JP6704289B2 - CGRP receptor expression enhancer, composition containing the same, and cosmetic method - Google Patents

Description

The present invention relates to a technique for improving the response reaction of CGRP.

CGRP (calcitonin gene-related peptide, calcitonin gene-related peptide) is a peptide consisting of 37 amino acids existing at the terminal and distal ends of peripheral primary sensory nerves such as the central nerve, heart and blood vessels.
Since CGRP has an action of expanding skin blood vessels, it is known to have an action of improving skin repair, an action of promoting blood circulation in the skin, and an action of improving skin metabolism (Patent Documents 1 to 3). In addition to vasodilatory action, CGRP has an action of regulating substance P in inflammation, an action of enhancing vascular permeability, a action of regulating nicotine-like receptors at the neuromuscular junction, an action of suppressing gluconeogenesis and an action of promoting glycolysis, and of pancreatic enzyme. Secretion promoting action, gastric acid secretion suppressing action, heart rate promoting action, nerve activity regulating action, calcium metabolism regulating action, bone formation promoting action, insulin secretion action, body temperature raising action, food intake lowering action, anti-inflammatory action, aging skin It is known to have the effect of decreasing the thickness of the liver and promoting the proliferation of neural stem cells, and also hypertension, heart failure, liver injury due to ischemia reperfusion, renal failure, gastrointestinal ulcer, sepsis, osteoporosis, arrhythmia, arachnoid membrane. It is known to be useful for the prevention and/or amelioration of diseases such as bleeding bleeding, pulmonary hypertension, delayed hypersensitivity, periodontal disease, toxemia of pregnancy, preterm delivery, and congestive heart dysfunction ( Patent documents 1, 3 to 6).

Non-Patent Document 1 describes that the secretory amount of CGRP in the skin is improved by warm stimulation, cold stimulation, brushing and scooping stimulation.
L-4-thiazolylalanine or its derivative (Patent Document 2), whey protein-derived IgG or its Fc fragment (Patent Document 7), capsaicin (Patent Document 8) and the like are known as components that promote the secretion of CGRP. ing.

CGRP is known to promote the production and release of IGF-1 (insulin-like growth factor-1) (Patent Document 9).

JP, 2014-114220, A Japanese Patent Publication No. 2011-507864 JP 2012-116765 A JP, 2013-063972, A Japanese Patent Publication No. 2006-514630 JP, 10-245346, A WO10/058517 pamphlet JP, 2008-195734, A JP, 2010-001282, A JP, 2013-177439, A

Tsuchiya et al, Neuropeptides (1996) 30 (2), 149-157

CGRP exerts its physiological action by binding to its receptor (Patent Document 1). Therefore, even if the secreted amount of CGRP, which is a ligand, is constant, the response of CGRP can be improved by improving the expression level of its receptor. Then, this invention makes it a subject to provide the novel technique which improves the expression of a CGRP receptor.

The present invention for solving the above-mentioned problems is a CGRP receptor expression-enhancing agent comprising an extract of a plant of the genus Prunus (Evolvulus) of the Convolvulaceae family. The present invention has an excellent effect of improving CGRP receptor expression.

In a preferred form of the present invention, the plant belonging to the genus Prunus communis is P. serrata (Evolvulus alsinoides L.).

The CGRP receptor expression-enhancing agent of the present invention is preferably used for increasing the expression of IGF-1, vasodilating and/or promoting collagen production.
Further, the CGRP receptor expression-enhancing agent of the present invention is preferably used for suppressing photoaging.

In a preferred embodiment of the present invention, the CGRP receptor expression-enhancing agent of the present invention is used in combination with a method for improving CGRP secretion. By using such a form, the response reaction of CGRP can be made stronger.

As a method for improving the secretion of CGRP, a group consisting of a step of applying cold stimulation to the skin, a step of applying thermal stimulation to the skin, a brushing step, a step of squeezing the skin, and a step of applying a composition having an action of enhancing CGRP secretion A method including one or more steps selected from is preferable.

The present invention also relates to a composition for improving CGRP receptor expression, which comprises the above-mentioned CGRP receptor expression improving agent as an active ingredient. The composition of the present invention has an excellent effect of improving CGRP receptor expression.

The composition for improving CGRP receptor expression of the present invention is preferably in the form of an external composition or an oral composition.
In addition, when the composition for improving CGRP receptor expression of the present invention is used as an oral composition, it is preferably in the form of a food composition.

