Moisturizing agent, skin barrier function improving agent, anti-inflammatory agent, hyaluronic acid increasing agent, and melanin production inhibitor

Abstract

Provided are a moisturizer, a skin barrier function improving agent, an anti-inflammatory agent, a hyaluronic acid increasing agent, and a melanin production inhibitor. Provided are a moisturizer, a skin barrier function improving agent, an anti-inflammatory agent, a hyaluronic acid increasing agent, and a melanin production inhibitor, each of which contains cis-3-hexenol as an active ingredient.

Description

Technical Field

[0001] This invention relates to moisturizers, skin barrier function improvers, anti-inflammatory agents, hyaluronic acid enhancers, and melanin production inhibitors containing cis-3-hexenol as an active ingredient. Background Technology

[0002] cis-3-hexenol is an aroma component found in green tea, and its aroma is known to provide fatigue relief (Patent Document 1). However, this effect is achieved through inhalation of the aroma, which differs from the effect of applying cis-3-hexenol directly to the skin. Patent Document 2 describes cis-3-hexenol as having the effect of inhibiting melanin production in melanoma cells.

[0003] Existing technical documents

[0004] Patent documents

[0005] Patent Document 1: International Publication No. 2005 / 000286

[0006] Patent Document 2: Japanese Patent Application Publication No. 2022-174825 Summary of the Invention

[0007] The problem that the invention aims to solve

[0008] The inventors aim to obtain moisturizers, skin barrier function improvers, anti-inflammatory agents, hyaluronic acid enhancers, and melanin production inhibitors.

[0009] Methods for solving problems

[0010] The inventors discovered that by directly applying cis-3-hexenol to the skin, it can exert beneficial effects on the skin, such as moisturizing, improving skin barrier function, anti-inflammation, increasing hyaluronic acid, and inhibiting melanin production, thus completing this invention.

[0011] Therefore, this invention relates to the following:

[0012] [1] A moisturizer containing cis-3-hexenol as an active ingredient.

[0013] [2] A skin barrier function improver containing cis-3-hexenol as an active ingredient.

[0014] [3] An anti-inflammatory agent containing cis-3-hexenol as the active ingredient.

[0015] [4] A hyaluronic acid enhancer containing cis-3-hexenol as an active ingredient.

[0016] [5] A melanin production inhibitor containing cis-3-hexenol as the active ingredient.

[0017] [6] An FLG gene expression promoter containing cis-3-hexenol as the active ingredient.

[0018] [7] A GBA gene expression promoter containing cis-3-hexenol as the active ingredient.

[0019] [8] A COX2 gene expression inhibitor containing cis-3-hexenol as the active ingredient.

[0020] [9] A HAS2 gene expression promoter containing cis-3-hexenol as the active ingredient.

[0021]

[10] A MIF gene expression inhibitor containing cis-3-hexenol as the active ingredient.

[0022] The effects of the invention

[0023] By directly applying cis-3-hexenol, one can expect skin moisturizing, barrier function improvement, anti-inflammatory effects, increased hyaluronic acid, and inhibition of melanin production. Detailed Implementation

[0024] Cis-3-hexenol (CAS No.: 928-96-1) is an unsaturated alcohol known as leaf alcohol along with its isomer trans-2-hexenol, and is an aroma component found in green tea and other teas.

[0025] As described in Patent Document 1 above, the aroma of cis-3-hexenol produces an anti-fatigue effect, but this effect is achieved through inhalation of the aroma. In fact, the examples demonstrate the effect of subjects inhaling cis-3-hexenol. Patent Document 2 describes that cis-3-hexenol inhibits melanin production in melanoma cells. The inventors have discovered that by directly applying cis-3-hexenol to the skin, it exerts beneficial effects on the skin, such as moisturizing, improving skin barrier function, anti-inflammation, increasing hyaluronic acid, and inhibiting melanin production.

[0026] Therefore, the present invention provides moisturizers, skin barrier function improvers, anti-inflammatory agents, hyaluronic acid increasers, and melanin production inhibitors containing cis-3-hexenol as an active ingredient (hereinafter, sometimes referred to together as agents of the present invention).

