Nicotinamide adenine dinucleotide (NAD) concentration increaser

Abstract

The purpose of the present invention is to provide a nicotinamide adenine dinucleotide (NAD) concentration increasing agent that is safe and derived from a food-containing component. The present invention pertains to a nicotinamide adenine dinucleotide (NAD) concentration increasing agent that includes one or more sesamins as active ingredients.

Description

[Technical field]

[0001] The present invention relates to an agent for increasing nicotinamide adenine dinucleotide (NAD) concentration. [Background technology]

[0002] In recent years, in countries with a high elderly population, extending healthy lifespan has become an issue. One of the factors that shorten healthy lifespan is the decrease in nicotinamide adenine dinucleotide (NAD) in the body with age. + ) production, resulting in a decline in physical functions, etc.

[0003] Here, nicotinamide adenine dinucleotide (NAD + (hereinafter, also referred to as NAD) is a coenzyme that mediates many redox reactions in the body. It is known that NAD levels decrease during the aging process, causing defects in nuclear and mitochondrial function and resulting in many age-related pathologies. For example, Non-Patent Document 1 states that aging and aging-related diseases are caused by the accumulation of nicotinamide adenine dinucleotide (NAD) in cells. + ) levels, and NAD + It has been suggested that this is related to the decreased activity of the longevity gene sirtuin, which is an NAD deacetylase. + It has been reported that increasing NAD activates sirtuins and provides an anti-aging effect (Non-Patent Document 2). + Intensive research is being conducted to find ingredients that are effective in preventing or improving the decline of the immune system and that can be applied to medicines, foods for specified health uses, functional foods, etc.

[0004] Specifically, Non-Patent Document 2 has shown that levels of extracellular nicotinamide phosphoribosyltransferase (eNAMPT) decrease with age in mice and humans, and has disclosed that an increase in eNAMPT promotes NAD levels, inhibits aging, and extends lifespan. It has also been suggested that supplementation with extracellular vesicles (EVs) containing eNAMPT improves physical activity and extends the lifespan of mice, making it a potential intervention for inhibiting aging.

[0005] On the other hand, there has been no suggestion or disclosure as to the effect of sesamin and / or episesamin in increasing nicotinamide adenine dinucleotide (NAD) levels in the body. [Prior art documents] [Non-patent literature]

[0006] [Non-Patent Document 1] Imai, S. & Guarente, L. (2014) Trends Cell Biol., 24, 464-471. “NAD+ and sirtuins in aging and disease” [Non-Patent Document 2] Yoshida M, Satoh A, Lin JB, Mills KF, Sasaki Y, Rensing N, Wong M, Apte RS, Imai SI., Cell Metab. (2019) 30(2):329-342.e5. “Extracellular Vesicle-Contained eNAMPT Delays Aging and Extends Lifespan in Mice” Summary of the Invention [Problem to be solved by the invention]

[0007] An object of the present invention is to provide a safe agent for increasing nicotinamide adenine dinucleotide (NAD) concentration derived from food ingredients. [Means for solving the problem]

[0008] The present inventors conducted intensive research to solve the above problems and discovered that sesamin-class compounds have the effect of increasing nicotinamide adenine dinucleotide (NAD) levels.

[0009] The present invention relates to the following nicotinamide adenine dinucleotide (NAD) concentration elevating agents: [1] A nicotinamide adenine dinucleotide (NAD) concentration enhancer containing one or more types of sesamin derivatives as active ingredients. [2] The agent according to the above [1], wherein one or more of the sesamin components is sesamin and / or episesamin. [3] The agent according to [1] or [2] above, which increases, inhibits a decrease in, maintains or improves NAD concentration. [4] The agent according to any one of [1] to [3] above, which enhances, inhibits the decline of, maintains or improves mitochondrial function through an increase in NAD concentration. [5] The agent according to any one of the above [1] to [3], which enhances, inhibits a decrease in, maintains or improves mitochondrial energy production ability through an increase in NAD concentration. [6] The agent according to any one of [1] to [5] above, which is used for inhibiting and / or delaying aging associated with a decrease in NAD concentration. [7] The agent according to any one of the above [1] to [6], which is an oral composition. [8] The agent according to any one of [1] to [7] above, which is a food or drink. [9] The agent according to any one of the above [1] to [8], which is labeled as "inhibiting and / or delaying aging associated with a decrease in NAD concentration" and / or "inhibiting and / or delaying cellular aging."

