WO2022230494A1 - 免疫細胞の代謝促進用組成物 - Google Patents

免疫細胞の代謝促進用組成物 Download PDF

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WO2022230494A1
WO2022230494A1 PCT/JP2022/014256 JP2022014256W WO2022230494A1 WO 2022230494 A1 WO2022230494 A1 WO 2022230494A1 JP 2022014256 W JP2022014256 W JP 2022014256W WO 2022230494 A1 WO2022230494 A1 WO 2022230494A1
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Prior art keywords
ergothioneine
composition
salt
present
metabolism
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English (en)
French (fr)
Japanese (ja)
Inventor
諒 勝部
斉志 渡辺
真梨子 小澤
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Suntory Holdings Ltd
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Suntory Holdings Ltd
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Priority to US18/286,634 priority Critical patent/US20240122899A1/en
Priority to EP22795412.0A priority patent/EP4331582A4/en
Priority to AU2022265114A priority patent/AU2022265114A1/en
Priority to JP2023517172A priority patent/JP7817249B2/ja
Priority to CN202280030903.7A priority patent/CN117255683A/zh
Publication of WO2022230494A1 publication Critical patent/WO2022230494A1/ja
Anticipated expiration legal-status Critical
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A61K31/4172—Imidazole-alkanecarboxylic acids, e.g. histidine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/17—Amino acids, peptides or proteins
    • A23L33/175—Amino acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/04—Immunostimulants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • the present invention relates to a composition for promoting metabolism of immune cells.
  • the present invention also relates to compositions for immunostimulation.
  • the present invention further relates to a method for promoting metabolism of immune cells, a method for activating immunity, and the like.
  • immune cells also called immunocompetent cells
  • leukocytes are generally classified into five types: monocytes (macrophages), lymphocytes, neutrophils, basophils, and eosinophils, which are immunocompetent cells involved in biological defense.
  • monocytes macrophages
  • lymphocytes lymphocytes
  • neutrophils neutrophils
  • basophils basophils
  • eosinophils immunocompetent cells involved in biological defense.
  • PBMC Peripheral blood mononuclear cells
  • Ergothioneine is an amino acid contained in mushrooms and the like, and naturally exists in the L form.
  • Patent Document 1 in mice to which ergothioneine was orally administered, peri-testicular fat weight was reduced compared to mice to which ergothioneine was not orally administered, and triglyceride (neutral fat) in plasma was reduced. It is stated that
  • ergothioneine and any one of Toll-like receptor ligands selected from lipopolysaccharide (LPS), Pam2CSK4, synthetic triacylated lipoproteins and imidanoquinoline compounds are used as active ingredients to activate an immune response.
  • Cytokine production-enhancing agents are disclosed, but in the absence of TLR ligands, IL-6, IL-12, IL-1 ⁇ and IL-10 were not detected in samples with both 0 and 10 mM ergothioneine. rice field.
  • IL-6, IL-12, IL-1 ⁇ and IL-10 were not detected when TLRs were not stimulated, regardless of the presence or absence of ergothioneine (claim 1, etc., and paragraph [0068]). Therefore, immune response-activating cytokine production-enhancing agents containing ergothioneine and a specific Toll-like receptor ligand as active ingredients are known, but immune response-activating cytokine production-enhancing effects of ergothioneine alone are not known.
  • US Pat. No. 6,200,303 discloses a method of protecting mitochondria from damage caused by irradiation, free radicals and reactive oxygen species, comprising administering a composition comprising L-ergothioneine to mitochondria parenterally, topically, transmucosally, transmucosally, or parenterally.
  • Pulmonary or percutaneous administration is disclosed (claim 1, claim 8, etc.).
  • the activation of mitochondrial function by L-ergothioneine is not disclosed at all, nor is there any description or suggestion of promotion of immune cell metabolism.
  • JP 2011-102286 A Japanese Patent No. 6121597 Japanese Patent Publication No. 2001-513760
  • L-ergothioneine or a salt thereof has the effect of promoting the metabolism of immune cells.
  • An object of the present invention is to provide a composition for promoting metabolism of immune cells. Another object of the present invention is to provide an immunostimulatory composition. Another object of the present invention is to provide a method for promoting metabolism of immune cells and a method for activating immunity.
  • L-ergothioneine has an effect of promoting the metabolism of immune cells.
  • the present invention relates to the following compositions for promoting metabolism of immune cells, compositions for activating immunity, and the like.
  • a composition for promoting metabolism of immune cells containing L-ergothioneine or a salt thereof as an active ingredient.
