Oxytocin signaling enhancer and oxytocin-induced keratinocyte proliferation promoter

Abstract

Provided are a new oxytocin signal enhancer and a new oxytocin-induced keratinocyte proliferation-promoting agent.　The present invention provides an oxytocin signal enhancer and an oxytocin-induced keratinocyte proliferation-promoting agent, which contain a shell ginger leaf extract and / or a ginger extract as an active ingredient.

Description

[Technical Field]

[0001] The present invention provides an oxytocin signal enhancer and an oxytocin-induced keratinocyte proliferation promoter. [Background Art]

[0002] Oxytocin is a peptide hormone also called the "love hormone" and "happiness hormone", and acts as a neurohormone, neurotransmitter or neuromodulator. It is known to have effects such as anxiolysis, stress relief, bond formation, feeding suppression, and analgesia. Oxytocin receptors have been confirmed to be expressed in various tissues throughout the body, including the central nervous system, uterus, mammary glands, skin, adipose tissue, kidneys, heart, thymus, and pancreas, and play physiological roles in various parts of the body.

[0003] Focusing on the skin, it has been reported that oxytocin is also present in the skin (Non-Patent Document 1, Patent Document 1). Regarding the direct action of oxytocin on the skin, it has been reported that it has an improving effect on wrinkles and skin softness (Patent Document 2), that it increases the production of components that enhance elasticity by acting on fibroblasts (Patent Document 3), and regarding indirect action, that an increase in the amount of oxytocin in the living body improves skin texture (Patent Document 4). From these findings, it can be inferred that enhancing the action of oxytocin in the skin brings about skin improvement.

[0004] Various means for increasing the amount of oxytocin in the skin have been explored. For example, Patent Document 2 discloses an oxytocin production promoter containing rose oil, ethyl trimethylcyclopentenyl butenol, methyl trimethylcyclopentenyl pentanol, and hexahydrohexamethylcyclopentabenzopyran. Patent Document 1 discloses that stimulation such as massage increases the amount of skin oxytocin. Patent Document 3 discloses that cinnamon bark extract increases the number of oxytocin receptors in fibroblasts. However, none of these documents provide a means for amplifying the response of oxytocin. [Prior Art Documents] [Patent Documents]

[0005] [Patent Document 1] Japanese Patent Publication No. 2010-117232 [Patent Document 2] Japanese Patent Publication No. 2011-98898 [Patent Document 3] Japanese Patent Publication No. 2020-200240 [Patent Document 4] Japanese Patent Publication No. 2019-105619 [Patent Document 5] Patent No. 4658290 [Patent Document 6] Patent No. 5822423 [Non-patent literature]

[0006] [Non-Patent Document 1] Exp Dermatol 2012 Jul;21(7):535-7 [Overview of the project] [Problems that the invention aims to solve]

[0007] The object of the present invention is to provide an oxytocin signaling enhancer and an oxytocin-induced keratinocyte proliferation promoter. [Means for solving the problem]

[0008] As a result of diligent research, the inventors have discovered that Alpinia zerumbet leaf extract and / or Zingiber officinale extract have a high oxytocin signaling-enhancing effect and an oxytocin-induced keratinocyte proliferation-promoting effect, and have completed the following invention: (1) An oxytocin signaling enhancer containing Alpinia zerumbet leaf extract and / or ginger extract as active ingredients. (2) An oxytocin-induced keratinocyte proliferation promoter containing Alpinia zerumbet leaf extract and / or ginger extract as active ingredients. (3) An oxytocin-induced keratinocyte proliferation promoter as described in (2), which promotes keratinocyte proliferation through oxytocin signaling enhancement. [Effects of the Invention]

[0009] According to the present invention, it is possible to provide a drug containing an oxytocin signaling enhancer and / or an oxytocin-induced keratinocyte proliferation promoter. If the proliferation of oxytocin-induced keratinocytes can be promoted by enhancing the oxytocin signaling pathway, it is expected that conditions and diseases in various tissues, including the skin, can be prevented and improved. [Brief explanation of the drawing]

