Agent for enhancing cell viability, agent for enhancing cell homeostasis-maintaining function, β3-adrenergic receptor agonist, and glucose metabolism inhibitor

Abstract

To provide an agent for enhancing cell viability and an agent for enhancing cell homeostasis-maintaining function.SOLUTION: The present invention provides an agent for enhancing cell viability and an agent for enhancing cell homeostasis-maintaining function, each containing a red clover flower extract as an active ingredient.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to an agent for enhancing cell viability, an agent for enhancing homeostasis function, a β3-adrenergic receptor agonist, and a glucose metabolism inhibitor. More specifically, the present invention relates to an agent for enhancing cell viability and an agent for enhancing homeostasis function, a β3-adrenergic receptor agonist, and a glucose metabolism inhibitor, which contain an extract of Acaena virginica flower as an active ingredient.

Background Art

[0002] The extract of Acaena virginica flower is known to have anti-inflammatory, antioxidant, estrogen-like, ceramidase inhibitory, elastase inhibitory, hair treatment effects, and the like. Patent Document 1 discloses an antioxidant preparation containing at least two extracts selected from bilberry extract, Acaena virginica flower extract, etc., and vitamin E and / or C. Patent Document 2 reports a synergistic effect between an estrogen-like agent selected from extracts such as dulse extract and red clover extract, and chlorella extract, an active oxygen scavenger, and an anti-inflammatory agent, which are collagen production promoters. Patent Document 3 discloses a ceramidase activity inhibitor characterized by containing extracts derived from various plants such as Malvaceae, Rubiaceae, and Poaceae, including the legume family to which Acaena virginica belongs, as active ingredients. Patent Document 4 reports the elastase inhibitory effects of various plants such as mushrooms belonging to the genus Fuscospora and plants belonging to the genus Trifolium to which Acaena virginica belongs, including the genus Vitis and the genus Oenothera.

Prior Art Documents

Patent Documents

[0003]

Patent Document 1

Patent Document 2

Patent Document 3

Patent Document 4

[0004] [Non-Patent Document 1] Nucleic Acids Res. 2010 Jul;38(Web Server issue):W71-7. [Summary of the Invention] [Problems to be Solved by the Invention]

[0005] An object of the present invention is to provide a novel function of the extract of the flower of Geranium thunbergii. [Means for Solving the Problems]

[0006] As a result of intensive studies on the effects of the extract of the flower of Geranium thunbergii, the present inventors have found that the extract of the flower of Geranium thunbergii has particularly high effects as an enhancer of cell viability and an enhancer of homeostasis maintenance function in addition to the known effects as described above, and have completed the following invention: (1) An enhancer for enhancing cell viability, comprising an extract of the flower of Geranium thunbergii as an active ingredient, which enhances cell viability by promoting the production of adenosine, inosine, hypoxanthine, guanosine, uric acid, and trigonelline. (2) An enhancer for enhancing the homeostasis maintenance function of cells, comprising an extract of the flower of Geranium thunbergii as an active ingredient, which enhances the homeostasis maintenance function of cells by promoting the production of adenosine, inosine, hypoxanthine, guanosine, and GABA. (3) A β3-adrenergic receptor agonist comprising an extract of the flower of Geranium thunbergii as an active ingredient, which activates the β3-adrenergic receptor by promoting the production of inosine, hypoxanthine, uric acid, xanthine, guanosine, and adenosine. (4) A glucose metabolism inhibitor containing the extract of the flower of Geranium thunbergii as an active ingredient, which inhibits glucose metabolism by promoting the production of inosine, adenosine, and hypoxanthine and suppressing the production of spermine, ATP, and spermidine. (5) The enhancer according to any one of (1) to (4), wherein the cell is a skin cell. (6) An adenosine production promoter containing the extract of the flower of Geranium thunbergii as an active ingredient. (7) An inosine production promoter containing the extract of the flower of Geranium thunbergii as an active ingredient. (8) A hypoxanthine production promoter containing the extract of the flower of Geranium thunbergii as an active ingredient. (9) A guanosine production promoter containing the extract of the flower of Geranium thunbergii as an active ingredient. (10) A uric acid production promoter containing the extract of the flower of Geranium thunbergii as an active ingredient. (11) A GABA production promoter containing the extract of the flower of Geranium thunbergii as an active ingredient. (12) A trigonelline production promoter containing the extract of the flower of Geranium thunbergii as an active ingredient. (13) A xanthine production promoter containing the extract of the flower of Geranium thunbergii as an active ingredient. (14) A spermine production inhibitor containing the extract of the flower of Geranium thunbergii as an active ingredient. (14) An ATP production inhibitor containing the extract of the flower of Geranium thunbergii as an active ingredient. (15) A spermidine production inhibitor containing the extract of the flower of Geranium thunbergii as an active ingredient.