[0027] Moisturizing, improving skin barrier function, anti-inflammatory effects, increasing hyaluronic acid, and inhibiting melanin production can be confirmed, for example, by measuring the increase in gene expression levels and / or protein production of FLG, GBA, HAS2, etc., and the decrease in gene expression levels and / or protein production of COX2, MIF, etc., in biological samples such as keratinocytes and skin fibroblasts. As for the measurement of gene expression levels, methods known in the art, such as quantitative PCR and RNA blotting, can be used. Probes targeting mRNA of FLG, GBA, COX2, HAS2, and / or MIF, for example, can be used. Regarding the amount of protein, methods known in the art, such as Western blotting, immunostaining, ICM, and ELISA, can be used. However, in addition to the methods described above, moisturizing, improving skin barrier function, anti-inflammatory effects, increasing hyaluronic acid, and inhibiting melanin production can also be confirmed, for example, by visual inspection, TEWL, measurement of the amount of keratinized capsule, measurement of specific proteins and / or lipids, measurement of hyaluronic acid levels in skin samples such as skin models and / or skin cells such as fibroblasts using ELISA, etc.

[0028] Furthermore, the present invention also provides FLG gene expression promoters, GBA gene expression promoters, COX2 gene expression inhibitors, HAS2 gene expression promoters, and MIF gene expression inhibitors containing cis-3-hexenol as an active ingredient. In one embodiment, the FLG gene expression promoter promotes FLG gene expression in epidermal keratinocytes. In one embodiment, the GBA gene expression promoter promotes GBA gene expression in epidermal keratinocytes. In one embodiment, the COX2 gene expression inhibitor inhibits COX2 gene expression in epidermal keratinocytes. In one embodiment, the HAS2 gene expression promoter promotes HAS2 gene expression in skin fibroblasts. In one embodiment, the MIF gene expression inhibitor inhibits MIF gene expression in skin keratinocytes.

[0029] FLG (Filaggrin) is the gene encoding filaggrin, a protein involved in skin hydration as a non-fibroin moisturizer (NMF). GBA (β-Glucocerebrosidase) is the gene encoding an enzyme that produces ceramide EOP (ceramide 1), which is related to skin barrier function. COX2 (Prostaglandin-Endoperoxide Synthase 2) is the gene encoding an enzyme that produces PGE2, an inflammatory mediator involved in melanin production. HAS2 (Hyaluronan Synthase 2) is the gene encoding an enzyme that synthesizes hyaluronic acid, produced by dermal cells and involved in skin hydration. MIF (Macrophage Migration Inhibitory Factor) is the gene encoding an enzyme that inhibits macrophage migration and enhances melanin production by blocking the breakdown of tyrosinase proteins.

[0030] As described above, gene expression can be measured using methods known in the art, such as quantitative PCR and RNA blotting. In one embodiment, promoting gene expression refers to an increase with a statistically significant difference (e.g., Student's t-test, Dunnett's test) at a significance level of 5%, and / or an increase of, for example, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, or more. Inhibiting gene expression refers, for example, a decrease with a statistically significant difference (e.g., Student's t-test, Dunnett's test) at a significance level of 5%, and / or a decrease of, for example, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100%.

[0031] As described above, protein expression can be measured using methods known in the art, such as Western blotting, immunostaining, ICM, and ELISA. In one embodiment, promoting protein expression refers to an increase with a statistically significant difference (e.g., Student's t-test, Dunnett's test) at a significance level of 5%, and / or an increase of, for example, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100%, or more. Inhibiting protein expression refers, for example, a decrease with a statistically significant difference (e.g., Student's t-test, Dunnett's test) at a significance level of 5%, and / or a decrease of, for example, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100%.

[0032] As a measure of hyaluronic acid, it can be performed using methods known in the art, such as sandwich ELISA. In one embodiment, an increase in hyaluronic acid refers to an increase with a statistically significant difference at a significance level of 5% (e.g., Student's t-test, Dunnett's test), and / or an increase of, for example, 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, or more.

[0033] Biological samples can be samples whose effects on moisturizing, improving skin barrier function, anti-inflammation, increasing hyaluronic acid, and inhibiting melanin production can be measured, or cell cultures whose gene expression levels of, for example, FLG, GBA, COX2, HAS2, and / or MIF, the amount of protein produced corresponding to these genes, and / or the amount of hyaluronic acid produced can be measured. Keratinocytes or fibroblasts, for example, can be used. Alternatively, skin samples can be used, or 3D constructed cultured skin models can be used. Cells can be derived from any animal, but from the viewpoint of cosmetics and pharmaceutical development, human-derived cells are preferred.