A preferred embodiment of the present invention comprises a component having a CGRP secretion enhancing action.
The composition in such a form can synergistically elicit the response action of CGRP.

The present invention also relates to a cosmetic method, characterized in that the extract of Evolvulus of the Convolvulaceae family is applied to a living body in combination with a method of enhancing secretion of CGRP. The cosmetic method of the present invention is excellent in the action of inducing a CGRP response reaction.

As a method for improving the secretion of CGRP, a group consisting of a step of applying cold stimulation to the skin, a step of applying thermal stimulation to the skin, a brushing step, a step of squeezing the skin, and a step of applying a composition having an action of enhancing CGRP secretion A method including one or more steps selected from is preferable.

In the cosmetic method of the present invention, the extract is preferably applied to the living body in the form of a composition for external use or an oral composition.

The present invention has an excellent effect of improving the expression of CGRP receptors. In addition, the preferred embodiment of the present invention can more strongly induce a CGRP response reaction.

It is a bar graph showing the expression level of CGRP receptor mRNA in fibroblasts irradiated with UVA. It is a bar graph showing the expression level of CGRP receptor mRNA in fibroblasts to which the morning glory extract was added. It is a bar graph showing the expression level of IGF-1 mRNA in the morning glory extract and CGRP-added fibroblasts. It is a bar graph showing the expression level of the mRNA of the type I collagen in the fibroblasts to which the morning glory extract and CGRP were added. It is a bar graph showing the expression level of IGF-1 mRNA in the epidermal keratinocyte to which the morning glory extract and CGRP were added. It is a bar graph showing the cell number in the epidermal keratinocyte which added the morning glory extract and CGRP.

The CGRP receptor expression-enhancing agent of the present invention comprises an extract of a plant of the genus Prunus (Evolvulus) belonging to the Convolvulaceae family.
Examples of the morning glory plant (Evolvulus) include the morning glory (Evolvulus alsinoides L.), the white ragweed (Evolvulus boninensis), the Malva morning glory (Evolvulus rotundiulus), the Evolvulus gloveratus (Evolvulus gloveratus). ), Evolvulus pilosus, Evolvulus arbuscula ssp. Canus, Evolvulus nummularius, Evolvulus sericeceus (Evolvulus serosericeus) It is particularly preferred to use alsinoides L.).

The plant extract may be prepared as a plant grown or grown in Japan, a Japanese product sold as a raw material for herbal medicines, or a plant extract such as Maruzen Co., Ltd. It is also possible to purchase and use a commercially available extract sold by the company.

The plant part to be extracted is not particularly limited, but whole grass is preferable.
As the form of the extract, a solvent extract or a solvent-removed product thereof can be preferably exemplified. The extraction solvent is preferably a polar solvent. Examples of such polar solvents include water, ethanol, methanol, alcohols such as 1,3-butanediol and propylene glycol, esters such as ethyl acetate and methyl formate, ketones such as acetone and methyl ethyl ketone, and chloroform and Preferable examples include one or more selected from halogenated hydrocarbons such as methylene chloride, nitriles such as acetonitrile, and ethers such as diethyl ether and tetrahydrofuran.
Of these, more preferable are water and/or alcohols. A particularly preferred solvent is 50% ethanol.

In the extraction, it is preferable to add 1 to 10 times the amount of the solvent to the plant or its processed product, and soak it for several days at room temperature and for several hours at a temperature near the boiling point. After extraction with a solvent, insoluble matter can be removed by filtration or the like, and the solvent can be removed by concentration under reduced pressure or lyophilization as necessary.

