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CN109890378A - Composition for inhibiting FOXO1 activity - Google Patents

Composition for inhibiting FOXO1 activity Download PDF

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Publication number
CN109890378A
CN109890378A CN201780066338.9A CN201780066338A CN109890378A CN 109890378 A CN109890378 A CN 109890378A CN 201780066338 A CN201780066338 A CN 201780066338A CN 109890378 A CN109890378 A CN 109890378A
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China
Prior art keywords
muscle
foxo1
acid
composition according
composition
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CN201780066338.9A
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Chinese (zh)
Inventor
三浦进司
守田昭仁
村山宣人
铃木寿荣
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Suntory Holdings Ltd
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Suntory Holdings Ltd
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    • A61K31/407—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
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    • A61K31/445—Non condensed piperidines, e.g. piperocaine
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    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A61K31/52—Purines, e.g. adenine
    • A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
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Abstract

本发明的目的在于提供一种生物安全性高且有助于FOXO1活性的阻碍的组合物。此外，本发明的目的还在于提供用于阻碍FOXO1活性的组合物的应用，及阻碍FOXO1活性的方法。本发明发现了来自天然物的化合物中的特定的化合物具有FOXO1活性的阻碍作用。本发明提供一种对抑制肌肉萎缩、促进肌肉合成及抑制骨密度降低有贡献的，有效且新颖的方法。An object of the present invention is to provide a composition that is highly biosafe and contributes to inhibition of FOXO1 activity. Moreover, the objective of this invention is to provide the use of the composition for inhibiting the activity of FOXO1, and the method of inhibiting the activity of FOXO1. The present inventors discovered that a specific compound among the compounds derived from natural products has an inhibitory effect on FOXO1 activity. The present invention provides an effective and novel method that contributes to inhibiting muscle atrophy, promoting muscle synthesis and inhibiting decrease in bone density.

Description

FOXO1 activity obstruction uses composition
Technical field
Useful composition is hindered FOXO1 activity containing specific compound the present invention relates to a kind of.
Background technique
In the Japan for welcoming Beyond senilityization society, with life-time dilatation, the raising of quality of life (QOL) or life-span Extension have become social project.It is high for the importance of the function protection of the project kinematic system, in recent years especially It is since chronic exercise deficiency is common in adult, the consciousness for improving kinematic system function is increasing year by year.
There is skeletal muscle as the Main Tissues for administering kinematic system function.Skeletal muscle is tissue most in human body, in energy The important role that play in amount metabolism, the intake of sugar, movement etc..The function of skeletal muscle depends on its quantity or quality. By keeping regularly moving, the quantity or quality of skeletal muscle can be improved, and opposite can drop when not carrying exercise load for a long time It is low, generate the atrophy of skeletal muscle.The atrophy of skeletal muscle as aging or the various state of an illness and generate.In addition, skeletal muscle is pancreas The function deficiency of the main target internal organs of island element, skeletal muscle is also related with metabolic syndrome.
As the factor relevant to the Metabolism regulation of skeletal muscle, FOXO1 (Forkhead box protein 01) is ripe Know.Known FOXO1 is turn for being under the jurisdiction of the subgroup " O " for the Forkhead family for possessing DNA structure domain Forkhead box (FOX) The factor and transcription regulaton factor are recorded, it is related to stress reaction, Metabolism control, cell cycle etc., it plays in skeletal muscle and flesh The relevant key player of meat atrophy.Have report to point out to send as an envoy to the transgenic mice that FOXO1 is overexpressed in skeletal muscle in production When, the mouse produce with red muscle fall off based on muscular atrophy (non-patent literature 1).It is found jointly in muscular atrophy There is the expression of FOXO1 to increase, implies the reason of it is muscular atrophy.Conjunction of the overexpression of known FOXO1 also with inhibition muscle Reduction (non-patent literature 3) at (non-patent literature 2) or bone density etc. is associated.
If the expression quantity of FOXO1 increases, endonuclear FOXO1 increases, and promotes to wither with muscle because of its activity It contracts the transcription of associated gene.Furthermore it is known that the downstream of FOXO1 insulin signaling in the cell is controlled.If insulin with Insulin receptor on cell membrane combines, then insulin inside cells signal is activated, and signal is passed by the sequence of PI3K, Pdk1, Akt It passs, the phosphorylation eventually by Akt, FOXO1 is shifted out of nucleus to outside core, to hinder the active (non-patent literature of FOXO1 4)。
Existing technical literature
Non-patent literature
Non-patent literature 1:J Biol Chem.2004 Sep 24；279(39):41114-23.
Non-patent literature 2:J Biol Chem.2007 Jul 20；282(29):21176-86.
Non-patent literature 3:J Clin Invest.120:357-368,2010
Non-patent literature 4:Bone.2012 Feb；50(2):437-43.
Summary of the invention
Expect to hinder the active compound of FOXO1 that can treat or prevent disease etc. because caused by being overexpressed it.However, so far For having the compound of so effect until the present, the safety that is easy to get and can be widely used for diet product field is not yet found High natural goods substance, its rapidly exploitation of strong expectation.
Here, high the purpose of the present invention is to provide a kind of biological safety and facilitate the group of the active obstruction of FOXO1 Close object.In addition, the object of the invention is also to provide for hindering the application of the active composition of FOXO1, and obstruction FOXO1 to live The method of property.
The present inventors conduct in-depth research in order to achieve the above objectives, as a result, it has been found that the compound from natural goods In specific compound have the active inhibition of FOXO1.The present inventors are based on this experience and complete the present invention.
That is, the present invention relates to the following contents, but it is not limited in these contents.
(1) a kind of FOXO1 activity hinders to use composition, which is characterized in that containing selected from chalcone, triterpenes, flavones The compound of at least one of class, monoterpenes, lignanoids, Coumarins and Phytochemistry class.
(2) composition according to (1), which is characterized in that chalcone is selected from 4- hydroxy chalcone, trans- looks into ear The compound of at least one of ketone and 2,3- dimethoxy -2'- hydroxy chalcone.
(3) composition according to (1) or (2), which is characterized in that triterpenes is Corosolic acid.
(4) composition according to any one of (1)~(3), which is characterized in that flavonoids is selected from 6,7- dihydroxy The chemical combination of at least one of flavones, 6- methyl flavones, 5- methoxy flavone, 7,8- dihydroxyflavone, Chrysin and saponarin Object.
(5) composition according to any one of (1)~(4), which is characterized in that monoterpenes are (±) isomenthone.