[0034] The present invention also provides methods for moisturizing, improving skin barrier function, anti-inflammatory, increasing hyaluronic acid and inhibiting melanin production in subjects, comprising the application of cis-3-hexenol or the agents of the present invention or compositions comprising the like.

[0035] Examples of objects to which the method of the present invention can be applied include, for example, those who have dry skin and need or wish to moisturize, those whose skin barrier function is reduced or wish to improve, those who have inflammation that needs to be suppressed or wish to prevent, those who have insufficient hyaluronic acid or wish to prevent it, or those whose gene expression and / or protein production of FLG, GBA and / or HAS2 is reduced or whose gene expression and / or protein production of COX2 and / or MIF is increased.

[0036] The methods involved in this application are for cosmetic purposes, and sometimes exclude medical procedures performed by doctors or medical practitioners. Furthermore, the methods involved in this application can be methods for supporting cosmetic procedures for the recipient.

[0037] Furthermore, the present invention also provides compositions comprising cis-3-hexenol or the agents of the present invention for moisturizing, improving skin barrier function, anti-inflammation, increasing hyaluronic acid, and inhibiting melanin production. The compositions of the present invention can be compositions for moisturizing, improving skin barrier function, anti-inflammation, increasing hyaluronic acid, and inhibiting melanin production. The compositions can be cosmetics, pharmaceuticals, or quasi-pharmaceuticals.

[0038] The application can be carried out via any route, including percutaneous, oral, mucosal, nasal, intravenous, intra-arterial, and subcutaneous. However, from the viewpoint of acting on the skin, percutaneous application is preferred. The skin can be used on any location, such as the face, head, neck, limbs, or trunk.

[0039] In the case of cosmetics, it can be mixed with facial or body cosmetics such as toners, lotions, serums, creams, cleansers, masks, essences, and gels; makeup cosmetics such as foundations, makeup bases, and concealers; and bath products. In the case of transdermal pharmaceuticals, it can be formulated into topical skin preparations. There are no particular limitations on the form as long as it can be applied to the skin; it can be in any dosage form, such as solution, emulsion, solid, semi-solid, powder, powder dispersion, water-oil two-layer separation, water-oil-powder three-layer separation, ointment, gel, aerosol, mousse, stick, etc. Furthermore, bases and excipients commonly used in cosmetics and topical skin preparations, such as preservatives, emulsifiers, and pH adjusters, can be used.

[0040] The amount of the active ingredient in the agent or composition of the present invention can be arbitrarily selected from the viewpoint of maximizing the effects of moisturizing, improving skin barrier function, anti-inflammation, and / or enhancing the effects of hyaluronic acid. For example, cis-3-hexenol can be mixed at concentrations of 0.0005 to 100.0 mM. From the viewpoint of maximizing the effect, it is preferable to mix at concentrations of 0.05 mM or higher, for example, 0.5 mM or higher. On the other hand, since cis-3-hexenol has an aromaticity, it is preferable to mix at concentrations of 10.0 mM or lower, and more preferably 5.0 mM or lower, from the viewpoint of avoiding an overly strong odor. The above-mentioned ingredients can be combined in any ratio, in which case it is preferable that the total amount of these ingredients is within the above-mentioned range.

[0041] Furthermore, the present invention also provides cis-3-hexenol for moisturizing, improving skin barrier function, anti-inflammation, and / or increasing hyaluronic acid, wherein, preferably, moisturizing, improving skin barrier function, anti-inflammation, and / or increasing hyaluronic acid is achieved through promoting the gene expression of FLG, GBA, and HAS2 and / or inhibiting the gene expression of COX2. In one embodiment, moisturizing is epidermal moisturizing. In one embodiment of such an embodiment, epidermal moisturizing is achieved by promoting the gene expression or protein production of FLG, GBA, and / or HAS2 in keratinocytes. In one embodiment, improving skin barrier function is achieved by improving the skin barrier function of the epidermis. In one embodiment of such an embodiment, improving the skin barrier function of the epidermis is achieved by promoting the gene expression or protein production of GBA in keratinocytes. In one embodiment, anti-inflammation is epidermal anti-inflammatory. In one embodiment of such an embodiment, epidermal anti-inflammatory is achieved by inhibiting the gene expression or protein production of COX2 in keratinocytes. In one embodiment, increasing hyaluronic acid is achieved by increasing dermal hyaluronic acid. In one embodiment of such a scheme, increasing dermal hyaluronic acid exerts its effect by promoting gene expression or protein production of HAS2 in skin fibroblasts. In another embodiment, inhibiting melanin production is achieved by inhibiting epidermal melanin production, which exerts its effect by inhibiting gene expression or protein production of MIF and / or COX2 skin in keratinocytes.