[10] A method for increasing nicotinamide adenine dinucleotide (NAD) levels by administering one or more types of sesamin derivatives.

[11] A method for increasing, inhibiting a decrease in, maintaining, or improving nicotinamide adenine dinucleotide (NAD) concentration by administering one or more types of sesamin derivatives.

[12] Use of one or more sesamin derivatives for increasing nicotinamide adenine dinucleotide (NAD) concentration.

[13] Use of one or more sesamin derivatives for increasing, inhibiting a decrease, maintaining or improving nicotinamide adenine dinucleotide (NAD) concentration. Effect of the Invention

[0010] According to the present invention, a nicotinamide adenine dinucleotide (NAD) concentration-increasing agent can be provided. Ingestion of one or more sesamin-class compounds can provide an effect of increasing nicotinamide adenine dinucleotide (NAD) concentration. The sesamin-class compounds used in the present invention are components that have been ingested as foods for a long time, and are advantageous in that they are highly safe and can be ingested continuously. [Brief description of the drawings]

[0011] [Figure 1] This is a graph showing the effect of a sesamin / episesamin mixture (SE) (sesamin:episesamin (weight ratio = 1:1)) on increasing intracellular NAD levels. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0012] The nicotinamide adenine dinucleotide (NAD) concentration-elevating agent of the present invention contains one or more types of sesamin-class compounds. One or more kinds of sesamin are used to increase nicotinamide adenine dinucleotide (NAD) concentration, and have the effect of increasing, suppressing, maintaining or improving nicotinamide adenine dinucleotide (NAD) concentration, and are used to increase NAD concentration, suppress the decrease in NAD concentration, maintain NAD concentration, or improve NAD concentration. In addition, the agent of the present invention is preferably used to increase, suppress the decrease, maintain or improve NAD concentration that has decreased due to aging. The nicotinamide adenine dinucleotide concentration increasing agent can also be called a nicotinamide adenine dinucleotide (NAD) amount increasing agent. Incidentally, NAD concentration means intracellular NAD concentration.

[0013] Sesamin compounds have the effect of increasing nicotinamide adenine dinucleotide (NAD) concentration, and are expected to contribute to the prevention or improvement of aging associated with a decrease in NAD concentration by increasing, inhibiting, maintaining, or improving NAD concentration. Aging is understood to be a phenomenon in which physical, physiological, and mental functions decline. Physical changes due to aging begin around the age of 40 after reaching maturity, and include wrinkles on the skin, loss of hair and teeth, graying of hair, accumulation of fatigue and decreased recovery, decreased eyesight and hearing, decreased motor function, decreased muscle strength and activity, decreased quality of sleep, and decreased bone mass. Although aging itself cannot be considered a disease, the decline in physical and physiological functions increases the risk of so-called geriatric diseases such as arteriosclerosis, glucose and lipid metabolism disorders, neurodegeneration, osteoporosis, and cataracts, and the decline in physical functions also leads to aging of mental functions such as memory and learning. Increasing the concentration of nicotinamide adenine dinucleotide (NAD) is effective in preventing or ameliorating aging associated with a decrease in NAD concentration.

[0014] In one embodiment, the nicotinamide adenine dinucleotide (NAD) concentration elevating agent of the present invention enhances, inhibits, maintains or improves NAD concentration, and is preferably used for enhancing, inhibiting, maintaining or improving NAD concentration that has decreased due to aging. In one embodiment, the agent is preferably used for enhancing, inhibiting, maintaining or improving NAD concentration that has decreased due to aging in middle-aged and elderly people. Middle-aged and elderly people include elderly people. Middle-aged and elderly people may be, for example, people aged 40 years or older, and elderly people may be, for example, people aged 60 years or older or 65 years or older. The NAD concentration in animals, such as humans, can be measured by a conventional method in the technical field to which the present invention pertains. For example, NAD + The NAD / NADH ratio can be measured by measuring the intracellular NAD concentration using the / NADH Quantification Colorimetric Kit (Biovision) or the Amplite (registered trademark) Colorimetric NAD / NADH Ratio Assay Kit (AAT Bioquest).