The CGRP receptor expression-enhancing agent of the present invention can be made into a composition, particularly preferably an external composition or an oral composition, by appropriately mixing it with an optional component.
Suitable examples of the composition for external use include cosmetics, quasi drugs, pharmaceuticals, and the like, and may also contain optional components that are commonly used, as long as the effects of the present invention are not impaired. Such optional ingredients include, for example, macadamia nut oil, avocado oil, corn oil, olive oil, rapeseed oil, sesame oil, castor oil, safflower oil, cottonseed oil, jojoba oil, coconut oil, palm oil, liquid lanolin, hardened coconut oil. Oils, waxes such as hardened oil, mokuro, castor oil, beeswax, candelilla wax, carnauba wax, carrot wax, lanolin, reduced lanolin, hard lanolin, jojoba wax; liquid paraffin, squalane, pristane, ozokerite, paraffin, ceresin, vaseline Hydrocarbons such as microcrystalline wax; higher fatty acids such as oleic acid, isostearic acid, lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid and undecylenic acid; cetyl alcohol, stearyl alcohol, isostearyl alcohol, behenyl alcohol Higher alcohols such as octyldodecanol, myristyl alcohol and cetostearyl alcohol; cetyl isooctanoate, isopropyl myristate, hexyldecyl isostearate, diisopropyl adipate, di-2-ethylhexyl sebacate, cetyl lactate, diisostearyl malate. , Ethylene glycol di-2-ethylhexanoate, neopentyl glycol dicaprate, glycerin di-2-heptylundecanoate, glyceryl tri-2-ethylhexanoate, trimethylolpropane tri-2-ethylhexanoate, triisostearate tri Oil agents such as synthetic ester oils such as methylolpropane and pentane erythritol tetra-2-ethylhexanoate; anions such as fatty acid soap (sodium laurate, sodium palmitate, etc.), potassium lauryl sulfate, triethanolamine ether alkyl sulfate, etc. Surfactants; cationic surfactants such as stearyltrimethylammonium chloride, benzalkonium chloride, and laurylamine oxide; imidazoline-based amphoteric surfactants (2-cocoyl-2-imidazolinium hydroxide-1-carboxyethyloxy) Disodium salts, etc.), betaine-based surfactants (alkylbetaines, amidobetaines, sulfobetaines, etc.), amphoteric surfactants such as acylmethyltaurine; sorbitan fatty acid esters (sorbitan monostearate, sorbitan sesquioleate, etc.) , Glycerin fatty acids (glycerin monostearate, etc.), propylene glycol fatty acid esters (monostearin) Acid propylene glycol, etc.), hydrogenated castor oil derivative, glycerin alkyl ether, POE sorbitan fatty acid ester (POE sorbitan monooleate, polystyrene sorbitan monostearate etc.), POE sorbit fatty acid ester (POE-sorbit monolaurate etc.) ), POE glycerin fatty acid esters (POE-glycerin monoisostearate, etc.), POE fatty acid esters (polyethylene glycol monooleate, POE distearate, etc.), POE alkyl ethers (POE2-octyldodecyl ether, etc.), POE alkylphenyl ethers (POE nonyl phenyl ether, etc.), Pluronic type, POE/POP alkyl ethers (POE, POP2-decyl tetradecyl ether, etc.), Tetronics, POE castor oil, hydrogenated castor oil derivative (POE castor oil, POE hardened) Castor oil, etc.), sucrose fatty acid esters, nonionic surfactants such as alkyl glucosides; polyhydric alcohols such as polyethylene glycol, glycerin, erythritol, sorbitol, xylitol, maltitol, propylene glycol and 2,4-hexanediol. Moisturizing ingredients such as sodium pyrrolidonecarboxylate, lactic acid and sodium lactate; paraaminobenzoic acid type UV absorbers; anthranilic acid type UV absorbers; salicylic acid type UV absorbers; cinnamic acid type UV absorbers; benzophenone type UV absorbers; Sugar-based UV absorbers; 2-(2'-hydroxy-5'-t-octylphenyl)benzotriazole, 4-methoxy-4'-t-butyldibenzoylmethane and other UV absorbers; ethanol, isopropanol, etc. Preferable examples include antibacterial agents such as lower alcohols such as phenoxyethanol.

The concentration of the plant extract in the composition for external use is preferably 0.0001 to 1% by mass, more preferably 0.001 to 0.5% by mass, as solid content.

As the oral composition, for example, general foods such as confectionery and bread, noodles, drink preparations, food groups having the purpose of promoting health in the form of capsules and tablets (for example, foods for specified health uses), granules, Examples thereof include powders, capsules, orally administered drugs in the form of tablets.
When it is in the form of an oral composition, it can contain an acceptable optional component. Examples of such optional ingredients include foods, salt, sugar, sodium glutamate, sodium inosinate, seasoning ingredients such as vinegar, coloring ingredients, flavoring ingredients such as flavors, thickeners, emulsifying/dispersing agents, preservatives. , Stabilizers, various vitamins and the like can be preferably exemplified, and in the case of foods or pharmaceuticals having the purpose of promoting health, crystalline cellulose, excipients such as lactose, binders such as arabic gum and hydroxypropyl cellulose, cross carme. Preferable examples include disintegrating agents such as sodium sodium and starch, lubricants such as magnesium stearate, flavoring agents, flavoring agents, coloring agents, and various vitamins. The orally administered composition of the present invention can be produced by treating these in accordance with a conventional method.