[0042] Furthermore, the present invention also provides the use of cis-3-hexenol in the manufacture of pharmaceuticals for moisturizing, improving skin barrier function, anti-inflammatory, increasing hyaluronic acid and inhibiting melanin production.

[0043] All references mentioned in this specification are incorporated herein by reference in their entirety.

[0044] The embodiments of the present invention described below are for illustrative purposes only and do not limit the technical scope of the present invention. The technical scope of the present invention is limited only by the claims. Modifications to the present invention can be made without departing from its spirit, such as adding, deleting, and replacing the constituent elements of the present invention.

[0045] Example

[0046] To confirm the moisturizing, skin barrier function improvement, anti-inflammatory, hyaluronic acid enhancement, and melanin production inhibition effects of cis-3-hexenol, an investigation was conducted by analyzing the expression of genes involved in these functions. More specifically, the expression levels of FLG, GBA, COX2, HAS2, and MIF were determined using the methods described below.

[0047] Example 1: Effects of cis-3-hexenol on keratinocytes

[0048] 1-1: Cell Culture

[0049] HaCaT cells were cultured in 24-well plates (Cat No. 3526, Corning, USA) at a rate of 10.0 × 10⁶ cells / well. 4 Cells were seeded at a density per well in Dulbecco's Modified Eagle Medium (DMEM, Cat No. 043-30085, Wako, Japan) containing 10.0% (v / v) fetal bovine serum (FBS, Cat No. SH30071.03, Hyclone, UK) and 1.0% (v / v) antifungal agent (Antibiotic-Antimycotic 100X, Cat No. 15240-062, Invitrogen, USA) and cultured in a CO2 incubator (5% CO2 concentration, 37°C) for 24 hours. After removing the medium, it was replaced with medium supplemented with cis-3-hexenol (CAS: 928-96-1, Wako Pure Chemicals) at the final concentrations shown in the table below, and cultured for an additional 48 hours in a CO2 incubator. A control was prepared using medium without cis-3-hexenol.

[0050] 1-2: RNA extraction / purification, quantification, and purity determination

[0051] RNA extraction / purification was performed using the PureLink™ RNA Mini Kit (Cat No. 12183018A, Invitrogen, USA). A portion of the purified RNA was aliquoted into UV-transmittance 96-well plates and diluted 10-fold with Tris-EDTA buffer. The absorbance (OD230, OD260, OD280) at 230 nm, 260 nm, and 280 nm was measured using a microplate reader (SPARK 10M TECAN, Switzerland). The RNA concentration was calculated using OD260 and then diluted with TE buffer to a concentration of 10 μg / mL.

[0052] 1-3: Gene expression analysis using real-time PCR

[0053] RNA reverse transcription was performed using SuperScript IV VILO™ Master Mix with ezDNase (Cat No. 11766050, Invitrogen, USA). 4 μL of SuperScript IV VILO™ Master Mix and 6 μL of Nuclease-free Water were added to each well of an 8-tube set. cDNA was synthesized using real-time PCR (QuantStudio 3, Applied Biosystems, USA) at 25°C for 10 minutes, 50°C for 10 minutes, and 85°C for 5 minutes. 10 μL of TaqMan Fast Advanced Master Mix (Cat No. 4444557, Applied Biosystems, USA), 1 μL of TaqMan Gene Expressior, 7 μL of UltraPure™ Distilled Water (Invitrogen, Cat No. 10977-015, USA) and 2 μL of cDNA were added to each well of the PCR plate, and the plate was sealed. Real-Time qPCR was performed using primers for FLG (Hs00856927_g1), GBA (Hs00986836_g1), COX2 (Hs00153133_m1), or MIF (Macrophage migration inhibitory factor) (Hs00236988_g1) and GAPDH (Hs02786624_g1) as an internal control gene. The Threshold Cycle (Ct) values ​​of FLG and other genes in cis-3-hexenol-added medium were calculated. The Ct values ​​were then corrected using GAPDH to obtain the ΔCt value. Furthermore, assuming that the gene amount doubled with each cycle, the gene expression level in cis-3-hexenol-added medium was calculated with the control gene expression level as 1. In the gene expression analysis, the average value of 24-well plates × 3 wells was used for each treatment group.

