CN109890378A - FOXO1 activity obstruction uses composition - Google Patents
FOXO1 activity obstruction uses composition Download PDFInfo
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- 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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- A61K31/19—Carboxylic acids, e.g. valproic acid
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- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
- A61K31/341—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine
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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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Abstract
It is high the purpose of the present invention is to provide a kind of biological safety and facilitate the composition of the active obstruction of FOXO1.In addition, the object of the invention is also to provide for hindering the application of the active composition of FOXO1, and the obstruction active method of FOXO1.Present invention finds the specific compounds in the compound of natural goods to have the active inhibition of FOXO1.The present invention provides one kind to inhibition muscular atrophy, the synthesis of promotion muscle and inhibits contributive, the effective and novel method of bone density reduction.
Description
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. a kind of FOXO1 activity hinders to use composition, which is characterized in that containing selected from chalcone, triterpenes, flavonoids, list
The compound of at least one of terpene, lignanoids, Coumarins and Phytochemistry class.
2. composition according to claim 1, which is characterized in that chalcone is selected from 4- hydroxy chalcone, trans- looks into
The compound of at least one of ear ketone and 2,3- dimethoxy -2'- hydroxy chalcone.
3. composition according to claim 1 or 2, which is characterized in that triterpenes is Corosolic acid.
4. composition described in any one of claim 1 to 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 claims 1 to 4, which is characterized in that monoterpenes are (±) isomenthone.
6. composition according to any one of claims 1 to 5, which is characterized in that lignanoids is enterodiol and/or network
Stone aglycon.
7. composition described according to claim 1~any one of 6, which is characterized in that Coumarins 3,4- dihydro tonka-bean
Element.
8. composition according to any one of claims 1 to 7, which is characterized in that Phytochemistry class is amygdalin.
9. composition described according to claim 1~any one of 8, which is characterized in that inhibit muscular atrophy to use, promoting flesh
Meat synthesis is used or bone density is inhibited to reduce and uses.
10. composition described according to claim 1~any one of 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 claim 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. by chalcone, triterpenes, flavonoids, monoterpenes, lignanoids, Coumarins and Phytochemistry class
At least one compound is for hindering the active application of FOXO1.
13. a kind of active method of obstruction FOXO1, which is characterized in that using selected from chalcone, triterpenes, flavonoids, monoterpene
The compound of at least one of class, lignanoids, Coumarins and Phytochemistry class.
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| JP2016-211109 | 2016-10-27 | ||
| JP2016211109 | 2016-10-27 | ||
| PCT/JP2017/038912 WO2018079715A1 (en) | 2016-10-27 | 2017-10-27 | Composition for inhibiting foxo1 activity |
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| CN109890378A true CN109890378A (en) | 2019-06-14 |
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| JP (2) | JPWO2018079715A1 (en) |
| CN (1) | CN109890378A (en) |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111888353A (en) * | 2020-08-04 | 2020-11-06 | 西安交通大学 | Application of daphnetin in preparation of medicine for preventing and/or treating muscular atrophy, sarcopenia and hypokinesia caused by aging |
| CN112739362A (en) * | 2019-06-19 | 2021-04-30 | 岭南大学校产学协力团 | Composition for preventing or treating muscular disease comprising licorice extract or compound isolated therefrom as active ingredient |