The content of the plant extract in the oral composition can be preferably 0.01 to 100% by mass, more preferably 0.1 to 50% by mass, as solid content.
In addition, it is preferable that the extract of the plant as the solid content be in the form of 1 to 200 mg per day to be drunk once or several times.

It is preferable that the composition of the present invention is an embodiment that further contains a component having a CGRP secretion enhancing action. With such a form, the CGRP response reaction can be synergistically enhanced.
The component having a CGRP secretion enhancing action is not particularly limited as long as it is a component having an action of improving CGRP secretion when applied to a living body. Examples of the component having such an action include L-4-thiazolylalanine or its derivative, whey protein-derived IgG or its Fc fragment, and capsaicin.

The CGRP receptor expression-enhancing agent of the present invention is preferably used for vasodilation, increase in IGF-1 expression and/or promotion of collagen production. More specifically, improvement of skin repair, promotion of blood circulation in skin, improvement of skin metabolism, anti-wrinkle, anti-aging, anti-inflammatory, vascular hyperpermeability, regulation of nicotinic receptor at neuromuscular junction, gluconeogenesis Suppression of glucose and promotion of glycolysis, promotion of secretion of pancreatic enzymes, suppression of gastric acid secretion, promotion of heartbeat, regulation of nerve activity, regulation of calcium metabolism, promotion of bone formation, insulin secretion, increase in body temperature, reduction of food intake, skin ageing It can be used for suppressing a decrease in thickness, proliferation of neural stem cells, and the like.
Further, the CGRP receptor expression-enhancing agent of the present invention is useful for hypertension, heart failure, ischemic reperfusion-induced liver injury, renal failure, gastrointestinal ulcer, sepsis, osteoporosis, arrhythmia, subarachnoid hemorrhage, pulmonary hypertension, delayed hypersensitivity. It can also be used for the prevention and/or amelioration of diseases such as periodontal disease, toxemia of pregnancy, preterm labor, and congestive heart dysfunction.
Furthermore, the CGRP receptor expression-enhancing agent of the present invention can be used for suppressing photoaging, more specifically, aging due to ultraviolet rays.

The CGRP receptor expression-enhancing agent of the present invention is preferably used in combination with a method for improving CGRP secretion. The method for improving the secretion of CGRP includes a step of applying cold stimulation to the skin, a step of applying thermal stimulation to the skin, a brushing step, a step of squeezing the skin, and a step of applying a composition having an action of increasing CGRP secretion. The method can be preferably exemplified.
Hereinafter, a method of using the CGRP receptor expression-enhancing agent in such a form, that is, the cosmetic method of the present invention will be described.

The step of giving a cold or warm stimulus to the skin may be performed by applying a cooling agent, a heat insulating material or the like to the skin. When the plant extract is used in the form of a composition for external use, the composition for external use may be cooled or heated and then applied to the skin.

The aspect of the brushing step is not particularly limited, and it can be performed by a usual method using a comb or a brush. The portion to be brushed is not particularly limited, and the hair portion of the head can be preferably exemplified. When the plant extract is used in the form of a composition for external use, it is preferable to adopt an embodiment in which the composition for external use is applied to the hair portion and then brushing is performed.

The mode of carrying out the step of squeezing the skin is not particularly limited, but it is preferable to squeeze the skin with a finger. When the plant extract is used in the form of a composition for external use, it is preferable to adopt an embodiment in which the composition for external use is applied to the skin together with a massage technique that includes a skin squeezing operation.

The composition having a CGRP secretion-enhancing effect is not particularly limited as long as it contains an active ingredient having an effect of improving the secretion of CGRP when applied to a living body. Examples of the component having such an action include L-4-thiazolylalanine or its derivative, whey protein-derived IgG or its Fc fragment, and capsaicin.
The composition having a CGRP secretion-enhancing action may be applied to the living body in any form, and is preferably applied to the living body in the form of an external composition or an oral composition.

