Nicotinamide adenine dinucleotide (NAD) concentrate

Abstract

DEPCT66 This invention aims to prepare a nicotinamide concentrate. Adenine dinucleotide (NAD) is a safe substance derived from food components; this invention relates to... with the nicotinamide adenine dinucleotide (NAD) concentrate, containing at least one Sesamin compounds -----------------------------------------------------------

Description

Nicotinamide adenine dinucleotide (NAD) concentration-increasing agent

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

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

[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 leading to many age-related pathologies. For example, Non-Patent Document 1 states that aging and age-related diseases are caused by the decrease in intracellular nicotinamide adenine dinucleotide (NAD ＋ ) levels, and NAD ＋ It has been suggested that this is related to the decreased activity of the longevity gene sirtuin, which is a NAD-dependent deacetylase. ＋ It has been reported that increasing NAD increases sirtuin activity and provides anti-aging effects (Non-Patent Document 2). ＋ Intensive research is being conducted to find ingredients that are effective in preventing or improving the decline in blood cholesterol levels and that can be applied to pharmaceuticals, foods for specified health uses, functional foods, etc.

[0004] Specifically, Non-Patent Document 2 has shown that the level of extracellular nicotinamide phosphoribosyltransferase (eNAMPT) decreases with age in mice and humans, and discloses that increasing eNAMPT promotes NAD levels, suppresses aging, and extends lifespan. Furthermore, supplementation with eNAMPT-containing extracellular vesicles (EVs) improves physical activity and extends lifespan in mice, suggesting that it may be a potential intervention for suppressing aging.

[0005] On the other hand, there has been no suggestion or disclosure whatsoever about the effect of sesamin and / or episesamin in increasing nicotinamide adenine dinucleotide (NAD) levels in the body.

[0006] Imai, S. & Guarente, L. (2014) Trends Cell Biol. , 24, 464-471. “NAD+ and sirtuins in aging and disease” 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”

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

[0008] The present inventors have conducted extensive research to solve the above problems and have found 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-elevating agent comprising one or more sesamin-class compounds as an active ingredient. [2] The agent according to [1] above, wherein the one or more sesamins are 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 of [1] to [3] above, which increases, inhibits a decrease in, maintains, or improves mitochondrial function through an increase in NAD concentration. [5] The agent according to any of [1] to [3] above, which increases, inhibits a decrease in, maintains, or improves mitochondrial energy production capacity through an increase in NAD concentration. [6] The agent according to any of [1] to [5] above, which is used to inhibit and / or delay aging associated with a decrease in NAD concentration. [7] The agent according to any of [1] to [6] above, 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 [1] to [8] above, 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) concentration by administering one or more sesamin derivatives.

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

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

[0011] 1 is a graph showing the effect of a sesamin / episesamin mixture (SE) (sesamin:episesamin (weight ratio = 1:1)) on increasing intracellular NAD levels.

[0012] The nicotinamide adenine dinucleotide (NAD) concentration-increasing agent of the present invention contains one or more sesamin compounds. One or more sesamin compounds are used to increase nicotinamide adenine dinucleotide (NAD) concentration, and have the effect of increasing, inhibiting a decrease, maintaining, or improving nicotinamide adenine dinucleotide (NAD) concentration, and are used to increase NAD concentration, inhibit a decrease in NAD concentration, maintain NAD concentration, or improve NAD concentration. In addition, the agent of the present invention is preferably used to increase, inhibit a 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. Note that NAD concentration refers to the intracellular NAD concentration.

[0013] Sesamin compounds have the effect of increasing nicotinamide adenine dinucleotide (NAD) levels and are expected to contribute to the prevention or improvement of aging associated with a decline in NAD levels by increasing, inhibiting, maintaining, or improving NAD levels. 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 wrinkled skin, hair and tooth loss, graying, fatigue accumulation and reduced recovery, decreased vision and hearing, decreased motor function, decreased muscle strength and activity, decreased sleep quality, and decreased bone mass. While aging itself is not considered a disease, declines in physical and physiological functions increase the risk of so-called geriatric diseases such as arteriosclerosis, abnormal glucose and lipid metabolism, neurodegeneration, osteoporosis, and cataracts. Furthermore, declines in physical functions can lead to aging of mental functions such as memory and learning. Increasing the nicotinamide adenine dinucleotide (NAD) concentration is effective in preventing or improving aging associated with a decrease in NAD concentration.