(6) composition according to any one of (1)~(5), which is characterized in that lignanoids be enterodiol and/or Trachelospermum jasminoide aglycon.
(7) composition according to any one of (1)~(6), which is characterized in that Coumarins 3,4- dihydro tonka-bean Element.
(8) composition according to any one of (1)~(7), which is characterized in that Phytochemistry class is amygdalin.
(9) composition according to any one of (1)~(8), which is characterized in that composition is to inhibit muscular atrophy With, promote muscle synthesis use or inhibit bone density reduce use.
(10) composition according to any one of (1)~(9), which is characterized in that be attached with by the active resistance of FOXO1 The expression of function for hindering and playing.
(11) composition according to (10), which is characterized in that function is expressed as selected from " maintaining muscle ", " inhibits Muscular atrophy ", " reduction of control muscle ", " decline for preventing muscle ", " controls declining for muscle at " reduction for preventing muscle " Move back ", " attached to give muscle ", " increase muscle " " forming muscle ", " supporting muscle ", " maintaining bone density ", " prevent the drop of bone density It is low ", the reduction of bone density " control ", " support bones ", " maintaining strong bone ", " health for maintaining bone " and " to bone It is healthy and beneficial ".
(12) a kind of application, which is characterized in that for chalcone, triterpenes, flavonoids, monoterpenes, lignanoid will be selected from The compound of at least one of class, Coumarins and Phytochemistry class is for hindering FOXO1 active.
(13) a kind of active method of obstruction FOXO1, which is characterized in that using selected from chalcone, triterpenes, flavones The compound of at least one of class, monoterpenes, lignanoids, Coumarins and Phytochemistry class.
According to the present invention it is possible to provide a kind of composition with good FOXO1 activity inhibition.If utilizing this hair Bright composition can obtain inhibiting muscular atrophy, promote muscle synthesis and inhibiting bone density drop by the active obstruction of FOXO1 Low effect.These effects and offer reached according to the present invention facilitate the new method of the QOL improvement of sufferer or People It is related.
Further, since specific compound used in the present invention is all therefore to be considered safety from natural goods It is high.Therefore, the present invention can provide one kind to have good FOXO1 activity inhibition, and the combination of safety and energy continuous ingestion Object.
Specific embodiment
(compound)
One embodiment of the present invention is the composition containing specific compound.Composition of the invention is by the spy Substance of the fixed compound as effective component.
In composition of the invention, containing selected from chalcone (Chalcones), triterpenes (Triterpenes), flavones Class (Flavones), monoterpenes (Monoterpenoids), lignanoids (Lignans), Coumarins (Coumarins) and plant The compound of at least one of object chemical classes (Phytochemical).In composition of the invention, it can contain on two or more Compound is stated, or containing there are three types of also may be used above.
Compound used in the present invention, can be trans- chalcone (trans-Chalcone), 2', dihydroxy -4 6'-, 4'- dimethoxychalcone (2', 6'-Dihydroxy-4,4'-dimethoxychalcone), acacetin (Acacetin), Acteoside (Acteoside), creat lactone (Andrographolide), apiolin (Apigenin), scutelloside (Baicalin), Chrysin (Chrysin), chlorination Cyanidin (Cyanidin chloride), anthocyanin (Cyanin), big Beans aglycon (Daidzein), delphinidin diglucoside (Delphin), chlorination delphinidin (Delphinidin Chloride), δ- (3,4- dihydroxy phenyl)-gamma-valerolactone (δ-(3,4-Dihydroxyphenyl)-γ-valerolactone), diosmetin (Diosmetin), diosmin (Diosmin), ellagic acid (Ellagic acid), eriodictyol (Eriodictyol), fisetin (Fisetin), garden burnet acid (Sanguisorbic acid), hesperetin (Hesperetin), isoliquiritigenin (Isoliquiritigenin), Kaempferol (Kaempferol), lipoic acid (Lipoic acid), Mahanine, myricetin (Myricetin), protocatechuic acid (Protocatechuic acid), procyanidin B 2 (Procyanidin B2), Quercetin (Quercetin dihydrate), sesamin (Sesamin), asarinin (Episesamin), trie horse element 1 (Tellimagrandin 1), trie horse element 2 (Tellimagrandin 2), theobromine (Theobromine), theophylline (Theophylline), wogonin (Wogonin), β-naphthoflavene (β-Naphthoflavone), silibinin (Silibinin), kamalin (Rottlerin), 6- flavonol (6-Hydroxyflavone), 7- flavonol (7- Hydroxyflavone), Isorhamnetin (Isorhamnetin), morin (Morin), chrysoeriol (Chrysoeriol), Formoononetin (Formononetin), Peonidin chloride (Peonidin Chloride), cypress biflavone (Cupressuflavone), 7,4'- dihydroxyflavone (7,4'-Dihydroxyflavone), 7,8- dihydroxyflavone (7,8- Dihydroxyflavone), 6,7- dihydroxyflavone (6,7-Dihydroxyflavone), 3', 4'- dimethoxy flavone (3', 