In the cosmetic method of the present invention, an embodiment in which a mixed composition of the above-mentioned active ingredient having an action of improving the secretion of CGRP and the extract of the plant is applied to a living body may be used.

In the cosmetic method of the present invention, the plant extract may be applied to the living body in any form, and is preferably applied to the living body in the form of an external composition or an oral composition.

In the present invention, "cosmetic method" does not include medical treatment.

<Preparation of plant extract>
100 g of dried whole grass of Datura esculenta (Evolvulus alsinoides L.) was extracted with 1 L of 50% ethanol at room temperature for 10 days, concentrated under reduced pressure, and lyophilized. It was dissolved in a concentration and used as a test sample.

<Test Example 1>
Fibroblasts were seeded on a 3.5 cm dish at 1.0×10 ⁵ cells/dish. After 24 hours, UVA was irradiated at the intensity shown in Table 1 and FIG. Eighteen hours after irradiation, mRNA was collected and the expression level of CGRP receptor mRNA was measured by RT-qPCR. The results are shown in Table 1 and FIG.

As shown in Table 1 and FIG. 1, the expression level of the CGRP receptor decreases in proportion to the UVA irradiation dose.

<Test Example 2>
Fibroblasts were seeded on a 24-well plate at 7.0×10 ⁴ cells/well. After 24 hours, the morning glory extract was added to the medium so that the final concentration was 0.04% (only the extraction solvent was added to the control). After 24 hours, mRNA was collected and the expression level of CGRP receptor mRNA was measured by the RT-qPCR method. The results are shown in Table 2 and FIG.

As shown in Table 2 and FIG. 2, the morning glory extract has an excellent effect of enhancing the expression of CGRP receptor. This result indicates that the extract of P. communis has an action of enhancing the response reaction of CGRP.

In addition, the results of Test Examples 1 and 2 suggest that the extract of Plutella xylostella can be applied for the purpose of suppressing the decrease in the expression level of the CGRP receptor caused by ultraviolet rays.

<Test Example 3>
Fibroblasts were seeded on a 24-well plate at 7.0×10 ⁴ cells/well. After 24 hours, CGRP and morning glory extract were added to the medium so that the final concentrations were 10 ⁻⁹ M and 0.04%, respectively, in the combinations shown in Table 3, FIGS. Only added). After 24 hours, mRNA was collected and the expression levels of IGF-1 and type I collagen (COL1A1) mRNA were measured by the RT-qPCR method. The results are shown in Table 3 and FIGS.

As shown in Table 3 and FIGS. 3 and 4, remarkable effects of improving IGF-1 expression and producing type I collagen were observed in the fibroblasts to which both the extract of Plutella xylostella and CGRP were added. This result indicates that the extract of P. mellifera exerts a remarkable IGF-1 expression improving effect and a type I collagen production improving effect on fibroblasts due to a synergistic effect with CGRP.

<Test Example 4>
The epidermal keratinocytes were seeded on a 24-well plate at 4.0×10 ⁴ cells/well. After 24 hours, CGRP and morning glory extract were added to the medium so that the final concentrations were 10 ⁻⁹ M and 0.04%, respectively, in the combinations shown in Table 4 and FIG. 5 (only the extraction solvent was used as a control). Added). After 48 hours, mRNA was collected and the expression level of IGF-1 mRNA was measured by the RT-qPCR method. The results are shown in Table 4 and FIG.

As shown in Table 4 and FIG. 5, in the epidermal keratinocytes to which both the extract of Plutella xylostella and CGRP were added, a remarkable effect of improving IGF-1 expression and an effect of producing type I collagen were observed. This result indicates that the extract of Plutella xylostella exerts a remarkable effect of improving IGF-1 expression and type I collagen production on epidermal keratinocytes due to a synergistic effect with CGRP.

<Test Example 5>
Epidermal keratinocytes were seeded on a 96-well plate at 5.5×10 ³ cells/well. After 24 hours, the combination of CGRP and morning glory extract was added to the medium so that the final concentrations were 10 ⁻⁹ M and 0.04%, respectively, in the combinations shown in Table 5 and FIG. 6 (only the extraction solvent was used as a control). Added). After 24 hours, the number of cells was measured by absorption measurement using a plate reader using tetrazolium salt WST-8 as a color-developing agent. The results are shown in Table 5 and FIG.