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

[0015] The nicotinamide adenine dinucleotide (NAD) concentration-elevating agent of the present invention can be used to treat conditions or diseases that can be prevented or improved by increasing, inhibiting, maintaining, or improving NAD concentration. Examples of such conditions or diseases include age-related decline in physical, physiological, and mental functions, specifically, the occurrence of skin aging symptoms (wrinkles, sagging, loss of skin elasticity, etc.), dry skin due to aging (decreased skin moisture retention), skin spots, freckles, and rough skin, decreased or increased secretion of hormones (growth hormone, thyroid hormone, adrenocortical hormone, sex hormone, prolactin, antidiuretic hormone, parathyroid hormone, melatonin, etc.), cell damage (brain cells, cardiac muscle cells, etc.) caused by active oxygen, hair and tooth loss, 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 the onset, delaying the 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, improving the symptoms of a condition or disease, delaying or preventing the progression of a condition or disease, etc.

[0016] In the present invention, "sesamins" refers to compounds including sesamin and its analogs. Sesamin is a major lignan compound found in sesame. Sesamin analogs include episesamin and, for example, the dioxabicyclo[3.3.0]octane derivatives described in Japanese Patent Application Laid-Open No. 4-9331. As one or more types of sesamin, one of these compounds may be used alone, or two or more may be used. Specific examples of sesamin analogs include sesamin, episesamin, sesaminol, episesaminol, sesamol, and sesamolin. These stereoisomers or racemates may be used alone or in mixtures. Furthermore, metabolites of sesamin analogs (e.g., those described in Japanese Patent Application Laid-Open No. 2001-139579) are also sesamin analogs included 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, with sesamin and episesamin being more preferred. When sesamin and episesamin are used, their ratio is not particularly limited, but for example, a weight ratio of sesamin:episesamin of 1:0.1 to 1:9 is preferred, 1:0.3 to 1:3 is more preferred, and 1:0.5 to 1:2 is even more preferred.

