ASMT gene expression promoter

Abstract

The present invention addresses the problem of providing a novel ASMT expression promoter and provides an ASMT expression promoter that contains, as an active ingredient, at least one substance selected from the group consisting of eucalyptus oil, olive leaf extract and pine extract. Also, the present invention provides a melatonin synthesis promoter that contains, as an active ingredient, at least one substance selected from the group consisting of eucalyptus oil, olive leaf extract and pine extract and that promotes melatonin synthesis through the promotion of ASMT expression. By promoting melatonin synthesis through the promotion of ASMT gene expression, effects of improving sleep disorders, boosting cognitive function, improving mood disorders, enhancing antioxidant activity and enhancing anti-inflammatory activity can be potentiated.

Description

ASMT gene expression promoter

[0001] The present invention relates to an agent for promoting ASMT expression.

[0002] Melatonin is a hormone found in plants and animals, and has been reported to have effects such as improving sleep disorders, enhancing cognitive function, improving mood disorders, and enhancing antioxidant and anti-inflammatory activities (Patent Documents 1 and 2, Non-Patent Document 1).

[0003] Acetylserotonin O-methyltransferase (ASMT) is known to promote melatonin synthesis. ASMT is produced in the body through expression of the ASMT gene and is an enzyme involved in the final step of the melatonin synthesis pathway. Therefore, promoting ASMT expression is thought to promote melatonin synthesis and increase melatonin levels (Patent Document 2, Non-Patent Documents 1-6).

[0004] Therefore, there is a need to discover substances that promote ASMT expression and thereby promote melatonin synthesis. International Publication No. 2019 / 193717 (Patent Document 5) discloses an ASMT expression promoter containing ectoine or a physiologically acceptable salt thereof as an active ingredient, but there is still a need to discover other substances that contribute to the ASMT expression promotion effect.

[0005] Japanese Patent Application Publication No. 2014-237700 Japanese Patent Application Publication No. 2009-511038 Japanese Patent Application Publication No. 2002-302444 Japanese Patent No. 5116917 International Publication Pamphlet No. 2019 / 193717

[0006] Hattori Atsuhiko, Review: Melatonin and Aging, Comparative Physiology and Biochemistry Vol. 34 (2017), No. 1, p.2-11Pagan et.al., Mutation screening of ASMT, the last enzyme of the melatonin pathway, in a large sample of patients with Intellectual Disability, BMC Medical Genetics 2011, 12:17Reiter et.al., Melatonin and its metabolites: new findings regarding their production and their radical scavenging actions, Acta Biochimica Polonica, Vol. 54 No. 1, 2007, 1-9Ribelayga et.al., HIOMT drives the photoperiodic changes in the amplitude of the melatonin peak of the Siberian hamster, American Journal of Physiology Regulatory Integrative Comparative Physiology, 278: R1339-R1345, 2000.Ceinos et.al., Analysis of Adrenergic Regulation of Melatonin Synthesis in Siberian Hamster Pineal Emphasizes the Role of HIOMT, Neurosignals 2004;13:308-317Monika Talarowska et. al., ASMT gene expression correlates with cognitive impairment in patients with recurrent depressive disorder, Medical Science Monitor, 2014; 20: 905-912Yi H1 et. al., Localization of the hydroxyindole-O-methyltransferase gene to the pseudoautosomal region: implications for mapping of psychiatric disorders, Human Molecular Genetics. 1993 Feb;2(2):127-31.Gaia Favero et. al., Melatonin as an Anti-Inflammatory Agent Modulating Inflammasome Activation, International Journal of Endocrinology Volume 2017, Article ID 1835195, 13 pages.Andrze Alominski, DJ Tobin, MA Zmijewski, et.al., Melatonin in the skin: synthesis, metabolism and functions. Trends in Endocrinology & Metabolism, 2008, 19:17-24DX Tan, LD Chen, B Poeggeler, et.al., Melatonin: a potent endogenous hydroxyl radical scavenger. Endocrine J, 1993, 1:57-60.

[0007] An object of the present invention is to provide a novel agent for promoting ASMT expression.

