TW201831173A - Composition for inhibiting foxo1 activity - Google Patents

Composition for inhibiting foxo1 activity Download PDF

Info

Publication number
TW201831173A
TW201831173A TW106137248A TW106137248A TW201831173A TW 201831173 A TW201831173 A TW 201831173A TW 106137248 A TW106137248 A TW 106137248A TW 106137248 A TW106137248 A TW 106137248A TW 201831173 A TW201831173 A TW 201831173A
Authority
TW
Taiwan
Prior art keywords
muscle
composition
foxo1
acid
compound
Prior art date
Application number
TW106137248A
Other languages
Chinese (zh)
Inventor
三浦進司
守田昭仁
村山宣人
鈴木寿栄
Original Assignee
日商三得利控股股份有限公司
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 日商三得利控股股份有限公司 filed Critical 日商三得利控股股份有限公司
Publication of TW201831173A publication Critical patent/TW201831173A/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/12—Ketones
    • A61K31/121—Ketones acyclic
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/12—Ketones
    • A61K31/122—Ketones having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid 
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/351—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom not condensed with another ring
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/357—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/357—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
    • A61K31/36—Compounds containing methylenedioxyphenyl groups, e.g. sesamin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
    • A61K31/385—Heterocyclic compounds having sulfur as a ring hetero atom having two or more sulfur atoms in the same ring
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—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
    • A61K31/401—Proline; Derivatives thereof, e.g. captopril
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—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
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4164—1,3-Diazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/45—Non condensed piperidines, e.g. piperocaine having oxo groups directly attached to the heterocyclic ring, e.g. cycloheximide
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The purpose of the invention is to provide a composition that has high biological safety and contributes to the inhibition of FOXO1 activity. Also, the purpose of the invention is to provide a use for said composition for inhibiting FOXO1 activity and a method for inhibiting FOXO1 activity. It was found that a specific compound, among naturally occurring compounds, has a FOXO1 activity inhibitory action. The invention provides a novel and effective means contributing to suppressing muscular atrophy, promoting muscle synthesis, and suppressing a reduction in bone density.

Description

ＦＯＸＯ１活性阻礙用組成物Composition for inhibiting FOXO1 activity

本發明係關於含有所定的化合物之對FOXO1活性阻礙為有用的組成物。The present invention relates to a composition containing a predetermined compound that is useful for inhibiting FOXO1 activity.

迎向超高齡化社會的我國對於壽命的延長，提高生活品質(QOL)或健康壽命的延長成為社會問題。對於該課題，運動器之功能保全的重要性提高，近年來特別對於成人而言因常見到慢性運動不足，故運動器功能的提高之意識成為年年增高的想法。In China, which is facing an ultra-aging society, it is a social problem to extend the life expectancy, to improve the quality of life (QOL) or to extend the healthy life expectancy. With regard to this issue, the importance of functional maintenance of exercise machines has increased. In recent years, especially for adults, chronic exercise deficiency has been common, so the awareness of improvement of exercise machine functions has been increasing every year.

作為操縱運動器功能的主要組織，有著骨骼肌。骨骼肌在人體中為最多組織者，其扮演著能量代謝、糖吸收、運動等中之重要角色。骨骼肌的功能則取決於該量或質。骨骼肌的量或質可藉由持續的定期運動而提高，但相反地，若經過長期間未有運動負荷時會降低，產生骨骼肌之萎縮。骨骼肌的萎縮會因老化或各種病態而產生。又，骨骼肌為胰島素的主要標的臟器，骨骼肌的功能障礙與代謝症候群有著關連性。As the main tissue for manipulating the function of the exerciser, it has skeletal muscle. Skeletal muscle is the most organizer in the human body, and it plays an important role in energy metabolism, sugar absorption, and exercise. The function of skeletal muscle depends on the quantity or quality. The amount or quality of skeletal muscle can be increased by continuous regular exercise, but on the contrary, if there is no exercise load after a long period of time, it will decrease, resulting in atrophy of skeletal muscle. Atrophy of skeletal muscle can be caused by aging or various pathological conditions. In addition, skeletal muscle is the main target organ of insulin, and dysfunction of skeletal muscle is related to metabolic syndrome.

作為與骨骼肌的代謝適應有關連性的因子，已知有FOXO1(Forkhead box protein O1)。已知FOXO1屬於具有DNA結合區域Forkhead box(FOX)之Forkhead家族的亞群“O”的轉印因子且藉由轉印調節因子，與壓力應答、代謝控制、細胞周期等相關，在骨骼肌扮演著與肌肉萎縮相關的重要角色。已有報告指出製作出FOXO1在骨骼肌過剩表現的轉基因老鼠時，該老鼠產生以紅色肌肉的脫落為主之肌肉萎縮(非專利文獻1)。又已知揭示FOXO1的表現增加與肌肉萎縮為共通，成為造成肌肉萎縮的原因。FOXO1的過剩表現亦與肌肉合成之抑制(非專利文獻2)或骨密度降低(非專利文獻3)等相關。As a factor related to the metabolic adaptation of skeletal muscle, FOXO1 (Forkhead box protein O1) is known. FOXO1 is known to be a transfer factor of the subgroup "O" of the Forkhead family with a DNA-binding region Forkhead box (FOX) and is related to stress response, metabolic control, cell cycle, and the like through the transfer regulator, and plays a role in skeletal muscle Plays an important role related to muscle atrophy. It has been reported that when a genetically modified mouse whose FOXO1 is overexpressed in skeletal muscle is produced, the mouse suffers from muscle atrophy that is dominated by the loss of red muscle (Non-Patent Document 1). It is also known that the increase in the performance of FOXO1 is in common with muscle atrophy, and has become a cause of muscle atrophy. Excessive expression of FOXO1 is also related to the inhibition of muscle synthesis (Non-Patent Document 2) or reduction of bone density (Non-Patent Document 3).

若FOXO1的表現量增加時，細胞核內的FOXO1會增加，藉由FOXO1活性會促進肌肉萎縮關連基因的轉印。又已知FOXO1在細胞內胰島素信號的下游受到控制。胰島素若與細胞膜上的胰島素受體結合時，細胞內胰島素信號被活化，以PI3K、Pdk1、Akt的順序傳達信號，最終藉由Akt進行磷酸化，FOXO1自核內往核外移動，阻礙FOXO1活性(非專利文獻4)。 [先前技術文獻] [非專利文獻]When the expression of FOXO1 increases, FOXO1 in the nucleus increases, and the transfer of genes associated with muscle atrophy is promoted by FOXO1 activity. It is also known that FOXO1 is controlled downstream of the intracellular insulin signal. When insulin binds to the insulin receptor on the cell membrane, the intracellular insulin signal is activated, and the signal is transmitted in the order of PI3K, Pdk1, and Akt. Finally, phosphorylation by Akt causes FOXO1 to move from the nucleus to the nucleus, and prevents FOXO1 activity (Non-Patent Document 4). [Prior Art Literature] [Non-Patent Literature]

[非專利文獻1] J Biol Chem. 2004 Sep 24; 279(39): 41114-23. 　　[非專利文獻2] J Biol Chem. 2007 Jul 20; 282(29): 21176-86. 　　[非專利文獻3] J Clin Invest. 120:357-368, 2010 　　[非專利文獻4] Bone. 2012 Feb; 50(2):437-43.[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 Document 4] Bone. 2012 Feb; 50 (2): 437-43.

[發明所解決的問題][Problems Solved by the Invention]

阻礙FOXO1活性的化合物可期待使用於因該過剩表現所引起的疾病等治療或預防。然而，至今對於具有如此作用的化合物，並未發現容易獲得且可廣泛使用於飲食品領域及安全性高的天然物系者，此快速開發極被期待。The compound that inhibits FOXO1 activity can be expected to be used for the treatment or prevention of diseases and the like caused by the excess manifestation. However, for compounds having such effects, no one who finds easily available, can be widely used in the field of food and drink, and has high safety of natural systems has not been found. This rapid development is highly anticipated.

於此，本發明係以提供一種生物安全性高且可賦予FOXO1活性之阻礙的組成物為目的。又，本發明係以提供對於使用於阻礙FOXO1活性的組成物之使用及阻礙FOXO1活性的方法為目的。 [解決課題的手段]The object of the present invention is to provide a composition having high biological safety and a barrier to the activity of FOXO1. It is another object of the present invention to provide a method for inhibiting FOXO1 activity by using a composition for inhibiting FOXO1 activity. [Means for solving problems]

本發明者們欲達成上述目的進行詳細檢討結果，發現由來自天然物的化合物中之特定化合物具有FOXO1活性之阻礙作用。本發明者基於此見解而完成本發明。The present inventors tried to achieve the above-mentioned object and conducted a detailed review. As a result, it was found that a specific compound among compounds derived from natural products has an inhibitory effect on FOXO1 activity. The present inventors have completed the present invention based on this knowledge.