4'-Dimethoxyflavone), 3-hydroxyflavone (3-Hydroxyflavone), Ipriflavone (Ipriflavone), 2'- first Oxygroup flavones (2'-Methoxyflavone), 5- methoxy flavone (5-Methoxyflavone), 3', 4', 5', five first of 5,7- Oxygroup flavones (3', 4', 5', 5,7-Pentamethoxyflavone), 3, ' 4,7,8- kaempferol (3', 4', 7,8- Tetrahydroxyflavone), 4', 6,7- tri hydroxy isoflavone (4', 6,7-Trihydroxyisoflavone), 7- hydroxyl are yellow Keto-alcohol (7-Hydroxyflavonol), 7- methoxyflavonol (7-Methoxyflavonol), 6-methoxy-2-phenyl-4H-chromen-4-one alcohol (6- Methoxyflavonol), 5,7- dihydroxy -3', 4', 5'- trimethoxy flavanones (5,7-Dihydroxy-3', 4', 5'- Trimethoxyflavanone), flavanones (Flavanone), Flavanone diacetyl hydrazone (Flavanone diacetyl Hydrazone), Flavanone hydrazone (Flavanone hydrazone), 2'- hydroxyl flavanones (2'-Hydroxyflavanone), 4'- hydroxyl flavanones (4'-Hydroxyflavanone), 3'- hydroxyl flavanones (3'-Hydroxyflavanone), α-naphthalene yellow Ketone (α-Naphthoflavone), 5- methoxy flavanone (5-Methoxyflavanone), 6- methoxy flavanone (6- Methoxyflavanone), 2', 6'- dihydroxy -4,4'- methylenedioxy dihydrocharcone (2', 6'-Dihydroxy-4,4'- Dimethoxydihydrochalcone), 2', 6'- dihydroxy -4'- methoxy chalcones (2', 6'-Dihydroxy-4'- Methoxychalcone), 2,3- dimethoxy -2'- hydroxy chalcone (2,3-Dimethoxy-2'- Hydroxychalcone), sesamin phenol (Sesaminol), rue aurantiin (Narirutin), quercetin -3,5,7,3', 4'- Five methyl ethers (Quercetin-3,5,7,3', 4'-pentamethylether), tetra- methyl ether of quercetin -3,7,3', 4'- (Quercetin-3,7,3', 4'-tetramethylether), Fisetinidin chloride (Fisetinidin chloride), wood Rhinoceros grass determines chloride (Luteolinidin chloride), 3', 4', 7,8- tetramethoxy flavones (3', 4', 7,8- Tetramethoxyflavone), O- acetyl dihydro Ou Shanqin ester (O-Acetylcolumbianetin), 3- acetyl group hydroxyl are fragrant Legumin (3-Acetylcoumarin), 8- acetyl -6,7- dimethoxycoumarin (8-Acetyl-6,7- Dimethoxycoumarin), 8- acetyl-umbelliferone (8-Acetyl-7-hydroxycoumarin), 8- acetyl -6- Hydroxyl-ayapanin (8-Acetyl-6-hydroxy-7-methoxycoumarin), 8- acetyl -7- methoxyl group tonka-bean Plain (8-Acetyl-7-methoxycoumarin), 3- aminocoumarin (3-Aminocoumarin), bergamot element (Bergamotin), majudin (Bergapten), bergaptol (Bergaptol), citropten (Citropten), 2- are fragrant Beans acid (2-Coumaric acid), 3- coumaric acid (3-Coumaric acid), cumarin (Coumarin), coumaric acid (Coumaric acid), coumestrol (Coumestrol), dephnetin (Daphnetin), dephnetin -7- methyl ether (Daphnetin-7-methylether), 3,4- dihydrocoumarin (3,4-Dihydrocoumarin), 5,7- dihydroxy -4- first Butylcoumariii (5,7-Dihydroxy-4-methylcoumarin), Esculetin dibenzylether (Esculetin Dibenzylether), 4- ethoxy coumarin (4-Ethoxycoumarin), 7-ethoxy coumarin (7- Ethoxycoumarin), fraxetin (Fraxetin), fraxetin pyridine (Fraxidin), ayapanin (Herniarin), 3- Hydroxycoumarin (3-Hydroxycoumarin), 4 hydroxy coumarin (4-Hydroxycoumarin), Imperatorin (Imperatorin), isobergapten (Isobergapten), isopimpinellin (Isopimpinellin), Isoscopoletin (Isoscopoletin), 6-Methylcoumarin (6-Methylcoumarin), umbelliferone (Umbelliferone), 3- acetyl group-α masticinic acid (3-Acetyl- α-boswellic acid), 3- acetyl group-beta boswellic acid (3-Acetyl- β-boswellic acid), alpha-amyrin (α-Amyrin), beta-amyrin (β-Amyrin), qinghaosu (Artemisinin), betulin (Betulin), betulic acid (Betulinic acid), Betulinic acid methylester (Betulinic Acid methyl ester), Bilobalide (Bilobalide), coffee oleyl alcohol (Cafestol), (-)-carvacrol ((-)- Carveol), (+)-carvol ((+)-Carvone), (-)-carvol ((-)-Carvone), catechol (Caulophyllogenin), deoxidation cimicifugae foetidae hydrocarbon (Deoxyactein), erythrodiol (Erythrodiol), ganoderic acid A (Ganoderic acid A), hederagenin (Hederagenin), d- isomenthol (d-Isomenthol), (±) are different Menthones ((±) Isomenthone), oleanolic acid (Oleanolic acid), alizarin (Alizarin), alkannin (Alkannin), anthraquinone (Anthraquinone), 1,4- benzoquinones (1,4-Benzoquinone), tert-butyl 1,4-benzoquinone (2- Tert-butyl-p-quinone), 1,4- dimethyl anthraquinone (1,4-Dimethylanthraquinone), rheum emodin (Emodin), Physcion (Physcion), Rhein (Rhein), southern candelilla Syringaresinol (Lyoniresinol), urolithin (Urolithin), amygdalin (Amarogentin), 6- methyl flavones (6-Methylflavone), 4- hydroxy chalcone (4- Hydroxychalcone), 4'- hydroxy chalcone (4'-Hydroxychalcone), coumaric acid (Coumalic acid), white Chenopodiaceae Reed alcohol (Resveratrol), kojic acid (Kojic acid), parithenolide (Parthenolide), icariin (Icariin), ginsenoside Rb1 (Ginsenoside Rb 1), gingerol (Gingerol), 10-HAD (10- Hydroxy-2-decenoic acid), Epipinoresinol-Glc, forsythin (Phillyrin), rosin element (Pinoresinol), table pinoresinol (Epipinoresinol), phillygenol (Phillygenin), 1 (Curcumin of curcumin 1), curcumin 2 (Curcumin 2), bisdemethoxycurcumin (Curcumin 3), Diasesamin, honokiol (Honokiol), cassia angustifolia Glucoside member A (Sennidine A), aesculetin (Esculetin), sesamol (Sesamol), scopolactone (Scopoletin), nordihydroguaiaretic acid (Nordihydroguaiaretic acid), vanillic