[0015] The nicotinamide adenine dinucleotide (NAD) concentration elevating agent of the present invention can be used for the treatment of conditions or diseases that can be prevented or improved by increasing, suppressing, maintaining or improving NAD concentration. Examples of such conditions or diseases include, for example, the decline of physical function, physiological function, and mental function associated with aging, specifically, for example, the occurrence of skin aging symptoms (wrinkles, sagging, loss of skin elasticity, etc.), dry skin due to aging (decrease in skin moisture retention), skin spots, freckles, and rough skin, the decrease or increase in secretion of hormones (growth hormone, thyroid hormone, adrenal cortical hormone, sex hormone, prolactin, antidiuretic hormone, parathyroid hormone, melatonin, etc.), damage to cells (brain cells, cardiac muscle cells, etc.) by active oxygen, loss of hair and teeth, decreased eyesight and hearing, decreased motor function, decreased bone mass, decreased physical strength, decreased memory, decreased learning ability, decreased immune function, and the occurrence of geriatric diseases. As used herein, prevention includes preventing onset, delaying onset, reducing the incidence, reducing the risk of onset, etc. Amelioration of a condition or disease includes recovering a subject from a condition or disease, alleviating the symptoms of a condition or disease, ameliorating the symptoms of a condition or disease, delaying or preventing the progression of a condition or disease, etc.

[0016] In the present invention, sesamin analogues are a general term for compounds including sesamin and its analogues. Sesamin is one of the main lignan compounds contained in sesame. In addition to episesamin, examples of sesamin analogues include dioxabicyclo[3.3.0]octane derivatives described in JP-A-4-9331. As one or more types of sesamin analogues, one of these compounds may be used alone, or two or more types may be used. Specific examples of sesamin analogues include sesamin, episesamin, sesaminol, episesaminol, sesamol, and sesamolin, and these stereoisomers or racemates may be used alone or in mixture. In addition, metabolites of sesamin analogues (for example, those described in JP-A-2001-139579) are also sesamin analogues contained in the sesamins of the present invention, and can be used in the present invention, so long as they exhibit the effects of the present invention. In the present invention, sesamin and / or episesamin can be preferably used as one or more of the sesamins, and sesamin and episesamin can be more preferably used. When sesamin and episesamin are used, the ratio thereof is not particularly limited, but for example, the weight ratio of sesamin:episesamin is preferably 1:0.1 to 1:9, more preferably 1:0.3 to 1:3, and even more preferably 1:0.5 to 1:2.

[0017] The sesamin compounds used in the present invention are not limited by their form or production method. For example, in the case of sesamin, sesamin (called sesamin extract or purified product) extracted from sesame oil by a known method (for example, the method described in JP-A-4-9331) can be used. Commercially available sesame oil (liquid) can also be used as is. However, when sesame oil is used, the flavor peculiar to sesame oil may be evaluated as being undesirable from an organoleptic perspective, so it is preferable to use a tasteless and odorless sesamin extract (or sesamin purified product) extracted from sesame oil. In addition, when sesame oil is used, the sesamin content is low, so when a desired amount of sesamin is to be incorporated, the volume per unit dose of the formulated composition becomes too large, which may cause inconvenience in ingestion. In particular, when formulated for oral administration, the formulation (tablet, capsule, etc.) becomes too large, which causes difficulties in ingestion. Therefore, from the viewpoint of a small intake amount, it is preferable to use a sesamin extract (or sesamin purified product) from sesame oil. Sesamin compounds can also be obtained by synthesis. For example, sesamin and episesamin can be synthesized by the method of Beroza et al. (J. Am. Chem. Soc., 78, 1242 (1956)). Metabolites of sesamin and episesamin can be synthesized by the method of Urata et al. (Chem. Pharm. Bull. (Tokyo), 56 (11) 1611-2 (2008)).

[0018] Sesamin-based compounds are contained in natural products and foods and beverages, have a wide dietary history, and are recognized for their high safety. Sesamin-based compounds with guaranteed safety are ideal for continuous and long-term ingestion. According to the present invention, a nicotinamide adenine dinucleotide (NAD) concentration-elevating agent containing a highly safe substance as an active ingredient can be provided.