即，本發明係關於以下者，但並未限定於此等。 　　(1)含有選自由查耳酮(Chalcone)類、三萜烯類、黃酮類、單萜類化合物類、木脂素類、香豆素類及植物化學物質類所成群的至少一種化合物之FOXO1活性阻礙用組成物。 　　(2)查耳酮類為選自由4-羥基查耳酮、trans-查耳酮及2,3-二甲氧基-2'-羥基查耳酮所成群的至少一種化合物之(1)所記載的組成物。 　　(3)三萜烯類為科羅索酸之(1)或(2)所記載的組成物。 　　(4)黃酮類為選自由6,7-二羥基黃酮、6-甲基黃酮、5-甲氧基黃酮、7,8-二羥基黃酮、白楊素、及皂草苷(Saponarin)所成群的至少一種化合物之(1)～(3)中任一項所記載的組成物。 　　(5)單萜類為(±)異薄荷酮之(1)～(4)中任一項所記載的組成物。 　　(6)木脂素類為腸內二醇(Enterodiol)及/或絡石甙元(trachelogenin)之(1)～(5)中任一項所記載的組成物。 　　(7)香豆素類為3,4-二氫香豆素之(1)～(6)中任一項所記載的組成物。 　　(8)植物化學物質類為苦杏苷(amarogentin)之(1)～(7)中任一項所記載的組成物。 　　(9)其為肌肉萎縮抑制用、肌肉合成促進用或骨密度降低抑制用之(1)～(8)中任一項所記載的組成物。 　　(10)附有藉由FOXO1活性之阻礙可發揮功能之表示的(1)～(9)中任一項所記載的組成物。 　　(11)功能的表示為選自由「維持肌肉」、「抑制肌肉萎縮」、「防止肌肉減少」、「抑制肌肉減少」、「防止肌肉衰退」、「抑制肌肉衰退」、「賦予肌肉」、「增加肌肉」、「製作肌肉」、「支持肌肉」、「維持骨密度」、「防止骨密度之降低」、「抑制骨密度的降低」、「支持骨格」、「維持強健的骨格」、「維持骨格的健康」及「對骨骼的健康有利」所成群者之(10)所記載的組成物。 　　(12)一種使用於阻礙FOXO1活性之選自由查耳酮類、三萜烯類、黃酮類、單萜類化合物類、木脂素類、香豆素類及植物化學物質類所成群的至少一種化合物之使用。 　　(13)使用選自由查耳酮類、三萜烯類、黃酮類、單萜類化合物類、木脂素類、香豆素類、及植物化學物質類所成群的至少一種化合物之阻礙FOXO1活性的方法。 [發明之效果]That is, this invention relates to the following, but it is not limited to these. (1) Containing at least one compound selected from the group consisting of Chalcones, triterpenes, flavones, monoterpenes, lignans, coumarins, and phytochemicals FOXO1 activity inhibits the composition for use. (2) Chalcones are at least one compound selected from the group consisting of 4-hydroxychalcone, trans-chalcone, and 2,3-dimethoxy-2'-hydroxychalcone The described composition. (3) Triterpenes are the composition described in (1) or (2) of corosolic acid. (4) Flavonoids are selected from the group consisting of 6,7-dihydroxyflavones, 6-methylflavones, 5-methoxyflavones, 7,8-dihydroxyflavones, chrysin, and saponarin The composition according to any one of (1) to (3) of at least one compound of. (5) Monoterpenes are the composition according to any one of (1) to (4) of (±) isomentone. (6) Lignans are the composition described in any one of (1) to (5) of Enterodiol and / or trachelogenin. (7) Coumarins are the composition described in any one of (1) to (6) of 3,4-dihydrocoumarins. (8) Phytochemicals are the composition according to any one of (1) to (7) of amarogentin. (9) The composition according to any one of (1) to (8) for inhibiting muscular atrophy, promoting muscle synthesis, or inhibiting bone density reduction. (10) The composition according to any one of (1) to (9), which shows that the function can be inhibited by FOXO1 activity. (11) The expression of function is selected from the group consisting of "maintain muscle", "inhibit muscle atrophy", "prevent muscle loss", "inhibit muscle loss", "prevent muscle decline", "inhibit muscle decline", "improve muscle", " Increase Muscle "," Make Muscle "," Support Muscle "," Maintain Bone Mineral Density "," Prevent Bone Density Decrease "," Suppress Bone Density Decrease "," Support Bone Frame "," Maintain Strong Bone Frame "," Maintain The composition described in (10) of the group of "bone health" and "beneficial to bone health". (12) at least one selected from the group consisting of chalcones, triterpenes, flavones, monoterpenes, lignans, coumarins, and phytochemicals used to inhibit FOXO1 activity Use of a compound. (13) Obstructive FOXO1 using at least one compound selected from the group consisting of chalcones, triterpenes, flavones, monoterpenes, lignans, coumarins, and phytochemicals Active method. [Effect of the invention]

依據本發明可提供一種具有優良FOXO1活性阻礙作用之組成物。若利用本發明之組成物，可達成FOXO1活性之阻礙，而得到肌肉萎縮抑制、肌肉合成促進及骨密度降低抑制之效果。藉由本發明可達成這些效果，此與病患或高齡者的QOL改善的有用新手段之提供相關。According to the present invention, a composition having excellent FOXO1 activity inhibiting effect can be provided. If the composition of the present invention is used, the effect of inhibiting FOXO1 activity can be achieved, and the effects of inhibiting muscle atrophy, promoting muscle synthesis, and inhibiting bone density decrease can be obtained. These effects can be achieved by the present invention, and this is related to the provision of useful new means for improving QOL in patients or elderly people.

又，使用於本發明的所定化合物皆為來自天然物者，故其安全性高。因此，本發明可提供一種具有優良的FOXO1活性阻礙作用，且安全又可繼續攝取之組成物。In addition, since the predetermined compounds used in the present invention are all derived from natural substances, they have high safety. Therefore, the present invention can provide a composition having excellent FOXO1 activity blocking effect, and safe and continuous ingestion.

[實施發明的形態][Mode for Carrying Out the Invention]

(化合物) 　　本發明之一態樣為含有所定化合物的組成物。本發明之組成物為將該所定化合物作為有效成分者。(Compound) 之一 One aspect of the present invention is a composition containing a predetermined compound. The composition of the present invention is one in which the specified compound is used as an active ingredient.

對於本發明之組成物為含有選自查耳酮類(Chalcones)、三萜烯類(Triterpenes)、黃酮類(Flavones)、單萜類化合物類(Monoterpenoids)、木脂素類(Lignans)、香豆素類(Coumarins)、及植物化學物質類(phytochemical)所成群的至少一種化合物。本發明之組成物中的前述化合物可含有二種以上，或亦可含有三種以上。The composition of the present invention contains a substance selected from the group consisting of Chalcones, Triterpenes, Flavones, Monoterpenoids, Lignans, and Fragrant Coumarins and at least one compound grouped by phytochemicals. The aforementioned compound in the composition of the present invention may contain two or more kinds, or may contain three or more kinds.