acid (Vanillic Acid), trans-cinnamic acid (trans-Cinnamic acid), allantoin (Allantoin), alpha-ararin (α-Asarone), (±)-synephrine ((±)-Synephrine), itaconic acid (Itaconic acid), asiatic acid (Asiatic acid), wave You determine alkali (Boldine), shikimic acid (Shikimic acid), tyrosol (Tyrosol), Corosolic acid (Corosolic acid), Picein (Picein), Rosmarinic acid (Rosmarinic acid), isosteviol (Isosteviol), Ah Ti woods C (Artepillin C), foreign celery brain (Apiole), glycosides chrysanthemum ring (Azulene) difficult to understand, marrubiin (Marrubiin), (-)-purple perilla Sour ((-)-Perillic acid), madecassoside sour (Madecassic acid), mangiferin (Mangiferin), fragrant camphor tree Alcohol (Linalool), 2- anisaldehyde (2-Anisaldehyde), 3- anisaldehyde (3-Anisaldehyde), 4- anisic acid (4- Anisic acid), urocanic acid (Urocanic acid), α-(-)-bisabolol (α-(-)-Bisabolol), (-)-trans- stone Bamboo alkene ((-)-trans-Caryophyllene), caryophyllene oxide (Caryophyllene oxide), hamameli tannin (Hamamelitannin), perillaldehyde (Perillaldehyde), Bavachinin A (Bavachinin A), left-handed water Revive alkali (Betonicine), (+)-cuparene ((+) Cuparene), nootkatone (Nootkatone), (-)-perillyl alcohol ((-)-Perillylalcohol), piperlongumine (Piperlongumine), chamazulene (Chamazulen), (-)-asarum rouge Element ((-)-Asarinin), (-)-sesamin ((-)-Sesamin), 2', 4,4', 6'- tetrahydroxy chalcone (2', 4,4', 6'- Tetrahydroxychalcone), Hinokitiol (Hinokitiol), fucoxanthine (Fucoxanthine), enterodiol (Enterodiol), matairesinol (Matairesinol), trigonelline monohydrate (Trigonelline Monohydrate), fraxin (Fraxin), lupeol (Lupeol), trachelospermum jasminoide aglycon (Trachelogenin), enoxolone (Glycyrrhetic acid), glycyrrhizic acid (Glycyrrhizic acid), 6- hydroxyl -4'- methoxy flavone (6-Hydroxy- 4'-methoxyflavone), dihydromyricetin (Dihydromyricetin), 2'- hydroxy chalcone (2'- Hydroxychalcone), zerumbone (zerumbone), Oleacein, crocetin (Crocetin), Dilatrate-SR (Isosorbide Dinitrate), high protocatechuic acid (Homoprotocatechuic acid), glutathione (Glutathione), corilagin (Corilagin), sesamolin (sesamolin), oleuropein (Oleuropein), calabash Lu Su B (Cucurbitacin B), cucurbitacin D (Cucurbitacin D), rue leaf glycosides (Rutin trihydrate), Vitex negundo var cannabifolia Element (Vitexin), orientoside (Orientin), Isovitexin (Isovitexin), Buddhist Lay heart glycosides (Violanthin), aurantiin (Naringin), saponarin (Saponarin), limonin (Limonin), Chafuroside B, Chafuroside A, sweet tea Orange element (Sinensetin) and 3', 4', 5,5', 6,7,8- Heptamethoxyflavone (3', 4', 5,5', 6,7,8- Heptamethoxyflavone).More than one containing above compound in the present compositions.
Above-mentioned specific compound, chemical formula shown in following table indicates respectively.
[table 1-1]
[table 1-2]
[table 1-3]
[table 1-4]
[table 1-5]
[table 1-6]
[table 1-7]
[table 1-8]
[table 1-9]
[table 1-10]
[table 1-11]
[table 1-12]
[table 1-13]
[table 1-14]
[table 1-15]
[table 1-16]
[table 1-17]
[table 1-18]
[table 1-19]
[table 1-20]
[table 1-21]
[table 1-22]
[table 1-23]
[table 1-24]
[table 1-25]
[table 1-26]
[table 1-27]
[table 1-28]
[table 1-29]
[table 1-30]
[table 1-31]
[table 1-32]
[table 1-33]
[table 1-34]
[table 1-35]
[table 1-36]
[table 1-37]
[table 1-38]
[table 1-39]
[table 1-40]
[table 1-41]
[table 1-42]
[table 1-43]
[table 1-44]
[table 1-45]
[table 1-46]
[table 1-47]
[table 1-48]
[table 1-49]
[table 1-50]
Above compound can be used market and sell product, it is possible to use be modulated by method known in those skilled in the art Object.Above compound, for example, can be appropriately carried out point from plant etc. containing various compounds using water or oily equal solvent From or purification etc. operation and modulate.Above compound can be crystallization compound, recrystallize any one form such as compound or concentrate, Its form is not particularly limited.
In addition, above compound, can be derived as glycocide etc.." glycocide " so-called in this specification refers to the hydroxyl of sugar Compound made of being bonded with non-saccharic compound.Sugar in glycocide, can be monosaccharide or disaccharides or be this with On plural number sugar can also, be not particularly limited.The type of sugar is also not particularly limited, glucose, mannose, gala can be enumerated The ketoses such as the aldoses such as sugar, fucose, rhamnose, arabinose, xylose, fructose, glucuronic acid, galacturonic acid, mannose The uronic acids such as aldehydic acid, apiose, rutinose etc..In addition, sugar used in glycocide can be the mixed of D body, L body or D body and L body It closes object (DL body), is not particularly limited.
Composition of the invention can be arbitrarily containing the arbitrary substance in two or more above compound.In addition, of the invention Composition can arbitrarily contain 3 kinds or more, 4 kinds or more, 5 kinds or more, 6 kinds or more, 7 kinds or more, 8 kinds or more, 9 kinds or more or 10 Kind or more arbitrary substance in above compound.
