CN115867289A - Composition containing NR and/or NMN and sesamin - Google Patents
Composition containing NR and/or NMN and sesamin Download PDFInfo
- Publication number
- CN115867289A CN115867289A CN202180049335.0A CN202180049335A CN115867289A CN 115867289 A CN115867289 A CN 115867289A CN 202180049335 A CN202180049335 A CN 202180049335A CN 115867289 A CN115867289 A CN 115867289A
- Authority
- CN
- China
- Prior art keywords
- nad
- concentration
- nicotinamide
- nmn
- composition
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
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- 239000000203 mixture Substances 0.000 title claims abstract description 137
- PEYUIKBAABKQKQ-AFHBHXEDSA-N (+)-sesamin Chemical compound C1=C2OCOC2=CC([C@H]2OC[C@H]3[C@@H]2CO[C@@H]3C2=CC=C3OCOC3=C2)=C1 PEYUIKBAABKQKQ-AFHBHXEDSA-N 0.000 title claims description 98
- PEYUIKBAABKQKQ-UHFFFAOYSA-N epiasarinin Natural products C1=C2OCOC2=CC(C2OCC3C2COC3C2=CC=C3OCOC3=C2)=C1 PEYUIKBAABKQKQ-UHFFFAOYSA-N 0.000 title claims description 94
- VRMHCMWQHAXTOR-CMOCDZPBSA-N sesamin Natural products C1=C2OCOC2=CC([C@@H]2OC[C@@]3(C)[C@H](C=4C=C5OCOC5=CC=4)OC[C@]32C)=C1 VRMHCMWQHAXTOR-CMOCDZPBSA-N 0.000 title claims description 61
- DAYLJWODMCOQEW-TURQNECASA-N NMN zwitterion Chemical compound NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](COP(O)([O-])=O)O2)O)=C1 DAYLJWODMCOQEW-TURQNECASA-N 0.000 claims abstract description 127
- 235000020956 nicotinamide riboside Nutrition 0.000 claims abstract description 120
- 239000011618 nicotinamide riboside Substances 0.000 claims abstract description 120
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- 239000004480 active ingredient Substances 0.000 claims abstract description 4
- BAWFJGJZGIEFAR-NNYOXOHSSA-N NAD zwitterion Chemical compound NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 BAWFJGJZGIEFAR-NNYOXOHSSA-N 0.000 claims description 151
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 claims description 115
- 229950006238 nadide Drugs 0.000 claims description 108
- JLEBZPBDRKPWTD-TURQNECASA-O N-ribosylnicotinamide Chemical compound NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](CO)O2)O)=C1 JLEBZPBDRKPWTD-TURQNECASA-O 0.000 claims description 105
- 229940101270 nicotinamide adenine dinucleotide (nad) Drugs 0.000 claims description 42
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- BOPGDPNILDQYTO-NNYOXOHSSA-N nicotinamide-adenine dinucleotide Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 BOPGDPNILDQYTO-NNYOXOHSSA-N 0.000 description 7
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Abstract
The purpose of the present invention is to provide a composition having an effect of increasing the concentration of NAD. The present invention relates to a composition characterized by containing 1 or more sesamins selected from Nicotinamide Riboside (NR), nicotinamide Mononucleotide (NMN) and salts thereof as an active ingredient.
Description
Technical Field
The present invention relates to a composition containing sesamin and at least one selected from Nicotinamide Riboside (NR), nicotinamide Mononucleotide (NMN) and salts thereof.
Background
In recent years, in countries with a high proportion of elderly people, the extension of health life has become a problem. One of the factors that contribute to the shortening of the healthy life is the accompanying yearsIncrease in age, nicotinamide Adenine Dinucleotide (NAD) in vivo + ) The production of (2) and the decrease in physical functions and the like.
Here, nicotinamide Adenine Dinucleotide (NAD) + (hereinafter also referred to as NAD)) is a coenzyme that mediates a variety of redox reactions in vivo. NAD levels are known to decrease during aging, causing nuclear and mitochondrial dysfunction, and causing a variety of age-associated pathologies. For example, non-patent document 1 suggests aging or aging-related diseases and intracellular Nicotinamide Adenine Dinucleotide (NAD) + ) Reduced levels, and as NAD + Sirtuin's enzymatic activity of deacetylase-dependent longevity genes is associated with a decrease in Sirtuin's enzymatic activity. In recent years, it has been reported that NAD is used + In addition, sirtuin is activated to obtain an anti-aging effect (non-patent document 2). Therefore, research is being conducted on NAD accompanying the increase in age + Is effective in preventing or improving the decrease of the content of the compound (I), and can be used for searching for ingredients of pharmaceuticals, specific health foods, functional foods, etc.
For example, non-patent document 3 discloses that Nicotinamide Ribose (NR), which is a NAD precursor, induces a protein response for mitochondrial unfolding and synthesis of an antiproliferative protein, thereby activating muscle stem cells (muscs) of aged mice. Furthermore, NR is disclosed to prevent MuSC aging in mouse models of muscular dystrophy, NR delays aging of neural SC (stem cells), melanocyte SC prolongs the lifespan of mice.
Further, nicotinamide Ribose (NR) is shown as NAD in non-patent document 4 + The precursor vitamins are widely used, through a single oral administration of NR, NAD in the blood of humans + The concentration dose dependence increases. Further, non-patent document 5 shows that NMN activates Sirtuin, and specifically shows that natural NAD is administered mainly to normal wild-type mice + Nicotinamide Mononucleotide (NMN) of the intermediate (also known as an intermediate metabolite) was effective at mitigating physiological decline associated with age increase in mice without significant toxicity for 12 months, demonstrating the great potential for NMN as an effective anti-aging intervention in humans.
On the other hand, sesamin and/or episesamin have not been suggested or disclosed at all for its action of elevating Nicotinamide Adenine Dinucleotide (NAD) in vivo.
Non-patent document
Non-patent document 1: imai, S. & Guarente, L. (2014) Trends Cell biol.,24, 464-471."NAD + and sirtuins in imaging 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 vector-connected eNAPT delay Aging and extensions Lifespan in Mice"
Non-patent document 3: zhang, h, ryu, D, wu, y, gariani, k, wang, x, luan, p, D' Amico, D, ropelle, e.r., lutolf, m.p., aebersold, r, schooljans, k.a., menzies, k.j., auwerx, j. (2016) Science,352, 1436-1443, "NAD + repetition approach mitochondondrial and stem cell function and hand life span in micro"
Non-patent document 4: trammel A. J. Trammel, mark S.Schmidt, benjamin J. Weidmemann, philip Redpath, frank Jaksch, ryan W.Dellinger, zhonggang Li, E Dale Abel, marie E.Migaud & Charles Brenner, (2016) nat. Commun.7, 12948."Nicotinamide rib is uniquely and always bioavailable in mice and humans"
Non-patent document 5: mills, K.F., yoshida, S.A., stein, L.R., grozio, A.A., kubota, S.A., sasaki, Y.A., redpath, P.A., migaud, M.E., apte, R.S., uchida, K.A., yoshino, J., & Imai, S.I. (2016) Cell method, 24, 795-806."Long-Term Administration of Nicotinamide monoglucoside Mitigates Age-Associated Physiological deficiency in Mice"
Disclosure of Invention
The purpose of the present invention is to provide a composition having an effect of increasing the concentration of NAD.