在本發明所使用的化合物可為trans-查耳酮(trans-Chalcone)、2',6'-二羥基-4,4'-二甲氧基查耳酮(2',6'-Dihydroxy-4,4'-dimethoxychalcone)、金合歡素(Acacetin)、麥角甾苷(Acteoside)、穿心蓮內酯(Andrographolide)、芹菜素(Apigenin)、黃芩苷(Baicalin)、白楊素(Chrysin)、矢車菊色素氯化物(Cyanidin chloride)、花菁(Cyanin)、大豆苷元(Daidzein)、海豚(Delphin)、花翠素氯化物(Delphinidin Chloride)、δ-(3,4-二羥基苯基)-γ-戊內酯(δ-(3,4-Dihydroxyphenyl)-γ-valerolactone)、香葉木素(Diosmetin)、香葉木(Diosmin)、鞣花酸(Ellagic acid)、聖草酚(Eriodictyol)、漆黃素(Fisetin)、血竭異味酸(Sanguisorbic acid)、橙皮素(Hesperetin)、異甘草素(Isoliquiritigenin)、山奈酚(Kaempferol)、硫辛酸(Lipoic acid)、馬哈尼(Mahanine)、楊梅黃酮(Myricetin)、原兒茶酸(Protocatechuic acid)、原花青素B2(Procyanidin B2)、槲皮素二水合物(Quercetin dihydrate)、芝麻素(Sesamin)、表芝麻素(Episesamin)、新嗩呐草素1(Tellimagrandin 1)、新嗩呐草素2(Tellimagrandin 2)、可可鹼(Theobromine)、茶鹼(Theophylline)、漢黃芩素(Wogonin)、β-萘黃酮(β-Naphthoflavone)、水飛薊賓(Silibinin)、羅特林(Rottlerin)、6-羥基黃酮(6-Hydroxyflavone)、7-羥基黃酮(7-Hydroxyflavone)、異鼠李素(Isorhamnetin)、莫林(Morin)、金聖草黃素(Chrysoeriol)、芒柄花素(Formononetin)、芍藥色素氯化物(Peonidin Chloride)、柏木雙黃桐(Cupressuflavone)、7,4’-二羥基黃酮(7,4'-Dihydroxyflavone)、7,8-二羥基黃酮(7,8-Dihydroxyflavone)、6,7-二羥基黃酮(6,7-Dihydroxyflavone)、3',4'-二甲氧基黃酮(3',4'-Dimethoxyflavone)、3-羥基黃酮(3-Hydroxyflavone)、依普黃酮(Ipriflavone)、2'-甲氧基黃酮(2'-Methoxyflavone)、5-甲氧基黃酮(5-Methoxyflavone)、3',4',5',5,7-五甲氧基黃酮(3',4',5',5,7-Pentamethoxyflavone)、3',4',7,8-四羥基黃酮(3',4',7,8-Tetrahydroxyflavone)、4',6,7-三羥基異黃酮(4',6,7-Trihydroxyisoflavone)、7-羥基黃酮醇(7-Hydroxyflavonol)、7-甲氧基黃酮醇(7-Methoxyflavonol)、6-甲氧基黃酮醇(6-Methoxyflavonol)、5,7-二羥基-3',4',5'-三甲氧基黃烷酮(5,7-Dihydroxy-3',4',5'-trimethoxyflavanone)、黃烷酮(Flavanone)、黃烷酮二乙醯腙(Flavanone diacetyl hydrazone)、黃烷酮腙(Flavanone hydrazone)、2'-羥基黃烷酮(2'-Hydroxyflavanone)、4'-羥基黃烷酮(4'-Hydroxyflavanone)、3'-羥基黃烷酮(3'-Hydroxyflavanone)、α-萘黃酮(α-Naphthoflavone)、5-甲氧基黃烷酮(5-Methoxyflavanone)、6-甲氧基黃烷酮(6-Methoxyflavanone)、2',6'-二羥基-4,4'-二甲氧基二氫查耳酮(2',6'-Dihydroxy-4,4'-dimethoxydihydrochalcone)、2',6'-二羥基-4'-甲氧基查耳酮(2',6'-Dihydroxy-4'-methoxychalcone)、2,3-二甲氧基-2'-羥基查耳酮(2,3-Dimethoxy-2'-hydroxychalcone)、芝麻明酚(Sesaminol)、芸香柚皮(Narirutin)、槲皮素-3,5,7,3',4'-五甲基醚(Quercetin-3,5,7,3',4'-pentamethylether)、槲皮素-3,7,3',4'-四甲基醚(Quercetin-3,7,3',4'-tetramethylether)、氯化非瑟酮定(Fisetinidin chloride)、鹽酸木犀草素(Luteolinidin chloride)、3',4',7,8-四甲氧基黃酮(3',4',7,8-Tetramethoxyflavone)、O-乙酰基哥倫比亞甙元(O-Acetylcolumbianetin)、3-乙醯香豆素(3-Acetylcoumarin)、8-乙醯-6,7-二甲氧基香豆素(8-Acetyl-6,7-dimethoxycoumarin)、8-乙醯-7-羥基香豆素(8-Acetyl-7-hydroxycoumarin)、8-乙醯-6-羥基-7-甲氧基香豆素(8-Acetyl-6-hydroxy-7-methoxycoumarin)、8-乙醯-7-甲氧基香豆素(8-Acetyl-7-methoxycoumarin)、3-胺基香豆素(3-Aminocoumarin)、佛手柑素(Bergamotin)、佛手柑內酯(Bergapten)、佛手酚(Bergaptol)、檸美內脂(Citropten)、2-香豆酸(2-Coumaric acid)、3-香豆酸(3-Coumaric acid)、香豆素(Coumarin)、香豆酸(Coumaric acid)、香豆雌酚(Coumestrol)、瑞香素(Daphnetin)、瑞香素-7-甲基醚(Daphnetin-7-methylether)、3,4-二氫香豆素(3,4-Dihydrocoumarin)、5,7-二羥基-4-甲基香豆素(5,7-Dihydroxy-4-methylcoumarin)、七葉內酯二苯甲基醚(Esculetin dibenzylether)、4-乙氧基香豆素(4-Ethoxycoumarin)、7-乙氧基香豆素(7-Ethoxycoumarin)、秦皮素(Fraxetin)、秦皮定(Fraxidin)、7-甲氧基香豆素(Herniarin)、3-羥基香豆素(3-Hydroxycoumarin)、4-羥基香豆素(4-Hydroxycoumarin)、歐前胡素(Imperatorin)、異佛手柑內酯(Isobergapten)、異虎耳草素(Isopimpinellin)、異莨菪亭(Isoscopoletin)、6-甲基香豆素(6-Methylcoumarin)、繖形花內酯(Umbelliferone)、3-乙醯-α-乳香酸(3-Acetyl-α-boswellic acid)、3-乙醯-β-乳香酸(3-Acetyl-β-boswellic acid)、α-香樹脂醇(α-Amyrin)、β-香樹脂醇(β-Amyrin)、青蒿素(Artemisinin)、白樺脂醇(Betulin)、白樺脂醇酸(Betulinic acid)、白樺脂醇酸甲基酯(Betulinic acid methyl ester)、白果內酯(Bilobalide)、咖啡醇(Cafestol)、(-)-葛縷醇((-)-Carveol)、(+)-香芹酮((+)-Carvone)、(-)-香芹酮((-)-Carvone)、類葉牡丹苷元(Caulophyllogenin)、脫氧肌氨酸(Deoxyactein)、高根二醇(Erythrodiol)、靈芝酸A(Ganoderic acid A)、常春藤皂苷(Hederagenin)、d-異薄荷醇(d-Isomenthol)、(±)異薄荷酮((±)Isomenthone)、齊墩果酸(Oleanolic acid)、茜素(Alizarin)、紫草素(Alkannin)、蒽醌(Anthraquinone)、1,4-苯醌(1,4-Benzoquinone)、2-tert-丁基-p-醌(2-Tert-butyl-p-quinone)、1,4-二甲基蒽醌(1,4-Dimethylanthraquinone)、大黃素(Emodin)、大黃素甲醚(Physcion)、萊茵(Rhein)、南燭木樹脂酚(Lyoniresinol)、尿石素(Urolithin)、苦杏苷(Amarogentin)、6-甲基黃酮(6-Methylflavone)、4-羥基查耳酮(4-Hydroxychalcone)、4'-羥基查耳酮(4'-Hydroxychalcone)、香豆素酸(Coumalic acid)、白藜蘆醇(Resveratrol)、曲酸(Kojic acid)、小白菊內酯(Parthenolide)、淫羊藿甙(Icariin)、人參皂苷Rb1(Ginsenoside Rb 1)、姜酚(Gingerol)、10-羥基-2-癸烯酸(10-hydroxy-2-decenoic acid)、右旋表松脂酚葡萄糖苷(Epipinoresinol-Glc)、連翹苷(Phillyrin)、松脂醇(Pinoresinol)、右旋表松脂酚(Epipinoresinol)、連翹苷元(Phillygenin)、薑黃素1(Curcumin 1)、薑黃素2(Curcumin 2)、薑黃素3(Curcumin 3)、直芝麻素(Diasesamin)、厚朴酚(Honokiol)、Sennidine A、七葉內酯(Esculetin)、芝麻酚(Sesamol)、東莨菪素(Scopoletin)、去甲二氫癒創木酸(Nordihydroguaiaretic acid)、香草酸(Vanillic acid)、trans-桂皮酸(trans-Cinnamic acid)、尿囊素(Allantoin)、α-細辛腦(α-Asarone)、(±)-辛弗林((±)-Synephrine)、衣康酸(Itaconic acid)、積雪草酸(Asiatic acid)、波爾定鹼(Boldine)、莽草酸(Shikimic acid)、酪醇(Tyrosol)、科羅索酸(Corosolic acid)、云杉苷(Picein)、迷迭香酸(Rosmarinic acid)、異甜菊醇(Isosteviol)、阿特匹靈C(Artepillin C)、阿皮奧(Apiole)、薁(Azulene)、夏至草苦素(Marrubiin)、(-)-紫蘇酸((-)-Perillic acid)、馬卡斯酸(Madecassic acid)、芒果苷(Mangiferin)、芳樟醇(Linalool)、2-茴香醛(2-Anisaldehyde)、3-茴香醛(3-Anisaldehyde)、4-茴香酸(4-Anisic acid)、尿刊酸(Urocanic acid)、α-(-)-紅沒藥醇(α-(-)-Bisabolol)、(-)-trans石竹烯((-)-trans-Caryophyllene)、石竹烯氧化物(Caryophyllene oxide)、金縷梅單寧(Hamamelitannin)、紫蘇醛(Perillaldehyde)、破故紙素甲醚A(Bavachinin A)、北通水蘇鹼(Betonicine)、(+)-花側柏烯((+)-Cuparene)、諾卡酮(Nootkatone)、(-)-苝基醇((-)-Perillylalcohol)、蓽拔醯胺(Piperlongumine)、天藍烴(Chamazulen)、(-)-細辛脂素((-)-Asarinin)、(-)-芝麻素((-)-Sesamin)、2',4,4',6'-四羥基查耳酮(2',4,4',6'-Tetrahydroxychalcone)、檜醇(Hinokitiol)、岩藻黃素(Fucoxanthine)、腸內二醇(Enterodiol)、羅漢松樹脂酚(Matairesinol)、胡蘆巴鹼一水合物(Trigonelline monohydrate)、秦皮苷(Fraxin)、羽扇豆醇(Lupeol)、絡石甙元(Trachelogenin)、甘草次酸(Glycyrrhetic acid)、甘草酸(Glycyrrhizic acid)、6-羥基-4'-甲氧基黃酮(6-Hydroxy-4'-methoxyflavone)、二氫楊梅黃酮(Dihydromyricetin)、2'-羥基查耳酮(2'-Hydroxychalcone)、花姜酮(zerumbone)、橄欖苦苷(oleacein)、藏紅花酸(Crocetin)、硝酸異山梨酯(Isosorbide Dinitrate)、高原兒茶酸(Homoprotocatechuic acid)、穀胱甘肽(Glutathione)、柯里拉京(Corilagin)、芝麻酚林(sesamolin)、橄欖苦苷(Oleuropein)、葫蘆素B(Cucurbitacin B)、葫蘆素D(Cucurbitacin D)、蘆丁三水合物(Rutin trihydrate)、牡荊素(Vitexin)、葒草(Orientin)、異牡荊素(Isovitexin)、三色堇黃酮甙(Violanthin)、柚皮甙(Naringin)、皂草苷(Saponarin)、檸檬烯(Limonin)、Chafuroside B、Chafuroside A、甜橙黃酮(Sinensetin)、及3',4',5,5',6,7,8-七甲氧基黃酮(3',4',5,5',6,7,8-Heptamethoxyflavone)。