invention contains the skin aging inhibitor of the present invention, and further contains components used in cosmetics, quasi-drugs, foods, pharmaceuticals, etc., as long as the effect is not impaired, It is a composition that can be used for suppressing skin aging.
The composition for suppressing skin aging of the present invention can be in the form of cosmetics, quasi-drugs, foods and drinks, pharmaceuticals, and the like. The mode of ingestion (application) is not particularly limited. Can be taken orally.

The total content of the Lamiaceae plant extract in the composition for suppressing skin aging of the present invention is not particularly limited, but is preferably 0.00001% by weight or more, more preferably 0.0001% by weight or more, based on the total composition. 0.001% by weight or more is more preferable. Also, the upper limit is not particularly limited, but it is preferably 30% by weight or less, more preferably 20% by weight or less, and even more preferably 10% by weight or less, relative to the entire composition.
Although the total content of the Lagerstroemia gossamer extract in the composition for preventing skin aging of the present invention is not particularly limited, it is preferably 0.00001% by weight or more, more preferably 0.0001% by weight or more, more preferably 0.0001% by weight or more, based on the total composition. 001% by weight or more is more preferable. Also, the upper limit is not particularly limited, but it is preferably 30% by weight or less, more preferably 20% by weight or less, and even more preferably 10% by weight or less, relative to the entire composition.
The weight ratio of the total content of the Lamiaceae plant extract to the content of the Lagerstroemia gossamer extract in the composition for suppressing skin aging of the present invention conforms to the description of the expression promoter of the present invention described above.

The composition for suppressing skin aging of the present invention can contain optional ingredients as appropriate according to each form. The composition for suppressing skin aging is produced by blending the skin aging inhibitor of the present invention and optional ingredients used in cosmetics, quasi-drugs, foods, pharmaceuticals, etc., and formulating according to a conventional method. be able to.

The composition for preventing skin aging of the present invention is more preferably in the form of cosmetics, and particularly preferably in the form of cosmetics for the lips. This is because enhancement of the expression of LINC00942 in lip fibroblasts is expected to improve elasticity of the lip skin and suppress lip wrinkles. In addition, it can be expected to achieve youthful and voluminous lips due to the effect of suppressing skin aging on the lips.

In addition, since the expression promoter of the present invention acts on the skin via unidirectional or bidirectional action (intercellular communication) between adjacent cells, the expression promoter of the present invention or the anti-skin aging agent of the present invention The composition can be suitably used as a lip cosmetic.
As shown in the reference example below, when skeletal muscle cells were cultured with the addition of the supernatant obtained by culturing lip-derived fibroblasts, muscle fiber constituent proteins (myosin heavy chain proteins; MYH2, MYH7) increased. It is presumed that some substance related to the activity of skeletal muscle cells is released from the lip-derived fibroblasts. That is, it is thought that intercellular communication exists between lip-derived fibroblasts and skeletal muscle cells.
In addition, as shown in Examples below, when the culture supernatant of lip-derived fibroblasts with enhanced expression of LINC00942 was added to skeletal muscle cells and cultured, the gene expression levels of MYH2 and MYH7 increased. , that the increased expression of LINC00942 in lip-derived fibroblasts can increase the release of certain substances involved in the activity of skeletal muscle cells, thereby increasing muscle fiber-constituting proteins in adjacent skeletal muscle cells. presumed.
It is known that muscle fiber constituent proteins decrease with age (T.Gomi, et al., Intr. J. Cosmetic Sci., 2020, 1-10), but LINC00942 restores muscle fiber constituent proteins. It can also be said to be an anti-aging gene from the viewpoint of promoting

Therefore, it can be said that the combination of the Labiatae plant extract and Lagerstroemia myrtle extract, which promotes the expression of LINC00942 in lip-derived fibroblasts, has the effect of increasing the proteins constituting the muscle fibers of the lip. Therefore, by blending such a combination in a lip cosmetic, it is possible to increase the muscle fiber-constituting protein of the lip, and to achieve three-dimensional, thick and voluminous lips, thereby achieving youthful or attractive lips. It is expected.
Therefore, the lip cosmetic of the present invention may be used to increase muscle fiber-constituting protein of the lip.
Here, the “increase” of the muscle fiber-constituting protein means that the expression-enhancing agent of the present invention, the composition for suppressing skin aging of the present invention, or the cosmetic of the present invention is not applied, compared to the case where the muscle fiber-constituting protein or its It includes increasing the expression level or expression rate of a gene, and suppressing a decrease in the expression level or expression rate.