[0010] [Figure 1] Figure 1 shows the change in fluorescence intensity ratio when ginger lily leaf extract was added in Experiment 3. The change in the fluorescence intensity ratio represents the change in intracellular calcium ion concentration. The horizontal axis represents time (seconds), and the vertical axis represents the fluorescence intensity ratio (f340 nm / f380 nm). The first dose of oxytocin alone was added for 2 minutes (1st OT applied for 2 minutes), and ginger lily leaf extract was added after the reaction caused by the 1st OT had finished. Two minutes after the addition of the extract, the second dose of oxytocin was added for 2 minutes (2nd OT applied for 2 minutes). [Figure 2] Figure 2 is a graph showing the change in fluorescence intensity ratio when ginger lily leaf extract was added in Experiment 3. The change in fluorescence intensity ratio (f340 nm / f380 nm) when oxytocin was added alone for the first time is set to 100% (change due to 1st OT), and the relative value of the change in fluorescence intensity ratio (f340 nm / f380 nm) when oxytocin was added for 2 minutes after the addition of ginger lily leaf extract for the second time is shown (change due to 2nd OT + ginger lily leaf extract). [Figure 3]Figure 3 is a graph showing the change in fluorescence intensity ratio when ginger extract was added in Experiment 3. The change in fluorescence intensity ratio (f340 nm / f380 nm) when oxytocin was added alone for the first time is set to 100% (change due to 1st OT), and the relative value of the change in fluorescence intensity ratio (f340 nm / f380 nm) when oxytocin was added for 2 minutes after the addition of ginger extract for the second time is shown (change due to 2nd OT + ginger extract). [Figure 4] Figure 4 is a graph showing the change in fluorescence intensity ratio when ginger lily leaf extract and ginger extract were added in Experiment 3. The change in fluorescence intensity ratio (f340 nm / f380 nm) when oxytocin was added alone for the first time is set to 100% (change due to 1st OT), and the relative value of the change in fluorescence intensity ratio (f340 nm / f380 nm) when oxytocin was added for 2 minutes after the addition of ginger lily leaf extract and ginger extract for the second time is shown (change due to 2nd OT + ginger lily leaf extract + ginger extract). [Figure 5] Figure 5 is a graph showing the change in fluorescence intensity ratio when no candidate sample is added in Experiment 3. The change in fluorescence intensity ratio (f340 nm / f380 nm) when oxytocin is added alone for the first time is set to 100% (change due to 1st OT), and the relative value of the change in fluorescence intensity ratio (f340 nm / f380 nm) when oxytocin is added for 2 minutes without the candidate sample is shown (change due to 2nd OT). [Figure 6] Figure 6 shows the absorbance (A450nm) detected by anti-BrdU antibody in keratinocyte cell proliferation in Experiment 4, under the conditions of no oxytocin addition (OT-free) and 10-10M oxytocin addition (OT10-10M addition), with or without Alpinia zerumbet leaf extract (extract addition) and with a concentration of 0.015% by weight of Alpinia zerumbet leaf extract (extract addition). White bars indicate the presence of oxytocin addition (OT(+)), and gray bars indicate the absence of oxytocin addition (OT(-)). The vertical axis shows the absorbance value for each case. The horizontal axis shows the presence or absence of extract addition. (Scheffé multiple comparison test, *; P<0.05, **; P<0.01). MODE FOR CARRYING OUT THE INVENTION

[0011] The present inventors discovered that Alpinia zerumbet leaf extract and / or ginger extract has an excellent oxytocin signal enhancing effect and an oxytocin-induced keratinocyte proliferation promoting effect. Based on these findings, the present invention provides an oxytocin signal enhancer and an oxytocin-induced keratinocyte proliferation promoter containing Alpinia zerumbet leaf extract and / or ginger extract as an active ingredient. In one aspect, the oxytocin-induced keratinocyte proliferation promoting effect is exerted via oxytocin signal enhancement.

[0012] Oxytocin (CAS No.: 50-56-6) is a peptide hormone consisting of 9 amino acids (Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Leu-Gly), and is one of the posterior pituitary hormones.