於本發明之組成物中含有前述化合物之一種以上。The compound used in the present invention may be trans-Chalcone, 2 ', 6'-dihydroxy-4,4'-dimethoxychalcone (2', 6'-Dihydroxy- 4,4'-dimethoxychalcone), Acacetin, Acteoside, Andrographolide, Apigenin, Baicalin, Chrysin, Cornflower Pigment Cyanidin chloride, Cyanin, Daidzein, Delphin, Delphinidin Chloride, δ- (3,4-dihydroxyphenyl) -γ- Valprolactone (δ- (3,4-Dihydroxyphenyl) -γ-valerolactone), Diosmetin, Diosmin, Ellagic acid, Eriodictyol, Lutein (Fisetin), Sanguisorbic acid, Hesperetin, Isoliquiritigenin, Kaempferol, Lipoic acid, Mahanine, Myricetin ), Protocatechuic acid, Procyanidin B2, Quercetin dihydrate, Sesamin, episesamin ( Episesamin), Tellimagrandin 1, Tellimagrandin 2, Theobromine, Theophylline, Wogonin, β-naphthoflavone (β -Naphthoflavone), Silibinin, Rottlerin, 6-Hydroxyflavone, 7-Hydroxyflavone, Isorhamnetin, Moline Morin), Chrysoeriol, Formononetin, Peonidin Chloride, Cupressuflavone, 7,4'-Dihydroxyflavone (7,4 ' -Dihydroxyflavone), 7,8-Dihydroxyflavone, 6,7-Dihydroxyflavone, 3 ', 4'-dimethoxyflavone (3', 4 '-Dimethoxyflavone), 3-Hydroxyflavone, Ipriflavone, 2'-Methoxyflavone, 5-Methoxyflavone, 3' , 4 ', 5', 5,7-pentamethoxyflavone (3 ', 4', 5 ', 5,7-Pentamethoxyflavone), 3', 4 ', 7,8-tetrahydroxyflavone (3', 4 ', 7,8-Tetrahydroxyflavone), 4', 6,7-Trihydroxyisoflavon vone), 7-Hydroxyflavonol, 7-Methoxyflavonol, 6-Methoxyflavonol, 5,7-dihydroxy-3 ', 4 ', 5'-trimethoxyflavanone (5,7-Dihydroxy-3', 4 ', 5'-trimethoxyflavanone), Flavanone, Flavanone diacetyl hydrazone , Flavanone hydrazone, 2'-Hydroxyflavanone, 4'-Hydroxyflavanone, 3'-Hydroxyflavanone ), Α-Naphthoflavone, 5-Methoxyflavanone, 6-Methoxyflavanone, 2 ', 6'-dihydroxy-4 2,4'-dimethoxydihydrochalcone (2 ', 6'-Dihydroxy-4,4'-dimethoxydihydrochalcone), 2', 6'-dihydroxy-4'-methoxychalcone (2 ', 6'-Dihydroxy-4'-methoxychalcone), 2,3-Dimethoxy-2'-hydroxychalcone, 2,3-Dimethoxy-2'-hydroxychalcone, Sesaminol, Rutin Naringin (Narirutin), Quercetin-3,5,7,3 ', 4'-pentamethyl ether (Quercetin-3,5,7,3', 4'-pentamethylether), Quercetin-3, 7,3 ', 4'-tetramethyl ether (Quercetin-3 , 7,3 ', 4'-tetramethylether), Fisetinidin chloride, Luteolinidin chloride, 3', 4 ', 7,8-tetramethoxyflavone (3' , 4 ', 7,8-Tetramethoxyflavone), O-Acetylcolumbianetin, 3-Acetylcoumarin, 8-Ethyl-6,7-dimethoxy Coumarin (8-Acetyl-6,7-dimethoxycoumarin), 8-Acetyl-7-hydroxycoumarin, 8-Acetyl-7-hydroxycoumarin, 8-Acetyl-6-hydroxy-7-methoxy Coumarin (8-Acetyl-6-hydroxy-7-methoxycoumarin), 8-Acetyl-7-methoxycoumarin (8-Acetyl-7-methoxycoumarin), 3-aminocoumarin (3- Aminocoumarin), Bergamotin, Bergapten, Bergaptol, Citropten, 2-Coumaric acid, 3-Coumaric acid ( 3-Coumaric acid, Coumarin, Coumaric acid, Coumestrol, Daphnetin, Daphnetin-7-methylether , 3,4-Dihydrocoumarin (3,4-Dihydrocoumarin), 5,7-Dihydroxy-4-methylcoumarin (5,7-Dihydroxy-4-methylcoumarin), Seven Esculetin dibenzylether, 4-Ethoxycoumarin, 7-Ethoxycoumarin, Fraxetin, Qinpidine ( Fraxidin), 7-methoxycoumarin (Herniarin), 3-hydroxycoumarin (3-Hydroxycoumarin), 4-hydroxycoumarin (4-Hydroxycoumarin), imperatorin (Imperatorin), isobergamot Lactone (Isobergapten), Isopimpinellin, Isoscopoletin, 6-Methylcoumarin, Umbelliferone, 3-Acetyl-α -Boswellic acid (3-Acetyl-α-boswellic acid), 3-Acetyl-β-boswellic acid (3-Acetyl-β-boswellic acid), α-Amyrin, β-Mervinyl alcohol (β-Amyrin), Artemisinin, Betulin, Betulinic acid, Betulinic acid methyl ester, Bilobalide, Cafestol, (-)-carveol ((-)-Carveol), (+)-carvone ((+)-Carvone), (-)-carvone ((-)-Carvone) , Caulophyllogenin, Deoxyactein, High Erythrodiol, Ganoderic acid A, Hederagenin, d-Isomenthol, (±) Isomenthone, Oleanolic acid (Oleanolic acid), Alizarin, Alkannin, Anthraquinone, 1,4-Benzoquinone, 2-tert-butyl-p-quinone (2 -Tert-butyl-p-quinone), 1,4-Dimethylanthraquinone, Emmodin, Physcion, Rhein, Southern Candlewood Resin Phenol (Lyoniresinol), Urolithin, Amarogentin, 6-Methylflavone, 4-Hydroxychalcone, 4'-Hydroxychalcone (4'-Hydroxychalcone) 4'-Hydroxychalcone), Coumalic acid, Resveratrol, Kojic acid, Parthenolide, Icariin, Ginsenoside Rb1 ( Ginsenoside Rb 1), Gingerol, 10-hydroxy-2-decenoic acid, Epipinoresinol-Glc, Forsythia, Pinoresinol, Epi-pinolol (Epi pinoresinol, forsythiagenin (Phillygenin), curcumin 1 (Curcumin 2), curcumin 3 (Curcumin 3), diasesamin, honokiol, Sennidine A , Esculetin, Sesamol, Scopoletin, Nordihydroguaiaretic acid, Vanillic acid, trans-Cinnamic acid), Allantoin, α-Asarone, (±) -Sinphrine ((±) -Synephrine), Itaconic acid, Asiatic acid , Boldine, Shikimic acid, Tyrosol, Corosolic acid, Picein, Rosmarinic acid, Isosteviol (Isosteviol), Artepillin C, Apiole, Azulene, Marrubiin, (-)-Perillic acid, Horse Madesassic acid, Mangiferin, Linalool, 2-Anisaldehyde, 3-Anisaldehyde, 4-Anisic acid ), Urine acid ( Urocanic acid), α-(-)-bisabolol, (-)-trans-caryophyllene, (-)-trans-Caryophyllene, Caryophyllene oxide, Witch hazel tannin (Hamamelitannin), Perillaldehyde, Bavachinin A, Betonicine, (+)-Purellene ((+)-Cuparene) , Nootkatone, (-)-Perylylalcohol, Piperlongumine, Chamazulen, (-)-Asaridin ((-)- Asarinin), (-)-sesamin ((-)-Sesamin), 2 ', 4,4', 6'-tetrahydroxychalcone, acetanol (Hinokitiol), Fucoxanthine, Enterodiol, Matairesinol, Trigonelline monohydrate, Fraxin, Lupinol ( Lupeol, Trachelogenin, Glycyrrhetic acid, Glycyrrhizic acid, 6-Hydroxy-4'-methoxyflavone, Dihydromyricetin (Dihydromyricetin), 2'-Hydroxychalcone, Zingerone (zerumbone), oleacein, Crocetin, Isosorbide Dinitrate, Homoprotocatechuic acid, Glutathione, Corilagin, Sesamolin, Oleuropein, Cucurbitacin B, Cucurbitacin D, Rutin trihydrate, Vitexin, Yarrow ( Orientin), Isovitexin, Violanthin, Naringin, Saponarin, Limonin, Chafuroside B, Chafuroside A, Sinensetin ), And 3 ', 4', 5,5 ', 6,7,8-heptamethoxyflavone (3', 4 ', 5,5', 6,7,8-Heptamethoxyflavone). One or more of the aforementioned compounds are contained in the composition of the present invention.