In the past, firm, plump and thick lips gave a youthful impression, so there was a high demand for a method to achieve this. For example, there is a method of producing a plump appearance by applying cosmetics such as lip gloss. In addition, hyaluronic acid is known as an ingredient that gives the skin firmness and volume. Cosmetic medicine is also known to give firmness and volume to the skin.
Under such circumstances, cosmetics that increase the muscle fiber constituent protein of the lips are new and meet the demands of consumers as a method that can replace hyaluronic acid to add firmness and volume to the lips to produce a youthful look. It is considered groundbreaking.

Embodiments of the lip cosmetic of the present invention are not particularly limited to lip cream, lipstick, lip gloss, lip balm, and the like.

Ingredients that can be contained when the composition for preventing skin aging of the present invention is in the form of a cosmetic will be described.
In addition to the active ingredients of the skin aging inhibitor of the present invention, that is, the Labiatae plant extract and Lagerstroemia myrtle extract, the composition for suppressing skin aging of the present invention further contains active ingredients having the same or different functions. good too.
Active ingredients include whitening ingredients, wrinkle-improving ingredients, anti-inflammatory ingredients, extracts derived from animals and plants, and the like.

The whitening component is not particularly limited as long as it is commonly used in cosmetics. For example, 4-n-butylresorcinol, ascorbic acid glucoside, 3-O-ethylascorbic acid, tranexamic acid, arbutin, 1-triphenylmethylpiperidine, 1-triphenylmethylpyrrolidine, 2-(triphenylmethyloxy)ethanol, 2-(triphenylmethylamino)ethanol, 2-(triphenylmethyloxy)ethylamine, triphenylmethylamine, triphenylmethanol, triphenylmethane and aminodiphenylmethane, N-(p-toluyl)cysteic acid, N-(p -methoxybenzoyl)cysteic acid and the like. Other whitening ingredients include N-benzoyl-serine, N-(p-methylbenzoyl)serine, N-(p-ethylbenzoyl)serine, N-(p-methoxybenzoyl)serine, and 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, niacinamide, D-pantothenyl alcohol and the like.

Some of these whitening ingredients are already commercially available, and others can be obtained by synthesis. For example, 3-O-ethylascorbic acid can be synthesized by a known method described in JP-A-8-134055. There is also a commercially available product ("VC Ethyl" manufactured by Nippon Fine Chemical), so it is possible to obtain and use these. 1-triphenylmethylpiperidine, 1-triphenylmethylpyrrolidine, 2-(triphenylmethyloxy)ethanol, 2-(triphenylmethylamino)ethanol, 2-(triphenylmethyloxy)ethylamine, triphenylmethylamine, tri Phenylmethanol, triphenylmethane and aminodiphenylmethane are described in Patent Document WO/2010/074052 pamphlet as N-(o-toluoyl)cysteic acid, N-(m-toluoyl)cysteic acid and N-(p-toluoyl)cysteic acid. , N-(p-methoxybenzoyl)cysteic acid, N-(4-phenylbenzoyl)cysteic acid, N-(p-toluoyl)homocysteic acid, are described in WO/2011/058730, N-benzoyl-serine, N-(p-methylbenzoyl)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 and the like are disclosed in WO/2011/074643 pamphlet, and can be synthesized according to the disclosure.

The wrinkle-improving component is not particularly limited as long as it is commonly used in cosmetics. For example, vitamin A or its derivatives, trifluoride isopropyloxopropylaminocarbonylpyrrolidinecarbonylmethylpropylaminocarbonylbenzoylaminoacetic acid Na, niacinamide, cyclohexylglycerin, retinol, retinal, retinoic acid, tretinoin, isotretinoin, tocopherol retinoate, palmitin Acid retinol, retinol acetate, ursolic acid benzyl ester, ursolic acid phosphate, betulinic acid benzyl ester, benzilic acid phosphate, N-(p-toluyl)cysteic acid, N-(p-methoxybenzoyl)cysteic acid, etc. mentioned.