The present inventors have intensively studied to solve the above problems, and as a result, have found that a composition containing a sesamin compound and at least 1 selected from Nicotinamide Ribose (NR), nicotinamide Mononucleotide (NMN) and a salt thereof, wherein the sesamin compound has a Nicotinamide Adenine Dinucleotide (NAD) elevating activity, effectively elevates Nicotinamide Adenine Dinucleotide (NAD).
The present invention relates to the following compositions.
[1] A composition comprising 1 or more sesamins selected from NR which is nicotinamide riboside, NMN which is nicotinamide mononucleotide and salts thereof as an active ingredient.
[2] The composition according to the above [1], wherein the 1 or more sesamins are sesamin and/or episesamin.
[3] The composition according to the above [1] or [2], wherein the molar ratio of 1 or more selected from the group consisting of NR, NMN and salts thereof to sesamins, that is, 1 or more selected from the group consisting of NR, NMN and salts thereof per sesamin is 1 to 100.
[4] The composition according to any one of the above [1] to [3], wherein the total content of the 1 or more sesamins is 0.001 to 10% by weight.
[5] The composition according to any one of the above [1] to [4], wherein the concentration of NAD, which is a nicotinamide adenine dinucleotide concentration, is increased, the decrease thereof is suppressed, and the concentration of NAD is maintained or improved.
[6] The composition according to any one of the above [1] to [5], which is characterized by enhancing mitochondrial function, suppressing the reduction thereof, maintaining or improving mitochondrial function.
[7] The composition according to any one of the above [1] to [6], characterized by increasing energy production energy of mitochondria, suppressing the decrease thereof, maintaining or improving the energy production energy of mitochondria.
[8] The composition according to any one of the above [1] to [7], which is used for suppressing and/or delaying aging accompanying a decrease in NAD concentration.
[9] The composition according to any one of the above [1] to [8], which is an anti-aging composition.
[10] The composition according to any one of the above [1] to [9], which is a composition for oral administration.
[11] The composition according to any one of the above [1] to [10], which is a food or drink.
[12] The composition according to any one of the above [1] to [11], which is characterized by being labeled "inhibition and/or delay of aging associated with decrease in NAD concentration" and/or "inhibition and/or delay of cell aging".
[13] A method for increasing the concentration of Nicotinamide Adenine Dinucleotide (NAD) which is characterized by administering 1 or more sesamins selected from the group consisting of Nicotinamide Ribose (NR), nicotinamide Mononucleotide (NMN) and salts thereof.
[14] A method for increasing, reducing, inhibiting, maintaining or improving the concentration of NAD (nicotinamide adenine dinucleotide), which is characterized in that 1 or more sesamins selected from NR, NMN, and salts thereof, which is nicotinamide ribose, and 1 or more sesamins are administered.
[15] An application, characterized in that 1 or more sesamins selected from the group consisting of Nicotinamide Riboside (NR), nicotinamide Mononucleotide (NMN) and salts thereof, and 1 or more sesamins are used for increasing Nicotinamide Adenine Dinucleotide (NAD) concentration.
[16] An application of 1 or more sesamins selected from the group consisting of Nicotinamide Riboside (NR), nicotinamide Mononucleotide (NMN) and salts thereof to increase, reduce, inhibit, maintain and improve the concentration of Nicotinamide Adenine Dinucleotide (NAD).
The present invention provides a composition having an effect of increasing the concentration of Nicotinamide Adenine Dinucleotide (NAD).
Drawings
FIG. 1 is a graph showing a structure in which 1: a graph showing the effect of increasing intracellular NAD concentration of sesamin or NR in a composition containing sesamin and episesamin mixture (SE) (sesamin: episesamin (weight ratio = 1): 1)) and NR at a molar ratio of 100.
FIG. 2 shows a graph in which 1: a composition containing sesamin and episesamin mixture (SE) (sesamin: episesamin (weight ratio = 1)) and NR at a molar ratio of 1, and a graph showing the effect of increasing intracellular NAD concentration of SE or NR.
FIG. 3 shows a graph in which 1:3.3 or 1.
FIG. 4 shows a graph in which 1:3 or 1.
Detailed Description
The composition of the present invention contains 1 or more sesamins.
Sesamins have an effect of increasing the concentration of Nicotinamide Adenine Dinucleotide (NAD), and have an effect of increasing, suppressing, maintaining or improving the concentration of intracellular Nicotinamide Adenine Dinucleotide (NAD), and are used for increasing the concentration of NAD, suppressing the decrease in the concentration of NAD, maintaining the concentration of NAD, or improving the concentration of NAD. The concentration of Nicotinamide Adenine Dinucleotide (NAD) is increased, and the amount of Nicotinamide Adenine Dinucleotide (NAD) is increased. The NAD concentration refers to the intracellular NAD concentration.
Sesamins have an effect of increasing the concentration of Nicotinamide Adenine Dinucleotide (NAD), and are expected to contribute to the prevention or improvement of aging associated with a decrease in the concentration of NAD by increasing, reducing, suppressing, maintaining, or improving the concentration of NAD. Aging is understood as the phenomenon of decline of physical, physiological and mental functions. After aging-based body changes reach maturity, wrinkles of the skin, loss of hair or teeth, graying of hair, accumulation of fatigue or reduction in recovery power, visual or auditory deterioration, motor function deterioration, reduction in muscle strength or activity, reduction in sleep quality, reduction in bone mass, and the like are observed from about 40 years old. Although aging itself is not called a disease, the decrease in physical function and physiological function increases the risk of so-called senile diseases such as arteriosclerosis, abnormal sugar and lipid metabolism, nerve loss degeneration, osteoporosis, and cataract, and aging related to mental functions such as memory and learning occurs with the deterioration of physical function. Increasing the concentration of Nicotinamide Adenine Dinucleotide (NAD) is effective for preventing or improving aging accompanying the decrease in NAD concentration.
(sesamin compounds)
In the present invention, sesamin compounds are a generic term for compounds including sesamin and analogues thereof. Sesamin is one of the main lignan compounds contained in sesame. Examples of the sesamin analogues include, in addition to episesamin, dioxabicyclo [3.3.0] octane derivatives described in jp-a-4-9331. As 1 or more sesamins, 1 or more of these compounds may be used alone, or 2 or more of them may be used. Specific examples of sesamin compounds include sesamin, episesamin, sesaminol, episesamin, sesamol, sesamolin, and the like, and stereoisomers or racemates thereof may be used alone or in combination. Metabolites of sesamins (for example, as described in Japanese patent application laid-open No. 2001-139579) are sesamin analogs included in sesamins of the present invention, as long as the effects of the present invention are exhibited, and can be used in the present invention. In the present invention, sesamin and/or episesamin may be preferably used as the 1 or more sesamins, and sesamin and episesamin may be more preferably used. When sesamin and episesamin are used, the ratio thereof is not particularly limited, and examples thereof include sesamin: episesamin (weight ratio) is preferably 1.