When using multiple several compounds, for example, can be applied in combination trachelospermum jasminoide aglycon, β-naphthoflavene, 6,7- dihydroxyflavone, 3,4- dihydrocoumarin, tert-butyl 1,4-benzoquinone, amygdalin, (±) isomenthone, saponarin, ganoderic acid A, flavanones diacetyl Hydrazone, Bilobalide, 3- Hydroxycoumarin, 2- coumaric acid, hederagenin, 1,4- dimethyl anthraquinone, erythrodiol, different Radix Glycyrrhizae Element, 8- acetyl-umbelliferone, Rhein, perillaldehyde, dephnetin -7- methyl ether, 3- acetyl group-α masticinic acid, (-)-purple perilla Acid, dephnetin, itaconic acid, scopolactone, 2- anisaldehyde, Physcion, Corosolic acid, Cucurbitacin B, oleanolic acid, purple Careless element, gingerol, Flavanone hydrazone, 1,4- benzoquinones, d- isomenthol, tetra- methyl ether of quercetin -3,7,3', 4'-, 3', 4', 5', 5,7- five Methoxy flavone, sesamol, forsythin, parithenolide, five methyl ether of quercetin -3,5,7,3', 4'-, 3-hydroxyflavone, 3, ' 4, 7,8- kaempferol, ayapanin, catechol, 8- acetyl -6,7- dimethoxycoumarin, tyrosol, citropten, 8- acetyl -6- hydroxyl-ayapanin, Betulinic acid methylester, anthraquinone, 5,7- dihydroxy -3', 4', 5'- trimethoxy flavane Ketone, bergamot element, trans-cinnamic acid, bergaptol, alpha-amyrin, 3- coumaric acid, O- acetyl dihydro Ou Shanqin ester, 2', 6'- dihydroxy Base -4,4'- methylenedioxy dihydrocharcone, (±)-synephrine, 4 hydroxy coumarin, isobergapten, hamameli tannin, Coffee oleyl alcohol, 5,7- dihydroxy -4- methylcoumarin, alizarin, majudin, (+)-carvol, 7- hydroxyl flavanols, tonka-bean Element, coumaric acid, theobromine, (-)-perillyl alcohol, boldine, 3- acetyl group-beta boswellic acid, bisdemethoxycurcumin, 2', 6'- dihydroxy Base -4'- methoxy chalcones, urocanic acid, 4', 6,7- tri hydroxy isoflavone, betulic acid, picein, 4- hydroxy chalcone, Ou Qian Hu Su, 3, ' 4,7,8- tetramethoxy flavones, rue aurantiin, procyanidin B 2, sennidin A, 3- anisaldehyde, rheum emodin, Huang Alkanone, 3- acetyl group Hydroxycoumarin, fraxetin pyridine, (-)-carvol, linalool, 10-HAD, resveratrol, Protocatechuic acid, umbelliferone, ginsenoside Rb1, fisetin, alpha-ararin, 4- anisic acid, coumestrol, 8- acetyl -7- first Oxygroup cumarin, (-)-carvacrol, table pinoresinol, Epipinoresinol-Glc, 6- methoxyl group flavanols, kojic acid, deoxidation liter Numb hydrocarbon, betulin, 2'- hydroxyl flavanones, 3- aminocoumarin, vanillic acid, Isoscopoletin, Isorhamnetin, allantoin, 5- first Oxygroup flavanones, 6-Methylcoumarin, curcumin 2, ellagic acid, nordihydroguaiaretic acid, 4- ethoxy coumarin, Herba Epimedii Glycosides, foreign celery brain, α-naphthoflavene, asiatic acid, beta-amyrin, rosin element, southern candelilla Syringaresinol, Diasesamin, Rosmarinic acid, (+)-cuparene, Esculetin dibenzylether, 2', 4,4', 6'- tetrahydroxy chalcone, honokiol, sesamin phenol, cucurbitacin D, Isosteviol, piperlongumine, caryophyllene oxide, phillygenol, marrubiin, (-)-Trans-caryophyllene, 3'- hydroxyl flavane Ketone, fraxetin, Hinokitiol, isopimpinellin, reseda determine chloride, fucoxanthine, madecassoside acid, nootkatone, 5- Methoxy flavone, mangiferin, 2', 6'- dihydroxy -4,4'- dimethoxychalcone, shikimic acid, limonin, chlorination Chinese herbaceous peony Element, formoononetin, sesamin, Fisetinidin chloride, high protocatechuic acid, glycosides chrysanthemum ring difficult to understand, anthocyanin, Quercetin, urolithin or Coumaric acid etc., but it is not particularly limited to this.Although preferably combination makes in above compound in addition, being not particularly limited to It is different with trachelospermum jasminoide aglycon, β-naphthoflavene, 6,7- dihydroxyflavone, 3,4- dihydrocoumarin, tert-butyl 1,4-benzoquinone, amygdalin, (±) Menthones, saponarin, ganoderic acid A, Flavanone diacetyl hydrazone, Bilobalide, 3- Hydroxycoumarin, 2- coumaric acid, ivy soap Aglycon, 1,4- dimethyl anthraquinone, erythrodiol, isoliquiritigenin, 8- acetyl-umbelliferone, Rhein, perillaldehyde, winter daphne Element -7- methyl ether, 3- acetyl group-α masticinic acid, (-)-perillic acid, dephnetin, itaconic acid, scopolactone, 2- anisaldehyde, rheum officinale Plain methyl ether, Corosolic acid, Cucurbitacin B, oleanolic acid, alkannin, gingerol, Flavanone hydrazone, 1,4- benzoquinones, d- isomenthol, oak Tetra- methyl ether of essence -3,7,3', 4'-, 3', 4', 5', 5,7- pentamethoxyl flavones, sesamol, forsythin, parithenolide, quercetin - Five methyl ether of 3,5,7,3', 4'-, 3-hydroxyflavone, 3, ' 4,7,8- kaempferol, ayapanin, catechol, 8- second Acyl -6,7- dimethoxycoumarin, tyrosol, citropten, 8- acetyl -6- hydroxyl-ayapanin, Betulinic acid methylester, Anthraquinone, 5,7- dihydroxy -3', 4', 5'- trimethoxy flavanones, bergamot element, trans-cinnamic acid, bergaptol, alpha-amyrin, 3- coumaric acid, O- acetyl dihydro Ou Shanqin ester, 2', 6'- dihydroxy -4,4'- methylenedioxy dihydrocharcone, (±)-synephrine, 4 hydroxy coumarin, isobergapten, hamameli tannin, coffee oleyl alcohol, 5,7- dihydroxy -4- methylcoumarin, alizarin, Buddhist Hand glycosides lactone, (+)-carvol, 7- hydroxyl flavanols, cumarin, coumaric acid, theobromine, (-)-perillyl alcohol, boldine, 3- acetyl group-beta boswellic acid, bisdemethoxycurcumin, 2', 6'- dihydroxy -4'- methoxy chalcones, urocanic acid, 4', the different Huang of tri- hydroxyl of 6,7- Ketone, betulic acid, picein, 4- hydroxy chalcone, Imperatorin or 3, ' 4,7,8- tetramethoxy flavones.
In composition of the invention, as chalcone it is preferable to use compound be 4- hydroxy chalcone, trans- look into ear Ketone and 2,3- dimethoxy -2'- hydroxy chalcone.
In composition of the invention, as triterpenes it is preferable to use compound be Corosolic acid.
In composition of the invention, as flavonoids it is preferable to use compound be 6,7- dihydroxyflavone, 6- methyl yellow Ketone, 5- methoxy flavone, 7,8- dihydroxyflavone, Chrysin and saponarin.
In composition of the invention, as monoterpenes it is preferable to use compound be (±) isomenthone.
In composition of the invention, as Coumarins it is preferable to use compound be 3,4- dihydrocoumarin.
In composition of the invention, as Phytochemistry class it is preferable to use compound be amygdalin.