  • the composition of [1] above which promotes metabolism of immune cells by activating mitochondrial function.
  • An immunostimulatory composition comprising the composition of [1] or [2] above.
  • [5] The composition according to any one of [1] to [4], which is a food or drink.
  • composition according to any one of [1] to [5] above, wherein the content of L-ergothioneine or a salt thereof is 2 to 50 mg in terms of L-ergothioneine per day for adults.
  • a method for promoting metabolism of immune cells comprising administering L-ergothioneine or a salt thereof.
  • a method for activating immunity comprising administering L-ergothioneine or a salt thereof.
  • Use of L-ergothioneine or a salt thereof for immune activation Use of L-ergothioneine or a salt thereof for immune activation.
  • a composition for promoting metabolism of immune cells can be provided.
  • FIG. 1A is a graph showing the effect of ergothioneine on oxygen consumption rate (OCR) on basal respiration
  • FIG. 1B is a graph showing the effect of ergothioneine on OCR on ATP-related respiration
  • FIG. 1C is a graph showing the OCR on maximal respiration of ergothioneine.
  • is a graph showing the effect on Figure 2 is a graph showing the effect of ergothioneine on oxygen consumption rate (OCR) in human PBMC over time.
  • composition for promoting metabolism of immune cells of the present invention contains L-ergothioneine or a salt thereof as an active ingredient.
  • composition for promoting metabolism of immune cells of the present invention may be referred to as the composition of the first aspect of the present invention.
  • L-ergothioneine is a kind of amino acid.
  • the salt of L-ergothioneine is not particularly limited as long as it is a pharmacologically acceptable salt or a salt acceptable for food and drink, and may be either an acid salt or a basic salt.
  • Acid salts include, for example, inorganic salts such as hydrochlorides, sulfates, nitrates, phosphates; Examples include organic acid salts such as acid salts and propionate salts.
  • Examples of basic salts include alkali metal salts such as sodium salts and potassium salts; alkaline earth metal salts such as calcium salts and magnesium salts;
  • L-ergothioneine or a salt thereof may be a chemically synthesized product, or may be extracted and purified from natural products.
  • a large amount of L-ergothioneine is contained in Golden/Yellow Oyster mushroom (scientific name: Pleurotus cornucopiae var. citrinopileatus), which is a mushroom belonging to the genus Oyster mushroom of the family Oysteraceae.
  • L-ergothioneine is found in white button mushrooms, crimini mushrooms, portabella mushrooms and other mushrooms (scientific name: Agaricus bisporus), gray oyster mushrooms (scientific name: Pleurotus ostreatus), shiitake mushrooms (scientific name: Lentinula edodes), maitake mushrooms (Scientific name: Grifola Frondosa), Reishi (Scientific name: Ganoderma lucidum), Hericium erinaceus (Scientific name: Hericium erinaceus), Willow matsutake (Scientific name: Agrocybeaegerita), Chanterelle (Scientific name: Cantharellus cibarius), Porcini mushroom (Scientific name: Boletus) It is also contained in mushrooms such as Morchella esculenta (scientific name: Morchella esculenta).
  • L-ergothioneine When L-ergothioneine is obtained from a natural product, it is preferably extracted from Pleurotus cornucopia. L-ergothioneine or a salt thereof can also be produced by microbial fermentation. An extract containing L-ergothioneine or a salt thereof produced by microbial fermentation, or a product purified therefrom may also be used. Extraction and purification from natural products and the like can be carried out by known methods. L-ergothioneine or a salt thereof may be isolated.
  • L-ergothioneine or a salt thereof is a compound that is contained in natural products and foods and drinks and has been eaten. Therefore, from the viewpoint of safety, long-term intake of L-ergothioneine or a salt thereof is considered to pose few problems.
  • L-ergothioneine increased the oxygen consumption rate (OCR) of peripheral blood mononuclear cells (PBMC) and also improved mitochondrial metabolism compared to the absence of L-ergothioneine. significantly increased.
  • Mitochondria are intracellular organelles present in all organisms that utilize oxygen to produce energy in the form of adenosine triphosphate (ATP) and reduce it to water.
  • Increased mitochondrial metabolism in peripheral blood mononuclear cells (PBMC) is indicated by increased mitochondrial basal respiration, maximal respiration, increased mitochondrial ATP production, and the like.
  • OCR oxygen consumption rate
  • compositions of the present invention preferably promote immune cell metabolism by activating mitochondrial function in immune cells.