The extract derived from animals and plants is not particularly limited as long as it is generally used in pharmaceuticals, cosmetics, foods, and the like. For example, akebi extract, asunaro extract, asparagus extract, avocado extract, amacha extract, almond extract, arnica extract, aloe extract, aronia extract, apricot extract, rose rose extract, ginkgo biloba extract, Indian kino extract, fennel extract, udo extract, ageitsu extract , Eleuthero extract, Trifolium extract, Scutellaria root extract, Phellodendron bark extract, Coptis extract, Panax ginseng extract, Hypericum extract, Dead nettle extract, Orange extract, Kakyoku extract, Hydrolyzed conchiolin liquid, Hydrolyzed silk, Kakon extract, Chamomile extract, Carrot extract, Kawara mugwort extract, licorice extract, kiwi extract, cucumber extract, guava extract, kujin extract, gardenia extract, kumazasa extract, clara extract, walnut extract, grapefruit extract, black rice extract, clove extract, chlorella extract, mulberry extract, licorice extract, alpinia extract , Gentian extract, Gennoshoko extract, Black tea extract, Burdock extract, Rice extract, Fermented rice extract, Fermented rice bran extract, Rice germ oil, Bilberry extract, Salvia extract, Saponaria extract, Sasa extract, Hawthorn extract, Sansha extract, Sansho extract, Shiitake mushroom extract, rhododendron extract, rhododendron extract, linden extract, meadowsweet extract, peony extract, ginger extract, calamus root extract, birch bark extract, horsetail extract, star fruit extract, stevia extract, fermented stevia, ivy extract, hawthorn extract, eucalyptus Elderberry Extract, Yarrow Extract, Mentha Extract, Mallow Extract, Cnidium Extract, Senninkokoku Extract, Assembly Extract, Sohakuhi Extract, Rheum Extract, Soybean Extract, Taisou Extract, Thyme Extract, Dandelion Extract, Tea Extract, Clove Extract, Chimp Extract, Sweet Tea Extract, red pepper extract, angelica extract, calendula officinalis extract, tonin extract, spruce extract, prickly pear extract, dokudami extract, tomato extract, natto extract, carrot extract, garlic extract, wild rose extract, hibiscus extract, Bakumondou extract, lotus extract, parsley extract, birch extract, adlay seed extract, hamamelis extract, cypress extract, cypress extract, loquat extract, coltsfoot extract, coltsfoot extract Bukuryou extract, butcher bloom extract, grape extract, grape seed extract, loofah extract, safflower extract, peppermint extract, bodaiju extract, button extract, hop extract, marjoram extract, pine extract, horse chestnut extract, skunk cabbage extract, soapberry extract, melissa extract , mozuku extract, peach extract, peach leaf extract, cornflower extract, eucalyptus extract, saxifrage extract, yuzu extract, lily extract, yokuinin extract, mugwort extract, green tea extract, lime extract, apple extract, rooibos tea extract, litchi extract, lettuce extract, lemon extract , forsythia extract, astragalus extract, rose extract, Roman chamomile extract, royal jelly extract, burnet extract and the like are preferred.

Examples of anti-inflammatory components include clarinone, glabridin, glycyrrhizic acid, glycyrrhetinic acid, pantothenyl alcohol, tranexamic acid, niacinamide and the like, preferably glycyrrhizic acid and its salts, alkyl glycyrrhetinate and its salts, and glycyrrhetinic acid. and its salt.