(FOXO1)
Composition of the invention can hinder FOXO1 active by using using above-mentioned compound as effective component.Cause This, composition of the invention can be used as FOXO1 activity obstruction and be used with composition.In this specification, so-called " FOXO1 " refers to Plug type transcription factor (Forkhead box protein O1).Due to causing amyotrophic various conditions, such as go on a hunger strike, The expression of the stimulations such as denervation, glucocorticoid come into operation, er stress, FOXO1 increases, due in nucleus with dephosphorylation FOXO1 existing for state, associated with muscular atrophy gene expression (such as the protein for passing through Ubiquitin-proteasome system Decomposition, inhibition of hyperfunction, further protein synthesis of autophagy etc.) increase.
Known FOXO1 is expressed in skeletal muscle, adipose tissue, liver, pancreas and hypothalamus etc..The mRNA of FOXO1 for The mankind are with GenBank number NM_002015 registration, for mouse with GenBank number NM_019739 registration.
So-called FOXO1 activity in this specification, it is meant that FOXO1 is detained in nucleus and can promote and muscular atrophy phase Associated gene (for example, 4EBP (eIF-4E-binding protein) relevant to protein translation is inhibited, with pass through it is general Element-proteasomal system breaks down proteins relevant Atrogin-1 or MuRFreesboro (Muscle RING-Finger Protein-1), Bnip3 or Catepsin L relevant to the breaks down proteins of autophagy lysosome system are passed through and inhibition are thin Born of the same parents are proliferated relevant Gadd45a etc.) expression activity.The function of FOXO1 with specific DNA base sequence (for example, IRS (Insulin Response Sequence) or CTSL (Cathepsin L upstream sequence) etc.) bonding, and as promote its under The effect of the transcription factor of the expression of the muscular atrophy related gene of trip, and and other transcription factors (such as LXR α (Liver X Receptor α) etc.) bonding, and the work of the transcription coupling factor as the expression for promoting muscular atrophy related gene With and know.For two kinds of activity of nondistinctive measurement, shown in following embodiments using from yeast GAL4DBD and with It is bonded UAS base sequence screening method be it is useful, also can use the method using IRS or CTSL or make other transcriptions The screening technique that the factor (LXR α etc.) and FOXO1 coexist.
The so-called active obstruction of FOXO1 is to instigate FOXO1 to inactivate, or induce or promote its inactivation in this specification.This Outside, the phosphorylation of FOXO1, there will be only FOXO1 in the nucleus of Skeletal Muscle Cell to cytoplasmic induction, pass through and Obstruction of the FOXO1 protein bonds of expression to the transcription function of FOXO1, the decomposition to FOXO1 protein promotion and FOXO1 gene translation is also contained in the active obstruction of FOXO1 of this specification at the obstruction of any stage of FOXO1 protein In.
As long as FOXO1 active measurement can select obstruction, FOXO1 is active is not particularly limited by trier.FOXO1 is living Property for example can be shown in embodiment described as follows, the plasmid as cDNA made of FOXO1 and GAL4DBD bonding will be incorporated into, and Defined cell is imported containing the plasmid of UAS base sequence and luciferase cDNA and detects the uciferase activity after co-expressing And it measures.It, can if obtaining value more lower than measured value under this condition at this point, preset the condition of object as a comparison To judge more hinder FOXO1 active than the condition.It, can be in addition, the test material as obtained from FOXO1 active measurement The practicality is further determined by zoopery etc., with the therapeutic agent or prophylactic eventually as the atrophy of skeletal muscle etc. The possibility utilized.
(composition)
About the amount of the above compound in composition of the invention, its come into operation form and commissioning method is considered Deng being not particularly limited as long as the effect expected of the present invention can be obtained.For example, the amount pair of above compound In composition of the invention full weight amount be 0.1 weight % or more, preferably 0.2,0.3,0.4,0.5,0.6,0.7,0.8, 0.9,1,1.5,2,5 or 10 weight % or more, 90 weight % or less, preferably 80,70,60,50,40,30,20 or 15 weight % Below.As described above, can only contain a kind of above compound in composition of the invention, can also contain two or more.Contain There are two types of when above compound, above-mentioned amount is defined as the aggregate value of the amount of various compounds.In addition, this explanation " weight % " used in book is if mean w/w (w/w) without special declaration.
Composition of the invention is characterized in that containing above compound as effective component, by the effect of the compound Hinder FOXO1 activity.In vivo, by obstruction FOXO1 activity, the effect with the functional correlation of FOXO1 can effectively be implemented, For example, inhibiting muscular atrophy, promoting muscle synthesis and bone density is inhibited to reduce.Therefore, composition of the invention can be used as suppression Muscular atrophy processed with, promote muscle synthesis use or inhibit bone density reduction composition use.
Composition of the invention, can be containing arbitrary additive other than above compound and common according to its form Any ingredient.As these additives and the example of ingredient, except vitamins, minerals class, nutrition such as vitamin E, vitamin Cs Except the physiologically active ingredients such as ingredient, fragrance, the excipient deployed in production process, bonding agent, emulsifier, anxiety can be also enumerated Agent (tonicity agent), buffer, dissolving adjuvant, preservative, stabilizer, antioxidant, colorant, coagulator or coating agent Deng, but it is not limited to this.
Tablet (including coated tablet), granule, powder, powder can be made in composition of the invention according to known methods Liquors such as the solid formulations such as last agent or capsule, common liquor, suspension or emulsion etc..These compositions can directly and water simultaneously It takes.Furthermore, it is possible to after being modulated into the form (for example, powder morphology or particle shape) for being easy allotment, as example curing The raw material of drug use.
As composition of the invention, medical composition, diet product composition, food compositions, drink composition can be enumerated Object, cosmetic composition etc., but it is not limited to this.As the not limiting example of food compositions, functional can be enumerated Food, healthy subsidy food, trophicity food, particular utility food, specific health food, nutritious subsidy food, dietotherapy With food, healthy food, replenishers, food additives etc..
Composition of the invention is suitable for pair of therapeutic use (medical application) or non-therapeutic use (non-medical purposes) Side.Specifically, the application as pharmaceuticals, medicine part outer article and cosmetic preparation etc. can be enumerated.In addition, can enumerate in medicine thing method It is not belonging to these but the property expressed or hint property opinion is as inhibiting muscular atrophy, muscle synthesis and bone density is promoted to reduce Inhibition etc. composition application.