[0008] As a result of extensive research into the effects of various ingredients as ASMT expression promoters, the inventors have found that eucalyptus oil, olive leaf extract, and pine extract are particularly effective as ASMT expression promoters, leading to the completion of the following inventions: (1) An ASMT expression promoter containing at least one substance selected from the group consisting of eucalyptus oil, olive leaf extract, and pine extract as an active ingredient. (2) A melatonin synthesis promoter containing at least one substance selected from the group consisting of eucalyptus oil, olive leaf extract, and pine extract as an active ingredient, which promotes melatonin synthesis through promotion of ASMT expression. (3) An antioxidant containing at least one substance selected from the group consisting of eucalyptus oil, olive leaf extract, and pine extract as an active ingredient, which enhances antioxidant activity by promoting melatonin synthesis through promotion of ASMT expression. (4) A composition containing the ASMT expression promoter described in (1). (5) A composition containing the melatonin synthesis promoter described in (2). (6) A composition containing the antioxidant described in (3). (7) The composition according to (4) or (5), which is for enhancing one or more effects selected from the group consisting of improvement of sleep disorders, improvement of cognitive function, improvement of mood disorders, enhancement of antioxidant activity, and enhancement of anti-inflammatory activity, by promoting melatonin synthesis through promotion of ASMT expression. (8) The composition according to any one of (4) to (7), which is a cosmetic composition or a food composition.

[0009] Administration of the ASMT expression promoter of the present invention can promote ASMT expression. According to the present invention, a composition containing the ASMT expression promoter can be provided. Promoting ASMT expression can promote melatonin synthesis, enhancing the effects of melatonin, such as improving sleep disorders, improving cognitive function, ameliorating mood disorders, and enhancing antioxidant and anti-inflammatory activities.

[0010] Figure 1 is a graph showing the results of comparing the ASMT expression-promoting effects of eucalyptus oil, olive leaf extract, and pine extract with a control without added test substance. The ASMT gene expression level of the control is shown as a comparison, with the control's ASMT gene expression level set to 1. The expression level of the RPLP0 gene, a housekeeping gene with a nearly constant expression level as an internal standard, was quantified, and the relative expression level to RPLP0 (ASMT / RPLP0) was calculated to determine the ASMT gene expression level.

[0011] The present invention provides an ASMT expression-promoting agent containing, as an active ingredient, at least one substance selected from the group consisting of eucalyptus oil, olive leaf extract, and pine extract.

[0012] Eucalyptus oil is an essential oil obtained by steam distillation of the leaves of Eucalyptus globulus Labillardiere, a plant in the Myrtaceae family. Its main uses include oral care, cough suppressants, and disinfectants, and it is also used as a synthetic fragrance ingredient. However, the fact that eucalyptus oil has a strong promoting effect on ASMT expression has not been reported to date, making this a very surprising discovery.

[0013] Olive leaf extract is an extract derived from the leaves of olive (Olea europaea), a plant of the Oleaceae family native to the Punjab region of India and the Mediterranean coast, or its related species, and is expected to have antioxidant, collagen production-promoting, anti-inflammatory, and anti-allergic effects. However, the fact that olive leaf extract has a strong ASMT expression-promoting effect has not been reported to date, making this a very surprising discovery.

[0014] Olive leaf extract is preferably extracted from olive leaves as a raw material, and any extraction method, such as steam distillation or solvent extraction, can be used. Any extraction solvent can be used, including a mixed solvent of butylene glycol and water.

[0015] Pine extract is an extract obtained from the cones of the common sylvestris tree (Pinus sylvestris), and has been reported to have anti-inflammatory effects. Common sylvestris (Pinus sylvestris), also known as Scots pine, is an evergreen coniferous tree of the Pinaceae family. However, it has not been reported that pine extract has a strong promoting effect on ASMT expression, making this a very surprising discovery.

[0016] The plant extracts used in the present invention, such as eucalyptus oil, olive leaf extract, and pine extract, can be extracted from plant materials by methods known to those skilled in the art, such as extraction methods using solvents, or methods including grinding and pressing steps.

[0017] The plant part to be extracted is washed with water if necessary to remove foreign matter, and then either left as is or dried, and then shredded or crushed as necessary, and then brought into contact with an extraction solvent for extraction. Extraction can be carried out by contacting with the extraction solvent using a conventional method such as immersion, but supercritical extraction or steam distillation may also be used.

[0018] When performing extraction, the plant body can be used as is, but crushing it into granules or powder before extraction allows for extraction of active ingredients under milder conditions in a shorter time with higher extraction efficiency. The extraction temperature is not particularly limited and can be set appropriately depending on the particle size of the crushed material, the type of solvent, etc. It is usually set within the range from room temperature to the boiling point of the solvent. The extraction time is also not particularly limited and can be set appropriately depending on the particle size of the crushed material, the type of solvent, the extraction temperature, etc. Furthermore, during extraction, stirring may be performed, the mixture may be left to stand without stirring, or ultrasound may be applied.