Other ingredients that can be contained in cosmetics are exemplified below.
Polar oil, volatile hydrocarbon oil, etc. are mentioned as an oily component.
Polar oils include synthetic ester oils such as isopropyl myristate, cetyl octanoate, octyldodecyl myristate, isopropyl palmitate, butyl stearate, hexyl laurate, myristyl myristate, decyl oleate, hexyldecyl dimethyloctanoate, and lactic acid. Cetyl, myristyl lactate, lanolin acetate, isocetyl stearate, isocetyl isostearate, cholesteryl 12-hydroxystearate, ethylene glycol di-2-ethylhexylate, dipentaerythritol fatty acid ester, N-alkyl glycol monoisostearate, neopentyl dicaprate Glycol, diisostearyl malate, glyceryl di-2-heptylundecanoate, trimethylolpropane tri-2-ethylhexylate, trimethylolpropane triisostearate, pentaneerythritol tetra-2-ethylhexylate, glyceryl tri-2-ethylhexylate , trimethylolpropane triisostearate.
In addition, cetyl 2-ethylhexanoate, 2-ethylhexyl palmitate, glyceryl trimyristate, tri-2-heptylundecanoic acid glyceride, castor oil fatty acid methyl ester, oleic oil, cetostearyl alcohol, acetoglyceride, palmitic acid 2 - heptylundecyl, diisobutyl adipate, N-lauroyl-L-glutamic acid 2-octyldodecyl ester, di-2-heptylundecyl adipate, ethyl laurate, di-2-ethylhexyl sebacate, 2-hexyl myristate Decyl, palmitic acid 2
-hexyldecyl, 2-hexyldecyl adipate, diisopropyl sebacate, 2-ethylhexyl succinate, ethyl acetate, butyl acetate, amyl acetate, triethyl citrate, octyl methoxycinnamate and the like.
In addition, as natural oils, avocado oil, camellia oil, turtle oil, macadamia nut oil, corn oil, mink oil, olive oil, rapeseed oil, egg yolk oil, sesame oil, persic oil, wheat germ oil, sasanqua oil, castor oil, linseed oil, Safflower oil, cottonseed oil, perilla oil, soybean oil, peanut oil, teaseed oil, kaya oil, rice bran oil, sinagiri oil, Japanese paulownia oil, jojoba oil, germ oil, triglycerin, glyceryl trioctanoate, glyceryl triisopalmitate etc.

Volatile hydrocarbon oils include isododecane, isohexadecane, and the like.

Surfactants include fatty acid soaps (sodium laurate, sodium palmitate, etc.), potassium lauryl sulfate, anionic surfactants such as alkyl sulfate triethanolamine ether, stearyltrimethylammonium chloride, benzalkonium chloride, laurylamine oxide. cationic surfactants, betaine surfactants (alkylbetaine, amidobetaine, sulfobetaine, etc.), imidazoline amphoteric surfactants (2-cocoyl-2-imidazolinium hydroxide-1-carboxyethyloxy-2 sodium salts, 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 ether, POE sorbitan fatty acid esters (POE sorbitan monooleate, polyoxyethylene sorbitan monostearate, etc.), POE sorbitol fatty acid esters (POE-sorbit monolaue) 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/POP2-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, and the like.

Polyhydric alcohols include polyethylene glycol, glycerin, 1,3-butylene glycol, erythritol, sorbitol, xylitol, maltitol, propylene glycol, dipropylene glycol, diglycerin, isoprene glycol, 1,2-pentanediol, 2,4 -hexylene glycol, 1,2-hexanediol, 1,2-octanediol and the like.

Thickeners include guar gum, quince seed, carrageenan, galactan, gum arabic, pectin, mannan, starch, xanthan gum, curdlan, methylcellulose, hydroxyethylcellulose, carboxymethylcellulose, methylhydroxypropylcellulose, chondroitin sulfate, dermatan sulfate, glycogen, Heparan sulfate, hyaluronic acid, sodium hyaluronate, tragacanth gum, keratan sulfate, chondroitin, mucoitin sulfate, hydroxyethyl guar gum, carboxymethyl guar gum, dextran, kerato sulfate, locust bean gum, succinoglucan, caroninic acid, chitin, chitosan, carboxymethyl Chitin, agar, polyvinyl alcohol, polyvinylpyrrolidone, carboxyvinyl polymer, alkyl-modified carboxyvinyl polymer, sodium polyacrylate, polyethylene glycol, bentonite and the like.