[0019] NAD in the body plays an important role in promoting the expression and synthesis of molecules involved in mitochondrial function and mitochondrial energy production by activating sirtuins and deacetylating downstream enzymes or transcription factors. Therefore, an increase in NAD concentration can improve, inhibit, maintain or improve mitochondrial function. The agent of the present invention can improve, inhibit, maintain or improve mitochondrial function through an increase in NAD concentration. In addition, the agent of the present invention can improve, inhibit, maintain or improve mitochondrial energy production ability through an increase in NAD concentration. In addition, the agent of the present invention thereby exerts an anti-cellular aging effect.

[0020] In this specification, mitochondrial function and mitochondrial energy production capacity may be evaluated based on common knowledge in the technical field to which the present invention belongs, and the method is not particularly limited. For example, the mitochondrial function can be evaluated by continuously measuring the oxygen consumption rate (hereinafter also referred to as "OCR") used by mitochondria during ATP synthesis in the cells to be measured using an extracellular flux analyzer while adding an ATP synthase inhibitor (e.g., oligomycin and rotenone) and an uncoupler (e.g., carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP)). The evaluation items can be, for example, basal respiration, ATP production capacity, and maximum respiration, which are considered to be major indicators in the evaluation of mitochondrial function.

[0021] The agent of the present invention can be used to inhibit and / or delay aging associated with a decrease in NAD concentration.

[0022] The agent of the present invention can be applied to either therapeutic use (medical use) or non-therapeutic use (non-medical use). Non-therapeutic use is a concept that does not include medical procedures, i.e., surgery, treatment or diagnosis of humans. The agent of the present invention can be in the form of a food or drink, a medicine, a quasi-drug, a feed, etc. The agent of the present invention may be a food or drink, a medicine, a quasi-drug, a feed, etc. that is used for increasing the concentration of nicotinamide adenine dinucleotide (NAD) or for increasing, suppressing a decrease, maintaining, or improving the NAD concentration, or may be a material or preparation that is mixed with these and used. Furthermore, the agent of the present invention may be a food or drink, medicine, quasi-drug, feed, etc., which is intended to improve, suppress the decline, maintain, or improve mitochondrial function through an increase in NAD concentration, or to improve, suppress the decline, maintain, or improve mitochondrial energy production ability through an increase in NAD concentration, or may be a material or preparation to be mixed with these. The agent of the present invention can be provided in the form of an agent as it is, but is not limited to this form. The agent can also be provided as a composition as it is, or as a composition containing the agent. The agent of the present invention may be either an oral agent or a parenteral agent, but is preferably an oral agent. The oral agent may be a food or drink, an oral medicine, a quasi-drug, a feed, etc., or may be included in these. The agent of the present invention is preferably a food or drink or an oral medicine, and more preferably a food or drink.

[0023] The agent of the present invention may contain any additives and any components in addition to one or more types of sesamin-class compounds, as long as the effects of the present invention are not impaired. These additives and components may be selected depending on the form of the agent or composition, and those that can be generally used in foods and beverages, medicines, quasi-drugs, feed, etc. may be used. When the agent of the present invention is used as a food and beverage, medicine, quasi-drug, feed, etc., the manufacturing method is not particularly limited, and it can be manufactured by a general method.

[0024] For example, when the agent of the present invention is made into a food or drink, one or more types of sesamin-class compounds can be mixed with ingredients that can be used in food or drink (e.g., food materials, food additives used as necessary, etc.) to make various foods and drinks. The foods and drinks are not particularly limited, and examples thereof include general foods and drinks, health foods, health drinks, functional foods, foods for specified health uses, and foods and drinks for sick people. The above-mentioned health foods, functional foods, foods for specified health uses, etc. can be used in various formulation forms such as fine granules, tablets, granules, powders, capsules, chewable agents, dry syrups, syrups, liquids, beverages, and liquid diets.