[0019] Examples of extraction solvents include water; lower alcohols such as methanol, ethanol, and propanol; higher alcohols such as oleyl alcohol, stearyl alcohol, and octyldodecanol; polyhydric alcohols such as ethylene glycol, 1,3-propanediol, 1,3-butylene glycol, and glycerin; esters such as ethyl acetate, butyl acetate, methyl propionate, and glyceryl trioctanoate; ketones such as acetone and methyl ethyl ketone; ethers such as ethyl ether, isopropyl ether, and hydrocarbon solvents such as n-hexane, toluene, and chloroform. These solvents can be used alone or in combination. Preferred solvents are polar solvents such as water, lower alcohols, and liquid polyhydric alcohols, and more preferably water or lower alcohols such as methanol, ethanol, and 1,3-butylene glycol. The lower alcohol may be, for example, a water-containing lower alcohol, in which case the water content may be, for example, 0 to 10 v / v%, 10 to 40 v / v%, 20 to 30 v / v%, 30 to 50 v / v%, 50 to 80 v / v%, 80 to 99.5 v / v%, etc. The lower alcohol may be, for example, a C1 to C5 lower alcohol. These solvents may be used alone or in combination. Furthermore, an enzyme may be added to the solvent to perform the extraction treatment.

[0020] When a mixed solvent is used, the mixing ratio (volume ratio) is preferably in the range of 1:1 to 25:1 for a mixed solvent of water and ethyl alcohol, 1:1 to 15:1 for a mixed solvent of water and glycerin, or 1:1 to 15:1 for a mixed solvent of water and 1,3-propanediol or 1,3-butylene glycol.

[0021] When preparing an extract, the pH is not particularly limited, but is generally preferably in the range of pH 3 to 9. If necessary, the extraction solvent may be blended with an alkalinity adjuster such as sodium hydroxide, sodium carbonate, or potassium hydroxide, or an acidity adjuster such as citric acid, hydrochloric acid, phosphoric acid, or sulfuric acid to adjust the pH to the desired level.

[0022] The extraction conditions, such as the extraction temperature and extraction time, vary depending on the type and pH of the solvent used and are not limited. For example, when water, 1,3-butylene glycol, or a mixture of water and 1,3-butylene glycol is used as the solvent, the extraction temperature may be in the range of 0°C to 90°C, and the extraction time may be 0.5 hours to 7 days.

[0023] By such an extraction procedure, the active ingredient is extracted and dissolved in the solvent. The solvent containing the extract may be used as is, or may be subjected to conventional purification treatments such as sterilization, washing, filtration, bleaching, and deodorization before use. It may also be concentrated or diluted as necessary before use. Furthermore, the solvent may be completely evaporated to form a solid (dried product), or the dried product may be redissolved in any solvent before use.

[0024] If necessary, the extracted area may be subjected to hydrolysis prior to or in parallel with the extraction process, which may improve the skin irritation, efficacy, storage stability, etc. of the extract, thereby enabling more effective use of the extract.

[0025] In addition, the squeezed liquid obtained by squeezing the raw plant material also contains the same active ingredients as the extract, so the squeezed liquid can also be used instead of the extract.

[0026] ASMT stands for acetylserotonin O-methyltransferase (CAS number 9029-77-0). ASMT is known as an enzyme that catalyzes the reaction converting normelatonin to melatonin, the final step in the melatonin synthesis pathway. ASMT is also known as hydroxyindole-O-methyltransferase (HIOMT) (Non-Patent Documents 1-5).

[0027] The ASMT gene is located in the pseudoautosomal region 1 (PAR1) common to the X and Y chromosomes and encodes acetylserotonin O-methyltransferase (ASMT) (Non-Patent Document 7). It has been suggested that low expression of the ASMT gene results in a decrease in melatonin production because normelatonin is not converted to melatonin, whereas high expression of the ASMT gene increases melatonin production (Non-Patent Documents 1-5).