As the powders, 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, may be used. Inorganic pigments such as red iron oxide, yellow iron oxide, black iron oxide, cobalt oxide, ultramarine blue, Prussian blue, titanium oxide, and zinc oxide that may be treated, mica titanium that may be treated, fish phosphorus foil, Pearl agents such as bismuth oxychloride, optionally laked 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 No., orange No. 201, red No. 213, yellow No. 204, yellow No. 203, blue No. 1, green No. 201, purple No. 201, red No. 204, etc., polyethylene powder, polymethyl methacrylate, nylon powder, Examples include organic powders such as organopolysiloxane elastomers.

UV absorbers include para-aminobenzoic acid UV absorbers, anthranilic acid UV absorbers, salicylic acid UV absorbers, cinnamic acid UV absorbers, benzophenone UV absorbers, sugar UV absorbers, 2-(2 UV absorbers such as '-hydroxy-5'-t-octylphenyl)benzotriazole, 4-methoxy-4'-t-butyldibenzoylmethane, and the like.

Cosmetics may additionally contain water, ethanol, fragrances, preservatives, pH adjusters, colorants, and the like.

In addition, in addition to the above-mentioned lip cosmetics, dosage forms when applied as cosmetics include commonly known lotion dosage forms, milky lotion dosage forms, essence dosage forms, cream dosage forms, and powder forms. Any body-containing dosage form or the like can be taken.

EXAMPLES The present invention will be specifically described below with reference to examples and reference examples, but these are examples of the present invention and the scope of the present invention is not limited to these.

<Material>
A commercially available plant extract was used as the plant extract used for evaluation. That is, perilla extract (Amino Up Co.), lavender extract (Maruzen Pharmaceutical Co.), sage extract (Ichimaru Farcos Co.), rosemary extract (Koei Kogyo Co.), vervain extract (Seti Co.), souhakuhi extract (Maruzen Pharmaceutical Co.), Clove Extract (Ichimaru Farcos), Carrot Extract (Maruzen Pharmaceutical Co.), Bukuryou Extract (Ichimaru Farcos Co.), Lime Extract (Maruzen Pharmaceutical Co.), Lagerstroemia Lagerstroemia Extract (Mikimoto Pharmaceutical Co.), Eucalyptus Extract (Koei Kogyo), Asenyaku Extract (Koei Kogyo), Bodaiju extract (Koei Kogyo), Kouki extract (Maruzen Pharmaceutical Co., Ltd.), and Senninkoku seed extract (Koei Kogyo) were used.
A commercially available compound was used for the evaluation. namely rosmanol
(PhytoLab), isorosmanol (Sigma-Aldrich), and carnosic acid (Tokyo Kasei Co., Ltd.).

<Reference Example 1> Verification test of LINC00942 expression-enhancing effect of extract of Labiatae plant Dermal fibroblasts derived from a 68-year-old Caucasian were used as aged cells.
Fibroblasts subcultured in 10% FBS-containing DMEM medium were seeded in a 96-well plate at 7000 cells/well, and cultured at 37° C. in a 5% CO ₂ environment for 24 hours. Thereafter, the medium was replaced with a medium containing each plant extract at each concentration (v/v%) shown in Table 1, and cultured for an additional 24 hours. As a solvent control, the cells were similarly cultured in a medium containing the solvent of each plant extract at the same concentration (v/v%) as the extract to be evaluated (3 wells for each group).
After the culture was completed, the cells were collected, and the expression level of LINC00942 was analyzed by quantitative real-time PCR using FastLane Cell SYBR Green Kit (Qiagen 216213) and LINC00942-specific primers (Qiagen Hs_LINC00942_1_SG). A relative value was obtained when the expression level was set to 1. Based on the results, Dunnett's test for the solvent control group was performed to evaluate whether the values were significantly larger than those of the solvent control group.

Table 1 shows the results. The plant names in Table 1 are perilla extract, perilla extract, lavender extract, sage extract, rosemary extract, rosemary, vervain extract, vervain extract, sohakuhi extract, clove extract, carrot extract, carrot extract, and bellflower extract. Bukuryo extract, lime extract, ethanol, EtOH, and 1,3-butylene glycol, BG. * indicates p<0.05, ** indicates p<0.01, and NS indicates no significant difference.
Excellent LINC00942 expression-enhancing activity was observed in Labiatae extract, lavender extract, sage extract, rosemary extract, and vervain extract, which are Labiatae plant extracts.