Advantages of the Invention

[0007] According to the present invention, the viability and homeostasis maintenance function of cells can be enhanced. Further, according to the present invention, the production of adenosine, inosine, hypoxanthine, guanosine, uric acid, trigonelline, xanthine, and GABA can be promoted, and the production of spermine, ATP, and spermidine can be suppressed.

Brief Description of the Drawings

[0008]

Figure 1

Figure 2

Figure 3

Figure 4

Modes for Carrying Out the Invention

[0009] The present invention provides an agent for enhancing cell viability, an agent for enhancing homeostasis maintenance function, a β3-adrenergic receptor agonist, and a glucose metabolism inhibitor. The viability of cells can be enhanced by promoting the production of adenosine, inosine, hypoxanthine, guanosine, uric acid, and trigonelline. The homeostasis maintenance function of cells can be enhanced by promoting the production of adenosine, inosine, hypoxanthine, guanosine, and GABA. The β3-adrenergic receptor can be activated by promoting the production of inosine, hypoxanthine, uric acid, xanthine, guanosine, and adenosine. Glucose metabolism can be inhibited by promoting the production of inosine, adenosine, and hypoxanthine and suppressing the production of spermine, ATP, and spermidine.

[0010] There are substances that can individually promote the production of adenosine, inosine, hypoxanthine, guanosine, uric acid, trigonelline, xanthine, or GABA, or individually suppress the production of spermine, ATP, or spermidine. However, it has been discovered for the first time by the present invention that the effect of enhancing cell viability and homeostasis maintenance function, activating the β3-adrenergic receptor, and suppressing glucose metabolism is present in the extract of Portulaca oleracea L. by simultaneously promoting or suppressing these substances.

[0011] Therefore, the present invention provides a cell viability enhancer containing an extract of Acanthopanax senticosus flowers as an active ingredient, which enhances the viability of cells by promoting the production of adenosine, inosine, hypoxanthine, guanosine, uric acid, and trigonelline; a cell homeostasis maintenance function enhancer containing an extract of Acanthopanax senticosus flowers as an active ingredient, which enhances the cell homeostasis maintenance function by promoting the production of adenosine, inosine, hypoxanthine, guanosine, and GABA; a β3-adrenergic receptor agonist containing an extract of Acanthopanax senticosus flowers as an active ingredient, which activates the β3-adrenergic receptor by promoting the production of inosine, hypoxanthine, uric acid, xanthine, guanosine, and adenosine; and a glucose metabolism inhibitor containing an extract of Acanthopanax senticosus flowers as an active ingredient, which inhibits glucose metabolism by promoting the production of inosine, adenosine, and hypoxanthine and suppressing the production of spermine, ATP, and spermidine.

[0012] Enhancement of cell viability means an increase in the ratio of healthy living cells within a cell population. In certain embodiments, enhancement of cell viability is also induced by β3 - adrenergic receptor agonists. Also, β3 - adrenergic receptor agonists are expected to increase lipolysis and thermogenesis. The effect as a β3 - adrenergic receptor agonist is exerted by CL - 316243. CL - 316243 refers to sodium 5 - [(2R)-2 - [[(2R)-2-(3 - chlorophenyl)-2 - hydroxyethyl]amino]propyl]-1,3 - benzodioxole - 2,2 - dicarboxylate (CAS number 138908 - 40 - 4). Enhancement of the cell's homeostatic function means an enhancement of the processes involved in maintaining internal homeostasis at the cellular level. In certain embodiments, the cell's homeostatic function is also induced by glucose metabolism inhibitors. Also, in addition to maintaining cell homeostasis, glucose metabolism inhibitors are expected to enhance the effect of anti - cancer drugs and reduce psoriatic lesions. The effect as a glucose metabolism inhibitor is exerted by 2 - deoxyglucose. Enhancement of cell viability by promoting the production of such substances as adenosine, inosine, hypoxanthine, guanosine, uric acid, and trigonelline, enhancement of the cell's homeostatic function by promoting the production of adenosine, inosine, hypoxanthine, guanosine, and GABA, activation of the β3 - adrenergic receptor by promoting the production of inosine, hypoxanthine, uric acid, xanthine, guanosine, and adenosine, promotion of the production of inosine, adenosine, and hypoxanthine, and inhibition of glucose metabolism by suppressing the production of spermine, ATP, and spermidine can be determined, for example, by metabolome analysis and enrichment analysis using cells such as skin cells like keratinocytes or fibroblasts.