[0013] Oxytocin signal enhancement refers to the enhancement of the oxytocin response, and can be investigated by measuring changes in fluorescence intensity over time using intracellular calcium ion measurement reagents (such as fura-2, fluo-3, fluo-4, fluo-8, etc.) (https: / / www.dojindo.co.jp / technical / beginner / calcium1.pdf). It can also be determined by measuring changes in intracellular calcium ion concentration using a microscope capable of measuring fluorescence intensity or high-throughput calcium imaging. For example, as described in the examples, if the oxytocin-induced intracellular calcium ion concentration increases when an oxytocin signal enhancement agent is applied compared to the state in which only oxytocin is applied (control), it can be determined that there is an oxytocin signal enhancement effect. An increase in calcium ion concentration may mean that, when the candidate drug is added, the concentration is enhanced by a statistically significant difference at a significance level of 5% (e.g., Student's t-test), or that it is enhanced by, for example, 5% or more, 10% or more, 20% or more, 30% or more, 40% or more, 50% or more, 60% or less, 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. Calcium ion influx may also be measured by any known technique, for example, other methods such as intracellular calcium imaging, but not limited to these.

[0014] Such oxytocin signaling enhancement can be measured by various methods, including in vivo, in vitro, and ex vivo. For example, the oxytocin signaling enhancement effect can be determined by administering the test substance to skin cells such as keratinocytes or fibroblasts, central nervous system cells, uterine cells, mammary gland cells, adipocytes, etc., and measuring the change in intracellular calcium ion concentration in those cells. Alternatively, in vivo or ex vivo methods may be employed, such as measuring the change in intracellular calcium ion concentration in tissue / model samples such as skin, central nervous system, uterus, mammary gland, or fat after administration to mammals. However, the measurement method is not limited to the above methods, and any other method may be used.

[0015] Oxytocin-induced promotion of keratinocyte proliferation refers to the promotion of keratinocyte proliferation by oxytocin. In one aspect, the oxytocin-induced keratinocyte proliferation promoting effect is exerted via enhancement of oxytocin signaling. Keratinocyte proliferation can be detected using, for example, proliferation markers such as BrdU, Ki67, MCM2, and PCNA, or tetrazolium salts (such as MTT) that develop color utilizing the reduction reaction of living cells. The signal intensity emitted from an antibody against any of these proliferation markers, such as a fluorescently labeled anti-BrdU antibody, may be measured. For example, keratinocyte proliferation means that the signal intensity emitted from an antibody against a proliferation marker is increased when an oxytocin signal enhancer is applied, compared to a state where nothing is applied to cultured epidermal cells or a state where only oxytocin is applied (control), for example, that it is enhanced with a statistically significant difference at a significance level of 5% (e.g., Scheffe's multiple comparison test), or alternatively that it is enhanced by 5% or more, 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. Similarly, the keratinocyte proliferation effect can be arbitrarily selected from any method, such as an in vitro method using keratinocytes, an ex vivo method using a skin model or skin tissue, or an in vivo method.

[0016] The shell ginger leaf extract used in the present invention is an extract obtained from the leaves of shell ginger. Shell ginger (Alpinia zerumbet) is a plant of the genus Alpinia in the Zingiberaceae family, distributed from tropical to subtropical Asia, and growing wild in Okinawa Prefecture and Kagoshima Prefecture in Japan. Commercially available products of shell ginger leaf extract that are used as cosmetic raw materials or health food materials can also be used. Shell ginger leaf extract is known to have a fibroblast proliferation promoting effect (Patent Document 5), a collagen production promoting effect (Patent Document 6), and the like.

[0017] The ginger extract used in this invention is an extract obtained from the rhizome of ginger. Ginger (Zingiber Officinale Roscoe) is a plant of the Zingiberaceae family, native to tropical Asia and distributed worldwide. Commercially available ginger extract can also be used as a cosmetic or health food ingredient. Ginger extract is known to have antipyretic, analgesic, and antitumor effects.

[0018] These extracts can be easily dried, purified, and extracted from the above-mentioned plants by known methods, and are readily available commercially. They can be used in their fresh or dried state, and can also be used as extracts, dried products, dried powders, raw material powders, juices, etc. The form used can be selected as appropriate, and sterilization or other treatments may be applied as needed.

[0019] The extraction method for the above extract can be carried out, for example, by solvent extraction. In the case of solvent extraction, the whole or part of the plant is dried as necessary, and then, as necessary, it is chopped or pulverized, and then extracted using an aqueous extractant, water, such as cold water, warm water, or hot water at or below its boiling point, or anhydrous or aqueous organic solvent, organic solvent, such as ethanol, methanol, ether, 1,3-butylene glycol, propylene glycol, etc., with the preferred solvent appropriately selected according to the properties of the raw material and the intended use of the composition, at room temperature or by heating. However, the extraction method is not limited to solvent extraction and may also be carried out by commonly known methods in the industry, 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 above extract may be the extract itself, or it may be diluted or concentrated as appropriate by commonly used methods, and it may also be a powder or a solid obtained by drying the extract.