  • the use of L-ergothioneine significantly increased basal mitochondrial respiration, ATP production, and maximal respiration in peripheral blood mononuclear cells (PBMCs) compared to the absence of L-ergothioneine, and increased mitochondrial metabolism. A significant increase, thus activating mitochondrial function.
  • the compositions of the invention can be used to promote immune cell metabolism by activating mitochondrial function.
  • immune cells are preferably at least one selected from T cells, B cells, natural killer cells and monocytes.
  • Peripheral blood mononuclear cells PBMCs
  • T cells peripheral blood mononuclear cells
  • B cells natural killer cells
  • monocytes a cell that stimulates T cells, B cells, natural killer cells and monocytes. This is because it consists of The composition of the present invention promotes metabolism of at least one immune cell selected from T cells, B cells, natural killer cells and monocytes by activating mitochondrial function in peripheral blood mononuclear cells (PBMC). is preferred.
  • L-ergothioneine or a salt thereof has an immunostimulatory effect because it has an effect of promoting the metabolism of immune cells and an effect of activating mitochondrial function in immune cells.
  • L-ergothioneine or a salt thereof can be used as an active ingredient for immune activation.
  • the composition for promoting immune cell metabolism can be used, for example, for immune activation. Therefore, the composition of the first aspect of the present invention can be used as an immunostimulatory composition.
  • a composition for immunostimulation containing the composition of the first aspect of the present invention is also one aspect of the present invention.
  • the composition for immunostimulation is also referred to as the composition of the second aspect of the present invention.
  • composition of the first aspect and the composition of the second aspect of the present invention have an immunostimulatory effect and can be used to prevent or improve conditions or diseases caused by weakened immune function.
  • Prevention of a condition or disease includes preventing onset, delaying onset, reducing the rate of onset, reducing the risk of onset, and the like.
  • Ameliorating a condition or disease includes ameliorating the subject from the condition or disease, alleviating symptoms of the condition or disease, ameliorating symptoms of the condition or disease, slowing progression of the condition or disease, preventing the condition or disease. etc.
  • Conditions or diseases caused by a weakened immune system include infectious diseases caused by microorganisms such as viruses and bacteria; Influenza due to infection, cold syndrome, stomatitis due to oral infection, periodontal disease, etc., various malignant tumors, for example, epithelial malignant tumors that occur in solid organs such as the gastrointestinal tract, respiratory mucosa, liver and kidneys, Examples include non-epithelial malignant tumors occurring in locomotive organs and soft tissues.
  • infectious diseases also include, for example, symptoms derived from viruses that have been infected in the past and are dormant inside the subject, such as herpes virus.
  • the composition of the present invention is preferably used for preventing or ameliorating at least one selected from the above symptoms or diseases.
  • composition for promoting metabolism of immune cells and the composition for activating immunity of the present invention may be collectively referred to simply as the composition of the present invention.
  • compositions of the present invention can be applied for either therapeutic use (medical use) or non-therapeutic use (non-medical use).
  • Non-therapeutic is a concept that does not involve medical intervention, i.e. human surgery, treatment or diagnosis.
  • the composition of the present invention can be provided in the form of a drug, but is not limited to this form.
  • the agent itself can be provided as a composition, or a composition containing the agent can be provided.
  • the composition for promoting immune cell metabolism of the present invention can also be referred to as an immune cell metabolism promoting agent.
  • the composition for immunostimulation of the present invention can also be called an immunostimulator.
  • the composition of the present invention is preferably an oral composition.
  • Oral compositions include food and drink, oral pharmaceuticals, quasi-drugs, and feeds, preferably food and drink or oral pharmaceuticals, and more preferably food and drink.
  • composition of the present invention can contain optional additives and components in addition to L-ergothioneine or its salt as long as the effects of the present invention are not impaired.
  • additives and components can be selected according to the form of the composition, etc., and those generally usable for foods and drinks, pharmaceuticals, quasi-drugs, feeds, etc. can be used.
  • the compositions of the present invention do not contain Toll-like receptor ligands.
  • the manufacturing method is not particularly limited, and it can be manufactured by a general method.
  • composition of the present invention when used as a food or drink, L-ergothioneine or a salt thereof is blended with ingredients that can be used for food or drink (for example, food materials, food additives used as necessary).
  • the food and drink are not particularly limited, and examples thereof include general food and drink, health food, health drink, food with function claims, food for specified health use, health supplement, and food and drink for the sick.