[0013] The cells may be skin cells such as keratinocytes or fibroblasts. By enhancing the viability and / or homeostatic function of such skin cells, effects such as improvement of rough skin, skin smoothness, brightness, blood flow, dullness, acne marks, and skin texture can be expected.

[0014] Promotion of the production of adenosine, inosine, hypoxanthine, guanosine, uric acid, trigonelline, xanthine, or GABA means that, for example, when the agent of the present invention is administered, the production amount of adenosine, inosine, hypoxanthine, guanosine, uric acid, trigonelline, xanthine, or GABA is increased with a statistically significant difference (e.g., T-test, etc.) with a significance level of 5% compared to the state (control) where the agent of the present invention is not administered, or, for example, increased by 10% or more, 20% or more, 30% or more, 40% or more, 50% or more, 60% or more, 70% or more, 80% or more, 90% or more, 100% or more, 200% or more, 300% or more, 400% or more, or 500% or more. The production amount of adenosine, inosine, hypoxanthine, guanosine, uric acid, trigonelline, xanthine, or GABA can be determined by, for example, metabolome analysis as described in Patent Document 5 and the examples to obtain the amount of these metabolites in vivo, or can also be determined by any known technique such as measuring the amount of adenosine, inosine, hypoxanthine, guanosine, uric acid, trigonelline, xanthine, or GABA.

[0015] Inhibition of the production of spermine, ATP, and spermidine means that, for example, when the agent of the present invention is administered, the production amount of spermine, ATP, and spermidine is increased with a statistically significant difference (e.g., T-test, etc.) with a significance level of 5% compared to the state (control) where the agent of the present invention is not administered, or, for example, decreased by 10% or more, 20% or more, 30% or more, 40% or more, 50% or more, 60% or more, 70% or more, 80% or more, 90% or more, 100%. The production amount of adenosine, inosine, hypoxanthine, guanosine, uric acid, trigonelline, or GABA can be determined by, for example, metabolome analysis as described in Patent Document 5 and the examples to obtain the amount of these metabolites in vivo, or can also be determined by any known technique such as measuring the amount of spermine, ATP, and spermidine.

[0016] Therefore, the present invention provides a composition containing an Acmella oleracea flower extract as an active ingredient, which enhances the viability of cells by promoting the production of adenosine, inosine, hypoxanthine, guanosine, uric acid, and trigonelline; a composition containing an Acmella oleracea flower extract as an active ingredient, which enhances the homeostasis maintenance function of cells by promoting the production of adenosine, inosine, hypoxanthine, guanosine, and GABA; a composition containing an Acmella oleracea flower extract as an active ingredient, which activates the β3 - adrenergic receptor by promoting the production of inosine, hypoxanthine, uric acid, xanthine, guanosine, and adenosine; and a composition containing an Acmella oleracea flower extract as an active ingredient, which suppresses glucose metabolism by promoting the production of inosine, adenosine, and hypoxanthine and suppressing the production of spermine, ATP, and spermidine.

[0017] Furthermore, the present invention provides a composition containing an Acmella oleracea flower extract as an active ingredient, which improves rough skin, skin smoothness, brightness, blood flow, dullness, acne marks, and skin touch through enhancing the viability and / or homeostasis maintenance function of cells.

[0018] The improvement effects on rough skin, skin smoothness, brightness, blood flow, dullness, acne marks, and skin touch can be determined, for example, by subjective, objective, or evaluation using a specific device as in the examples, or by any other known technique.