[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 (referred to as sesamin extract or purified product) extracted from sesame oil by known methods (e.g., the method described in Japanese Patent Application Laid-Open No. 4-9331) can be used. Alternatively, commercially available sesame oil (liquid) can be used as is. However, when sesame oil is used, the characteristic flavor of sesame oil can be perceived as sensorily undesirable. Therefore, it is preferable to use a tasteless and odorless sesamin extract (or purified sesamin product) extracted from sesame oil. Furthermore, when sesame oil is used, the sesamin content is low, and if a desired amount of sesamin is to be incorporated, the volume per unit dose of the formulated composition becomes too large, which can cause ingestion problems. In particular, when formulated for oral administration, the formulation (e.g., tablet, capsule) becomes too large, hindering ingestion. Therefore, from the viewpoint of requiring a small intake amount, it is preferable to use a sesamin extract (or purified sesamin 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-related compounds are found in natural products and foods and beverages, have a wide dietary history, and are recognized for their high safety. Sesamin-related compounds, with their 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 activating sirtuins and deacetylating downstream enzymes or transcription factors, thereby promoting the expression and synthesis of molecules involved in mitochondrial function and mitochondrial energy production. Therefore, an increase in NAD concentration can improve, inhibit decline, maintain, or improve mitochondrial function. The agent of the present invention can improve, inhibit decline, maintain, or improve mitochondrial function through an increase in NAD concentration. Furthermore, the agent of the present invention can improve, inhibit decline, maintain, or improve mitochondrial energy production capacity through an increase in NAD concentration. This also allows the agent of the present invention to exhibit 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 pertains, and the method for doing so is not particularly limited. For example, mitochondrial function can be evaluated by using an extracellular flux analyzer to continuously measure the oxygen consumption rate (hereinafter also referred to as "OCR") used by mitochondria during ATP synthesis in the cells being measured while adding an ATP synthase inhibitor (e.g., oligomycin and rotenone) and an uncoupler (e.g., carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP)). Mitochondrial function can be evaluated, for example, by analyzing 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 used for either therapeutic (medical) or non-therapeutic (non-medical) purposes. Non-therapeutic does not include medical procedures, i.e., surgery, treatment, or diagnosis in humans. The agent of the present invention can be in the form of a food or beverage, a drug, a quasi-drug, a feed, or the like. The agent of the present invention may be a food or beverage, a drug, a quasi-drug, a feed, or the like that is used to increase nicotinamide adenine dinucleotide (NAD) concentration, or to improve, inhibit decline, maintain, or improve NAD concentration, or may be a material or preparation that is incorporated therein. Furthermore, the agent of the present invention may be a food or beverage, a drug, a quasi-drug, a feed, or the like that is used to improve, inhibit decline, maintain, or improve mitochondrial function through an increase in NAD concentration, or to improve, inhibit decline, maintain, or improve mitochondrial energy production capacity through an increase in NAD concentration, or may be a material or preparation that is incorporated therein. For example, the agent of the present invention can be provided in the form of a drug, but is not limited to this form. The agent can also be provided as a composition as 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. Oral agents may be foods and beverages, oral medicines, quasi-drugs, feeds, etc. themselves, or may be contained in these. The agent of the present invention is preferably a food and beverage or oral medicine, more preferably a food and beverage.

[0023] The agent of the present invention can contain any additives and any components in addition to one or more sesamin-class compounds, as long as the effects of the present invention are not impaired. These additives and components can be selected depending on the form of the agent or composition, and those that can generally be used in foods and beverages, pharmaceuticals, quasi-drugs, feed, etc. can be used. When the agent of the present invention is used as a food and beverage, pharmaceutical, 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 beverage, various foods and beverages can be prepared by blending one or more sesamin-class compounds with ingredients that can be used in foods and beverages (e.g., food ingredients, food additives used as needed, etc.). The foods and beverages are not particularly limited, and examples include general foods and beverages, health foods, health drinks, functional foods, foods for specified health uses, and foods and beverages for patients. The health foods, functional foods, foods for specified health uses, etc. can be used in various dosage forms, such as fine granules, tablets, granules, powders, capsules, chewable tablets, dry syrups, syrups, liquids, beverages, and liquid diets.

[0025] When the agent of the present invention is used as a pharmaceutical or quasi-drug, various dosage forms of pharmaceutical or quasi-drug products can be prepared by blending one or more sesamin compounds with a pharmacologically acceptable carrier and optional additives. Such carriers, additives, etc. may be any pharmacologically acceptable carriers that can be used in pharmaceuticals or quasi-drugs, and may include, for example, one or more of excipients, binders, disintegrants, lubricants, antioxidants, colorants, etc. Pharmaceutical or quasi-drug administration forms include oral and parenteral (transdermal, transmucosal, enteral, injection, etc.) administration forms. When the agent of the present invention is used as a pharmaceutical or quasi-drug, oral pharmaceutical or quasi-drug products are preferred. Dosage forms for oral administration include liquids, tablets, powders, fine granules, granules, sugar-coated tablets, capsules, suspensions, emulsions, chewable tablets, etc. Pharmaceuticals may also be used for non-human animals.

[0026] When the agent of the present invention is used as feed, one or more sesamin-class compounds may be blended into 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.; and pet food for dogs, cats, small birds, etc.