上述具體化合物各以下述表所示化學式表示。Each of the specific compounds is represented by a chemical formula shown in the following table.

上述化合物可使用販買品，亦可使用斯業者使用公知方法所調製者。上述化合物，例如可自含有各種化合物的植物等使用水或油等溶劑進行分離或純化等操作進行適當而調製。上述化合物可為結晶化者，亦可為經再結晶化者或濃縮物等中任一種形態，該形態並無特別限定。The above-mentioned compounds may be used commercially, or they may be prepared by a well-known method by a trader. The compound can be appropriately prepared, for example, by performing operations such as separation or purification using a solvent such as water or oil from a plant or the like containing various compounds. The compound may be in the form of a crystallized one, a recrystallized one, or a concentrate, and the form is not particularly limited.

又，上述化合物可衍生化為如配醣體等。所謂本說明書中之「配醣體」表示糖的羥基與非糖質化合物鍵結而成的化合物。配醣體中之糖可為單糖，或可為二糖或此以上的複數糖，並無特別限定。糖的種類亦無特別限定，可舉出葡萄糖、甘露糖、半乳糖、岩藻糖、鼠李糖、阿拉伯糖、木糖等醛糖、果糖等酮糖、葡萄糖醛酸、半乳醣醛酸、甘露醣醛酸等醣醛酸、芹菜糖、芸香等。又，使用於配醣體的糖可為D體、L體或D體與L體的混合物(DL體)，並無特別限定。The above compounds can be derivatized into, for example, a glycoside. The "glycoside" in this specification means a compound in which a hydroxyl group of a sugar is bonded to a non-glycan compound. The sugar in the glycoside may be a monosaccharide, or may be a disaccharide or a plurality of sugars, and is not particularly limited. The type of sugar is not particularly limited, and examples thereof include glucose, mannose, galactose, fucose, aldose such as rhamnose, arabinose, and xylose, ketose such as fructose, glucuronic acid, and galacturonic acid. , Uronic acid such as mannuronic acid, celery sugar, rue, etc. The sugar used for the glycoside may be D-form, L-form, or a mixture of D-form and L-form (DL form), and is not particularly limited.

本發明之組成物可含有上述化合物中任意者以任意2種以上含有。又，本發明之組成物可含有上述化合物中任意者的3種以上、4種以上、5種以上、6種以上、7種以上、8種以上、9種以上或10種以上。The composition of the present invention may contain any one of the above compounds and any two or more of them. In addition, the composition of the present invention may contain 3 or more, 4 or more, 5 or more, 6 or more, 7 or more, 8 or more, 9 or more or 10 or more of any of the compounds described above.