The sesamin-based compound used in the present invention is not limited at all in terms of its form, production method, and the like. For example, in the case of sesamin, sesamin (referred to as sesamin extract or purified product) extracted from sesame oil by a known method (for example, the method described in japanese patent application laid-open No. 4-9331) can be used. In addition, commercially available sesame oil (liquid) may be used as it is. However, when sesame oil is used, since the flavor peculiar to sesame oil may not be evaluated good in a sensory manner, it is preferable to use a sesamin extract (or a sesamin purified product) which is extracted from sesame oil and is odorless. In addition, when sesame oil is used, since the sesamin content is low, if a preferred amount of sesamin is to be formulated, the volume per unit dose of the formulation composition becomes excessively large, and thus inconvenience may occur at the time of ingestion. In particular, when the preparation is prepared for oral administration, the preparation (tablet, capsule, etc.) becomes too large and causes a trouble in ingestion. Accordingly, from the viewpoint that the intake amount can be small, it is preferable to use a sesamin extract (or a sesamin purified product) derived from sesame oil. Sesamin can also be obtained by synthesis. As a method therefor, for example, sesamin and episesamin can be synthesized by a method of Beroza et al (j.am. Chem. Soc.,78, 1242 (1956)). Sesamin and episesamin metabolites can be synthesized by the method of Urata et al (chem. Pharm. Bull. (Tokyo), 56 (11) 1611-2 (2008)).
Sesamins are contained in natural products or foods and drinks, and are compounds that have been recognized for their high safety because of their abundant experience in eating. Sesamin compounds with ensured safety are suitable for continuous intake and long-term intake.
(nicotinamide riboside (NR), nicotinamide Mononucleotide (NMN) and salts thereof)
The composition of the present invention contains 1 or more selected from Nicotinamide Riboside (NR), nicotinamide Mononucleotide (NMN), and salts thereof.
NR and NMN are intermediates of NAD. NR is known to be converted to NMN by Nicotinamide Ribokinase (NRK) to synthesize NAD + . NR, NMN, and salts thereof are known compounds, and can be produced by known production methods, and commercially available products can be used.
As the salt of NR and/or NMN, a pharmacologically acceptable salt can be used, and examples thereof include an acid addition salt and a base addition salt. Specific examples thereof include metal salts (for example, alkali metal salts such as sodium salt and potassium salt; alkaline earth metal salts such as calcium salt, magnesium salt and barium salt), ammonium salts, salts with inorganic acids (for example, salts with inorganic acids such as hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid and phosphoric acid), and salts with organic acids (for example, salts with organic acids such as acetic acid, phthalic acid, fumaric acid, oxalic acid, tartaric acid, maleic acid, citric acid, succinic acid, methanesulfonic acid and p-toluenesulfonic acid).
The salt of NR and/or NMN is preferably a salt that can be used in foods, drinks, pharmaceuticals, and the like, and examples thereof include chloride; alkali metal salts such as sodium salt and potassium salt; alkaline earth metal salts such as calcium salts and magnesium salts. As the salt of NR, nicotinamide ribochloride (chloride) is preferred.
(composition containing 1 or more sesamin selected from Nicotinamide Riboside (NR), nicotinamide Mononucleotide (NMN) and their salts and 1 or more sesamin)
The composition of the present invention contains 1 or more selected from the group consisting of Nicotinamide Riboside (NR), nicotinamide Mononucleotide (NMN) and salts thereof, and 1 or more sesamins. The composition of the present invention contains 1 or more selected from Nicotinamide Riboside (NR), nicotinamide Mononucleotide (NMN) and salts thereof, and 1 or more sesamins as active ingredients. The composition of the present invention may be a composition for increasing the concentration of Nicotinamide Adenine Dinucleotide (NAD).
In the composition of the present invention, the molar ratio of 1 or more selected from NR, NMN and salts thereof to sesamins (1 or more selected from NR, NMN and salts thereof/sesamin) is preferably 1 to 100 from the viewpoint of effectively increasing the effect of increasing the concentration of Nicotinamide Adenine Dinucleotide (NAD), that is, from the viewpoint of effectively increasing the effect of increasing the concentration of NAD, reducing the inhibitory effect, maintaining the effect or improving the effect. The molar ratio of 1 or more selected from NR, NMN and salts thereof to sesamins (1 or more selected from NR, NMN and salts thereof per sesamin) is more preferably 3 to 80, and still more preferably 5 to 50. Since the anti-aging effect is exerted by increasing the concentration of Nicotinamide Adenine Dinucleotide (NAD), that is, increasing, decreasing, inhibiting, maintaining, or improving the concentration of NAD, the composition of the present invention preferably has the molar ratio of NR, NMN, or a salt thereof to sesamins in the above specific range from the viewpoint of the anti-aging effect.
In the present specification, when the amount of NR, NMN or a salt thereof is expressed, a value converted to the amount of Nicotinamide Ribose (NR) is used. The equivalent weight of 1 or more NR selected from NR, NMN and salts thereof is the equivalent value of NR to the total weight of NR, NMN and salts thereof.
The total content of 1 or more sesamins contained in the composition of the present invention is not particularly limited, and may be set according to the form and the like.
The total content of sesamins in the composition of the present invention is, for example, preferably 0.001 wt% or more, more preferably 0.01 wt% or more, still more preferably 0.05 wt% or more, and further preferably 10 wt% or less, more preferably 5 wt% or less in the composition. In one embodiment, the total content of sesamins in the composition is preferably 0.001 to 10% by weight, more preferably 0.01 to 5% by weight, and still more preferably 0.05 to 5% by weight. The total content is a total content of 2 or more sesamin-based compounds when they are contained.
The total content of 1 or more selected from Nicotinamide Ribose (NR), nicotinamide Mononucleotide (NMN), and salts thereof contained in the composition of the present invention is not particularly limited, and may be set according to the form thereof.
The total content of 1 or more selected from Nicotinamide Riboside (NR), nicotinamide Mononucleotide (NMN) and salts thereof in the composition of the present invention is, for example, preferably 0.001% by weight or more, more preferably 0.01% by weight or more, further preferably 0.05% by weight or more, and further preferably 95% by weight or less, more preferably 80% by weight or less in the composition. In one embodiment, the total content of 1 or more selected from Nicotinamide Riboside (NR), nicotinamide Mononucleotide (NMN), and salts thereof is preferably 0.001 to 95% by weight, more preferably 0.01 to 80% by weight, and still more preferably 0.05 to 70% by weight in the composition. When the total content of the above-mentioned compounds is 2 or more compounds selected from Nicotinamide Riboside (NR), nicotinamide Mononucleotide (NMN) and salts thereof, the total content is the content of these compounds.
The composition of the present invention is a composition capable of increasing the concentration of Nicotinamide Adenine Dinucleotide (NAD), suppressing the decrease of Nicotinamide Adenine Dinucleotide (NAD), and maintaining or improving the concentration of Nicotinamide Adenine Dinucleotide (NAD), and a composition capable of increasing the concentration of Nicotinamide Adenine Dinucleotide (NAD) decreased with age, suppressing the decrease of Nicotinamide Adenine Dinucleotide (NAD), and maintaining or improving the concentration of Nicotinamide Adenine Dinucleotide (NAD) decreased with age.
NAD in vivo activates Sirtuin to deacetylate downstream enzymes and transcription factors, thereby playing an important role in promoting expression and synthesis of molecules involved in mitochondrial function and energy production of mitochondria. Thus, by increasing, decreasing, inhibiting, maintaining, or improving the NAD concentration, an effect of increasing, decreasing, inhibiting, maintaining, or improving mitochondrial function can be obtained. The composition of the present invention can increase, inhibit, maintain or improve mitochondrial function. In addition, the composition of the invention can increase energy production energy of mitochondria, inhibit the energy production energy from mitochondria from decreasing, maintain or improve the energy production energy of mitochondria. Furthermore, the composition of the present invention thus exerts an anti-cell aging effect.