[0054] The results are shown in Table 1 below.

[0055]

[0056]

[0057]

[0058]

[0059] As shown in Tables 1-4, the addition of cis-3-hexenol significantly increased the expression of FLG and GBA, while significantly decreasing the expression of COX2 and MIF. These results suggest that by promoting FLG and GBA expression and inhibiting COX2 and MIF expression, it may contribute to moisturizing, hydrating, improving skin barrier function, anti-inflammation, increasing hyaluronic acid, and / or inhibiting melanin production.

[0060] Example 2: Effects of cis-3-hexenol on fibroblasts

[0061] For cis-3-hexenol, which showed effects in keratinocytes in Example 1, in this example, instead of keratinocytes, the dermal fibroblast cell line NB1RGB cells (RIKENBRC, Japan) derived from human newborns was used. Primers (Hs00193435_m1) encoding the hyaluronic acid synthase HAS2 (human hyaluronic acid synthase 2) were used. Otherwise, the HAS2 gene expression level was determined using the same materials and methods as in Example 1.

[0062] The results are shown in Table 5 below.

[0063]

[0064] According to the results in Table 5, the expression of HAS2 in dermal fibroblasts was significantly increased. This suggests that the synthesis of dermal hyaluronic acid, promoted by HAS2 expression via cis-3-hexenol, is enhanced, which may contribute to moisturizing.

[0065] Example 3: Effect of cis-3-hexenol on the amount of hyaluronic acid

[0066] In this example, cis-3-hexenol, which was observed to promote HAS2 gene expression in dermal fibroblasts in Example 2, was used to confirm whether it had the effect of increasing the amount of hyaluronic acid in dermal fibroblasts.

[0067] 3-1: Cell Culture

[0068] The same NB1RGB cells as in Example 2 were used in 24-well plates (Cat No. 3526, Corning, USA) at 10.0 × 10⁻⁶. 4Cells were seeded at a density per well in Eagle's Minimal Essential Medium (EMEM, Cat No. 051-07615, Wako, Japan) containing 10.0% (v / v) fetal bovine serum (FBS, Cat No. SH30071.03, Hyclone, UK) and 1.0% (v / v) antifungal agent (Antibiotic-Antimycotic 100X, Cat No. 15240-062, Invitrogen, USA) and cultured for 24 hours in a CO2 incubator (5% CO2 concentration, 37°C). After 24 hours, the medium was removed and replaced with medium supplemented with cis-3-hexenol (CAS: 928-96-1, Wako Pure Chemicals) at the final concentrations shown in Table 6 below, and cultured for another 48 hours in a CO2 incubator. A control was prepared using medium without cis-3-hexenol.

[0069] 3-2: Evaluation of cell activation

[0070] The effects of cis-3-hexenol on the proliferation of dermal fibroblasts were evaluated using the following methods.

[0071] The 96-well plates, after the culture medium was removed, were washed with 100 μL of PBS(-). Then, 100 μL of 0.5 mg / mL 3-(4,5-dimethylthiazolyl-2-yl)-2,5-diphenyltetrazolium bromide (MTT, CAS No. 298-93-1, Sigma-Aldrich, USA) solution was added, and the plates were incubated in a CO2 incubator for 2 hours. After removing the MTT solution, the plates were washed with 100 μL of PBS(-), and the insoluble formazan was dissolved in 200 μL of 2-propanol (CAS No. 67-63-0, Wako, Japan). The pigment in the 96-well plates was uniformly dispersed, and the absorbance (OD570) at 570 nm was measured using a microplate reader (SPARK 10M, TECAN, Switzerland). Using the OD570 of the control group as 100%, the OD570 of the cis-3-hexenol-added group, representing the cell proliferation effect, was calculated as the cell activation effect (%) of cis-3-hexenol. In the analysis of cell activation effect, the average value of 96-well plates × 3 wells was used for each treatment group.