The present invention is related to being attached with the group of the expression of the function played by the active obstruction of FOXO1 in other side Close object.Such expression or functional expression are not particularly limited, for example, can enumerate " maintain muscle ", " inhibiting muscular atrophy ", " reduction for preventing muscle ", the reduction of muscle " control ", " decline for preventing muscle ", " decline of control muscle ", " attached to give flesh Meat ", " increasing muscle " " forming muscle ", " supporting muscle ", " maintaining bone density ", " reduction for preventing bone density ", " control bone is close The reduction of degree ", " support bones ", " maintaining strong bone ", the health of bone " maintain " and " to the healthy and beneficial of bone " etc., Or the expression for being equivalent to these or functional indicate.It, can be with as the expression and functional indicate such expression in this specification It is additional to composition itself, can also be additional on the container or packaging of composition.
Composition of the invention can absorb in a suitable approach according to its form.Composition of the invention, such as can be with Be made the oral liquid preparations such as solid pharmaceutical preparation for oral use, mixture for internal use or syrup or injection, external preparation, suppository or The non-oral forms such as preparation such as transdermic absorbent, but it is not limited to this.In addition, " intake " so-called in this specification is made To be used comprising the vocabulary for all modes such as absorbing, taking or drink.
The dosage of composition of the invention according to its form, commissioning method, use purpose and as the trouble for the object that comes into operation The age of person or infected animal, weight, symptom and suitably set, not necessarily.Effective human consumption of composition of the invention Amount might not, but for example, weight as the above compound for being the effective component, the mankind of weight 50kg are daily, excellent 100mg or more, more preferably 500mg or more, further preferably 1000mg or more, preferably 10g are selected as hereinafter, more preferably 5g is hereinafter, further preferably 3g or less.In addition, coming into operation among one day can be with single in desired throwing amount ranges Or implement several times.It is also any during coming into operation.In addition, effective human consumption amount of so-called composition of the invention refers in people The intake that the composition of the invention of effective effect can be shown in class, simultaneously to the type of the compound contained in the composition It is not particularly limited.
The applicable object of composition of the invention is preferably the mankind, be also possible to the livestock animals such as ox, horse, goat, dog, The experimental animals such as the pet animals such as cat, rabbit, mouse, rat, cavy, monkey.When animal other than the mankind is come into operation as object, The every 1 day usage amount of 20g about every for rat individual, because the amount of the effective component in composition, applicable object state, The conditions such as weight, gender and age and it is different, for example, total blending amount as above compound, preferably 10mg/kg or more, More preferably 50mg/kg or more, further preferably 100mg/kg or more, preferably 1g/kg are hereinafter, more preferably 500mg/kg Hereinafter, the following are ingestible amounts by further preferably 300mg/kg.
(for hindering the active application of FOXO1)
One embodiment of the present invention is a kind of application, for that will be selected from chalcone, triterpenes, flavonoids, monoterpene The compound of at least one of class, lignanoids, Coumarins and Phytochemistry class is for hindering FOXO1 active.
In the present invention, above-mentioned specific compound can be used.In application of the invention, as the preferred 4- of chalcone Hydroxy chalcone, trans- chalcone and 2,3- dimethoxy -2'- hydroxy chalcone.
In application of the invention, as the preferred Corosolic acid of triterpenes.
In application of the invention, as flavonoids preferably 6,7- dihydroxyflavone, 6- methyl flavones, 5- methoxy flavone, 7,8- dihydroxyflavone, Chrysin and saponarin.
In application of the invention, as monoterpenes preferably (±) isomenthone.
In application of the invention, as Coumarins preferably 3,4- dihydrocoumarin.
In application of the invention, as the preferred amygdalin of Phytochemistry class.
In an application of the invention, comprising being used for for example, inhibiting muscular atrophy, the synthesis of promotion muscle or inhibiting under bone density The application of the above compound of drop, it is not limited to these.In addition, the application is answering in the mankind or non-human animal With can be the application that therapeutic application is also possible to non-therapeutic.Here, so-called " non-therapeutic " refers to not include medical treatment Behavior, that is, carry out the concept of processing behavior to human body according to treatment.
(hindering the active method of FOXO1)
One embodiment of the present invention is a kind of active method of obstruction FOXO1, for using selected from chalcone, three The compound of at least one of terpene, flavonoids, monoterpenes, lignanoids, Coumarins and Phytochemistry class.In addition, with The relevant other embodiments of this method are a kind of active method of obstruction FOXO1 comprising to needing the active resistance of FOXO1 The object hindered comes into operation therapeutically effective amount using above compound as effective component.
In composition of the invention, above-mentioned specific compound can be used, in method of the invention, as chalcone Class it is preferable to use compound be 4- hydroxy chalcone, trans- chalcone and 2,3- dimethoxy -2'- hydroxy chalcone.
In method of the invention, as triterpenes it is preferable to use compound be Corosolic acid.
In method of the invention, as flavonoids it is preferable to use compound be 6,7- dihydroxyflavone, 6- methyl flavones, 5- methoxy flavone, 7,8- dihydroxyflavone, Chrysin and saponarin.
In method of the invention, as monoterpenes it is preferable to use compound be (±) isomenthone.
In method of the invention, as Coumarins it is preferable to use compound be 3,4- dihydrocoumarin.
In method of the invention, as Phytochemistry class it is preferable to use compound be amygdalin.
In the above method, the object of the active obstruction of FOXO1 and the above-mentioned applicable object phase of composition of the invention are needed Together.In addition, so-called therapeutically effective amount refers to composition of the invention comes into operation when above-mentioned object in this specification, and do not come into operation Object compare, be obstructed the active amount of FOXO1.As specific effective quantity, according to the form that comes into operation, commissioning method, use The age of purpose and object, weight, symptom etc. are suitably set, not necessarily.
In the method for the invention, to reach above-mentioned therapeutically effective amount, above compound is direct, or as containing upper Stating the composition of compound, come into operation can also.
Method according to the invention it is possible to not generate side effect and hinder FOXO1 active.
Embodiment
Hereinafter, by embodiment, the present invention will be described in more detail, but not limits the scope of the invention therefrom. Those skilled in the art can carry out various changes to method of the invention, modify and use, these are also contained in of the invention In range.In addition, following embodiments found Implementation of College in Shizuoka, Japan.
The D-MEM that the HEK293T cell from human foetus' kidney of market sale is put into 60mm culture dish (is contained 10%FBS+ antibiotic (penicillin, streptomysin agent and amphotericin B)) in culture medium, in CO2In 37 DEG C, 5%CO in insulating box2 Squamous subculture is carried out under conditions of+95%air and humidity 100%.After confirmation cell density reaches 70~90% converging states, use PBS washs HEK293T cell, later, with trypsin solution (0.05% (w/v) trypsase, 0.53mM EDTA4Na) cell is handled, processing recycling is centrifuged with 1,200rpm to the cell of peeling.By recycling Cell is suspended in D-MEM (containing 10%FBS) again, cell number is measured, to squamous subculture and test.