In the present specification, the mitochondrial function and energy generation ability of mitochondria may be evaluated based on general knowledge in the technical field to which the present invention pertains, and the method is not particularly limited. For example, mitochondrial function can be evaluated by continuously measuring the oxygen consumption rate (hereinafter also referred to as "OCR") used by mitochondria in ATP synthesis in a cell to be measured, using an extracellular flow analyzer, while adding an ATP synthase inhibitor (e.g., oligomycin or rotenone) and a decoupling agent (e.g., trifluoromethoxyphenylhydrazone carbonyl cyanide (FCCP)). The evaluation items can evaluate mitochondrial function by analyzing the basal respiration rate, ATP production energy, and maximum respiration rate, which are main indicators for evaluating mitochondrial function, for example.
The compositions of the present invention are useful for inhibiting and/or retarding aging, preferably for inhibiting and/or retarding aging with a decrease in NAD concentration.
In one embodiment, the composition of the present invention is a substance that increases, inhibits, maintains or improves the concentration of NAD, and is preferably used for increasing, inhibiting, maintaining or improving the concentration of NAD that decreases with age.
In one embodiment, the method is preferably used for increasing, decreasing, inhibiting, maintaining or improving the concentration of NAD that decreases with age in middle-aged and elderly people. The middle-aged and the elderly include the elderly. The elderly may be, for example, humans over the age of 40, and the elderly may be, for example, humans over the age of 60 or over the age of 65.
The NAD concentration of animals such as humans can be measured by a method generally used in the art to which the present invention pertains, and for example, amplite (registered trademark) Colorimetric NAD/NADH Ratio Assay Kit (AAT Bioquest Co., ltd.) or NAD can be used + The NADH Quantification Colorimetric Kit (Biovision) measures intracellular NAD concentration.
The composition of the present invention can be used for treating a condition or disease for which prevention or improvement is expected, by inhibiting, maintaining or improving the increase or decrease in NAD concentration. Such conditions or diseases include, for example, aging symptoms (wrinkles, sagging, loss of skin firmness, etc.), skin spots, freckles, rough skin, reduction or acceleration of secretion of hormones (growth hormone, thyroid hormone, adrenocortical hormone, sex hormone, lactation hormone, antidiuretic hormone, parathyroid hormone, melatonin, etc.), damage of cells by active oxygen (brain cells, cardiac myocytes, etc.), loss of hair or teeth, visual or auditory deterioration, motor function deterioration, bone mass deterioration, physical strength deterioration, memory deterioration, learning ability deterioration, immune function deterioration, and the occurrence of senile diseases.
In the present specification, prevention includes: preventing the onset of the disease, delaying the onset of the disease, reducing the rate of the disease, reducing the risk of the disease, and the like. The amelioration of the condition or disease comprises: recovering the subject from the condition or disease, alleviating symptoms of the condition or disease, ameliorating symptoms of the condition or disease, delaying or preventing the progression of the condition or disease, and the like.
The composition of the present invention is suitable for either therapeutic use (medical use) or non-therapeutic use (non-medical use). Non-therapeutic is a concept that does not include medical actions, i.e., operations, treatments, or diagnoses of humans.
The composition of the present invention can be prepared into forms of drinks and foods, pharmaceuticals, quasi drugs, feeds, and the like. The composition of the present invention may be a food, drink, drug, quasi-drug, feed, etc. for increasing, suppressing, maintaining, or improving the concentration of Nicotinamide Adenine Dinucleotide (NAD), or may be a material or a preparation used by being mixed with the above.
The composition of the present invention may be a food, drink, drug, quasi-drug, feed, etc. for improving mitochondrial function, suppressing the reduction of mitochondrial function, maintaining or improving mitochondrial function, or for improving energy production of mitochondria, suppressing the reduction of mitochondrial energy production, maintaining or improving energy production of mitochondria, or may be a material or a preparation formulated and used for these.
The composition of the present invention may be provided as a preparation as it is, but is not limited to this embodiment. The formulation may also be provided directly as a composition, or as a composition containing the formulation.
The composition of the present invention may be either an oral composition or a non-oral composition, and is preferably an oral composition. The composition for oral administration may be a food or drink, a pharmaceutical product for oral administration, a quasi-drug, a feed, or the like, or may be contained in these. The composition of the present invention is preferably a food or drink or a pharmaceutical product for oral use, and more preferably a food or drink.
The composition of the present invention may contain any additive and any component in addition to 1 or more sesamins selected from NR, NMN and salts thereof, as long as the effects of the present invention are not impaired. These additives and components can be selected according to the form of the composition, and general substances usable in foods, drinks, pharmaceuticals, quasi drugs, feeds, and the like can be used. The composition of the present invention can be prepared into foods, drinks, pharmaceuticals, quasi drugs, feeds, etc., and the production method thereof is not particularly limited, and the composition can be produced by a general method.
For example, when the composition of the present invention is prepared into foods and beverages, various foods and beverages can be prepared by blending components (for example, food materials, food additives used as needed, and the like) that can be used in foods and beverages with 1 or more kinds of sesamins selected from NR, NMN, and salts thereof. The food or drink is not particularly limited, and examples thereof include general foods or drinks, health foods, health beverages, functional foods, specific health foods, and foods or drinks for patients. The health food, functional marker food, specific health food, etc. can be used in various forms of preparations such as fine granules, tablets, granules, powders, capsules, chewables, dry syrups, liquids, beverages, liquid foods, etc.
When the composition of the present invention is formulated into a pharmaceutical or quasi-drug, for example, a pharmacologically acceptable carrier is blended with 1 or more sesamins selected from NR, NMN and salts thereof and 1 or more sesamins, and a pharmaceutical or quasi-drug in various dosage forms can be prepared by adding additives and the like as needed. Such carriers and additives may be pharmacologically acceptable substances that can be used in pharmaceuticals or quasi drugs, and examples thereof include 1 or 2 or more of excipients, binders, disintegrants, lubricants, antioxidants, colorants, and the like. Examples of administration (ingestion) of the drug or quasi-drug include oral or non-oral administration (transdermal, transmucosal, enteral, injection, etc.). When the composition of the present invention is formulated into a pharmaceutical or quasi-pharmaceutical, it is preferably formulated into an oral pharmaceutical or quasi-pharmaceutical. Examples of dosage forms for oral administration include liquid, tablet, powder, fine granule, sugar-coated tablet, capsule, suspension, emulsion, and chewable agent. The pharmaceutical product may be a non-human animal pharmaceutical product.
When the composition of the present invention is formulated into a feed, 1 or more sesamins selected from NR, NMN and salts thereof and 1 or more sesamins may be blended into the feed. The feed also includes feed additives. Examples of the feed include livestock feeds for cattle, pigs, chickens, sheep, horses, and the like; a feed for a small animal such as a rabbit, a rat, or a mouse; pet food for dog, cat, bird, etc.
The composition of the present invention is preferably a composition for oral administration (a composition for oral intake (oral administration)). The amount of the composition of the present invention to be administered (may also be referred to as an intake amount) is not particularly limited. The amount of the composition of the present invention to be administered may be an amount that can achieve the effect of increasing, suppressing decrease, maintaining or improving the concentration of Nicotinamide Adenine Dinucleotide (NAD), and may be appropriately set according to the administration form, the administration method, the body weight of the subject, and the like.