[0020] 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. However, the extraction solvent used in the present invention is preferably a polar solvent such as water, lower alcohols, and liquid polyhydric alcohols, and is particularly preferably water, or a lower alcohol such as methanol, ethanol, or 1,3-butylene glycol. The lower alcohol may be, for example, a hydrated lower alcohol, in which case the water content may be, for example, 0-10 v / v%, 10-40 v / v%, 20-30 v / v%, 30-50 v / v%, 50-80 v / v%, 80-99.5 v / v%, etc. The lower alcohol may be, for example, a C1-C5 lower alcohol. These solvents may be used individually or as a mixture of two or more.

[0021] The oxytocin signaling enhancer and / or oxytocin-induced keratinocyte proliferation promoter of the present invention (hereinafter collectively referred to as the "agent of the present invention") may be in any form, such as a transdermal or oral preparation, but a transdermal preparation is preferred from the viewpoint of enhancing oxytocin signaling in the skin. The agent of the present invention can be administered via various routes of administration, such as transderm and oral, and it is preferable to apply Alpinia zerumbet leaf extract and / or Zingiber officinale extract in an amount that allows the effects of the present invention to be fully exhibited. The amount of each can be appropriately determined depending on their type, purpose, form, and method of use.

[0022] Furthermore, this application also provides compositions comprising the agent of the present invention. The compositions of the present invention may be cosmetic compositions or food compositions. The compositions of the present invention may, for example, be compositions for enhancing oxytocin signaling and / or promoting the proliferation of oxytocin-induced keratinocytes, or for improving skin conditions through such action.

[0023] Furthermore, this application also provides a cosmetic method for enhancing oxytocin signaling and / or promoting the proliferation of oxytocin-induced keratinocytes, or for improving skin condition through such action, by administering the agent or composition of the present invention to a target. The method of the present invention is for cosmetic purposes and may not be a treatment performed by a physician or medical professional.

[0024] The agent or composition of the present invention can be administered by any route, such as topical or oral administration. Topical administration can take the form of, for example, a cream, lotion, liquid, sheet, spray, or gel. Oral administration can take the form of, for example, a tablet, supplement, beverage, or powder.

[0025] The cosmetic composition of the present invention may be various cosmetics such as emulsions, creams, serums, lotions, packs, facial cleansers, soaps, body washes, and shampoos, and may be in various forms such as liquid, emulsion, cream, solid, sheet, spray, gel, foam, and powder. The food composition of the present invention may be a powder, beverage, or tablet, and may be in various forms such as powder, liquid, solid, granular, granular, paste, and gel.

[0026] Furthermore, the frequency of administration can be arbitrarily selected, but is not limited to, once every four weeks, once every two weeks, 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 administered as needed.

[0027] The amount of Alpinia zerumbet leaf extract and / or Zingiber officinale extract in the agent or composition of the present invention can be appropriately determined according to their type, purpose, form, and method of use. For example, the amount of Alpinia zerumbet leaf extract and / or Zingiber officinale extract can be 0.0001 to 100% by weight, 0.0001 to 90% by weight, 0.001 to 50% by weight, 0.01 to 5% by weight, 0.01 to 1% by weight, 0.01 to 0.5% by weight, 0.05 to 0.2% by weight, 0.1 to 0.15% by weight, 0.15% by weight, 0.1% by weight, etc., per the total weight of the agent or composition of the present invention, but is not limited as long as the effects of the present invention are achieved.

[0028] The agents and compositions of the present invention can be manufactured by conventional methods in formulations that are appropriately combined with excipients, carriers and / or diluents and other components, depending on the dosage form. Additives can be arbitrarily selected and used as needed. As additives, known ones such as excipients, colorants, preservatives, thickeners, binders, disintegrants, dispersants, stabilizers, gelling agents, antioxidants, surfactants, preservatives, and pH adjusters can be appropriately selected and used. [Examples]

[0029] The present invention will now be described in more detail with reference to examples. However, the present invention is not limited thereto.