[0027] The content of sesamin 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 compounds in the agent of the present invention is, for example, preferably 0.001 wt% or more, more preferably 0.01 wt% or more, even more preferably 0.05 wt% or more, and preferably 10 wt% or less, more preferably 5 wt% or less. In one embodiment, the total content of sesamin compounds in the agent is preferably 0.001 to 10 wt%, more preferably 0.01 to 5 wt%, even more preferably 0.05 to 5 wt%. When two or more types of sesamin compounds are contained, the 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 referred to as 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 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 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 to a human (adult). It is preferable to ingest or administer the above amount once or more times per day, for example, once or several times (e.g., 2 to 3 times) per day. In one embodiment, it is preferable to orally ingest or administer the above amount of sesamin compounds to a human. In one embodiment, the agent of the present invention can be used to ingest or administer the above amount of sesamin compounds per day per 60 kg body weight to a human. When two or more sesamin compounds are used, the above total dosage is the combined amount of these compounds. In one aspect, it is preferable that sesamin and / or episesamin be 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 ingested or administered continuously. It is expected that the above-mentioned effects will be enhanced by the continuous ingestion or administration of sesamin-class compounds. In one embodiment, the agent of the present invention is preferably ingested or administered continuously for at least one week, more preferably at least four weeks, even more preferably at least eight weeks, and particularly preferably at least 12 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 improving, inhibiting, maintaining, or improving NAD concentration. For example, such a label may be labeled with one or more functions selected from the group consisting of "improving, inhibiting, maintaining, or improving mitochondrial function through an increase in NAD concentration," "improving, inhibiting, maintaining, or improving mitochondrial energy production capacity through an increase in NAD concentration," "inhibiting and / or delaying aging through a decrease in NAD concentration," "inhibiting aging through an increase in NAD concentration," and "inhibiting and / or delaying cellular aging." In one aspect of the present invention, the agent of the present invention is preferably a food or beverage labeled with the above-mentioned label. The above-mentioned label may also be a label indicating that the agent is used to achieve the above-mentioned function.

[0032] The subject (which can also be referred to as the administration subject) to which the agent of the present invention is administered or ingested is not particularly limited, and can be humans or 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, while laboratory animals refer to animals used in research in fields such as medicine, biology, agriculture, and pharmacy, such as mice, rats, guinea pigs, beagles, minipigs, rhesus monkeys, and cynomolgus monkeys.

[0033] The subject (which can also be referred to as the administration subject) to whom the agent of the present invention is ingested or administered is preferably a human or non-human mammal, more preferably a human. In one embodiment, the administration subject includes a subject requiring or desiring an increase in nicotine adenine dinucleotide (NAD) concentration; a subject requiring or desiring an increase, suppression of decline, maintenance, or improvement of NAD concentration, etc. Examples of such subjects include middle-aged and elderly subjects, subjects requiring or desiring an improvement, suppression of decline, maintenance, or improvement of mitochondrial function through an increase in NAD concentration, subjects requiring or desiring an improvement, suppression of decline, maintenance, or improvement of mitochondrial energy production capacity through an increase in NAD concentration, and subjects requiring or desiring an inhibition and / or delay of cellular aging through an increase in NAD concentration. Middle-aged and elderly subjects may be, for example, humans aged 40 or older. In one embodiment, among middle-aged and elderly subjects, elderly subjects are preferred. Elderly subjects may be, for example, humans aged 60 or older or 65 or older. The agent of the present invention can also be used in healthy individuals for the purpose of, for example, increasing nicotinamide adenine dinucleotide (NAD) concentration, or preventing or improving symptoms or diseases that can be expected to be prevented or improved by improving, suppressing a decrease, maintaining, or improving 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 sesamin derivatives; A method for increasing, inhibiting a decrease in, maintaining, or improving NAD levels by administering one or more sesamin derivatives; A method for increasing, inhibiting a decrease in, maintaining, or improving NAD levels that have decreased with age by administering one or more sesamin derivatives.