In one embodiment, when the composition of the present invention is orally taken or administered to a human (adult), the total amount of sesamins to be administered is preferably 0.5mg or more, more preferably 1mg or more, further preferably 3mg or more, and further preferably 200mg or less, more preferably 100mg or less, and further preferably 80mg or less per 1 day of body weight. In one embodiment, the total amount of sesamins to be administered is 60kg, preferably 0.5 to 200mg, more preferably 1 to 100mg, and still more preferably 3 to 80mg per 1 day in human (adult) patients. The above amount is preferably taken or administered in 1 or more times per day, for example, 1 or more times (for example, 2 to 3 times) per day. In one embodiment, the sesamin is preferably orally ingested or administered to a human in the above-mentioned amount. In one embodiment, the composition of the present invention can be used to administer or administer the sesamin compounds to a human in an amount of 60kg per body weight per 1 day. The total amount of administration is the total amount of 2 or more sesamin compounds when used. In one embodiment, the total amount of sesamin and episesamin to be administered is preferably 0.5 to 200mg, more preferably 1 to 100mg, and still more preferably 3 to 80mg of sesamin and/or episesamin, which is orally administered to a human (adult) or administered to the human per 1 day of 60 kg.
In one embodiment, when the composition of the present invention is orally ingested or administered to a human (adult), the total amount of 1 or more selected from Nicotinamide Riboside (NR), nicotinamide Mononucleotide (NMN) and salts thereof is preferably 0.5mg or more, more preferably 1mg or more, further preferably 3mg or more, further preferably 20000mg or less, more preferably 10000mg or less, and further preferably 8000mg or less per 1 day of the body weight in terms of NR. In one embodiment, the total amount of 1 or more selected from Nicotinamide Riboside (NR), nicotinamide Mononucleotide (NMN) and salts thereof to be administered is 60kg, preferably 0.5 to 20000mg, more preferably 1 to 10000mg, and still more preferably 3 to 8000mg per 1 day in terms of NR equivalent to human (adult). The above amount is preferably taken or administered in 1 or more times per day, for example, 1 or more times per day (for example, 2 to 3 times). In one embodiment, 1 or more selected from Nicotinamide Riboside (NR), nicotinamide Mononucleotide (NMN) and salts thereof are preferably administered to a human by oral ingestion or administration in the above-mentioned amount. In one embodiment, the composition of the present invention can be used for causing a human to ingest or administer the above amount of 1 or more selected from Nicotinamide Riboside (NR), nicotinamide Mononucleotide (NMN) and salts thereof every 1 day for 60kg per body weight. The total amount of the above-mentioned compounds to be used is the total amount of 2 or more compounds selected from Nicotinamide Riboside (NR), nicotinamide Mononucleotide (NMN) and salts thereof.
The composition of the present invention is preferably ingested or administered continuously. Sesamins are expected to improve the above-mentioned effects by continuous intake or administration. Further, compounds selected from Nicotinamide Riboside (NR), nicotinamide Mononucleotide (NMN) and salts thereof are expected to improve the above-mentioned effects by continuous intake or administration. In one embodiment, the composition of the present invention is administered by ingestion or administration for preferably 1 week or more, more preferably 4 weeks or more, still more preferably 8 weeks or more, and particularly preferably 12 weeks or more.
The composition of the present invention may also be accompanied by a marker indicating a function exerted by an increase, decrease inhibition, maintenance or improvement in the concentration of Nicotinamide Adenine Dinucleotide (NAD). Such a label may be accompanied by 1 or 2 or more kinds of functions selected from "the increase, decrease, inhibition, or maintenance of mitochondrial function", "the increase, decrease, inhibition, or maintenance of energy production of mitochondria", "the inhibition and/or delay of aging due to a decrease in NAD concentration", "the inhibition and/or delay of cell aging", and "aging inhibition".
In one embodiment of the present invention, the composition of the present invention is preferably a food or drink having the above-mentioned label attached thereto. The above-mentioned symbol may mean a symbol for obtaining the above-mentioned function.
The subject to which the composition of the present invention is ingested or administered (may also be referred to as administration subject) is not particularly limited, and may be ingested by humans or animals other than humans. Examples of the non-human animal include industrial animals, pets, and laboratory animals. Specifically, the industrial animals include livestock such as cattle, horses, pigs, goats, and sheep, poultry such as chickens, ducks, quails, turkeys, and ostriches, and fish such as seriola quinqueradiata, yellowtail, snapper, horse mackerel, carps, rainbow trout, and eel. The pet is a so-called ornamental animal such as a dog, cat, marmoset, bird, hamster, or a companion animal, and the experimental animal is an animal to be studied in the medical, biological, agricultural, and pharmaceutical fields such as a mouse, a rat, a guinea pig, a beagle dog, a mini pig, a macaca, and a cynomolgus monkey.
The subject (also referred to as the subject of administration) taking or administering the composition of the invention is preferably a human or non-human mammal, more preferably a human.
In one embodiment, the administration subject may be a subject for which an increase, decrease, inhibition, maintenance, or improvement in Nicotinamide Adenine Dinucleotide (NAD) concentration is required or desired. Examples of such subjects include middle-aged and elderly people, subjects who need or desire to improve mitochondrial function, inhibit a decrease in mitochondrial function, and maintain or improve mitochondrial function, subjects who need or desire to improve energy production of mitochondria, inhibit a decrease in mitochondrial energy production, and maintain or improve mitochondrial energy production, and subjects who need or desire to inhibit and/or delay aging due to a decrease in NAD concentration. The elderly may be, for example, humans over the age of 40. In one embodiment, the elderly are preferably the subjects. An elderly person may be, for example, a human over the age of 60 or over the age of 65. The composition of the present invention can be used for a healthy person for the purpose of, for example, preventing symptoms or diseases which can be expected to be prevented or improved by increasing, decreasing, suppressing, maintaining or improving the concentration of Nicotinamide Adenine Dinucleotide (NAD).
The present invention also includes the following methods.
A method for increasing the concentration of Nicotinamide Adenine Dinucleotide (NAD), characterized by administering 1 or more members selected from Nicotinamide Ribose (NR), nicotinamide Mononucleotide (NMN) and salts thereof, and 1 or more members selected from sesamins.
A method for increasing, decreasing, inhibiting, maintaining or improving the concentration of Nicotinamide Adenine Dinucleotide (NAD), characterized by administering 1 or more sesamins selected from Nicotinamide Ribose (NR), nicotinamide Mononucleotide (NMN) and salts thereof.
A method for increasing, reducing, inhibiting, maintaining or improving the concentration of Nicotinamide Adenine Dinucleotide (NAD) that decreases with age, characterized by administering 1 or more sesamins selected from Nicotinamide Ribose (NR), nicotinamide Mononucleotide (NMN) and salts thereof.
The invention also comprises the following applications.
An application of 1 or more sesamins selected from Nicotinamide Riboside (NR), nicotinamide Mononucleotide (NMN) and salts thereof to increase the concentration of Nicotinamide Adenine Dinucleotide (NAD).
Use of 1 or more sesamins selected from Nicotinamide Riboside (NR), nicotinamide Mononucleotide (NMN) and salts thereof for increasing, reducing, inhibiting, maintaining or improving the concentration of Nicotinamide Adenine Dinucleotide (NAD).
Use of 1 or more sesamins selected from Nicotinamide Riboside (NR), nicotinamide Mononucleotide (NMN) and salts thereof for increasing, reducing, inhibiting, maintaining or improving the concentration of Nicotinamide Adenine Dinucleotide (NAD) which decreases with age. The methods and uses described above may be therapeutic methods or uses, or may be non-therapeutic methods or uses.