[0030] Examples: The following experiments 1-3 were conducted. Experiment 1: Sample Selection As candidate samples, 300 types of samples were selected from the cosmetic material library, including naturally derived and synthetic ingredients such as 1,3-butylene glycol dilution of Alpinia zerumbet leaf (product name: Alpinia zerumbet leaf extract BG) purchased from Maruzen Pharmaceutical, ethanol dilution of Ginger (product name: Ginger extract E) purchased from Ichimaru Falcos, and other plant extracts. The samples were prepared to a concentration of 20% by weight using DMSO and diluted to the following concentrations using extracellular fluid during the experiment. Extracellular fluid with a similar concentration of DMSO was used as a control.

[0031] Experiment 2: Cell Culture Normal human epidermal keratinocytes purchased from Kurabo were used. Serum-free basal medium (Epilife (Thermo Fisher Scientific) or Humedia KG2 (Kurabo)) was mixed with additive factors (hydrocortisone 0.67 mg / mL, bovine pituitary extract 0.4%, insulin 10 mg / mL, EGF 0.1 μg / mL) (e.g., HumediaGG growth factor set (Kurabo)), and these cells were cultured according to the operating procedure.

[0032] Experiment 3: Screening of oxytocin signaling enhancers using calcium imaging. Oxytocin signaling enhancers were screened by measuring the intracellular calcium ion concentration of epidermal keratinocytes cultured using the method described above. After attaching the cells to a glass chamber surface-treated with collagen, the calcium-sensitive fluorescent dye Fura-2AM (Sigma-aldrich, etc.) was dissolved in an extracellular solution (an aqueous solution prepared by dissolving 150 mM NaCl, 5 mM KCl, 21.8 mM CaCl, 21.2 mM MgCl, 10 mM D-glucose, and 25 mM HEPES in ultrapure water and adjusting the pH to 7.4 with NaOH), and added to the cells at a concentration of 5 μM in the well. After addition, incubation was performed at room temperature for 60 minutes to allow for uptake of the fluorescent dye into the cells. After uptake was complete, the fluorescent dye that had nonspecifically bound to the cells was washed with the extracellular solution, and fresh extracellular solution was added and left to stand for 15 minutes. After standing, the chamber was placed on the stage of a phase-contrast microscope (Olympus Corporation), and cells were alternately irradiated with near-ultraviolet excitation light at 340 nm and 380 nm using an ORCA-ER (Hamamatsu Photonics Corporation). The fluorescence intensity was measured by measuring and calculating the fluorescence ratio (510 nm) of the amount of light emitted from a single cell according to each excitation wavelength using HCImage analysis software. Each stored raw material sample was set to 100% concentration, and a 20% solution was prepared using DMSO (stored at -40°C). The test solution was prepared by dissolving it with extracellular fluid to a final concentration of 0.1%. Extracellular fluid containing the same amount of DMSO was used as a control. Oxytocin (CAS number: 50-56-6) was purchased from the Peptide Institute, dissolved in ultrapure water, and then diluted to a concentration of 1 μM using extracellular fluid.

[0033] Extracellular fluid was perfused into the cell seeding chamber using a peristaltic pump before the start of the measurement. After confirming that the baseline was stable, a solution adjusted to an oxytocin concentration of 1 μM was applied to the cells for 2 minutes (first oxytocin response: 1 stOT). Approximately 300 seconds after the start of measurement, a small increase in the fluorescence intensity ratio (f340 / f380) due to oxytocin was observed. Once the reaction subsided (approximately 500 seconds after the start of measurement), the candidate sample was applied using a peristaltic pump to a concentration of 0.1% by weight (if multiple samples were added, each was added at 0.1% by weight). Two minutes after the start of application of the candidate sample (approximately 700 seconds after the start of measurement), oxytocin was again applied under reflux for 2 minutes to a concentration of 1 μM (second oxytocin reaction: 2 nd OT).