[0019] Moreover, according to the present invention, since it is possible to simultaneously promote the production of adenosine, inosine, hypoxanthine, guanosine, uric acid, trigonelline, and GABA at a preferable ratio, it becomes possible to enhance the viability and / or homeostasis maintenance function of cells, and thus, it leads to the improvement of rough skin, skin smoothness, brightness, blood flow, dullness, acne marks, and skin touch, and a complex effect can be expected.

[0020] Red clover flower extract is an extract obtained by extracting the flowers of red clover (scientific name: Trifolium pratense). As described above, red clover flower extract is known to have anti-inflammatory, antioxidant, estrogen-like, ceramidase inhibitory, elastase inhibitory, hair treatment, and other effects (Patent Documents 1 to 4). The present inventors have discovered that Red Clover Flower Extract enhances cell viability by promoting the production of adenosine, inosine, hypoxanthine, guanosine, uric acid, and trigonelline; enhances cell homeostasis by promoting the production of adenosine, inosine, hypoxanthine, guanosine, and GABA; induces activation of β3 adrenergic receptors similar to the effect of CL-316243 by promoting the production of inosine, hypoxanthine, uric acid, xanthine, guanosine, and adenosine; and inhibits glucose metabolism similar to the effect of 2-deoxyglucose by promoting the production of inosine, adenosine, and hypoxanthine and inhibiting the production of spermine, ATP, and spermidine.

[0021] The method for extracting red clover flower extract can be carried out, for example, by solvent extraction. In the case of solvent extraction, red clover flowers are dried as necessary, and further chopped or crushed as necessary, and then extracted with an aqueous extractant, water, for example, cold water, warm water, or hot water at or below the boiling point, or a water-containing organic solvent, for example, water-containing ethanol, water-containing methanol, water-containing ether, water-containing 1,3-butylene glycol, etc., or an organic solvent, for example, ethanol, methanol, ether, 1,3-butylene glycol, etc., selected appropriately according to the properties of the raw material and the use of the composition, at room temperature or with heating. However, the extraction method is not limited to solvent extraction, and may be a conventional method known in the art, and the extraction method and form of the extract used in the present invention are arbitrary as long as they do not impair the effects of the present invention. The form of the extract may be not only the extract itself, but also a product appropriately diluted or concentrated by a conventional method, and may further be a powder or lump solid obtained by drying the extract, or a squeezed juice appropriately diluted or concentrated by a conventional method.

[0022] As examples of the organic solvent, lower alcohols (e.g., C1 to C4) such as ethanol, methanol, isopropanol, propylene glycol, and 1,3-butylene glycol may be used. As examples of the water-containing organic solvent, hydrates of the above lower alcohols may be used, and the water content in that case may be, for example, 0 to 10 v / v%, 10 to 40 v / v%, 20 to 30 v / v%, 30 to 40 v / v%, 30 to 50 v / v%, 60 to 70 v / v%, 50 to 80 v / v%, 80 to 99.5 v / v%, etc.

[0023] The cell viability enhancer, homeostasis maintenance function enhancer, β3-adrenergic receptor agonist, and glucose metabolism inhibitor of the present invention (hereinafter sometimes collectively referred to as "the agent of the present invention") may be formulated in a composition such as a cosmetic and applied to the skin, formulated in a composition such as a pharmaceutical or quasi-drug and topically administered to animals such as humans, formulated in a composition such as various foods, foodstuffs, nutritional supplements such as supplements, and orally administered to animals such as humans, or administered as a pharmaceutical preparation to animals such as humans. As the form of skin application or topical administration, for example, creams, emulsions, liquids, sheets, sprays, gels, etc. can be arbitrarily selected. As the form of oral administration, for example, tablets, beverages, powders, etc. can be arbitrarily selected. However, the administration form is not limited to the above.

[0024] The cosmetic composition of the present invention may be various cosmetics such as emulsions, creams, beauty essences, lotions, packs, facial washes, soaps, body soaps, shampoos, microneedles, and fine needle-like structures, and can be in various forms such as liquid, emulsion, cream, solid, sheet, spray, gel, foam, powder, and fine needle-like. Further, the food composition of the present invention may be a powder, beverage, or tablet, and can be in various forms such as powder, liquid, solid, granular, pellet, paste, and gel.