[0028] Melatonin refers to N-acetyl-5-methoxytryptamine (CAS number 73-31-4). Melatonin is produced in the pineal gland in animals, including humans. Recently, it has been reported that melatonin is also produced in various organs, including the skin, retina, brain, spinal cord, gastrointestinal tract, heart, kidneys, testes, ovaries, thymus, spleen, lens, cochlea, bone marrow, and lymphocytes (Non-Patent Documents 1, 9, and 10). Melatonin has also been reported to have various effects, including regulating circadian rhythms, improving sleep disorders, enhancing cognitive function, alleviating mood disorders, and exerting antioxidant and anti-inflammatory effects in organs such as the skin (Patent Documents 1 and 2; Non-Patent Documents 1, 2, 6-10). Therefore, if melatonin could be promoted by ectoine, which the present inventors discovered to have a strong ASMT-promoting effect, the aforementioned various effects of melatonin would be enhanced.

[0029] "Promotion of ASMT expression" can mean, for example, that the expression level of the ASMT gene is increased with a statistically significant difference (e.g., Student's t-test) at a significance level of 5% when an ASMT expression promoter is administered compared to a state (control) in which no ASMT expression promoter is administered. Alternatively, "promotion of ASMT expression" can mean, for example, that the expression level of the ASMT gene is 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 when an ASMT expression promoter is administered compared to a state (control) in which no ASMT expression promoter is administered. The expression level of the ASMT gene can be determined by any known technique, for example, the method described in Non-Patent Document 6.

[0030] Thus, the present invention provides a melatonin synthesis promoter containing at least one substance selected from the group consisting of eucalyptus oil, olive leaf extract, and pine extract as an active ingredient, which promotes melatonin synthesis through the promotion of ASMT expression. It also provides an antioxidant containing at least one substance selected from the group consisting of eucalyptus oil, olive leaf extract, and pine extract as an active ingredient, which enhances antioxidant activity by promoting melatonin synthesis through the promotion of ASMT expression. The antioxidant activity may be in an organ such as the skin. The present invention also provides a composition containing an ASMT expression promoter, melatonin synthesis promoter, or antioxidant containing at least one substance selected from the group consisting of eucalyptus oil, olive leaf extract, and pine extract as an active ingredient. The composition of the present invention may be a cosmetic composition or a food composition. Furthermore, the composition of the present invention may be a composition for enhancing melatonin synthesis through the promotion of ASMT expression, thereby enhancing one or more effects selected from the group consisting of improvement of sleep disorders, improvement of cognitive function, improvement of mood disorders, enhancement of antioxidant activity, and enhancement of anti-inflammatory activity.

[0031] The ASMT expression promoter, melatonin synthesis promoter, antioxidant, or composition of the present invention may contain at least one substance selected from the group consisting of eucalyptus oil, olive leaf extract, and pine extract as an active ingredient, for example, at a concentration of 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. The ASMT expression promoter, melatonin synthesis promoter, antioxidant, or composition of the present invention may contain two or all three substances selected from the group consisting of eucalyptus oil, olive leaf extract, and pine extract. In one embodiment, the ASMT expression promoter, melatonin synthesis promoter, or antioxidant of the present invention may consist of at least one substance selected from the group consisting of eucalyptus oil, olive leaf extract, and pine extract. The at least one substance selected from the group consisting of eucalyptus oil, olive leaf extract, and pine extract used in the present invention can be obtained by any method, and is not limited by its manufacturing method, source, or the like.

[0032] The ASMT expression promoter, melatonin synthesis promoter, antioxidant, or composition of the present invention can be administered topically or orally. The topical administration form can be selected from any of a variety of forms, such as cream, emulsion, liquid, sheet, spray, and gel. The oral administration form can be selected from any of a variety of forms, such as tablets, supplements, beverages, and powders.

[0033] The cosmetic composition of the present invention may be any of a variety of cosmetics such as emulsion, cream, serum, lotion, pack, facial cleanser, soap, body wash, shampoo, etc., and may be in various forms such as liquid, emulsion, cream, solid, sheet, spray, gel, foam, powder, etc. 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, granule, particulate, paste, gel, etc.

[0034] The ASMT expression promoter, melatonin synthesis promoter, antioxidant, or composition of the present invention preferably contains at least one substance selected from the group consisting of eucalyptus oil, olive leaf extract, and pine extract in an amount sufficient to fully exert the effect of promoting ASMT expression.

[0035] The amount of at least one substance selected from the group consisting of eucalyptus oil, olive leaf extract, and pine extract in the ASMT expression promoter, melatonin synthesis promoter, antioxidant, or composition of the present invention can be determined appropriately depending on their type, purpose, form, method of use, etc.