Administration of 1 or more sesamins selected from Nicotinamide Riboside (NR), nicotinamide Mononucleotide (NMN) and salts thereof can increase the concentration of Nicotinamide Adenine Dinucleotide (NAD), inhibit the decrease, and maintain or improve the concentration of Nicotinamide Adenine Dinucleotide (NAD). Thus, mitochondrial function can be increased, decreased mitochondrial activity can be inhibited, mitochondrial function can be maintained or improved, energy production by mitochondria can be increased, decreased mitochondrial energy production can be inhibited, mitochondrial energy production can be maintained or improved, and aging due to decreased NAD concentration can be inhibited and/or delayed.
In the above-mentioned method and application, a compound selected from Nicotinamide Riboside (NR), nicotinamide Mononucleotide (NMN) and a salt thereof, sesamins, and preferred embodiments thereof are the same as those of the above-mentioned composition of the present invention. As the 1 or more sesamins, 1 kind of sesamin compound may be used, and 2 or more kinds may be used. Further, as the compound selected from Nicotinamide Riboside (NR), nicotinamide Mononucleotide (NMN) and salts thereof, 1 or more species of the compound may be used, and 2 or more species may be used. In the above method and application, it is preferable to administer (take) 1 or more sesamins selected from Nicotinamide Riboside (NR), nicotinamide Mononucleotide (NMN) and salts thereof to a subject 1 or more times a day, for example, 1 to a plurality of times (for example, 2 to 3 times) a day. In the above methods and uses, the composition of the present invention is preferably administered orally (allowed to be taken orally). The above-mentioned use is preferably in a human or non-human mammal, more preferably in a human.
In the above-mentioned method and application, it is sufficient to use 1 or more and 1 or more sesamins selected from Nicotinamide Riboside (NR), nicotinamide Mononucleotide (NMN) and salts thereof in an amount (also referred to as an effective amount) capable of obtaining a desired effect (an effect of increasing the concentration of Nicotinamide Adenine Dinucleotide (NAD), that is, an effect of increasing, decreasing, inhibiting, maintaining or improving the concentration of NAD, an effect of increasing, decreasing, inhibiting, maintaining or improving the function of mitochondrial function based on the increase, decreasing, inhibiting, maintaining or improving the function, an effect of increasing energy production of mitochondria, decreasing, inhibiting, maintaining or improving the function, and/or an effect of inhibiting and/or delaying aging due to a decrease in the concentration of NAD). Preferred amounts of administration and administration subjects of 1 or more sesamins selected from Nicotinamide Riboside (NR), nicotinamide Mononucleotide (NMN) and salts thereof are the same as those of the composition of the present invention. 1 or more and 1 or more sesamins selected from Nicotinamide Riboside (NR), nicotinamide Mononucleotide (NMN) and salts thereof can be administered directly or as a composition containing the same. For example, the above-described composition of the present invention may also be used.
In the above-mentioned applications, a composition containing 1 or more sesamins and a composition containing 1 or more selected from Nicotinamide Ribose (NR), nicotinamide Mononucleotide (NMN) and salts thereof are prepared separately, and they are administered substantially simultaneously or after one composition is administered, another composition is administered for a duration of the effect thereof, and the effect of increasing NAD concentration (i.e., the effect of increasing NAD concentration, decreasing inhibition, maintaining or improving NAD concentration, the effect of increasing mitochondrial function based on the effect of increasing NAD concentration, the effect of decreasing inhibition, maintaining or improving NAD concentration, the effect of increasing mitochondrial energy production, the effect of decreasing inhibition, maintaining or improving mitochondrial energy production, and/or the effect of inhibiting and/or delaying aging due to a decrease in NAD concentration) intended by the present invention can be obtained. Thus, it comprises: compositions containing 1 or more sesamins, kits containing 1 or more compositions selected from Nicotinamide Riboside (NR), nicotinamide Mononucleotide (NMN), and salts thereof, and the like are within the scope of the composition of the present invention.
The present invention also encompasses the use of 1 or more sesamins selected from Nicotinamide Riboside (NR), nicotinamide Mononucleotide (NMN) and salts thereof for the manufacture of the composition of the invention.
Examples
The present invention will be described more specifically below with reference to examples. The present invention is not limited to these examples.
In examples and comparative examples, as a sesamin and episesamin mixture (SE), a mixture of sesamin and episesamin (sesamin: episesamin (weight ratio) = 1.
Comparative examples 1 to 3, example 1: based on sesamin and episesamin mixture (SE) and nicotinamide ribosideIntracellular NAD of sugars (NR) + Evaluation test of concentration (intracellular NAD concentration) >
To investigate intracellular NAD + The effect of concentration will be 0.5X 10 4 cells/well of Hepa1-6 cells were seeded in 96-well plates at 37 ℃ with CO 2 (5%) was cultured in DMEM (Nacalai Tesque, containing 10% FBS) for 96 hours. After culturing for 96 hours, a DMEM medium (containing 1% albumin and no FBS (comparative example 1)) containing no sesamin, episesamin mixture (SE) and nicotinamide ribose (NR chloride (manufactured by Carbosynth Limited)), a DMEM medium (containing 1% albumin and no FBS (comparative example 2)) containing 0.3. Mu.M SE, a DMEM medium (containing 1% albumin and no FBS (comparative example 3)) containing 30. Mu.M NR, or a DMEM medium (containing 1% albumin and no FBS (example 1)) containing 0.3. Mu.M SE and 30. Mu.M NR was exchanged with the medium in each well and cultured for further 24 hours. Then, the added medium was removed, the cells in the wells were washed with D-PBS (Nacalai Tesque Co., ltd.), then lysine Buffer (Amplite (registered trademark) Colorimetric NAD/NADH Ratio Assay Kit, AAT Bioquest Co.) was added thereto, and the cell extract was collected. Then, intracellular NAD was analyzed according to the manual of the kit + And (4) concentration. For intracellular NAD + In terms of concentration, the Protein concentration of the cell extract (Pierce (registered trademark) BCA Protein Assay Kit, thermo Scientific Co.) was measured and calculated as a value relative to the Protein concentration. Significant difference test was performed with no corresponding t-test (significant level: p < 0.05 vs. control)
The obtained results (average of N = 3) are shown in fig. 1. (. P < 0.05).
As confirmed from FIG. 1, intracellular NAD + The concentration was increased by 2.3% in the SE 0.3. Mu.M group of comparative example 2 and 3.1% in the NR 30. Mu.M group of comparative example 3, respectively, with respect to that in comparative example 1 (medium containing neither SE nor NR). On the other hand, an increase of 14.6% was found in the combination group of SE0.3 μ M and NR30 μ M of example 1, which is significantly larger than a value (5.4%) in which the increase ratio based on the SE0.3 μ M treatment of comparative example 2 and the increase ratio based on the NR30 μ M treatment of comparative example 3 were simply added. From the above, it was confirmed that the molar ratio (S) was changedE: NR) 1:100 ratio of SE and NR, intracellular NAD + The concentrations showed a synergistic effect.