<Reference Example 2> Verification test of LINC00942 expression promoting action by rosmanol and analogues thereof Various compounds contained in Labiatae plants were evaluated for the expression promoting action of LINC00942.
Dermal fibroblasts derived from a 68-year-old Caucasian were used as senescent cells.
Fibroblasts subcultured in DMEM medium containing 10% FBS were seeded in a 96-well plate at 7000 cells/well, and cultured at 37° C. in a 5% CO ₂ environment for 24 hours. Thereafter, the medium was replaced with a medium containing the evaluation compound (Table 2) dissolved in DMSO at a final concentration of 0.0005% (w/v), and the cells were further cultured for 24 hours. again,
As a solvent control, the cells were similarly cultured in a medium containing 0.1% (v/v%) DMSO.
At the end of culture, the expression level of LINC00942 was analyzed by quantitative real-time PCR using FastLane Cell SYBR Green Kit (Qiagen 216213) and LINC00942-specific primers (Qiagen Hs_LINC00942_1_SG). A relative value was obtained when Each group was 3 wells, n=3. Based on the results, Dunnett's test for the solvent control group was performed to evaluate whether the values were significantly larger than those of the solvent control group.

Table 2 shows the results. DMSO in Table 2 indicates dimethylsulfoxide. * indicates p<0.05, ** indicates p<0.01.
Rosmanol and its analogues, rosmanol, isorosmanol and carnosic acid, contained in Labiatae plants, were found to have excellent effects of promoting the expression of LINC00942.

<Example 1> Verification test of LINC00942 expression-enhancing action by combined use of Labiatae plant extract and other plant extracts
1000 μL of normal human lip-derived fibroblasts NF125 (Chinese, Female, Cell Research Corporation) suspended in D-MEM medium containing 10% FBS were seeded in a 24-well plate (3.0×10 ⁴ cells/mL). After culturing for 24 hours at 37°C in a 5% CO ₂ environment, the medium was removed and 450 µL of sage extract-containing medium (extract final concentration 0.5 v/v%) and 50 µL of other extract-containing medium (extract final concentration 0.025 v) were added. /v%
) was added to each well (4 wells for each group). As other extracts, Crape myrtle extract, Eucalyptus extract, Ashenyak extract, Bodaiju extract, Kouki extract, or Sesame seeds extract were used. After culturing for another 24 hours at 37°C in a 5% CO2 environment, cells were harvested and treated with Fast SYBR Green Master Mix (Applied: 4385617), RNeasy Mini Kit-8 (250) (Qiagen: 74106), Superscript VILO cDNA. Synthesis kit 250T (Invitrogen: 11754-250), Hs_LINC00942_2_SG QuantiTect Primer Assay (QIAGEN: QT02305933), and Hs_ACTB_2_SG QuantiTect Primer Assay (QIAGEN: QT01680476) were used to analyze the expression level of LINC00942 by quantitative real-time PCR. A relative value was obtained when the expression level in the control was set to 1. Based on the results, Dunnett's test was performed against the solvent control group.

The results are shown in FIG. It was confirmed that the lip-derived fibroblasts to which both the sage extract and the crape myrtle extract were added tended to increase the expression of the LINC00942 gene, compared to the case where only the sage extract was added.