  • Health foods, foods with function claims, foods for specified health uses, health supplements, etc. are various formulations such as fine granules, tablets, granules, powders, capsules, chewable formulations, syrups, liquid formulations, and liquid diets. can be in the form
  • composition of the present invention is used as a drug or quasi-drug, for example, L-ergothioneine or a salt thereof is blended with a pharmacologically acceptable carrier, an additive added as necessary, and the like, It can be used as pharmaceuticals or quasi-drugs in various dosage forms.
  • Such carriers, additives, etc. may be those that can be used for pharmaceuticals or quasi-drugs and are pharmacologically acceptable.
  • antioxidants, coloring agents and the like can be mentioned.
  • the dosage form of the drug or quasi-drug includes oral or parenteral dosage form, and oral dosage form is preferable from the viewpoint of obtaining the effect of the present invention more sufficiently.
  • composition of the present invention When used as a drug or quasi-drug, it is preferably an oral drug or quasi-drug.
  • Dosage forms for oral administration include liquids, tablets, powders, fine granules, granules, dragees, capsules, suspensions, emulsions, chewables and the like.
  • Dosage forms for parenteral administration include injections and infusions.
  • Pharmaceuticals and quasi-drugs may be for non-human animals.
  • feed When the composition of the present invention is used as a feed, L-ergothioneine or a salt thereof may be added to the feed.
  • Feed also includes feed additives. Examples of feeds include livestock feeds for cows, pigs, chickens, sheep, horses, etc.; small animal feeds for rabbits, rats, mice, etc.; pet foods for dogs, cats, small birds, etc.;
  • the content of L-ergothioneine or a salt thereof contained in the composition of the present invention is not particularly limited, and can be set according to its form and the like.
  • the content of L-ergothioneine or a salt thereof in the composition of the present invention is, for example, preferably 0.0001% by weight or more, more preferably 0.001% by weight or more, and 90% by weight or less in terms of L-ergothioneine. is preferred, and 50% by weight or less is more preferred.
  • the content of L-ergothioneine or a salt thereof in the composition is preferably 0.0001 to 90% by weight, more preferably 0.001 to 50% by weight in terms of L-ergothioneine.
  • the content of L-ergothioneine or a salt thereof is preferably within the above range.
  • the amount in terms of L-ergothioneine or a similar expression is obtained by multiplying the amount in the case of L-ergothioneine or the number of moles of the salt in the case of a salt of L-ergothioneine by the molecular weight of L-ergothioneine. value.
  • the composition of the present invention can be ingested or administered by an appropriate method depending on its form. From the viewpoint of obtaining the effect of the present invention more sufficiently, the composition of the present invention is preferably taken orally (orally administered).
  • the intake amount (can also be referred to as dosage) of the composition of the present invention is not particularly limited as long as it is an amount that can obtain the effect of promoting the metabolism of immune cells, and the amount that can obtain the effect of activating immune function. It may be set as appropriate according to the dosage form, administration method, body weight of the subject, and the like.
  • the intake of L-ergothioneine or a salt thereof is preferably 2 mg or more in terms of L-ergothioneine per day. , more preferably 5 mg or more, still more preferably 10 mg or more, more preferably 50 mg or less, more preferably 25 mg or less, still more preferably 20 mg or less.
  • the intake of L-ergothioneine or a salt thereof is preferably 2 to 50 mg, more preferably 5 mg per day in terms of L-ergothioneine.
  • the composition of the present invention may be an oral composition for ingesting or administering L-ergothioneine or a salt thereof in the above amount per 60 kg body weight per day to humans.
  • the dose of L-ergothioneine or a salt thereof is preferably 2 to 50 mg, for example, preferably 2 to 50 mg per day, in terms of L-ergothioneine.
  • It is preferably 5 to 25 mg, more preferably 5 to 20 mg, particularly preferably 10 to 20 mg.
  • the composition of the present invention preferably has a content of L-ergothioneine or a salt thereof of 2 to 50 mg in terms of L-ergothioneine per day for adults.
  • the content of L-ergothioneine or a salt thereof is more preferably 5 to 25 mg, more preferably 5 to 20 mg, and particularly preferably 10 mg per day for adults in terms of L-ergothioneine. ⁇ 20 mg.
  • compositions of the present invention are taken or administered continuously.
  • the composition of the present invention is preferably taken or administered continuously for one week or more, more preferably two weeks or more.
  • Subjects to whom the composition of the present invention is ingested or administered are not particularly limited.
  • the subject is preferably a human or non-human mammal, more preferably a human.