[0025] The frequency of administration can be arbitrarily selected, such as once every four weeks, once every two weeks, once a week, once every three days, once every two days, once a day, twice a day, three times a day, four times a day, five times a day, or administration each time, etc., but is not limited thereto.

[0026] The agent or composition of the present invention contains kudzu flower extract, or a plant of the genus Astragalus in the legume family that is similar in properties thereto, or a composition known to be contained in kudzu flower extract, for example, formononetin or biochanin A, in an amount sufficient to fully exhibit the effect of promoting the production of adenosine, inosine, hypoxanthine, guanosine, uric acid, trigonelline, xanthine, GABA, the effect of suppressing the production of spermine, ATP, and spermidine, the effect as a β3 - adrenergic receptor agonist, and the effect as a glucose metabolism inhibitor, or the effect of suppressing skin pigmentation, suppressing papules, suppressing pustules, promoting blood flow, improving rough skin, suppressing sebum secretion, or promoting wound healing. It can be appropriately determined according to their types, purposes, forms, usage methods, etc. For example, in one embodiment, the agent of the present invention contains kudzu flower extract as an active ingredient, for example, 10% by weight or more, 20% by weight or more, 30% by weight or more, 40% by weight or more, 50% by weight or more, 60% by weight or more, 70% by weight or more, 80% by weight or more, 90% by weight or more, 95% by weight or more, or 99% by weight or more. In one embodiment, the agent of the present invention may consist of kudzu flower extract. For example, in one embodiment, the blending amount (dry weight) of kudzu flower extract per total weight of the composition of the present invention can be 0.0001 - 0.0005% by weight, 0.0005 - 0.001% by weight, 0.001 - 0.005% by weight, 0.005 - 0.01% by weight, 0.01 - 0.05% by weight, 0.01 - 5.0% by weight, 0.05 - 0.1% by weight, 0.05 - 1.0% by weight, 0.1 - 0.5% by weight, 0.1 - 1.0% by weight, 0.5 - 5.0% by weight, 1.0 - 5.0% by weight, 5.0 - 10.0% by weight, 10.0 - 50.0% by weight, 50.0 - 100.0% by weight.

[0027] The agent or composition of the present invention can arbitrarily select and use additives as needed. Excipients and the like can be included as additives.

[0028] As excipients, any excipients can be used as long as they are commonly used when the desired dosage form is obtained. For example, starches such as wheat starch, rice starch, corn starch, potato starch, dextrin, cyclodextrin, crystalline celluloses, lactose, glucose, sucrose, reduced maltose, malt syrup, fructooligosaccharide, emulsified oligosaccharide and other saccharides, sugar alcohols such as sorbitol, erythritol, xylitol, lactitol, mannitol and the like can be mentioned. These excipients can be used alone or in combination of two or more.

[0029] As other additives, known ones such as colorants, preservatives, thickeners, binders, disintegrants, dispersants, stabilizers, gelling agents, antioxidants, surfactants, preservatives, pH adjusters, oils, water, alcohols, chelating agents, silicones, ultraviolet absorbers, humectants, fragrances, various medicinal components, antiseptics, neutralizing agents and the like can be appropriately selected and used.

[0030] In addition, the present invention provides a method for obtaining a β3 - adrenergic receptor agonist and / or a glucose metabolism inhibitor using the extract of the flower of Acanthopanax senticosus. An increase in lipolysis and thermogenesis is expected due to the effect of the β3 - adrenergic receptor agonist. In addition to maintaining cell homeostasis, the glucose metabolism inhibitor is expected to enhance the effect of anticancer drugs and reduce psoriatic lesions. In some embodiments of such an invention, a method for enhancing cell viability and / or enhancing the homeostasis - maintaining function through the effect as a β3 - adrenergic receptor agonist and / or the effect as a glucose metabolism inhibitor obtained by applying the extract of the flower of Acanthopanax senticosus, a method for activating the β3 - adrenergic receptor by promoting adenosine, inosine, hypoxanthine, guanosine, uric acid, and xanthine, a method for promoting the production of adenosine, inosine, and hypoxanthine, and a method for suppressing glucose metabolism by suppressing the production of spermine, spermidine, and ATP are also provided. The method of the present invention is a method for cosmetic purposes and may exclude medical acts by doctors and medical staff.