<Reference Example 3> Effect of lip-derived fibroblast culture supernatant on muscle fiber constituent proteins in skeletal muscle cells
1000 μL of normal human lip-derived fibroblasts NF125 (Chinese, Female, Cell Research Corporation) suspended in D-MEM medium containing 10% FBS were seeded in a 24-well plate (3.0×10 ⁴ cells/mL). After culturing for 24 hours at 37°C in a 5% CO ₂ environment, 300 µL/well of the supernatant was collected.
500 μL of normal human skeletal muscle myoblasts HSMM (Caucasian, Female, CC-2580, Lonza) suspended in growth medium (SkGM-2 BulletKit (Lonza: CC-3245)) were seeded in 24-well plates (9.0
×10 ⁴ cells/mL). After culturing for 24 hours at 37°C in a 5% CO ₂ environment, the medium was removed and washed with 1000 µL/well of PBS. There, 250 μL / well of differentiation medium (SkMC Differentiation medium (TaKaRa: D12045)) and the previously collected lip-derived fibroblast culture supernatant in D-MEM medium at 100, 50, or 25 (v / v)% 250 μL/well of the diluted product was added. As a solvent control, 250 μL/well of differentiation medium and 250 μL/well of D-MEM medium were added. 4 at 37℃, 5% _CO2 environment
After culturing for 8 hours, skeletal muscle cells were harvested and treated with Superscript VILO cDNA Synthesis kit 250T (Invitrogen: 11754-250), RNeasy Mini Kit-8 (250) (QIAGEN: 74106), Fast SYBR Green Master Mix (Applied: 4385617 ), Hs_MYH2_1_SG QuantiTect Primer Assay (QIAGEN: QT00082495), Hs_MYH7_1_SG QuantiTect Primer Assay (QIAGEN: QT01680476), Hs_ACTB_2_SG QuantiTect Primer Assay (QIAGEN: QT01680476), by quantitative real-time PCR method, myofiber constituent proteins (MYH7, MYH2 ) The expression level of the gene was analyzed, and the relative value when the expression level in the solvent control was set to 1 was calculated. Based on the results, Dunnett's test was performed against the solvent control group.
In addition, the skeletal muscle cells cultured above at a final concentration of 50 (v/v)% of the lip-derived fibroblast culture supernatant were cultured at 37 ° C. in a 5% CO ₂ environment for 72 hours. Fluorescent immunostaining was performed using an antibody or anti-MYH7 antibody, and observed under a fluorescence microscope.

2 and 3 show fluorescence staining photographs of skeletal muscle cells. It can be seen that in the skeletal muscle cells cultured with the addition of the supernatant obtained by culturing lip-derived fibroblasts, the amounts of MYH2 and MYH7 are increased compared to the control.
4 and 5 show the relative expression levels of MYH2 gene and MYH7 gene in skeletal muscle cells. It can be seen that in skeletal muscle cells cultured with the addition of the supernatant obtained by culturing lip-derived fibroblasts, the expression levels of the MYH2 gene and MYH7 gene are each enhanced compared to the control.

<Example 2> Effect of lip-derived fibroblast culture supernatant with enhanced expression of LINC00942 on proteins constituting muscle fibers in skeletal muscle cells
1000 μL of normal human lip-derived fibroblasts NF125 (Chinese, Female, Cell Research Corporation) suspended in D-MEM medium containing 10% FBS were seeded in a 24-well plate (3.0×10 ⁴ cells/mL). Cultured for 24 hours at 37°C, 5% CO ₂ environment.
The cultured fibroblasts were transfected with the plasmid. Specifically, Lipofectamine 3000 Reagent (Thermofisher Scientific) was diluted with Opti-MEM medium, vortexed for 2-3 seconds and then lightly centrifuged, and the plasmid (control plasmid: pcDNA-DEST47 (Thermofisher Scientific), or LINC00942 expression plasmid: DEST47-3E), after diluting P3000 with Opti-MEM, mix well by pipetting.
Incubated at room temperature. 50 μL of plasmid solution after incubation and 500 D-MEM medium
μL was added to fibroblasts and cultured at 37° C., 5% CO ₂ for 72 hours. After culturing, the medium was removed, fibroblasts were washed with 1000 μL/well of PBS, 500 μL/well of D-MEM medium containing 10% FBS was added, and the fibroblasts were further cultured at 37° C. in a 5% CO ₂ environment for 24 hours. . 300 μL/well of the supernatant after culture was collected.
500 μL of normal human skeletal muscle myoblasts HSMM (Caucasian, Female, CC-2580, Lonza) suspended in growth medium (SkGM-2 Bullet Kit (Lonza: CC-3245)) were plated in 24-well plates (9.0 × 10 ⁴ cells/mL). After culturing for 24 hours at 37°C and 5% CO ₂ environment, the medium was removed and PBS 1000 was added.
Washed with μL/well. There, 250 μL/well of differentiation medium (SkMC Differentiation medium (TaKaRa: D12045)) and the lip-derived fibroblast culture supernatant collected earlier were diluted to 25 (v/v)% in D-MEM medium. 250 μL/well was added. After culturing for 48 hours at 37°C in a 5% _CO2 environment, the skeletal muscle cells were collected and analyzed by quantitative real-time PCR in the same manner as in Reference Example 3 to measure the expression levels of muscle fiber constituent protein (MYH2, MYH7) genes. A relative value was calculated, with the expression level being 1 when the fibroblast culture supernatant containing the control plasmid was added.