GAL4DBD (GAL4-DNA Binding Domain) from yeast and the FOXO1 from mouse are bonded CDNA insertion expression plasmid in, FOXO1 plasmid is made.By this FOXO1 plasmid and plasmid containing UAS base sequence and contain The internal standard plasmid of luciferase gene imports HEK293T cell.
HEK293T cell after quiding gene is in CO2In 37 DEG C, 5%CO in insulating box2+ 95%air and humidity 100% Under the conditions of cultivate 24 hours, later, the test material being dissolved in water or DMSO is added, until its ultimate density is 1 μ g/mL Or 10 μ g/mL.
Measurement luciferase (Luc) activity after addition test material 24 hours, by this measured value divided by internal standard The value that the active measured value of Luc obtains is as FOXO1 activity.In addition, in order to assess the FOXO1 of test material activity, by water Or DMSO as test material when FOXO1 activity as 100%, by the FOXO1 activity of all test materials with phase Comparative example indicates.Its result is shown in the following table.
[table 2]
[table 3]
As described above, illustrating that ultimate density is set as 1 μ g/mL or the measured value (relative scale) of 10 μ g/mL is lower than 60% compound all has the active obstruction ability of FOXO1.In addition, testing 36 kinds of compounds other than the above, really It accepts and does not find the active obstruction ability of FOXO1 for the compound.
Industrial availability
The invention reside in provide it is a kind of contain specific compound as effective component FOXO1 activity hindered it is useful Composition.Since the present invention is to provide for inhibiting muscular atrophy, promoting muscle synthesis and bone density reduction being inhibited to contribute New method invention, so usability industrially is high.

Claims (13)

1.一种FOXO1活性阻碍用组合物，其特征在于，含有选自查耳酮类、三萜类、黄酮类、单萜类、木脂素类、香豆素类及植物化学类中的至少一种的化合物。1. A composition for inhibiting FOXO1 activity, characterized in that it contains at least one selected from the group consisting of chalcones, triterpenes, flavonoids, monoterpenes, lignans, coumarins and phytochemicals. a compound. 2.根据权利要求1所述的组合物，其特征在于，查耳酮类为选自4-羟基查耳酮、反式查耳酮及2,3-二甲氧基-2'-羟基查耳酮中的至少一种的化合物。2. The composition according to claim 1, wherein the chalcones are selected from 4-hydroxychalcone, trans-chalcone and 2,3-dimethoxy-2'-hydroxychalcone A compound of at least one of ear ketones. 3.根据权利要求1或2所述的组合物，其特征在于，三萜类为科罗索酸。3. The composition according to claim 1 or 2, wherein the triterpenoid is corosolic acid. 4.根据权利要求1～3中任一项所述的组合物，其特征在于，黄酮类为选自6,7-二羟基黄酮、6-甲基黄酮、5-甲氧基黄酮、7,8-二羟基黄酮、白杨素及皂草苷中的至少一种的化合物。4. The composition according to any one of claims 1 to 3, wherein the flavonoids are selected from the group consisting of 6,7-dihydroxyflavonoids, 6-methylflavonoids, 5-methoxyflavonoids, 7,7-dihydroxyflavonoids A compound of at least one of 8-dihydroxyflavone, chrysin and saponin. 5.根据权利要求1～4中任一项所述的组合物，其特征在于，单萜类为(±)异薄荷酮。5. The composition according to any one of claims 1 to 4, wherein the monoterpenes are (±)isomenthone. 6.根据权利要求1～5中任一项所述的组合物，其特征在于，木脂素类为肠二醇及/或络石苷元。6. The composition according to any one of claims 1 to 5, wherein the lignans are enterodiol and/or aglycone. 7.根据权利要求1～6中任一项所述的组合物，其特征在于，香豆素类为3,4-二氢香豆素。7 . The composition according to claim 1 , wherein the coumarins are 3,4-dihydrocoumarins. 8 . 8.根据权利要求1～7中任一项所述的组合物，其特征在于，植物化学类为苦杏苷。8. The composition according to any one of claims 1 to 7, wherein the phytochemical is amygdalin. 9.根据权利要求1～8中任一项所述的组合物，其特征在于，为抑制肌肉萎缩用、促进肌肉合成用或抑制骨密度降低用。9 . The composition according to claim 1 , which is for inhibiting muscle atrophy, promoting muscle synthesis, or inhibiting decrease in bone density. 10 . 10.根据权利要求1～9中任一项所述的组合物，其特征在于，附加有由FOXO1活性的阻碍而发挥的机能的表示。10 . The composition according to claim 1 , wherein an indication of a function exhibited by inhibition of FOXO1 activity is added. 11 . 11.根据权利要求10所述的组合物，其特征在于，机能的表示为选自“维持肌肉”、“抑制肌肉萎缩”、“防止肌肉的减少”、“控制肌肉的减少”、“防止肌肉的衰退”、“控制肌肉的衰退”、“附予肌肉”、“增加肌肉”“养成肌肉”、“支持肌肉”、“维持骨密度”、“防止骨密度的降低”、“控制骨密度的降低”、“支持骨骼”、“维持强健的骨骼”、“维持骨骼的健康”及“对骨骼的健康有益”。11. The composition according to claim 10, wherein the expression of function is selected from "maintaining muscle", "inhibiting muscle atrophy", "preventing muscle reduction", "controlling muscle reduction", "preventing muscle atrophy" decline in muscle, control muscle decline, attach to muscle, increase muscle, build muscle, support muscle, maintain bone density, prevent bone density decrease, control bone density "Reduces", "Supports Bone", "Maintains Strong Bone", "Maintains Bone Health" and "Benefits Bone Health". 12.将选自查耳酮类、三萜类、黄酮类、单萜类、木脂素类、香豆素类及植物化学类中的至少一种的化合物用于阻碍FOXO1活性的应用。12. Use of at least one compound selected from the group consisting of chalcones, triterpenes, flavonoids, monoterpenes, lignans, coumarins and phytochemicals for inhibiting the activity of FOXO1. 13.一种阻碍FOXO1活性的方法，其特征在于，使用选自查耳酮类、三萜类、黄酮类、单萜类、木脂素类、香豆素类及植物化学类中的至少一种的化合物。13. A method for inhibiting the activity of FOXO1, characterized in that, using at least one selected from the group consisting of chalcones, triterpenes, flavonoids, monoterpenes, lignans, coumarins and phytochemicals. species of compounds.
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