Comparative examples 4 to 6 and example 2: intracellular NAD based on sesamin and episesamin mixture (SE) and Nicotinamide Riboside (NR) + Evaluation test of concentration (intracellular NAD concentration) >
To investigate intracellular NAD + The effect of concentration will be 1.0X 10 4 cells/well of Hepa1-6 cells were seeded in 96-well plates at 37 ℃ with CO 2 (5%) in DMEM (Nacalai Tesque, containing 10% FBS) for 48 hours. After 48 hours of culture, DMEM medium (containing 1% albumin and no FBS (comparative example 4)) containing no sesamin and episesamin mixture (SE) and nicotinamide ribose (using NR chloride), DMEM medium (containing 1% albumin and no FBS (comparative example 5)) containing 10. Mu.M SE, DMEM medium (containing 1% albumin and no FBS (comparative example 6)) containing 10. Mu.M NR, or DMEM medium (containing 1% albumin and no FBS (example 2)) containing 10. Mu.M SE and 10. Mu.M NR was exchanged with the medium in each well and cultured for a further 24 hours. Then, the added medium was removed, the cells in the wells were washed with D-PBS (Nacalai Tesque Co., ltd.), then lysine Buffer (Amplite (registered trademark) Colorimetric NAD/NADH Ratio Assay Kit, AAT Bioquest Co.) was added thereto, and the cell extract was collected. Then, intracellular NAD was analyzed according to the manual of the kit + And (4) concentration. For intracellular NAD + In terms of concentration, the Protein concentration of the cell extract (Pierce (registered trademark) BCA Protein Assay Kit, thermo Scientific Co.) was measured and calculated as a value relative to the Protein concentration. The obtained results (average of N = 3) are shown in fig. 2. (. P < 0.05).
As confirmed from FIG. 2, intracellular NAD + The concentration was increased by 1.5% in the SE 10. Mu.M group of comparative example 5 and 11.6% in the NR 10. Mu.M group of comparative example 6, respectively, relative to that in comparative example 4 (medium containing neither SE nor NR). On the other hand, it was confirmed that an increase of 15.7% was observed in the combination group of SE 10. Mu.M and NR 10. Mu.M of example 2, which is also significantly larger than the increase ratio of SE 10. Mu.M-based treatment of comparative example 5 to NR 1-based treatment of comparative example 6The increase ratio of the 0 μ M treatment was simply the additive value (13.1%). From the above, it was confirmed that the molar ratio (SE: NR) 1:1 ratio of SE and NR, intracellular NAD + The concentrations showed a synergistic effect.
< comparative examples 7 to 9, examples 3 and 4: intracellular NAD based on sesamin and episesamin mixture (SE) and Nicotinamide Riboside (NR) + Evaluation test of concentration (intracellular NAD concentration) >
To investigate intracellular NAD + The effect of concentration will be 1.0X 10 4 cells/well of Hepa1-6 cells were seeded in 96-well plates at 37 ℃ with CO 2 (5%) in DMEM medium (Nacalai Tesque, 10% FBS) for 48 hours. After 48 hours of culture, a DMEM medium (containing 1% albumin, without FBS (comparative example 7)) containing no sesamin and episesamin mixture (SE) and nicotinamide ribose (using NR chloride), a DMEM medium (containing 1% albumin, without FBS (comparative example 8)) containing 10. Mu.M NR, a DMEM medium (containing 1% albumin, without FBS (comparative example 9)) containing 30. Mu.M NR, a DMEM medium (containing 1% albumin, without FBS (example 3)) containing 3. Mu.M SE and 10. Mu.M NR, or a DMEM medium (containing 1% albumin, without FBS (example 4)) containing 3. Mu.M SE and 30. Mu.M NR was exchanged with the medium in each well, and further cultured for 24 hours. Then, the added medium was removed, the cells in the wells were washed with D-PBS (Nacalai Tesque Co., ltd.), then lysine Buffer (Amplite (registered trademark) Colorimetric NAD/NADH Ratio Assay Kit, AAT Bioquest Co.) was added thereto, and the cell extract was collected. Then, intracellular NAD was analyzed according to the manual of the kit + And (4) concentration. Intracellular NAD + In terms of concentration, the Protein concentration of the cell extract (Pierce (registered trademark) BCA Protein Assay Kit, thermo Scientific Co.) was measured and calculated as a value relative to the Protein concentration. The obtained results (average of N = 3) are shown in fig. 3. (. P < 0.05).
As confirmed from FIG. 3, intracellular NAD + In terms of concentration, the increase in concentration was 11.6% in the NR 10. Mu.M group of comparative example 8 and 15.5% in the NR 30. Mu.M group of comparative example 9, relative to that in comparative example 7 (medium containing neither SE nor NR)%. On the other hand, there was an increase of 17.5% in the combined group of SE 3. Mu.M and NR 10. Mu.M of example 3 and 21.8% in the combined group of SE 3. Mu.M and NR 30. Mu.M of example 4. Although there was no test example in which the sample was treated with DEME medium containing 3. Mu.M of SE, it was concluded that the NAD concentration in the SE 3. Mu.M group was increased at the same rate as in the SE 0.3. Mu.M group of comparative example 2 by 2.3% and the NAD concentration in the SE 10. Mu.M group of comparative example 5 by 1.5%. Therefore, the increase ratio of NAD concentration in comparative example 8 or 9, which is obtained by simply adding the increase ratio of NAD concentration (2.3 to 1.5%) considered from SE3 μ M, is significantly larger in example 3 and example 4 than in example 3 and example 4. From the above, it was confirmed that the molar ratio (SE: NR) 1:3.3 or 1:10 ratio of SE and NR, intracellular NAD + The concentrations showed a synergistic effect.
Comparative examples 10 to 12 and example 5: intracellular NAD based on sesamin and episesamin mixture (SE) and Nicotinamide Riboside (NR) + Evaluation test of concentration (intracellular NAD concentration) >
To investigate intracellular NAD + Influence of concentration, 1.5X 10 4 cells/well HepG2 cells were seeded in 96-well plates at 37 ℃ with CO 2 (5%) was cultured in DMEM (Nacalai Tesque, containing 10% FBS) for 96 hours. After 96 hours of culture, DMEM medium (1% albumin, FBS-free (comparative example 10)) containing no sesamin and episesamin mixture (SE) and nicotinamide ribose (NR chloride was used), DMEM medium (1% albumin, FBS-free (comparative example 11)) containing 0.3 μ M SE, DMEM medium (1% albumin, FBS-free (comparative example 12)) containing 10 μ M NR, DMEM medium (1% albumin, FBS-free (comparative example 12)) containing 0.3 μ M SE and 10 μ M NR, were exchanged with the medium in each well and further cultured for 24 hours. Then, the added medium was removed, the cells in the well were washed with D-PBS (Nacalai Tesque Co., ltd.), and lysine Buffer (Amplite (registered trademark) Colorimetric NAD/NADH Ratio Assay Kit, AAT Bioqu was addedest company) and recovering the cell extract. Then, intracellular NAD was analyzed according to the manual of the kit + And (4) concentration. Intracellular NAD + Concentration the Protein concentration of the cell extract (Pierce (registered trademark) BCA Protein Assay Kit, thermo Scientific Co.) was measured and calculated as a value relative to the Protein concentration.
For intracellular NAD + In terms of concentration, an increase of 5.0% was observed in the SE 0.3. Mu.M group of comparative example 11 and an increase of no 5.0% was observed in the NR 10. Mu.M group of comparative example 12, relative to comparative example 10 (Cont, medium containing neither SE nor NR). On the other hand, an increase of 8.0% was confirmed in the combination group of SE 0.3. Mu.M and NR 10. Mu.M of example 5, which is also significantly larger than the value (5.0%) in which the increase ratio based on the SE 0.3. Mu.M treatment was simply added to the increase ratio based on the NR 10. Mu.M treatment. From the above, it was confirmed that the molar ratio (SE: NR) 1:33 to SE and NR, intracellular NAD + The concentrations showed a synergistic effect.