[0072] 3-3: Determination of Hyaluronic Acid

[0073] The supernatant of the culture cultured in 3-1 was aliquoted / frozen in a new 96-well plate (-80°C), and the amount of hyaluronic acid in the culture supernatant was determined by sandwich ELISA to evaluate the effect of cis-3-hexenol in promoting hyaluronic acid production.

[0074] 100 μL of a hyaluronic acid-binding protein (HABP, Cat No. BC40, Hokudo, Japan, 1:5500) solution prepared with PBS was added to a high-absorption 96-well plate and incubated overnight at 4°C. The solid HABP solution was removed, and the plate was washed with 200 μL of PBS-T solution. Then, 150 μL of 1% BSA solution was added, and the plate was incubated at room temperature for 1 hour. After removing the BSA solution, the plate was washed with 200 μL of PBS-T solution, and then 100 μL of culture supernatant diluted 100-fold with PBS(-) was added. The plate was incubated at room temperature for 1 hour. Sodium hyaluronate (Cat No. 087-04511, Wako, Japan) was used as the standard. After removing the culture supernatant, the sample was washed with 200 μL of PBS-T, and then 100 μL of a biotin-labeled HABP solution (Cat No. BC41, Hokudo, Japan, 1:2000) prepared with PBS(-) containing 0.5% BSA was added. The plate was incubated overnight at 4°C. After removing the biotin-labeled HABP solution, the sample was washed with 200 μL of PBS-T, and then 100 μL of a streptavidin-HRP solution (1:10000) prepared with PBS(-) containing 0.5% BSA was added. The plate was incubated at room temperature for 30 minutes. After removing the streptavidin-HRP solution, the sample was washed with 200 μL of PBS-T, and then 100 μL of ABTS solution was added to confirm color development. After homogenizing the pigment in the 96-well plate, the absorbance (OD405) at 405 nm was measured using a microplate reader.

[0075] The hyaluronic acid production rate of cis-3-hexenol was calculated using the OD405 of the control group as 100%. Furthermore, the hyaluronic acid production rate per cell was calculated by dividing the OD405 of both the control and cis-3-hexenol-added samples by the OD570 measured in section 3-2. The hyaluronic acid production rate per cell for the cis-3-hexenol-treated group was calculated using the hyaluronic acid production rate per cell of each treatment group as 100%. In the analysis of hyaluronic acid production rate, the average value of 96-well plates × 3 wells was used for each treatment group.

[0076] The results of 3-2 showed that no significant increase or decrease in fibroblast proliferation was observed, confirming that cis-3-hexenol had no cell-activating effect or toxicity. The results of 3-3 are presented in Table 6 as the hyaluronic acid production rate using cis-3-hexenol when the control hyaluronic acid production rate was 100%.

[0077]

[0078] The addition of cis-3-hexenol significantly increased the hyaluronic acid production rate per cell. These results confirm that cis-3-hexenol contributes to increasing hyaluronic acid in fibroblasts. Furthermore, considering the results of Example 2, it is also suggested that the hyaluronic acid-increasing effect of cis-3-hexenol may be due to the promotion of HAS2 expression.

[0079] The results above indicate that cis-3-hexenol promotes the expression of FLG, GBA, and HAS2 genes, while inhibiting the expression of COX2 and MIF genes, leading to an increase in hyaluronic acid. This could further lead to beneficial effects on the skin, such as moisturizing, improving skin barrier function, anti-inflammation, and inhibiting melanin production.

Claims

1. A moisturizer containing cis-3-hexenol as an active ingredient.

2. A skin barrier function improver containing cis-3-hexenol as an active ingredient.

3. An anti-inflammatory agent containing cis-3-hexenol as the active ingredient.

4. A hyaluronic acid enhancer containing cis-3-hexenol as an active ingredient.

5. An FLG gene expression promoter containing cis-3-hexenol as the active ingredient.

6. A GBA gene expression promoter containing cis-3-hexenol as the active ingredient.

7. A COX2 gene expression inhibitor containing cis-3-hexenol as the active ingredient.

8. A HAS2 gene expression promoter containing cis-3-hexenol as the active ingredient.

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