使用複數種化合物時，例如可舉出使用絡石甙元(trachelogenin)、β-萘黃酮、6,7-二羥基黃酮、3,4-二氫香豆素、2-tert-丁基-p-醌、苦杏苷(amarogentin)、(±)異薄荷酮、皂草苷、靈芝酸A、黃烷酮二乙醯腙、白果內酯、3-羥基香豆素、2-香豆酸、常春藤皂苷、1,4-二甲基蒽醌、高根二醇、異甘草素、8-乙醯-7-羥基香豆素、萊茵、紫蘇醛、瑞香素-7-甲基醚、3-乙醯-α-乳香酸、(-)-紫蘇酸、瑞香素、衣康酸、東莨菪素、2-茴香醛、大黃素甲醚、科羅索酸、葫蘆素B、齊墩果酸、紫草素、姜酚、黃烷酮腙、1,4-苯醌、d-異薄荷醇、槲皮素-3,7,3',4'-四甲基醚、3',4',5',5,7-五甲氧基黃酮、芝麻酚、連翹苷、小白菊內酯、槲皮素-3,5,7,3',4'-五甲基醚、3-羥基黃酮、3',4',7,8-四羥基黃酮、7-甲氧基香豆素、類葉牡丹苷元、8-乙醯-6,7-二甲氧基香豆素、酪醇、檸美內脂、8-乙醯-6-羥基-7-甲氧基香豆素、白樺脂醇酸甲基酯、蒽醌、5,7-二羥基-3',4',5'-三甲氧基黃烷酮、佛手柑素、trans-桂皮酸、佛手酚、α-香樹脂醇、3-香豆酸、O-乙酰基哥倫比亞甙元、2',6'-二羥基-4,4'-二甲氧基二氫查耳酮、(±)-辛弗林、4-羥基香豆素、異佛手柑內酯、金縷梅單寧、咖啡醇、5,7-二羥基-4-甲基香豆素、茜素、佛手柑內酯、(+)-香芹酮、7-羥基黃酮醇、香豆素、香豆酸、可可鹼、(-)-苝基醇、波爾定鹼、3-乙醯-β-乳香酸、薑黃素3、2',6'-二羥基-4'-甲氧基查耳酮、尿刊酸、4',6,7-三羥基異黃酮、白樺脂醇酸、云杉苷、4-羥基查耳酮、歐前胡素、3',4',7,8-四甲氧基黃酮、芸香柚皮、原花青素B2、SennidineA、3-茴香醛、大黃素、黃烷酮、3-乙醯香豆素、秦皮定、(-)-香芹酮、芳樟醇、10-羥基-2-癸烯酸、白藜蘆醇、原兒茶酸、繖形花內酯、人參皂苷Rb1、漆黃素、α-細辛腦、4-茴香酸、香豆雌酚、8-乙醯-7-甲氧基香豆素、(-)-葛縷醇、右旋表松脂酚、右旋表松脂酚葡萄糖苷、6-甲氧基黃酮醇、曲酸、脫氧肌氨酸、白樺脂醇、2'-羥基黃烷酮、3-胺基香豆素、香草酸、異莨菪亭、異鼠李素、尿囊素、5-甲氧基黃烷酮、6-甲基香豆素、薑黃素2、鞣花酸、去甲二氫癒創木酸、4-乙氧基香豆素、淫羊藿甙、阿皮奧、α-萘黃酮、積雪草酸、β-香樹脂醇、松脂醇、南燭木樹脂酚、直芝麻素、迷迭香酸、(+)-花側柏烯、七葉內酯二苯甲基醚、2',4,4',6'-四羥基查耳酮、厚朴酚、芝麻明酚、葫蘆素D、異甜菊醇、蓽拔醯胺、石竹烯氧化物、連翹苷元、夏至草苦素、(-)-trans石竹烯、3'-羥基黃烷酮、秦皮素、檜醇、異虎耳草素、鹽酸木犀草素、岩藻黃素、馬卡斯酸、諾卡酮、5-甲氧基黃酮、芒果苷、2',6'-二羥基-4,4'-二甲氧基查耳酮、莽草酸、檸檬烯、芍藥色素氯化物、芒柄花素、芝麻素、氯化非瑟酮定、高原兒茶酸、薁、花菁、槲皮素二水合物、尿石素或香豆素酸等組合，並無特別限定。又，雖無特別限定，前述化合物中較佳者為絡石甙元(trachelogenin)、β-萘黃酮、6,7-二羥基黃酮、3,4-二氫香豆素、2-tert-丁基-p-醌、苦杏苷(amarogentin)、(±)異薄荷酮、皂草苷、靈芝酸A、黃烷酮二乙醯腙、白果內酯、3-羥基香豆素、2-香豆酸、常春藤皂苷、1,4-二甲基蒽醌、高根二醇、異甘草素、8-乙醯-7-羥基香豆素、萊茵、紫蘇醛、瑞香素-7-甲基醚、3-乙醯-α-乳香酸、(-)-紫蘇酸、瑞香素、衣康酸、東莨菪素、2-茴香醛、大黃素甲醚、科羅索酸、葫蘆素B、齊墩果酸、紫草素、姜酚、黃烷酮腙、1,4-苯醌、d-異薄荷醇、槲皮素-3,7,3',4'-四甲基醚、3',4',5',5,7-五甲氧基黃酮、芝麻酚、連翹苷、小白菊內酯、槲皮素-3,5,7,3',4'-五甲基醚、3-羥基黃酮、3',4',7,8-四羥基黃酮、7-甲氧基香豆素、類葉牡丹苷元、8-乙醯-6,7-二甲氧基香豆素、酪醇、檸美內脂、8-乙醯-6-羥基-7-甲氧基香豆素、白樺脂醇酸甲基酯、蒽醌、5,7-二羥基-3',4',5'-三甲氧基黃烷酮、佛手柑素、trans-桂皮酸、佛手酚、α-香樹脂醇、3-香豆酸、O-乙酰基哥倫比亞甙元、2',6'-二羥基-4,4'-二甲氧基二氫查耳酮、(±)-辛弗林、4-羥基香豆素、異佛手柑內酯、金縷梅單寧、咖啡醇、5,7-二羥基-4-甲基香豆素、茜素、佛手柑內酯、(+)-香芹酮、7-羥基黃酮醇、香豆素、香豆酸、可可鹼、(-)-苝基醇、波爾定鹼、3-乙醯-β-乳香酸、薑黃素3、2',6'-二羥基-4'-甲氧基查耳酮、尿刊酸、4',6,7-三羥基異黃酮、白樺脂醇酸、云杉苷、4-羥基查耳酮、歐前胡素或3',4',7,8-四甲氧基黃酮之組合。When plural compounds are used, for example, trachelogenin, β-naphthoflavone, 6,7-dihydroxyflavonoid, 3,4-dihydrocoumarin, and 2-tert-butyl-p-quinone can be mentioned. , Bitter aglycon (amarogentin), (±) isomentholone, saponin, ganoderma acid A, flavone diethylamidine, ginkgolide, 3-hydroxycoumarin, 2-coumaric acid, ivy Saponin, 1,4-dimethylanthraquinone, homoroot diol, isoliquiritigenin, 8-acetamidine-7-hydroxycoumarin, rhine, perillaldehyde, rhizol-7-methyl ether, 3-acetamidine -α-boswellic acid, (-)-perillanic acid, daphsin, itaconic acid, scopolamine, 2-anisaldehyde, emodin methyl ether, corosolic acid, cucurbitin B, oleanolic acid, shikonin , Gingerol, flavanone hydrazone, 1,4-benzoquinone, d-isomenthol, quercetin-3,7,3 ', 4'-tetramethyl ether, 3', 4 ', 5', 5,7-pentamethoxyflavones, sesaminol, forsythiaside, berberide, quercetin-3,5,7,3 ', 4'-pentamethyl ether, 3-hydroxyflavones, 3', 4 ', 7,8-tetrahydroxyflavonoids, 7-methoxycoumarin, leaf-like peony aglycones, 8-acetam-6,7-dimethoxycoumarin, tyrosol, citrate, 8-Ethyl-6-hydroxy-7-methoxyl Leptin, Betulin Alcohol Methyl Ester, Anthraquinone, 5,7-Dihydroxy-3 ', 4', 5'-trimethoxyflavone, Bergamotin, trans-cinnamic acid, Bergamot, α- Balsamic alcohol, 3-coumaric acid, O-acetyl Colombian aglycone, 2 ', 6'-dihydroxy-4,4'-dimethoxydihydrochalcone, (±) -sinphorin, 4-hydroxycoumarin, isobergamot lactone, witch hazel tannin, coffee alcohol, 5,7-dihydroxy-4-methylcoumarin, alizarin, bergamot lactone, (+)-fragrant Apigenone, 7-hydroxyflavonol, coumarin, coumaric acid, theobromine, (-)-fluorenyl alcohol, poldine, 3-acetamidine-β-boswellic acid, curcumin 3, 2 ', 6'-Dihydroxy-4'-methoxychalcone, uric acid, 4 ', 6,7-trihydroxy isoflavones, betulinic acid, sprucein, 4-hydroxychalcone, europian Husu, 3 ', 4', 7,8-tetramethoxyflavonoids, rue pomelo peel, proanthocyanidins B2, SennidineA, 3-anisaldehyde, emodin, flavanone, 3-acetocoumarol, Qin peel (-)-Carvone, linalool, 10-hydroxy-2-decenoic acid, resveratrol, protocatechuic acid, umbelliferone, ginsenoside Rb1, lutein, α- Asarum, 4-Anisic acid, Coumarin , 8-Ethyl-7-methoxycoumarin, (-)-carvitol, d-epipinol, d-epipinol glucoside, 6-methoxyflavone, kojic acid, deoxygenated muscle Amino acid, betulin, 2'-hydroxyflavanone, 3-aminocoumarin, vanillic acid, isoxetine, isorhamnetin, allantoin, 5-methoxyflavanone, 6- Methyl coumarin, curcumin 2, ellagic acid, nordihydroguaiaretic acid, 4-ethoxycoumarin, icariin, Apio, alpha-naphthoflavonoids, asiatic acid, beta -Aromatic resin alcohol, pinoresinol, odoriferous resin phenol, orthosesamin, rosmarinic acid, (+)-purellene, esculetyl diphenylmethyl ether, 2 ', 4,4', 6'-tetrahydroxychalcone, magnolol, sesaminol, cucurbitacin D, isosteviol, scopolamine, caryophyllene oxide, forsythiagenin, soldiolol, (-)-trans carnation Ene, 3'-hydroxyflavanone, hempin, scopolamine, iso saxifrane, luteolin hydrochloride, fucoxanthin, marcas acid, nocardione, 5-methoxyflavone, mangiferin , 2 ', 6'-dihydroxy-4,4'-dimethoxychalcone, shikimic acid, limonene, peony pigment chloride, mansard Combination florigen, sesamin, chloride, fisetin set, plateau catechin, azulene, cyanine, quercetin dihydrate, acid urolithiasis coumarin biotin or the like, is not particularly limited. In addition, although not particularly limited, preferred among the aforementioned compounds are trachelogenin, β-naphthoflavone, 6,7-dihydroxyflavone, 3,4-dihydrocoumarin, and 2-tert-butyl- p-quinone, amarogentin, (±) isomentholone, saponin, ganoderma acid A, flavone diethylamidine, ginkgolide, 3-hydroxycoumarin, 2-coumaric acid , Ivy saponin, 1,4-dimethylanthraquinone, high root glycol, isoglycyrrhizin, 8-acetamidine-7-hydroxycoumarin, rhine, perillaldehyde, rhizolin-7-methyl ether, 3 -Acetamidine-α-boswellic acid, (-)-perillic acid, stearin, itaconic acid, scopolamine, 2-anisaldehyde, emodin methyl ether, corosolic acid, cucurbitin B, oleanolic acid, Shikonin, gingerol, flavanone hydrazone, 1,4-benzoquinone, d-isomenthol, quercetin-3,7,3 ', 4'-tetramethyl ether, 3', 4 ', 5 ', 5,7-pentamethoxyflavones, sesaminol, forsythiaside, parthenolide, quercetin-3,5,7,3', 4'-pentamethyl ether, 3-hydroxyflavonoids, 3 ', 4', 7,8-tetrahydroxyflavonoids, 7-methoxycoumarin, leaf-like peony aglycone, 8-acetam-6,7-dimethoxycoumarin, tyrosol, lime Lipid, 8-acetam-6-hydroxy-7-methoxy Coumarin, betulinate methyl ester, anthraquinone, 5,7-dihydroxy-3 ', 4', 5'-trimethoxyflavone, bergamotin, trans-cinnamic acid, bergamot, α-Mercuryl alcohol, 3-coumaric acid, O-acetyl Colombian aglycone, 2 ', 6'-dihydroxy-4,4'-dimethoxydihydrochalcone, (±) -Sinfer Lin, 4-hydroxycoumarin, isobergamot lactone, witch hazel tannin, coffee alcohol, 5,7-dihydroxy-4-methylcoumarin, alizarin, bergamot lactone, (+) -Carvone, 7-hydroxyflavonol, coumarin, coumaric acid, theobromine, (-)-fluorenyl alcohol, poldine, 3-acetamidine-β-boswellic acid, curcumin 3, 2 ', 6'-dihydroxy-4'-methoxychalcone, uric acid, 4', 6,7-trihydroxy isoflavone, betulinic acid, sprucein, 4-hydroxychalcone, Imperatorin or a combination of 3 ', 4', 7,8-tetramethoxyflavone.

對於本發明之組成物，作為查耳酮類，較佳可使用的化合物為4-羥基查耳酮、trans-查耳酮、及2,3-二甲氧基-2'-羥基查耳酮。For the composition of the present invention, as the chalcones, preferred compounds that can be used are 4-hydroxychalcone, trans-chalcone, and 2,3-dimethoxy-2'-hydroxychalcone .

對於本發明之組成物，作為三萜烯類，較佳可使用的化合物為科羅索酸。For the composition of the present invention, as the triterpene, the compound that can be preferably used is corosolic acid.

對於本發明之組成物，作為黃酮類，較佳可使用的化合物為6,7-二羥基黃酮、6-甲基黃酮、5-甲氧基黃酮、7,8-二羥基黃酮、白楊素及皂草苷。For the composition of the present invention, as the flavones, compounds which can be preferably used are 6,7-dihydroxyflavones, 6-methylflavones, 5-methoxyflavones, 7,8-dihydroxyflavones, chrysin Saponin.

對於本發明之組成物，作為單萜類化合物類，較佳可使用的化合物為(±)異薄荷酮。As the composition of the present invention, as the monoterpenoid compound, it is preferable that the compound is (±) isomentone.

對於本發明之組成物，作為香豆素類，較佳可使用的化合物為3,4-二氫香豆素。For the composition of the present invention, as the coumarins, the compound which can be preferably used is 3,4-dihydrocoumarin.

對於本發明之組成物，作為植物化學物質類，較佳可使用的化合物為苦杏苷(amarogentin)。As the composition of the present invention, as the phytochemical substance, it is preferable to use amaroxin (amarogentin).

(FOXO1) 　　本發明之組成物可藉由使用上述化合物作為有效成分而阻礙FOXO1活性。因此，本發明之組成物可作為FOXO1活性阻礙用組成物使用。本說明書中，所謂「FOXO1」表示叉頭(Forkhead)型轉印因子(Forkhead box protein O1)作為引起肌肉萎縮的種種條件，例如藉由絶食、徐神經、糖皮質激素投與、小胞體壓力等刺激，使FOXO1的表現上昇，於細胞核內以脫磷酸化狀態存在的FOXO1，增加肌肉萎縮關連基因表現(例如藉由泛蛋白-蛋白酶體(Proteasome)系使蛋白質分解、自噬(Autophagy)亢進，進一步抑制蛋白質合成等)。(FOXO1) 之 The composition of the present invention can inhibit FOXO1 activity by using the above-mentioned compound as an active ingredient. Therefore, the composition of the present invention can be used as a composition for inhibiting FOXO1 activity. In this specification, "FOXO1" means a forkhead type transfer factor (Forkhead box protein O1) as various conditions that cause muscle atrophy, for example, by fasting, neurosurgery, glucocorticoid administration, and small cell stress Isostimulation increases the expression of FOXO1, and the presence of FOXO1 in a dephosphorylated state in the nucleus increases the expression of genes associated with muscle atrophy (e.g., protein breakdown by the ubiquitin-proteasome system and autophagy increase) , To further inhibit protein synthesis, etc.).