[0025] When the agent of the present invention is used as a drug or quasi-drug, for example, one or more types of sesamin-class compounds may be mixed with a pharmacologically acceptable carrier, additives added as necessary, and the like to produce a drug or quasi-drug in various dosage forms. Such carriers, additives, and the like may be any pharmacologically acceptable carriers that can be used in drugs or quasi-drugs, and examples of such carriers, additives, and the like include one or more of excipients, binders, disintegrants, lubricants, antioxidants, colorants, and the like. Examples of the administration (ingestion) form of the drug or quasi-drug include oral or parenteral (transdermal, transmucosal, enteral, injection, and the like) administration forms. When the agent of the present invention is used as a drug or quasi-drug, it is preferable to use an oral drug or quasi-drug. Examples of dosage forms for oral administration include liquids, tablets, powders, fine granules, granules, sugar-coated tablets, capsules, suspensions, emulsions, chewables, and the like. The drug may be a drug for non-human animals.

[0026] When the agent of the present invention is used as feed, one or more kinds of sesamin compounds may be added to the feed. Feed also includes feed additives. Examples of feed include livestock feed for cows, pigs, chickens, sheep, horses, etc.; small animal feed for rabbits, rats, mice, etc.; pet food for dogs, cats, small birds, etc.

[0027] The amount of sesamin-class compounds contained in the agent of the present invention is not particularly limited and can be set depending on the form, etc. The total content of sesamin-class compounds in the agent of the present invention is, for example, preferably 0.001% by weight or more in the agent, more preferably 0.01% by weight or more, even more preferably 0.05% by weight or more, and preferably 10% by weight or less, more preferably 5% by weight or less. In one embodiment, the total content of sesamin-class compounds in the agent is preferably 0.001 to 10% by weight, more preferably 0.01 to 5% by weight, even more preferably 0.05 to 5% by weight. When two or more types of sesamin-class compounds are contained, the above total content is the total content of these compounds.

[0028] The agent of the present invention is preferably an oral composition (a composition that is taken orally (administered orally)). The dosage (which can also be called the intake amount) of the agent of the present invention is not particularly limited. The dosage of the agent of the present invention may be an amount that can obtain the effect of increasing nicotinamide adenine dinucleotide concentration, or the effect of improving, inhibiting a decrease, maintaining or improving NAD concentration, and may be appropriately set depending on the dosage form, administration method, subject weight, etc.

[0029] In one embodiment, when the agent of the present invention is orally administered to a human (adult), the total dosage of sesamin-class compounds is preferably 0.5 mg or more, more preferably 1 mg or more, even more preferably 3 mg or more, and preferably 200 mg or less, more preferably 100 mg or less, and even more preferably 80 mg or less per day per 60 kg body weight. In one embodiment, the total dosage of sesamin-class compounds is preferably 0.5 to 200 mg, more preferably 1 to 100 mg, and even more preferably 3 to 80 mg per day per 60 kg body weight for a human (adult). The above amount is preferably ingested or administered once or more times a day, for example, once a day or in divided doses several times (for example, 2 to 3 times). In one embodiment, the above amount of sesamin-class compounds is preferably orally ingested or administered to a human. In one embodiment, the agent of the present invention can be used to ingest or administer the above amount of sesamin-class compounds per day per 60 kg body weight to a human. When two or more types of sesamin-class compounds are used, the above total dosage is the total amount of these compounds. In one aspect, sesamin and / or episesamin are preferably orally ingested or administered to a human (adult) at a total dosage of sesamin and episesamin of preferably 0.5 to 200 mg, more preferably 1 to 100 mg, and even more preferably 3 to 80 mg per day per 60 kg body weight.

[0030] The agent of the present invention is preferably one that is continuously ingested or administered. It is expected that the above-mentioned effects of sesamin-class compounds will be enhanced by continuously ingesting or administering them. In one embodiment, the agent of the present invention is preferably continuously ingested or administered for at least one week, more preferably at least four weeks, even more preferably at least eight weeks, and particularly preferably at least twelve weeks.

[0031] The nicotinamide adenine dinucleotide (NAD) concentration elevating agent of the present invention may be labeled with a function exhibited by an increase in nicotinamide adenine dinucleotide (NAD) concentration, or a function exhibited by an increase, suppression of a decrease, maintenance, or improvement of NAD concentration. For example, one or more functions selected from the group consisting of "improvement, suppression of a decrease, maintenance, or improvement of mitochondrial function via an increase in NAD concentration", "improvement, suppression of a decrease, maintenance, or improvement of mitochondrial energy production ability via an increase in NAD concentration", "suppression and / or delay of aging due to a decrease in NAD concentration", "suppression of aging via an increase in NAD concentration", and "suppression and / or delay of cellular aging". In one aspect of the present invention, the agent of the present invention is preferably a food or drink labeled with the above-mentioned label. The above-mentioned label may be a label indicating that the agent is used to obtain the above-mentioned function.