6 and 7 show the relative expression levels of MYH2 gene and MYH7 gene in skeletal muscle cells.
In skeletal muscle cells cultured with the addition of the culture supernatant of lip-derived fibroblasts in which the expression of LINC00942 was enhanced by the introduction of the expression plasmid, the expression levels of the MYH2 gene and MYH7 gene were enhanced compared to the control. I understand.
As shown in Reference Example 3, lip-derived fibroblasts release some substance related to the activity of skeletal muscle cells and can increase muscle fiber-constituting proteins in skeletal muscle cells. Example 2 that the expression of LINC00942 is enhanced in cells
can be understood from

<Example 3> Investigation of the effects on the lips of continuous use of lip cosmetics containing sage extract and Lagerstroemia myrtle extract All the ingredients shown in Table 3 were stirred and mixed until they were uniformly dispersed, and the sage extract and A liquid-type lip cosmetic containing an Lagerstroemia speciosa extract was prepared.

Twenty-five healthy Japanese adult females (30 to 54 years old, average 43.32 years old) were asked to voluntarily cooperate in the continuous use test of the cosmetics. The subjects were those who had a problem with their lips, such as lack of three-dimensional effect on their lips. The subjects were asked to apply an appropriate amount of sunscreen (SPF50, PA+++) to the entire face every morning, and to apply an appropriate amount of the lip cosmetic to the lips every morning, noon and evening. After 0, 4, and 12 weeks of continuous use, the subject's lips were evaluated. Specifically, after removing makeup with cleansing and facial cleansing, the skin was conditioned for 10 minutes in a constant temperature and humidity room (around 23°C, humidity 50±5%), and then image correction was performed using a digital single-lens reflex camera. The face was photographed from the front, 45 degrees to the left and right, and 90 degrees to the left and right with the eyes open, with the color chart for eyebrows attached between the eyebrows.
FIG. 8 shows photographs of two of the subjects (subjects A and B) who showed significant improvement in lip volume and vertical wrinkles at 4 weeks and 12 weeks.

Claims (8)

An agent for promoting expression of LINC00942, which contains one or more lamiaceous plant extracts selected from sage extract, perilla extract, lavender extract, rosemary extract and vervain extract, and Lagerstroemia myrtle extract. 2. The expression promoter according to claim 1, which promotes the expression of LINC00942 in lip-derived fibroblasts. 3. The expression promoter according to claim 1 or 2, wherein the dry weight ratio of the contents of the Lamiaceae plant extract and Lagerstroemia myrtle extract is 20:1 to 100:1. A composition for suppressing skin aging, containing one or more lamiaceae plant extracts selected from sage extract, perilla extract, lavender extract, rosemary extract and vervain extract, and Lagerstroemia myrtle extract. 5. The composition according to claim 4, wherein the anti-skin aging is one or more selected from the group consisting of prevention of skin elasticity reduction, wrinkle prevention, sagging prevention, stain formation prevention, dullness prevention and pore enlargement prevention. The composition according to claim 4 or 5, which is a lip cosmetic. A lip cosmetic containing one or more Labiatae plant extracts selected from sage extract, perilla extract, lavender extract, rosemary extract and vervain extract, and Lagerstroemia myrtle extract. 8. The cosmetic according to claim 7, which is used to increase muscle fiber-constituting proteins of the lips.

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