  • Subjects to which the composition of the present invention is to be ingested or administered include those who require or desire immune cell metabolism promotion and those who require or desire immune activation.
  • the subject of administration includes a subject with a condition or disease caused by a weakened immune system.
  • the subject of administration of the composition of the present invention may be a healthy subject.
  • the subject of administration of the composition of the present invention may be a healthy person whose immune function by immune cells is declining with age.
  • the composition of the present invention may be labeled with a function exerted by promoting the metabolism of immune cells or a function exerted by activating the immune function.
  • the composition of the present invention may be labeled with one or more functions such as "metabolism promotion of immune cells", “activation of mitochondrial function", “immune activation” and the like.
  • the composition of the present invention is preferably a food or drink labeled as above.
  • the above display may be a display to the effect that it is used to obtain the above functions.
  • the label may be attached to the composition itself, or may be attached to the container or package of the composition.
  • the invention also includes the following methods and uses.
  • a method for promoting metabolism of immune cells comprising ingesting or administering L-ergothioneine or a salt thereof.
  • a method for promoting metabolism of immune cells by activating mitochondrial function comprising ingesting or administering L-ergothioneine or a salt thereof.
  • a method for activating immunity comprising ingesting or administering L-ergothioneine or a salt thereof.
  • Use of L-ergothioneine or a salt thereof for promoting metabolism of immune cells Use of L-ergothioneine or a salt thereof for promoting immune cell metabolism by activating mitochondrial function.
  • the metabolism of immune cells can be promoted, and the activation effect of mitochondrial function can promote the metabolism of immune cells, resulting in an immunostimulatory effect. can be obtained.
  • the method of promoting immune cell metabolism can be used, for example, for immune activation.
  • L-ergothioneine or a salt thereof is taken or administered orally.
  • the method may be a therapeutic method or a non-therapeutic method.
  • the use may be therapeutic use or non-therapeutic use.
  • L-ergothioneine or salts thereof, preferred embodiments thereof, etc. are the same as those of the composition of the present invention described above.
  • the subject take or administer L-ergothioneine or a salt thereof once or more times a day, for example, once to several times (eg, 2 to 3 times) a day.
  • the above uses are preferably in humans or non-human mammals, more preferably in humans.
  • L-ergothioneine or a salt thereof can be used to obtain an immunostimulatory effect by promoting immune cell metabolism and by promoting immune cell metabolism by activating mitochondrial function.
  • an amount of L-ergothioneine or a salt thereof that provides an effect of promoting the metabolism of immune cells may be used.
  • L-ergothioneine or a salt thereof may be used in an amount that provides an activating effect on mitochondrial function (can also be called an effective amount).
  • an amount of L-ergothioneine or a salt thereof that provides an immunostimulatory effect may be used.
  • the preferred dose, administration subject, etc. of L-ergothioneine or a salt thereof are the same as those of the composition of the present invention described above.
  • L-ergothioneine or a salt thereof may be ingested or administered as is, or may be ingested or administered as a composition containing it.
  • a composition of the invention may be ingested or administered.
  • L-ergothioneine or a salt thereof can be used for the production of foods and drinks, pharmaceuticals, quasi-drugs, feeds, etc., which are used to promote the metabolism of immune cells.
  • the present invention also includes the use of L-ergothioneine or a salt thereof for producing a composition for promoting metabolism of immune cells.
  • the present invention also includes L-ergothioneine or a salt thereof, which is used for promoting metabolism of immune cells.
  • L-ergothioneine or a salt thereof can be used for the production of foods and drinks, pharmaceuticals, quasi-drugs, feeds, etc. used for mitochondrial function activation.
  • the present invention also includes the use of L-ergothioneine or a salt thereof for manufacturing a composition for activating mitochondrial function.
  • the present invention also includes L-ergothioneine or a salt thereof used for mitochondrial function activation.
  • L-ergothioneine or a salt thereof can be used for the production of foods and drinks, pharmaceuticals, quasi-drugs, feeds, etc. used for immune activation.
  • the present invention also includes the use of L-ergothioneine or a salt thereof for manufacturing an immunostimulatory composition.
  • the present invention also includes L-ergothioneine or a salt thereof used for immune activation.
  • Example 1 The effect of the compound of the invention (L-ergothioneine) on mitochondrial function was analyzed.
  • Ergothioneine was added to human peripheral blood mononuclear cells (PBMC) under the following conditions, and extracellular oxygen levels and pH were measured in real time using an XFe96 flux analyzer (manufactured by Agilent Technologies).
  • XFe96 flux analyzer manufactured by Agilent Technologies.