[0032] The subject to which the agent of the present invention is ingested or administered (which may also be called the administration subject) is not particularly limited, and may be ingested by humans and non-human animals. Examples of non-human animals include industrial animals, pets, and laboratory animals. Specifically, industrial animals refer to animals that need to be raised industrially, such as livestock such as cows, horses, pigs, goats, and sheep, poultry such as chickens, ducks, quails, turkeys, and ostriches, and fish such as yellowtail, yellowtail, red sea bream, horse mackerel, carp, rainbow trout, and eels. Pets refer to so-called pets and companion animals such as dogs, cats, marmosets, small birds, and hamsters, and laboratory animals refer to animals used for research in the fields of medicine, biology, agriculture, and pharmacy, such as mice, rats, guinea pigs, beagles, miniature pigs, rhesus monkeys, and cynomolgus monkeys.

[0033] The subject to which the agent of the present invention is ingested or administered (which can also be referred to as an administration subject) is preferably a human or a non-human mammal, more preferably a human. In one embodiment, the subjects of administration include subjects who need or want to increase the nicotine adenine dinucleotide (NAD) concentration; subjects who need or want to improve, suppress, maintain or improve the NAD concentration. Examples of such subjects include middle-aged and elderly people, subjects who need or want to improve, suppress, maintain or improve mitochondrial function through an increase in NAD concentration, subjects who need or want to improve, suppress, maintain or improve the energy production ability of mitochondria through an increase in NAD concentration, and subjects who need or want to suppress and / or delay cellular aging through an increase in NAD concentration. Middle-aged and elderly people may be, for example, humans aged 40 years or older. In one embodiment, among middle-aged and elderly people, elderly people are preferred as subjects. Elderly people may be, for example, humans aged 60 years or older or 65 years or older. The agent of the present invention can also be used for healthy people for the purpose of preventing symptoms or diseases that can be prevented or improved by increasing the nicotinamide adenine dinucleotide (NAD) concentration, or by increasing, suppressing, maintaining or improving the NAD concentration.

[0034] The present invention also encompasses the following methods. A method for increasing nicotinamide adenine dinucleotide (NAD) levels by administering one or more types of sesamin derivatives. A method for increasing, inhibiting a decrease, maintaining or improving NAD concentration by administering one or more types of sesamin. A method for increasing, inhibiting a decrease, maintaining or ameliorating NAD concentration that has decreased with age, comprising administering one or more types of sesamin derivatives.

[0035] The present invention also encompasses the following uses: Use of one or more sesamin derivatives for increasing nicotinamide adenine dinucleotide (NAD) concentration. Use of one or more types of sesamin for increasing, inhibiting a decrease, maintaining or improving NAD concentration. Use of one or more types of sesamin for increasing, inhibiting the decrease, maintaining or improving NAD concentration that has decreased due to aging. The above methods and uses may be therapeutic or non-therapeutic methods or uses. By administering one or more types of sesamin, it is possible to increase the concentration of nicotinamide adenine dinucleotide (NAD). That is, it is possible to increase, suppress the decrease, maintain or improve the NAD concentration. It is also possible to increase, suppress the decrease, maintain or improve the NAD concentration that has decreased due to aging. This makes it possible to improve, suppress the decrease, maintain or improve mitochondrial function through the increase in NAD concentration, improve, suppress the decrease, maintain or improve mitochondrial energy production ability through the increase in NAD concentration, and suppress and / or delay cellular aging through the increase in NAD concentration.

[0036] In the above-mentioned method and use, the sesamin-class compounds and their preferred embodiments are the same as those of the agent of the present invention described above. As the one or more types of sesamins, one or more compounds of sesamin-class compounds may be used. In the above-mentioned method and use, it is preferable to administer (have the subject ingest) one or more types of sesamins to the subject at least once a day, for example, once to several times (for example, 2 to 3 times) a day. In the above-mentioned method and use, it is preferable to orally administer (have the subject ingest) the sesamin-class compounds. The above-mentioned use is preferably in humans or non-human mammals, more preferably in humans.