已知FOXO1表現於骨骼肌、脂肪組織、肝臟、胰臟及丘腦下部等。FOXO1的mRNA在人類中已以GenBank登錄號碼NM_002015做登記，在老鼠中已以GenBank登錄號碼NM_019739做登記。FOXO1 is known to be expressed in skeletal muscle, adipose tissue, liver, pancreas, and lower thalamus. FOXO1 mRNA has been registered in humans with GenBank accession number NM_002015, and in mice has been registered with GenBank accession number NM_019739.

所謂本說明書中之FOXO1活性表示可促進FOXO1滯留於細胞核內的肌肉萎縮關連基因(例如與蛋白質翻譯抑制有關的4EBP(eIF-4E-binding protein)、在泛蛋白･蛋白酶體系統與蛋白質分解有關的Atrogin-1或MuRF1(Muscle RING-Finger Protein-1)、在自噬･溶酶體(Lysosome)系統與蛋白質分解有關的Bnip3或Catepsin L、與細胞增殖抑制有關的Gadd45a等)之表現的活性。已知FOXO1的工作為鍵結於特定DNA鹼基序列(例如IRS(Insulin Response Sequense)或CTSL(Cathepsin L上游配列)等)，作為促進該下游肌肉萎縮關連基因的表現之轉印因子的作用，及與其他轉印因子(例如LXRα(Liver X Receptor α)等)鍵結，作為促進肌肉萎縮關連基因的表現之轉印偶聯因子(Conjugation factor)的作用。若要無區分兩者活性而進行測定時，利用在後述實施例所示來自酵母的GAL4DBD與鍵結於此的UAS鹼基序列而進行的篩選法為有用，但使用IRS或CTSL的方法或共存其他轉印因子(LXRα等)與FOXO1之篩選法亦可利用。The FOXO1 activity in the present specification means a muscle atrophy-associated gene that promotes FOXO1 retention in the nucleus (e.g., 4EBP (eIF-4E-binding protein), which is involved in protein translation inhibition, and a protein that is involved in proteolysis in the ubiquitin-proteasome system. Atrogin-1 or MuRF1 (Muscle RING-Finger Protein-1), Bnip3 or Catepsin L related to proteolysis in the Lysosome system, Gadd45a related to cell proliferation inhibition, etc.). It is known that the work of FOXO1 is to bind to a specific DNA base sequence (such as IRS (Insulin Response Sequense) or CTSL (Cathepsin L upstream alignment), etc.) as a transfer factor that promotes the performance of the downstream muscle atrophy-related gene. And binding with other transfer factors (such as LXRα (Liver X Receptor α), etc.), as a transfer coupling factor (Conjugation factor) to promote the expression of genes associated with muscle atrophy. In order to measure the activity without distinguishing between the two, a screening method using GAL4DBD derived from yeast and a UAS base sequence bound thereto shown in the examples described later is useful, but a method or coexistence using IRS or CTSL Screening methods for other transfer factors (LXRα, etc.) and FOXO1 can also be used.

對於本說明書，所謂FOXO1活性之阻礙，表示使FOXO1惰性化，或誘導或促進該惰性化的意思。又，使FOXO1進行磷酸化時，將局在骨骼肌細胞的細胞核之FOXO1誘導於細胞質、藉由鍵結於表現的FOXO1蛋白質而阻礙FOXO1之轉印功能、促進FOXO1蛋白質的分解，及FOXO1基因被翻譯成FOXO1蛋白質的任一段階進行阻礙者，皆含於本說明書中之FOXO1活性的阻礙之意思。As used herein, the term "inhibition of FOXO1 activity" means inertizing FOXO1 or inducing or promoting the inertization. In addition, when FOXO1 is phosphorylated, FOXO1 localized in the nucleus of skeletal muscle cells is induced in the cytoplasm, and the FOXO1 protein is bound to the expressed FOXO1 protein to hinder the transfer function of FOXO1, promote the decomposition of FOXO1 protein, and the FOXO1 gene is blocked Anyone who blocks the progress of translation into FOXO1 protein has the meaning of blocking the FOXO1 activity in this specification.

FOXO1活性的測定若可選擇阻礙FOXO1活性的被驗物質即可，並無特別限定。FOXO1活性，例如如後述實施例所示，插入鍵結FOXO1與GAL4DBD的cDNA之質體，及將含有UAS鹼基序列及熒光素酶cDNA的質體導入於所定細胞中，藉由調查經共表現後的熒光素酶活性而可測定。此時設定作為比較對象的條件，若可得到比在該條件之測定値更低的測定値，可判斷藉由該條件可使FOXO1活性受到阻礙。且，由FOXO1活性之測定所得之被驗物質可進一步藉由動物實驗等確認該實用性，最終可作為骨骼肌之萎縮等治療劑或預防劑而被利用。The measurement of FOXO1 activity is not particularly limited if a test substance that inhibits FOXO1 activity can be selected. FOXO1 activity, for example, as shown in the examples described below, is inserted into a plastid that binds FOXO1 and GAL4DBD, and a plastid containing a UAS base sequence and luciferase cDNA is introduced into a given cell, and co-expressed by investigation. The latter luciferase activity can be measured. In this case, the conditions to be compared are set. If a lower measurement value than the measurement conditions under these conditions can be obtained, it can be judged that the FOXO1 activity can be hindered by the conditions. In addition, the test substance obtained from the measurement of FOXO1 activity can be further confirmed by animal experiments and the like, and can finally be used as a therapeutic or preventive agent such as skeletal muscle atrophy.

(組成物) 　　本發明之組成物中之上述化合物的含有量為考慮到該投與形態及投與方法等，若可得到本發明所望效果的量即可，並無特別限定。例如，上述化合物的含有量對於本發明之組成物的全重量而言為0.1重量%以上，較佳為0.2、0.3、0.4、0.5、0.6、0.7、0.8、0.9、1、1.5、2、5或10重量%以上且90重量%以下，更佳為80、70、60、50、40、30、20或15重量%以下。如上述，對於本發明之組成物，可僅含有1種上述化合物，或亦可含有二種以上。含有二種以上化合物時，前述含有量可由各種化合物之含有量合計値來規定。且，在本說明書所使用的「重量%」若無特別說明，其表示重量/重量(w/w)。(Composition) 的 The content of the compound in the composition of the present invention is not particularly limited as long as it takes into account the form of administration, the method of administration, and the like to obtain the desired effect of the present invention. For example, the content of the above compound is 0.1% by weight or more with respect to the total weight of the composition of the present invention, and preferably 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.5, 2, 5 Or 10% by weight or more and 90% by weight or less, more preferably 80, 70, 60, 50, 40, 30, 20, or 15% by weight or less. As described above, the composition of the present invention may contain only one kind of the above-mentioned compounds, or may contain two or more kinds. When two or more kinds of compounds are contained, the aforementioned content can be determined by the total content of the various compounds. In addition, "weight%" used in this specification means weight / weight (w / w) unless there is particular notice.

本發明之組成物係以含有上述化合物作為有效成分為特徵者，藉由該化合物之作用，阻礙FOXO1活性。在體內因FOXO1活性被阻礙，可有效地抑制作為FOXO1之功能相關效果，例如肌肉萎縮抑制、肌肉合成促進及骨密度降低抑制。因此，本發明之組成物可作為肌肉萎縮抑制用、肌肉合成促進用或骨密度降低抑制用之組成物使用。The composition of the present invention is characterized by containing the above-mentioned compound as an active ingredient, and the action of the compound inhibits FOXO1 activity. Because FOXO1 activity is blocked in the body, it can effectively inhibit the function-related effects as FOXO1, such as inhibition of muscle atrophy, promotion of muscle synthesis, and inhibition of bone density reduction. Therefore, the composition of the present invention can be used as a composition for inhibiting muscle atrophy, for promoting muscle synthesis, or for inhibiting bone density reduction.

本發明之組成物為配合該形態，可含有上述化合物以外，亦可含有任意添加劑及一般使用的任意成分。作為這些添加劑及成分之例子，可舉出維他命E、維他命C等維他命類、礦物質類、營養成分、香料等生理活性成分以外，亦可舉出於製劑化中添加的賦形劑、結合劑、乳化劑、緊張化劑(等張化劑)、緩衝劑、溶解補助劑、防腐劑、安定化劑、抗氧化劑、著色劑、凝固劑或塗布劑等，但並未限定於此等。The composition of the present invention may contain such additives in addition to the above-mentioned compounds, and may also contain any additives and any components generally used. Examples of these additives and ingredients include vitamins such as vitamin E and vitamin C, minerals, nutritional ingredients, and flavors, as well as physiologically active ingredients, as well as excipients and binding agents added to the formulation , Emulsifier, tonicity agent (isotonizing agent), buffering agent, dissolution aid, preservative, stabilizer, antioxidant, colorant, coagulant or coating agent, etc., but it is not limited to these.