  • XFe technology uses solid-state sensors to simultaneously measure both oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) to simultaneously determine effects on oxidative phosphorylation (OXPHOS) and glycolysis. It is.
  • OXPHOS oxidative phosphorylation
  • FIG. Cells were then sequentially exposed to different inhibitors of mitochondrial function to assess cellular metabolism.
  • Human PBMC were maintained in XF assay medium (XF RPMI1640 medium). At that time, L-ergothioneine was adjusted to final concentrations of 0, 10, 30 and 100 ⁇ M. 30,000 cells/50 ⁇ L/well of cells were seeded on a PDL-coated XF96-well cell culture plate and centrifuged at 200 g for 1 minute to adhere the cells. After 20 minutes of incubation at 37°C in the absence of CO2 , 130 ⁇ L of XF assay medium was gently added and incubated for an additional 40 minutes at 37°C in the absence of CO2 . The human PBMC to which ergothioneine was added was subjected to the following mitochondrial stress test.
  • ⁇ Mitochondrial stress test> The XF Mitostress Kit (manufactured by Agilent Technologies) was used for the experiment. The following compounds (1) to (3) were sequentially added to the human PBMCs to which ergothioneine was added, and OCR was measured to determine basal respiration, ATP production, maximum Parameters such as respiration were calculated. The results obtained are shown in FIG. 1A (basal respiration), FIG. 1B (ATP production) and FIG. 1C (maximal respiration). This can aid in understanding the possible mechanisms of mitochondrial metabolism.
  • Compound (1) 1 ⁇ M oligomycin, (2) 1 ⁇ M FCCP (carbonyl cyanide-p-trifluoromethoxyphenylhydrazone), and (3) 0.5 ⁇ M rotenone and antimycin A
  • FCCP carbonyl cyanide-p-trifluoromethoxyphenylhydrazone
  • Oligomycin is a known inhibitor of ATP synthase and prevents the production of ATP. Oligomycin treatment provides a measure of oxygen consumption associated with ATP production and ATP turnover. Addition of oligomycin results in decreased OCR under normal conditions, and residual OCR is associated with spontaneous proton leakage.
  • FCCP is a protonophore and a known oxygen-consuming uncoupler from ATP production. FCCP processing allows the highest achievable electron transfer and oxygen consumption rates and provides a measure of reserve capacity.
  • Rotenone and antimycin A are known inhibitors of complexes I and III of the electron transport chain, respectively. Upon treatment with these components, electron transfer is completely inhibited and residual oxygen consumption is due to non-mitochondrial activity by oxygen-requiring enzymes.
  • FIG. 1A is a graph showing the effect of ergothioneine on OCR on basal respiration, and it can be confirmed that mitochondrial basal respiration is significantly increased in human PBMCs to which ergothioneine was added at final concentrations of 10 ⁇ M, 30 ⁇ M, and 100 ⁇ M. .
  • FIG. 1B is a graph showing the effect of ergothioneine on OCR on ATP-related respiration, confirming that mitochondrial ATP production is significantly increased in human PBMCs to which ergothioneine was added at final concentrations of 10 ⁇ M, 30 ⁇ M, and 100 ⁇ M. can.
  • FIG. 1C is a graph showing the effect of ergothioneine on OCR on maximal respiration, and it can be confirmed that maximal respiration of mitochondria is significantly increased in human PBMCs to which ergothioneine was added at final concentrations of 10 ⁇ M, 30 ⁇ M, and 100 ⁇ M. .
  • FIG. 2 is a graph showing the effect of ergothioneine on oxygen consumption rate (OCR) in human PBMC over time. Ergothioneine added at final concentrations of 10 ⁇ M, 30 ⁇ M, and 100 ⁇ M increased mitochondrial oxygen consumption rate in human PBMC. It can be confirmed that

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PCT/JP2022/014256 2021-04-26 2022-03-25 免疫細胞の代謝促進用組成物 Ceased WO2022230494A1 (ja)

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AU2022265114A AU2022265114A1 (en) 2021-04-26 2022-03-25 Composition for stimulating immune cell metabolism
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WO2024172002A1 (ja) * 2023-02-16 2024-08-22 サントリーホールディングス株式会社 エルゴチオネインを含有する血管拡張用組成物

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WO2024172002A1 (ja) * 2023-02-16 2024-08-22 サントリーホールディングス株式会社 エルゴチオネインを含有する血管拡張用組成物

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AU2022265114A1 (en) 2023-10-12
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