[0031] Furthermore, the present invention also provides the use of the extract of the flower of *Acalypha hispida* Burm. f. in the production of a β3-adrenergic receptor agonist and / or a glucose metabolism inhibitor. The present invention also provides an extract of the flower of *Acalypha hispida* Burm. f. for activating a β3-adrenergic receptor and / or inhibiting glucose metabolism, wherein preferably, by promoting the production of adenosine, inosine, hypoxanthine, guanosine, uric acid, and xanthine in skin cells such as keratinocytes, it has an effect as a β3-adrenergic receptor agonist similar to CL-316243, and / or by promoting the production of adenosine, inosine, and hypoxanthine and inhibiting the production of spermine, spermidine, and ATP, it has an effect as a glucose metabolism inhibitor similar to 2-deoxyglucose.

[0032] In addition, the present invention also provides a method for improving rough skin, skin smoothness, brightness, blood flow, dullness, acne marks, and skin texture by applying an extract of the flower of *Acalypha hispida* Burm. f. In some embodiments of such an invention, a method for improving rough skin, skin smoothness, brightness, blood flow, dullness, acne marks, and skin texture by applying an extract of the flower of *Acalypha hispida* Burm. f. through enhancing cell viability and / or enhancing the homeostasis maintenance function, a method for enhancing cell viability by promoting the production of adenosine, inosine, hypoxanthine, guanosine, uric acid, and trigonelline by applying an extract of the flower of *Acalypha hispida* Burm. f., and a method for enhancing the homeostasis maintenance function of cells by promoting the production of adenosine, inosine, hypoxanthine, guanosine, and GABA by applying an extract of the flower of *Acalypha hispida* Burm. f. are also provided. The method of the present invention is a method for cosmetic purposes and may exclude medical acts by doctors or medical practitioners.

[0033] Furthermore, the present invention also provides the use of the extract of Acacia farnesiana flower in the manufacture of a medicament for improving rough skin, skin smoothness, brightness, blood flow, dullness, acne marks, and skin touch. The present invention also provides an extract of Acacia farnesiana flower for use in improving rough skin, skin smoothness, brightness, blood flow, dullness, acne marks, and skin touch, wherein preferably, the viability of cells is enhanced by promoting the production of adenosine, inosine, hypoxanthine, guanosine, uric acid, and trigonelline in skin cells such as keratinocytes, and / or the function of maintaining cell homeostasis is enhanced by promoting the production of adenosine, inosine, hypoxanthine, guanosine, and GABA, thereby improving rough skin, skin smoothness, brightness, blood flow, dullness, acne marks, and skin touch.

Example

[0034] Next, the present invention will be described in more detail by way of examples. It should be noted that the present invention is not limited thereto.

[0035] Example 1: Promotion of the production of adenosine, inosine, hypoxanthine, guanosine, uric acid, trigonelline, xanthine, and GABA by the extract of Acacia farnesiana flower, and inhibitory effects on spermine, spermidine, and ATP 1. Preparation of samples As the sample, the extract of Acacia farnesiana flower used was the extract of Acacia farnesiana flower (product name Stem Clover RF) manufactured by Technoble Co., Ltd.

[0036] 2. Culture of normal human epidermal keratinocytes Normal human neonatal male epidermal keratinocytes were pre-cultured for 24 hours in a medium for human epithelial cells (CELLnTEC) and then cultured for 4 hours at an oxygen pressure of 3%. After the culture, the medium was replaced with a medium containing 0.38% by weight of the extract of Acacia farnesiana flower per medium. As a control, the culture was carried out under the same conditions in a medium having the same composition except that the extract of Acacia farnesiana flower was not added.

[0037] 3. Metabolome pretreatment Metabolome pretreatment was performed according to the method described in Patent Document 5. More specifically, after culturing the above epidermal keratinocytes, the medium was removed, and mannitol washing was performed twice. A methanol solution was added thereto and stirred. Milli-Q water containing 1 μM of the internal standard substance was added thereto and stirred, followed by centrifugation (2,300×g, 4°C, 5 minutes). After centrifugation, the extract was transferred to an ultrafiltration tube (Ultrafree MC PLHCC, HMT, centrifugal filter unit 5 kDa). This was centrifuged (9,100×g, 4°C, 120 minutes) and subjected to ultrafiltration treatment. The filtrate was dried and dissolved again in Milli-Q water for measurement. 1.26×10 6 cells per sample were used, and measurements were carried out with N = 5.