[0035] The present invention also encompasses the following uses: Use of one or more sesamin compounds for increasing nicotinamide adenine dinucleotide (NAD) levels; Use of one or more sesamin compounds for increasing, inhibiting decline, maintaining, or improving NAD levels; Use of one or more sesamin compounds for increasing, inhibiting decline, maintaining, or improving NAD levels that have declined due to aging. The above methods and uses may be therapeutic or non-therapeutic. By administering one or more sesamin compounds, it is possible to increase nicotinamide adenine dinucleotide (NAD) levels. That is, it is possible to increase, inhibit decline, maintain, or improve NAD levels. It is also possible to increase, inhibit decline, maintain, or improve NAD levels that have declined due to aging. This makes it possible to improve, inhibit decline, maintain, or improve mitochondrial function through an increase in NAD levels, improve, inhibit decline, maintain, or improve mitochondrial energy production capacity through an increase in NAD levels, and inhibit and / or delay cellular aging through an increase in NAD levels.

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

[0037] In the above-mentioned methods and uses, one or more sesamin compounds may be used in an amount (which may also be called an effective amount) that will achieve the desired effect (improvement, inhibition of decline, maintenance or improvement of mitochondrial function, improvement, inhibition of decline or maintenance of mitochondrial energy production capacity, and / or inhibition and / or delay of cellular aging due to an increase in nicotinamide adenine dinucleotide (NAD) concentration). The preferred dosage and administration subjects of sesamin compounds are the same as those of the agent or composition of the present invention described above. Sesamin compounds may be administered as is, 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.

[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: Intracellular NAD by 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 1000 cells / well and incubated at 37°C under CO ２ The cells were cultured for 24 hours in DMEM medium (Nacalai Tesque, Inc., containing 10% FBS) under conditions of (5%). After 24 hours of culture, the medium in each well was replaced with DMEM medium (containing 1% albumin, no FBS (Comparative Example 1: control)) containing no sesamin / episesamin mixture (SE), DMEM medium (containing 1% albumin, no FBS (Example 1)) containing 1 μM SE, or DMEM medium (containing 1% albumin, no FBS (Example 2)) containing 10 μM SE, 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 NADH / NAD Extraction Buffer (NAD ＋A NADH / NADH Quantification Colorimetric Kit (Biovision) was added to the cells, and the cell suspension was collected. Then, a cell extract was obtained according to the kit manual, and intracellular NAD ＋ The concentration of intracellular NAD ＋ 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 Figure 1.

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

Claims

DEPCT661 Nicotinamide adenine dinucleotide (NAD) concentrate, which contains:

1. at least one sesamin compound as the active ingredient; 2. a substance under claim 1, in which at least one sesamin compound includes at least one sesamin or episesamin; 3. a substance under claim 1 or 2, in which the substance improves, maintains, or enhances NAD concentration or reduces degradation in NAD concentration; 4. any one of claims 1 through 3, in which the substance improves, maintains, or enhances mitochondrial function or 5. Any substance under claims 1 through 3, where the substance improves, maintains, or enhances mitochondrial energy production capacity or reduces deterioration in mitochondrial energy production capacity through an increase in NAD concentration.

6. Any substance under claims 1 through 5, where the substance is used to inhibit and / or delay aging associated with a decrease in NAD concentration.

7. Any substance under claims 1 through 6, where the substance is an orally administered component. 8.

9. Any substance under any of the claims 1 through 7, where the substance is a food or beverage.

10. Any substance under any of the claims 1 through 8, where the substance is labeled with at least one of the "inhibition and / or delay of aging associated with a reduction in NAD concentration" or "inhibition and / or delay of cellular aging processes".

11. A method of increasing the concentration of nicotinamide adenine dinucleotide (NAD), which involves the action of at least one sesamin compound.

12. A method of improving, maintaining, or enhancing the concentration of The use of at least one sesamin compound for increasing the concentration of nicotinamide adenine dinucleotide (NAD) or reducing the degradation of NAD concentration, which involves the action of at least one sesamin compound.

12. The use of at least one sesamin compound for increasing the concentration of nicotinamide adenine dinucleotide (NAD).

13. The use of at least one sesamin compound for improving, maintaining, or enhancing the concentration of nicotinamide adenine dinucleotide (NAD) or reducing the degradation of NAD concentration.

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