[0036] Regarding the dosage of at least one substance selected from the group consisting of eucalyptus oil, olive leaf extract, and pine extract, when administered topically, the amount of the at least one substance selected from the group consisting of eucalyptus oil, olive leaf extract, and pine extract may be, for example, 0.001 to 50 wt %, 0.01 to 5 wt %, 0.01 to 1 wt %, 0.01 to 0.1 wt %, 0.02 to 0.05 wt %, etc., based on the total weight of the ASMT expression promoter, melatonin synthesis promoter, antioxidant, or composition of the present invention, but is not limited to these.

[0037] When administered orally, the amount of at least one substance selected from the group consisting of eucalyptus oil, olive leaf extract, and pine extract may be, but is not limited to, 0.001 to 50 wt %, 0.01 to 5 wt %, 0.01 to 1 wt %, 0.01 to 0.1 wt %, 0.02 to 0.05 wt %, etc., based on the total weight of the ASMT expression promoter, melatonin synthesis promoter, antioxidant, or composition of the present invention.

[0038] The administration frequency can be selected arbitrarily, such as once every 4 weeks, once every 2 weeks, once a week, once every 3 days, once every 2 days, once a day, twice a day, three times a day, four times a day, five times a day, or administration as needed, but is not limited to these.

[0039] The ASMT expression promoter, melatonin synthesis promoter, antioxidant, or composition of the present invention can be used in combination with any additive selected as needed. The additive can include an excipient or the like.

[0040] The excipient may be any one that is normally used when preparing the desired dosage form, and examples thereof include starches such as wheat starch, rice starch, corn starch, potato starch, dextrin, and cyclodextrin, crystalline celluloses, sugars such as lactose, glucose, sugar, reduced maltose, starch syrup, fructooligosaccharides, and emulsified oligosaccharides, and sugar alcohols such as sorbitol, erythritol, xylitol, lactitol, and mannitol. These excipients can be used alone or in combination of two or more.

[0041] Other additives that can be used include colorants, preservatives, thickeners, binders, disintegrants, dispersants, stabilizers, gelling agents, antioxidants, surfactants, preservatives, pH adjusters, oils, water, alcohols, chelating agents, silicones, ultraviolet absorbers, moisturizers, fragrances, various medicinal ingredients, antiseptics, and neutralizing agents, and can be appropriately selected and used.

[0042] The present invention also provides a method for promoting melatonin synthesis through the promotion of ASMT expression by administering at least one substance selected from the group consisting of eucalyptus oil, olive leaf extract, and pine extract. The present invention also provides a method for enhancing one or more effects selected from the improvement of sleep disorders, cognitive function, mood disorders, antioxidant activity, and anti-inflammatory activity of the skin by promoting melatonin synthesis through the promotion of ASMT expression by administering at least one substance selected from the group consisting of eucalyptus oil, olive leaf extract, and pine extract. The methods of the present invention are cosmetic methods and may not be performed by a physician or medical professional. The present invention also provides a therapeutic method for enhancing one or more effects selected from the improvement of sleep disorders, cognitive function, mood disorders, antioxidant activity, and anti-inflammatory activity of the skin, comprising the step of administering at least one substance selected from the group consisting of eucalyptus oil, olive leaf extract, and pine extract to a subject in need of treatment.

[0043] The present invention also provides use of at least one substance selected from the group consisting of eucalyptus oil, olive leaf extract, and pine extract in the manufacture of a medicament for enhancing one or more effects selected from the group consisting of improvement of sleep disorders, improvement of cognitive function, improvement of mood disorders, enhancement of antioxidant activity in the skin, and enhancement of anti-inflammatory activity in the skin.The present invention also provides a pharmaceutical composition comprising at least one substance selected from the group consisting of eucalyptus oil, olive leaf extract, and pine extract for enhancing one or more effects selected from the group consisting of improvement of sleep disorders, improvement of cognitive function, improvement of mood disorders, enhancement of antioxidant activity in the skin, and enhancement of anti-inflammatory activity in the skin.The present invention also provides at least one substance selected from the group consisting of eucalyptus oil, olive leaf extract, and pine extract for use in a method for enhancing one or more effects selected from the group consisting of improvement of sleep disorders, improvement of cognitive function, improvement of mood disorders, enhancement of antioxidant activity in the skin, and enhancement of anti-inflammatory activity in the skin by promoting melatonin synthesis through promotion of ASMT expression.