[0034] Figure 1 shows the reaction when ginger lily leaf extract was added. For the results obtained using the calcium imaging method described above, the change in fluorescence intensity f340 / f380 ratio obtained from the first addition of oxytocin alone was set to 100%, and the responses obtained from the second addition of oxytocin after or without each candidate sample were converted to percentages and are shown in Figures 2-5. Data are expressed as mean ± standard deviation (N=33-152). Addition of oxytocin alone increased intracellular calcium ion concentration, and adding ginger lily leaf extract followed by oxytocin further increased the intracellular calcium ion concentration (Figures 1 and 2). Similarly, adding ginger extract (Figure 3), and adding both ginger extract and ginger lily leaf extract, also resulted in a significant increase in intracellular calcium ion concentration (Figure 4). Compared to the fluorescence intensity ratio (indicating the increase or decrease in intracellular calcium ion concentration) with the addition of oxytocin alone, the addition of Alpinia zerumbet leaf extract increased it by 275% (Figure 2), the addition of Ginger extract increased it by 183% (Figure 3), and the addition of both Alpinia zerumbet leaf extract and Ginger extract increased it by 388% (Figure 4). On the other hand, Figure 5 shows the results when oxytocin alone was applied twice at the same time points (approximately 300 seconds and approximately 700 seconds after the start of measurement) as when the candidate sample was added without the addition of any candidate drug. There was almost no change in the reaction with oxytocin in the second application compared to the reaction with oxytocin in the first application.

[0035] These results suggest that Alpinia zerumbet leaf extract and Zingiber officinale extract have the effect of enhancing oxytocin-mediated signaling.

[0036] Experiment 4: Oxytocin-induced keratinocyte proliferation-promoting effect of Alpinia zerumbet leaf extract Next, to confirm that Alpinia zerumbet leaf extract, which was judged to have an oxytocin signaling-enhancing effect in Experiment 3, promotes keratinocyte proliferation via oxytocin signaling enhancement, keratinocyte proliferation was measured when stimulated with Alpinia zerumbet leaf extract in the presence or absence of oxytocin.

[0037] Normal human epidermal keratinocytes (Kurabo) were subcultured in cell culture dishes at 37°C under 5% CO2 conditions using Epilife medium (Thermo Fisher Scientific) as described in Experiment 2.

[0038] The above cultured epidermal keratinocytes were cultured for 24 hours in a collagen-coated 96-well microplate in basal medium without growth factors, and then 10 -10 Cell proliferation was measured by adding or not adding oxytocin (CAS number: 50-56-6) at concentration M, and then adding or not adding the Alpinia zerumbet leaf extract prepared in Experiment 1 at a concentration of 0.15% by weight, and culturing for a further 72 to 96 hours. Subsequently, cell proliferation was measured by detecting fluorescence from the fluorescently labeled anti-BrdU antibody using a microplate reader (ARVO, PerkinElmer, 2030 Multilabel reader ARVO® X3) and measuring the absorbance (A450nm) using a Cell Proliferation ELISA BrdU kit (Roche, Cell Proliferation ELISA, BrdU (colorimetric, No. 11 647 229 001)).

[0039] The results are shown in Figure 6. Figure 6 is a graph showing the absorbance (A450nm) when ginger lily leaf extract was added with and without oxytocin in Experiment 4. When oxytocin alone was added, keratinocyte proliferation was significantly promoted compared to when oxytocin was not added (Figure 6 left). On the other hand, when only ginger lily leaf extract was added, no significant increase in keratinocyte proliferation was observed compared to when oxytocin was not added (Figure 6 right, gray bar). However, when ginger lily leaf extract was added in addition to oxytocin, keratinocyte proliferation increased even more significantly compared to when oxytocin was added alone (Figure 6 right, white bar).

[0040] The results above suggest that Alpinia zerumbet leaf extract has the effect of promoting oxytocin-induced keratinocyte proliferation. Furthermore, the results of experiments 2 and 3 suggest that ginger extract also has a similar oxytocin-induced keratinocyte proliferation-promoting effect as Alpinia zerumbet leaf extract.

Claims

1. An oxytocin signaling enhancer containing Alpinia zerumbet leaf extract and / or ginger extract as active ingredients.

2. An oxytocin-induced keratinocyte proliferation promoter derived from Alpinia zerumbet leaf extract.

3. An oxytocin-induced keratinocyte proliferation promoter containing ginger extract as an active ingredient.

4. An oxytocin-induced keratinocyte proliferation promoter containing Alpinia zerumbet leaf extract and Zingiber officinale extract as active ingredients.

5. An oxytocin-induced keratinocyte proliferation promoter according to any one of claims 2 to 4, which promotes keratinocyte proliferation through oxytocin signaling enhancement.

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