| CN115040465A (en) * | 2022-07-06 | 2022-09-13 | 浙江爱尚日用品有限公司 | Whitening toothpaste capable of effectively removing dental plaque and tartar |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| JP7125106B2 (en) * | 2018-08-10 | 2022-08-24 | 学校法人東京医科大学 | MuRF-1 expression inhibitor and myopathy therapeutic agent |
| WO2023019147A1 (en) * | 2021-08-09 | 2023-02-16 | Ergo Health Llc | Methods for extending the lifespan of cells and organisms |
| US11739050B2 (en) * | 2021-09-07 | 2023-08-29 | Sci Pharmtech Inc. | Method for purification of terpenoid amino alcohol derivatives |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| JP4390428B2 (en) * | 2001-05-01 | 2009-12-24 | 株式会社林原生物化学研究所 | Calcium-containing tissue strengthening agent |
| JP2007530417A (en) * | 2003-07-01 | 2007-11-01 | プレジデント・アンド・フェロウズ・オブ・ハーバード・カレッジ | Composition for manipulating the longevity and stress response of cells and organisms |
| JPWO2005074962A1 (en) * | 2004-02-10 | 2007-09-13 | アサヒビール株式会社 | Muscle tension enhancer |
| JP2005261203A (en) * | 2004-03-16 | 2005-09-29 | Japan Science & Technology Agency | Method for screening medicine for improving composition and amount of skeletal muscle |
| JP5224719B2 (en) * | 2007-05-11 | 2013-07-03 | 丸善製薬株式会社 | Hair papilla cell growth promoter, testosterone 5α-reductase inhibitor, androgen receptor binding inhibitor, vascular endothelial growth factor production promoter, bone morphogenetic protein-2 production promoter, insulin-like growth factor-1 production promoter, hair restorer And hair cosmetics |
| WO2009028839A1 (en) * | 2007-08-31 | 2009-03-05 | Korea Research Institute Of Chemical Technology | Pharmaceutical composition for preventing or treating bone diseases comprising licochalcone a |
| JP2010195695A (en) * | 2009-02-24 | 2010-09-09 | Ichimaru Pharcos Co Ltd | PREPARATION FOR ACTIVATING Akt-mTOR-p70S6K OF MUSCLE STRENGTHENING SYSTEM AND METHOD THEREOF |
| WO2011108499A1 (en) * | 2010-03-03 | 2011-09-09 | 株式会社エリナ | Osteoblast differentiation promoter, pharmaceutical composition for promoting ossification, and health food containing auraptene analog as active ingredient |
| AU2011255495A1 (en) * | 2010-05-20 | 2012-12-06 | The United States Of America, As Represented By The Secretary Of The Department Of Veterans Affairs | Methods for inhibiting muscle atrophy |
| JP2014141444A (en) * | 2012-12-27 | 2014-08-07 | Nippon Flour Mills Co Ltd | Osteoporosis preventive containing triterpenes as active ingredient |
| JP2015178480A (en) * | 2014-03-19 | 2015-10-08 | 国立大学法人九州大学 | Osteopenia improver and loquat extract production method |
| JP2016199536A (en) * | 2015-04-07 | 2016-12-01 | 株式会社ニュートリション・アクト | Compositions for enhancing muscles and improving metabolic syndrome, as well as improving qol |
-
2017
- 2017-10-27 JP JP2018547785A patent/JPWO2018079715A1/en active Pending
- 2017-10-27 CN CN201780066338.9A patent/CN109890378A/en active Pending
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112739362A (en) * | 2019-06-19 | 2021-04-30 | 岭南大学校产学协力团 | Composition for preventing or treating muscular disease comprising licorice extract or compound isolated therefrom as active ingredient |
| CN112739362B (en) * | 2019-06-19 | 2022-08-23 | 新可利玛股份有限公司 | Composition for preventing or treating muscular disease comprising licorice extract or compound isolated therefrom as active ingredient |
| CN111888353A (en) * | 2020-08-04 | 2020-11-06 | 西安交通大学 | Application of daphnetin in preparation of medicine for preventing and/or treating muscular atrophy, sarcopenia and hypokinesia caused by aging |
| CN115040465A (en) * | 2022-07-06 | 2022-09-13 | 浙江爱尚日用品有限公司 | Whitening toothpaste capable of effectively removing dental plaque and tartar |
| CN115040465B (en) * | 2022-07-06 | 2023-01-24 | 浙江爱尚日用品有限公司 | Whitening toothpaste capable of effectively removing dental plaque and tartar |
| US11771644B1 (en) | 2022-07-06 | 2023-10-03 | Zhejiang Airsun Commodity Co., Ltd. | Whitening toothpaste capable of effectively removing dental plaque and tartar |
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| Publication number | Publication date |
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| WO2018079715A1 (en) | 2018-05-03 |
| TW201831173A (en) | 2018-09-01 |
| JPWO2018079715A1 (en) | 2019-09-19 |
| JP2022130618A (en) | 2022-09-06 |
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