[0044] The present invention will now be described in more detail with reference to examples, although the present invention is not limited thereto.

[0045] Example 1: Effect of eucalyptus oil, olive leaf extract, and pine extract on ASMT gene expression (Sample preparation) Eucalyptus oil, olive leaf extract, and pine extract were diluted with ethanol to 3%, 10%, and 10%, respectively. Ethanol was used as a control.

[0046] (Culture of epidermal keratinocytes) Commercially available normal adult skin-derived keratinocytes (Kurabo) were cultured at 5 x 10 5 The keratinocytes were seeded into a T75 flask at 2 × 10 cells / flask and cultured in keratinocyte medium (Humedia-KG2, Kurabo Industries, Ltd.) at 37°C in a 5% CO atmosphere until they reached semi-confluence. These keratinocytes were harvested by trypsinization and plated at 2 × 10 cells / flask in a 24-well plate. 4 The cells were seeded at 100 cells / well and cultured in a keratinocyte medium (Humedia-KG2, Kurabo) at 37°C in a 5% CO 2 atmosphere until the cells reached confluence.

[0047] (Sample addition) Ethanol-diluted eucalyptus oil, olive leaf extract, and pine extract were added to confluent epidermal keratinocytes at 1 / 100 volume (v / v) of the medium to achieve concentrations of 0.03%, 0.1%, and 0.1%, respectively, and the cells were cultured at 37°C in a 5% CO2 atmosphere. As a control, ethanol alone was added at 1 / 100 volume of the medium.

[0048] (Extraction of RNA from cells) Ten hours after the addition of eucalyptus oil, olive leaf extract, and pine extract, the medium was removed, and cells were lysed and RNA was extracted using a commercially available RNA extraction reagent (RNeasy Mini Kit, Qiagen).

[0049] (Assessment of ASMT expression levels by quantitative PCR) Using the extracted RNA as a template, quantitative PCR was performed using commercially available quantitative PCR reagents (Brilliant II QRT-PCR kit, Agilent) and a quantitative PCR device (Mx-3005P, Agilent) to measure the expression level of the ASMT gene. The expression level of the RPLP0 gene, which has a nearly constant expression level, was also measured simultaneously as an internal standard. Commercially available PCR primers specific to each gene (Takara Bio Inc.) were used for PCR.

[0050] The results are shown in Figure 1. The level of ASMT gene expression when each sample was added is shown as a comparison with the control ASMT gene expression level, which was set to 1. Figure 1 confirms that eucalyptus oil, olive leaf extract, and pine extract have a significantly higher ASMT expression-promoting effect than when cultured in medium alone.

[0051] The present invention provides a method for promoting the expression of the ASMT gene by administering an ASMT expression promoter containing as an active ingredient at least one substance selected from the group consisting of eucalyptus oil, olive leaf extract, and pine extract. By promoting ASMT gene expression and thereby promoting the synthesis of melatonin, the present invention can enhance effects such as improving sleep disorders, improving cognitive function, improving mood disorders, enhancing antioxidant activity, and enhancing anti-inflammatory activity.

Claims

1. An ASMT expression promoter containing, as an active ingredient, at least one substance selected from the group consisting of eucalyptus oil, olive leaf extract, and pine extract.

2. A melatonin synthesis promoter containing, as an active ingredient, at least one substance selected from the group consisting of eucalyptus oil, olive leaf extract, and pine extract, and promoting the synthesis of melatonin through promoting ASMT expression.

3. An antioxidant containing, as an active ingredient, at least one substance selected from the group consisting of eucalyptus oil, olive leaf extract, and pine extract, and enhancing antioxidant activity by promoting the synthesis of melatonin through promoting ASMT expression.

4. A composition comprising the ASMT expression promoter according to Claim 1.

5. A composition comprising the melatonin synthesis promoter according to Claim 2.

6. A composition comprising the antioxidant according to Claim 3.

7. For enhancing one or more actions selected from improvement of sleep disorder, improvement of cognitive function, improvement of mood disorder, enhancement of antioxidant activity, and enhancement of anti-inflammatory activity by promoting the synthesis of melatonin through promoting ASMT expression, the composition according to Claim 4 or 5.

8. The composition according to any one of Claims 4 to 6, which is a cosmetic composition or a food composition.

9. The composition according to Claim 7, which is a cosmetic composition or a food composition.