[0038] 4. Detection of metabolites Detection of metabolites was performed according to the method described in Patent Document 5. More specifically, cationic metabolites and anionic metabolites were comprehensively detected by a CE-MS system combining capillary electrophoresis (Agilent CE system) and a mass spectrometer (MS). Peaks with a signal / noise (S / N) ratio of 3 or more were automatically extracted from the detected peaks using automatic integration software to obtain the mass-to-charge ratio (m / z), peak area value, and migration time (MT). Based on the values of m / z and MT, collation and search were performed with all substances registered in the HMT metabolite library to identify the amount of metabolites, and the relative area value was calculated using the following calculation formula.

[0039]

Equation

[0040] The results are shown in Table 1. Table 1 shows the relative values of the amounts of each metabolite in the cells to which the extract of Oxalis latifolia flower was added, with the case of the control being set to 1. From Table 1, it was confirmed that the extract of Oxalis latifolia flower has a significantly higher promoting effect on the production of adenosine, inosine, hypoxanthine, guanosine, uric acid, trigonelline, xanthine, and GABA, and also has an inhibitory effect on the production of spermine, ATP, and spermidine, compared with the control.

[0041]

Table 1

[0042] 5. Functional identification and identification of regulatory factors by enrichment analysis Using Ingenuity Pathway Analysis (IPA) software (Qiagen), the metabolite set in which the list of fluctuating metabolite groups was enriched was statistically analyzed according to the method described in Non-Patent Document 1. Using the functional group database of metabolites and the upstream regulatory factor database incorporated in the software as the population, the functional groups enriched in 32 metabolites found to increase by the addition of the extract of Oxalis latifolia flower were tested by Fisher's exact test. At the same time, the direction (enhancement / suppression) of the change in the found functional groups was evaluated by Z-test. For example, adenosine, inosine, hypoxanthine, guanosine, uric acid, and trigonelline are metabolites that significantly increase in an Oxalis latifolia flower extract-dependent manner and are related to cell viability. By calculating the p-value using Fisher's exact probability test for the contingency table of the number of metabolites related to cell viability included in the IPA database, the number of metabolites not related to cell viability, the number of metabolites that significantly increase in an Oxalis latifolia flower extract-dependent manner and are related to cell viability, and the number of metabolites that significantly increase in an Oxalis latifolia flower extract-dependent manner and are not related to cell viability, a significant enhancement of cell viability was found.

[0043] The results are shown in FIGS. 1 and 2. The table above FIG. 1 shows the results of function identification by enrichment analysis in keratinocytes supplemented with the extract of A. paniculata flower, and the figure below shows schematically the enhancement of cell viability by the promotion of adenosine, inosine, hypoxanthine, guanosine, uric acid, and trigonelline, and the enhancement of cell homeostasis maintenance by the promotion of the production of adenosine, inosine, hypoxanthine, guanosine, and GABA. From the enrichment analysis, it was confirmed that the extract of A. paniculata flower has an effect of enhancing cell viability by promoting the production of adenosine, inosine, hypoxanthine, guanosine, uric acid, and trigonelline, and an effect of enhancing the cell homeostasis maintenance function by promoting the production of adenosine, inosine, hypoxanthine, guanosine, and GABA.

[0044] The table above FIG. 2 shows the results of identification of upstream regulatory factors by enrichment analysis in keratinocytes supplemented with the extract of A. paniculata flower, and the figure below shows schematically the promotion of adenosine, inosine, hypoxanthine, guanosine, uric acid, and xanthine by CL-316243 which is a β3-adrenergic receptor agonist, the promotion of the production of adenosine, inosine, and hypoxanthine by 2-deoxyglucose which is a glucose metabolism inhibitor, and the inhibitory effect on the production of spermine, spermidine, and ATP. From the enrichment analysis, it was confirmed that the extract of A. paniculata flower has an effect as a β3-adrenergic receptor agonist similar to CL-316243 by promoting the production of adenosine, inosine, hypoxanthine, guanosine, uric acid, and xanthine, and an effect as a glucose metabolism inhibitor similar to 2-deoxyglucose by promoting the production of adenosine, inosine, and hypoxanthine and the inhibitory effect on the production of spermine, spermidine, and ATP.