From the above, it was clarified that the composition containing the mixture of sesamin and episesamin and Nicotinamide Riboside (NR) expresses intracellular NAD + Synergistic effect of concentration increasing effect.
< comparative examples 13 to 16, examples 6 and 7: intracellular NAD based on sesamin and episesamin mixture (SE) and Nicotinamide Mononucleotide (NMN) + Evaluation test of concentration (intracellular NAD concentration) >
To investigate intracellular NAD + Influence of concentration, 2.5X 10 4 cells/well HepG2 cells were seeded in 96-well plates at 37 ℃ with CO 2 (5%) in DMEM (Nacalai Tesque, containing 10% FBS) for 48 hours. After 48 hours of culture, DMEM medium (containing 1% albumin and no FBS (comparative example 13)) containing no sesamin, episesamin mixture (SE) and Nicotinamide Mononucleotide (NMN), DMEM medium (containing 1% albumin and no FBS (comparative example 14)) containing 10. Mu.M SE, DMEM medium (containing 1% albumin and no FBS (comparative example 15)) containing 30. Mu.M NMN, DMEM medium (containing 1% albumin and no FBS (comparative example 16)) containing 100. Mu.M NMN, DMEM medium (containing 1% albumin and no FBS (comparative example 16)) containing 10. Mu.M SE and 30. Mu.M NMN, were culturedFBS-free (example 6)) or DMEM medium containing 10 μ M SE and 100 μ M NMN (1% albumin-free, FBS-free (example 7)) was exchanged with the medium in each well and cultured for a further 24 hours. Then, the added medium was removed, the cells in the wells were washed with D-PBS (Nacalai Tesque Co., ltd.), then lysine Buffer (Amplite (registered trademark) Colorimetric NAD/NADH Ratio Assay Kit, AAT Bioquest Co.) was added thereto, and the cell extract was collected. Then, intracellular NAD was analyzed according to the manual of the kit + And (4) concentration. For intracellular NAD + In terms of concentration, the Protein concentration of the cell extract (Pierce (registered trademark) BCA Protein Assay Kit, thermo Scientific Co.) was measured and calculated as a value relative to the Protein concentration. The obtained results (average of N = 3) are shown in fig. 4. (. P < 0.05).
As confirmed from FIG. 4, intracellular NAD + The concentration was increased by 14.2% in the SE 10. Mu.M group of comparative example 14, 18.9% in the NMN 30. Mu.M group of comparative example 15 and 21.3% in the NMN 100. Mu.M group of comparative example 16, relative to comparative example 13 (medium without SE and NMN). On the other hand, an increase of 38.0% was confirmed in the combination group of SE 10. Mu.M and NMN 30. Mu.M of example 6, which is also significantly larger than a value (33.1%) in which the increase ratio based on the SE 10. Mu.M treatment of comparative example 14 and the increase ratio based on the NMN 30. Mu.M treatment of comparative example 15 are simply added.
In addition, an increase of 74.6% was confirmed in the combination group of SE10 μ M and NMN100 μ M of example 7, which is also significantly greater than a value (35.5%) in which the increase ratio based on the SE10 μ M treatment of comparative example 14 and the increase ratio based on the NMN100 μ M treatment of comparative example 16 are simply added.
From the above, it was confirmed that the molar ratio (SE: NMN) 1:3 or 1:10 to SE and NMN, intracellular NAD + The concentrations showed a synergistic effect.
From the above, it was found that intracellular NAD in a composition containing a combination of NMN and/or a salt thereof known as an intermediate metabolite of NAD and 1 or more kinds of sesamins (preferably a mixture of sesamin and episesamin) was the same as in a composition containing a mixture of sesamin and episesamin and NR + Synergy with increasing concentrationAnd (5) effect.
Claims (16)
1. A composition comprising 1 or more sesamins selected from NR which is nicotinamide riboside, NMN which is nicotinamide mononucleotide and salts thereof as an active ingredient.
2. The composition according to claim 1, wherein the 1 or more sesamins are sesamin and/or episesamin.
3. The composition according to claim 1 or 2, wherein the molar ratio of 1 or more selected from the group consisting of NR, NMN and salts thereof to sesamins is 1 to 100 per sesamin.
4. The composition according to any one of claims 1 to 3, wherein the total content of the 1 or more sesamins is 0.001 to 10% by weight.
5. The composition of any one of claims 1 to 4, wherein the concentration of nicotinamide adenine dinucleotide, NAD, is increased, inhibited from decreasing, maintained or improved.
6. The composition according to any one of claims 1 to 5, wherein mitochondrial function is increased, inhibited, maintained or improved.
7. The composition according to any one of claims 1 to 6, wherein the energy production of mitochondria is increased, inhibited, maintained or improved.
8. The composition according to any one of claims 1 to 7, for inhibiting and/or delaying aging with a decrease in NAD concentration.
9. The composition according to any one of claims 1 to 8, which is an anti-aging composition.
10. The composition according to any one of claims 1 to 9, which is a composition for oral administration.
11. The composition according to any one of claims 1 to 10, which is a food or drink.
12. The composition according to any one of claims 1 to 11, wherein the indication "inhibition and/or delay of aging accompanying a decrease in NAD concentration" and/or "inhibition and/or delay of cellular aging" is attached.
13. A method for increasing the concentration of Nicotinamide Adenine Dinucleotide (NAD), which comprises administering 1 or more sesamins selected from the group consisting of Nicotinamide Ribose (NR), nicotinamide Mononucleotide (NMN) and salts thereof.
14. A method for increasing, reducing, inhibiting, maintaining or improving the concentration of NAD (nicotinamide adenine dinucleotide), which is characterized in that 1 or more sesamins selected from NR, NMN, and salts thereof, which is nicotinamide ribose, and 1 or more sesamins are administered.
15. An application, characterized in that 1 or more sesamins selected from the group consisting of Nicotinamide Riboside (NR), nicotinamide Mononucleotide (NMN) and salts thereof, and 1 or more sesamins are used for increasing Nicotinamide Adenine Dinucleotide (NAD) concentration.
16. An application of 1 or more sesamins selected from the group consisting of Nicotinamide Riboside (NR), nicotinamide Mononucleotide (NMN) and salts thereof to increase, reduce, inhibit, maintain and improve the concentration of Nicotinamide Adenine Dinucleotide (NAD).
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| JP2020-083462 | 2020-05-11 | ||
| JP2020083462 | 2020-05-11 | ||
| PCT/JP2021/017472 WO2021230146A1 (en) | 2020-05-11 | 2021-05-07 | Composition containing sesamin or like and nr and/or nmn |
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| JP (1) | JPWO2021230146A1 (en) |
| KR (1) | KR20230010217A (en) |
| CN (1) | CN115867289A (en) |
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| JP7210459B2 (en) * | 2017-09-14 | 2023-01-23 | めぐみ 田中 | Antiaging agent and antiaging method |
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- 2021-05-07 AU AU2021271500A patent/AU2021271500A1/en active Pending
- 2021-05-07 JP JP2022521871A patent/JPWO2021230146A1/ja active Pending
- 2021-05-07 KR KR1020227042556A patent/KR20230010217A/en active Search and Examination
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| AU2021271500A1 (en) | 2022-12-15 |
| JPWO2021230146A1 (en) | 2021-11-18 |
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