As shown in Table 5 and FIG. 6, a remarkable cell growth promoting effect was observed in the epidermal keratinocytes to which both the extract of Plutella xylostella and CGRP were added. This result indicates that the extract of Plutella xylostella exerts a remarkable cell growth promoting effect on epidermal keratinocytes by a synergistic effect with CGRP.

The present invention can be applied to cosmetics, pharmaceuticals, foods and beauty methods.

Claims (10)

Family Convolvulaceae (Convolvulaceae) Ri Do from A Sagaokarakusa genus (Evolvulus) extract of morning glory color grasses (Evolvulus alsinoides L.), skin repair, blood circulation of the skin, skin metabolism improving regulation of substance P in inflammation, vascular permeability , Regulation of nicotinic receptors at neuromuscular junction, suppression of gluconeogenesis and promotion of glycolysis, promotion of secretion of pancreatic enzymes, suppression of gastric acid secretion, promotion of heartbeat, regulation of nerve activity, regulation of calcium metabolism, promotion of bone formation, insulin Secretion, increase in body temperature, decrease in food intake, anti-inflammatory, decrease in skin thickness due to aging, promotion of proliferation of neural stem cells, increase in expression of IGF-1, or vasodilation,
Alternatively, hypertension, heart failure, liver injury due to ischemic reperfusion, renal failure, gastrointestinal ulcer, sepsis, osteoporosis, arrhythmia, subarachnoid hemorrhage, pulmonary hypertension, delayed hypersensitivity, periodontal disease, toxemia of pregnancy, preterm delivery Alternatively, a CGRP receptor expression enhancer used for prevention and/or amelioration of congestive heart dysfunction disease . It is characterized in that it is used in combination with one or more steps selected from the group consisting of a step of applying thermal stimulus to the skin, a step of squeezing the skin, and a step of applying a composition having a CGRP secretion enhancing action , A CGRP receptor expression-enhancing agent comprising an extract of Convolvulaceae, Convolvulaceae (Evolvulus), Convolvulacea (Evolvulus alsinoides L.) . See containing as an active ingredient a CGRP receptor expression enhancing agent according to claim 1 or 2, skin repair, blood circulation of the skin, skin metabolism improving regulation of substance P in inflammation, vascular permeability, neuromuscular junction Of nicotinic receptors, suppression of gluconeogenesis and promotion of glycolysis, promotion of secretion of pancreatic enzymes, suppression of gastric acid secretion, promotion of heartbeat, regulation of nerve activity, regulation of calcium metabolism, promotion of bone formation, insulin secretion, elevation of body temperature, Decreased food intake, anti-inflammation, reduced skin thickness due to aging, accelerated proliferation of neural stem cells, increased expression of IGF-1, or vasodilation,
Alternatively, hypertension, heart failure, liver injury due to ischemic reperfusion, renal failure, gastrointestinal ulcer, sepsis, osteoporosis, arrhythmia, subarachnoid hemorrhage, pulmonary hypertension, delayed hypersensitivity, periodontal disease, toxemia of pregnancy, preterm delivery Or a composition for improving the expression of CGRP receptor, which is used for preventing and/or ameliorating a disease of congestive heart dysfunction . Family Convolvulaceae (Convolvulaceae) A Sagaokarakusa genus (Evolvulus) morning glory color grasses (Evolvulus alsinoides L.) extract and CGRP secretion enhancing containing a component having an effect, C GRP receptor expression enhancing composition. The CGRP according to claim 4, wherein the component having a CGRP secretion-enhancing effect is at least one selected from L-4-thiazolylalanine or a derivative thereof, whey protein-derived IgG or an Fc fragment thereof, or capsaicin. A composition for improving receptor expression. The composition for improving CGRP receptor expression according to any one of claims 3 to 5, which is an external composition. The composition for improving CGRP receptor expression according to any one of claims 3 to 5, which is an oral composition. The composition for improving CGRP receptor expression according to claim 7 , which is a food composition. Step of providing a temperature stimulation to the skin, in combination with one or more steps selected from the group consisting of applying a composition having a step and CGRP secretion enhancing action pinch skin family Convolvulaceae (Convolvulaceae) A Sagaokarakusa A beauty method comprising applying an extract of a genus ( Evolvulus) morning glory (Evolvulus alsinoides L.) to a living body. The cosmetic method according to claim 9 , wherein the extract is applied to a living body in the form of a composition for external use or an oral composition.