[0045] Example 2: Various effects of the extract of A. paniculata flower on the skin 1. Improvement of rough skin An oil-in-water cream containing 0.38% by weight of the extract of the flower of *Anemone vitifolia* Buch.-Ham. was applied to 36 healthy human subjects aged 40 to 60. It was used daily for 6 weeks, and the roughness of the skin on the cheeks after 2, 4, and 6 weeks of continuous use was evaluated by professional evaluators using a roughness score on a 10-point scale from "very smooth" to "very rough" as described in Table 2 below, and a significance test was performed by Wilcoxon's signed-rank test.

Table 2

[0046] The results are shown in Figure 3. As shown in Figure 3, by using the cosmetic containing the extract of the flower of *Anemone vitifolia* Buch.-Ham., improvement in skin roughness was observed at 2, 4, and 6 weeks after use.

[0047] 2. Improvement in skin smoothness, brightness, blood flow, dullness, and acne marks An oil-in-water cream containing 0.38% by weight of the extract of the flower of *Anemone vitifolia* Buch.-Ham. was applied to 126 healthy subjects aged 40 to 70, and used daily for 42 days. The subjects were asked to evaluate the improvement effects on skin smoothness, brightness, blood flow, dullness, and acne marks as "yes" or "no" according to the criteria described in Figure 3, and compared with before the start of the test.

[0048] The results are shown in Figure 4. As shown in Figure 4, it became clear that by using the cosmetic containing the extract of the flower of *Anemone vitifolia* Buch.-Ham., improvement in skin smoothness, brightness, blood flow, dullness, and acne marks was felt.

[0049] By administering an agent or composition containing an extract of the flower of Oxalis latifolia as an active ingredient, various effects such as improvement of rough skin, skin smoothness, brightness, blood flow, dullness, acne marks, and skin texture can be expected. Such effects are considered to be due to enhancement of cell viability by promoting the production of adenosine, inosine, hypoxanthine, guanosine, uric acid, and trigonelline, and / or enhancement of the cell homeostasis maintenance function by promoting the production of adenosine, inosine, hypoxanthine, guanosine, and GABA. Enhancement of cell viability is also induced by activation of the β3-adrenergic receptor, and the cell homeostasis maintenance function can also be induced by suppression of glucose metabolism. Furthermore, by administering an agent or composition containing an extract of the flower of Oxalis latifolia as an active ingredient, an action as a β3-adrenergic receptor agonist and an action as a glucose metabolism inhibitor can be expected. The action as a β3-adrenergic receptor agonist is expected to exhibit an action similar to CL-316243 by promoting the production of inosine, hypoxanthine, uric acid, xanthine, guanosine, and adenosine. The action as a glucose metabolism inhibitor is expected to exhibit an action similar to 2-deoxyglucose by promoting the production of inosine, adenosine, and hypoxanthine and suppressing the production of spermine, ATP, and spermidine.

Claims

1. A cell viability enhancer containing an extract of Aka-tsume-kesa flower as an active ingredient, which enhances cell viability by promoting the production of adenosine, inosine, hypoxanthine, guanosine, uric acid, and trigonelline.

2. A cell homeostasis maintenance function enhancer containing an extract of Aka-tsume-kesa flower as an active ingredient, which enhances the cell homeostasis maintenance function by promoting the production of adenosine, inosine, hypoxanthine, guanosine, and GABA.

3. The enhancer according to Claim 1 or 2, wherein the cell is a skin cell.

4. An adenosine production promoter containing an extract of Aka-tsume-kesa flower as an active ingredient.

5. An inosine production promoter containing an extract of Aka-tsume-kesa flower as an active ingredient.

6. A hypoxanthine production promoter containing an extract of Aka-tsume-kesa flower as an active ingredient.

7. A guanosine production promoter containing an extract of Aka-tsume-kesa flower as an active ingredient.

8. A uric acid production promoter containing an extract of Aka-tsume-kesa flower as an active ingredient.

9. A GABA production promoter containing an extract of Aka-tsume-kesa flower as an active ingredient.

10. A trigonelline production promoter containing an extract of Aka-tsume-kesa flower as an active ingredient.

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