[0037] In the above-mentioned methods and uses, one or more types of sesamin compounds may be used in an amount (which may also be called an effective amount) that provides the desired effect (improvement, inhibition of decline, maintenance or improvement of mitochondrial function by increasing nicotinamide adenine dinucleotide (NAD) concentration, improvement, inhibition of decline or maintenance of mitochondrial energy production ability, and / or inhibition and / or delay of cellular aging). The preferred dosage and administration subjects of the sesamin compounds are the same as those of the agent or composition of the present invention described above. The sesamin compounds may be administered as they are, or as an agent or composition containing them. For example, the agent or composition of the present invention described above may be used.

[0038] The present invention also encompasses the use of one or more sesamin-class compounds for producing the agent or composition of the present invention. EXAMPLES

[0039] The present invention will be described in more detail below with reference to examples, although the present invention is not limited to these examples.

[0040] Examples 1 and 2, Comparative Example 1: Sesamin / episesamin mixture (SE) (sesamin:episesamin (weight ratio = 1:1)) + Concentration (NAD concentration) evaluation test> Intracellular NAD + To examine the effect on concentration, 1.0×10 5 HepG2 cells were seeded in a 12-well plate at 100 cells / well and cultured in DMEM medium (Nacalai Tesque, Inc., containing 10% FBS) for 24 hours under conditions of 37°C and CO2 (5%). After 24 hours of culture, the medium in each well was replaced with DMEM medium without sesamin / episesamin mixture (SE) (containing 1% albumin, no FBS (Comparative Example 1: control)), DMEM medium containing 1 μM SE (containing 1% albumin, no FBS (Example 1)), or DMEM medium containing 10 μM SE (containing 1% albumin, no FBS (Example 2)), and cultured for another 24 hours. Thereafter, the supplemented medium was removed, and the cells in the wells were washed with D-PBS (Nacalai Tesque, Inc.), and then extracted with NADH / NAD Extraction Buffer (NADH + The cell suspension was then collected by adding a NADH / NADH Quantification Colorimetric Kit (Biovision). Then, a cell extract was obtained according to the kit manual, and intracellular NAD + The concentration of intracellular NAD was analyzed. + The protein concentration of the cell extract was measured (Pierce (registered trademark) BCA Protein Assay Kit, Thermo Scientific) and the concentration was calculated as a value per protein concentration. The obtained results (average of N=2) are shown in FIG. 1.

[0041] As shown in Figure 1, intracellular NAD +The concentration was increased by 20% in the SE 1 μM group in Example 1 and 37% in the SE 10 μM group in Example 2, compared to the control group (medium not containing SE) in Comparative Example 1. From the above, it was found that intracellular NAD + A dose-dependent increase in concentration was observed.

Claims

1. A compound comprising sesamin and / or episesamin as active ingredients. Nicotinamide adenine dinucleotide (NAD) concentration increasing agent.

2. The agent according to claim 1, which increases, inhibits a decrease in, maintains or improves NAD concentration.

3. An agent as described in claim 1 or 2 for preventing or improving skin blemishes, freckles, hair loss, tooth loss, decreased eyesight, decreased hearing or decreased immune function mediated by an increase in NAD concentration.

4. The agent according to any one of claims 1 to 3, which is an oral composition.

5. The agent according to any one of claims 1 to 4, which is a food or drink.

6. A method for increasing nicotinamide adenine dinucleotide (NAD) concentrations by administering sesamin and / or episesamin (excluding medical procedures performed on humans).

7. A method for increasing, inhibiting a decrease, maintaining or improving nicotinamide adenine dinucleotide (NAD) concentration by administering sesamin and / or episesamin (excluding medical procedures performed on humans).

8. Use of sesamin and / or episesamin for increasing nicotinamide adenine dinucleotide (NAD) concentration (excluding medical treatment for humans).

9. Use of sesamin and / or episesamin for increasing, inhibiting a decrease, maintaining or improving nicotinamide adenine dinucleotide (NAD) concentration (excluding medical treatment for humans).

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