本發明之組成物可依據公知方法，可製劑化為錠劑(含有被覆錠劑)、顆粒劑、散劑、粉末劑、或膠囊劑等固形劑，或一般液劑、懸浮劑或乳劑等液劑等。這些組成物可直接與水等一起服用。又，調成可容易添加的形態(例如粉末形態或顆粒形態)後，例如可作為醫藥品之原材料使用。The composition of the present invention can be formulated into solids such as troches (containing coated tablets), granules, powders, powders, or capsules, or liquids such as general liquids, suspensions, or emulsions according to known methods. Wait. These compositions can be taken directly with water or the like. In addition, after being adjusted to a form that can be easily added (for example, a powder form or a granular form), it can be used as a raw material for pharmaceuticals, for example.

作為本發明之組成物，可舉出醫藥組成物、飲食品組成物、食品組成物、飲料組成物、化妝用組成物等，但並未限定於此等。作為食品組成物的非限定例子，可舉出功能性食品、健康補助食品、營養功能食品、特別用途食品、特定保健用食品、營養補助食品、食事療法用食品、健康食品、補充劑、食品添加劑等。Examples of the composition of the present invention include, but are not limited to, a pharmaceutical composition, a food and beverage composition, a food composition, a beverage composition, and a cosmetic composition. Non-limiting examples of food compositions include functional foods, health supplements, nutritional functional foods, special purpose foods, specific health foods, nutritional supplements, food therapy foods, health foods, supplements, and food additives Wait.

本發明之組成物可適用於治療用途(醫療用途)或非治療用途(非醫療用途)中任一種。具體可舉出作為醫藥品、醫藥部外品及化妝料等使用，又不歸屬於藥事法者，可舉出作為明示或暗示有肌肉萎縮抑制、肌肉合成促進及骨密度降低之抑制等訴求之組成物使用。The composition of the present invention can be applied to either a therapeutic use (medical use) or a non-therapeutic use (non-medical use). Specific examples include use as pharmaceuticals, quasi-drugs, cosmetics, etc., which are not covered by the Pharmaceutical Affairs Act, and include explicit or implied inhibition of muscle atrophy, promotion of muscle synthesis, and inhibition of bone density reduction. Composition.

本發明的另一側面為，有關賦予藉由FOXO1活性阻礙所發揮的功能表示之組成物。如此表示或功能性表示並未特別限定，例如可舉出「維持肌肉」、「抑制肌肉萎縮」、「防止肌肉減少」、「抑制肌肉減少」、「防制肌肉衰退」、「抑制肌肉衰退」、「賦予肌肉」、「增加肌肉」、「製造肌肉」、「支持肌肉」、「維持骨密度」、「防止骨密度降低」、「抑制骨密度降低」、「支持骨骼」、「維持建壯骨格」、「維持骨格的健康」、「協助骨格健康」等或與可相當於這些的表示或功能性表示。對於本說明書，如此該表示及功能性表示的表示可附於組成物本身或附於組成物之容器或包裝上。Another aspect of the present invention relates to a composition that imparts a function expression inhibited by FOXO1 activity. Such expressions or functional expressions are not particularly limited, and examples include "maintenance of muscles", "inhibition of muscle atrophy", "prevention of muscle loss", "inhibition of muscle loss", "prevention of muscle decline", "inhibition of muscle decline" , "Giving muscle", "increasing muscle", "creating muscle", "supporting muscle", "maintaining bone density", "preventing bone density decrease", "inhibiting bone density decrease", "supporting bones", "maintaining strength" "Bone", "maintaining bone health", "assisting bone health", etc. or equivalent or functional expressions. For the purposes of this specification, such and functional representations may be attached to the composition itself or to a container or package of the composition.

本發明之組成物可配合該形態而藉由適當方法進行攝取。本發明之組成物，例如可為經口用固體製劑、內服液劑或者糖漿劑等經口用液體製劑，或注射劑、外用劑、塞劑或者經皮吸收劑等非經口用製劑等形態，但並未限定於此等。且，對於本說明書中所謂的「攝取」表示含有作為攝取、服用或飲用等全態樣使用。The composition of the present invention can be ingested by an appropriate method in accordance with this form. The composition of the present invention may be in the form of an oral liquid preparation such as an oral solid preparation, an oral solution or a syrup, or a parenteral preparation such as an injection, an external preparation, a suppository, or a transdermal absorbent. It is not limited to these. The term "ingestion" as used in this specification means that it is contained in all forms such as ingestion, consumption, or drinking.

本發明之組成物的適用量可配合該形態、投與方法、使用目的及投與對象之患者或生病動物的年齡、體重、症狀而做適時設定，並非為一定量。雖本發明之組成物的有效人類攝取量並非一定，但例如作為該有效成分的上述化合物之重量，在體重50kg的人類之每一日，以100mg以上為佳，較佳為500mg以上，更佳為1000mg以上，以10g以下為佳，較佳為5g以下，更佳為3g以下。又，投與次數在所望投與量範圍內，於1天內可單次或分為數次進行。投與期間亦為任意。且，所謂本發明之組成物的有效人類攝取量表示對於人類顯示有效的效果之本發明的組成物之攝取量，含於該組成物之化合物的種類並無特別限定。The applicable amount of the composition of the present invention can be set in a timely manner according to the form, the method of administration, the purpose of use, and the age, weight, and symptoms of the patient or sick animal to be administered, but it is not a certain amount. Although the effective human intake of the composition of the present invention is not constant, for example, the weight of the above-mentioned compound as the active ingredient is preferably 100 mg or more, more preferably 500 mg or more, and more preferably 50 mg of human body weight per day. It is 1,000 mg or more, preferably 10 g or less, more preferably 5 g or less, and even more preferably 3 g or less. In addition, the number of administrations is within the range of the desired administration amount, and it can be carried out in one or several times within one day. The period of investment is also arbitrary. The effective human intake of the composition of the present invention means the intake of the composition of the present invention which exhibits an effect effective for humans, and the type of the compound contained in the composition is not particularly limited.

本發明之組成物的適用對象，以人類為佳，但亦可為牛、馬、羊等家畜動物、狗、貓、兔子等寵物，或老鼠、大鼠、豚鼠、猴子等實驗動物。將人類以外的動物作為投與對象時，對於每大鼠1個體約20g之每1日的使用量會依組成物中之有效成分的含有量、適用對象者之狀態、體重、性別及年齡等條件而相異，例如作為上述化合物之總配合量，以10mg/kg以上為佳，較佳為50mg/kg以上，更佳為100mg/kg以上，以1g/kg以下為佳，較佳為500mg/kg以下，更佳為300mg/kg以下之可攝取量為佳。The applicable object of the composition of the present invention is preferably human, but it can also be livestock animals such as cattle, horses, sheep, pets such as dogs, cats, rabbits, or experimental animals such as mice, rats, guinea pigs, and monkeys. When animals other than humans are administered, the daily dosage of approximately 20g per rat will depend on the content of active ingredients in the composition, the status of the subject, weight, sex, and age, etc. The conditions vary, for example, the total compounding amount of the above compound is preferably 10 mg / kg or more, more preferably 50 mg / kg or more, more preferably 100 mg / kg or more, preferably 1 g / kg or less, and preferably 500 mg. The ingestible amount is preferably less than 300 kg / kg, more preferably less than 300 mg / kg.

(使用於阻礙FOXO1活性的方法) 　　本發明之一態樣為欲阻礙FOXO1活性的選自由查耳酮類、三萜烯類、黃酮類、單萜類化合物類、木脂素類、香豆素類及植物化學物質類所成群的至少一種化合物之使用。(Method for inhibiting FOXO1 activity) One aspect of the present invention is to be selected from the group consisting of chalcones, triterpenes, flavones, monoterpenoids, lignans, and coumarins that are intended to inhibit FOXO1 activity. Use of at least one compound in a group of phytochemicals and phytochemicals.

對於本發明，可使用上述具體化合物。對於本發明之使用，作為查耳酮類，以4-羥基查耳酮、trans-查耳酮及2,3-二甲氧基-2'-羥基查耳酮為佳。For the present invention, the above-mentioned specific compounds can be used. For the use of the present invention, as the chalcones, 4-hydroxychalcone, trans-chalcone and 2,3-dimethoxy-2'-hydroxychalcone are preferred.

對於本發明之使用，作為三萜烯類以科羅索酸為佳。For the use of the present invention, corosolic acid is preferred as the triterpene.

對於本發明之使用，作為黃酮類，以6,7-二羥基黃酮、6-甲基黃酮、5-甲氧基黃酮、7,8-二羥基黃酮、白楊素及皂草苷為佳。For the use of the present invention, as the flavones, 6,7-dihydroxyflavones, 6-methylflavones, 5-methoxyflavones, 7,8-dihydroxyflavones, chrysin and saponin are preferred.

對於本發明之使用，作為單萜類化合物類，以(±)異薄荷酮為佳。For the use of the present invention, as the monoterpenoids, (±) isomentholone is preferred.

對於本發明之使用，作為香豆素類，以3,4-二氫香豆素為佳。For the use of the present invention, as the coumarins, 3,4-dihydrocoumarin is preferred.

對於本發明之使用，作為植物化學物質類，以苦杏苷(amarogentin)為佳。For the use of the present invention, as a phytochemical, amarogentin is preferred.

在本發明之使用中，例如含有使用於肌肉萎縮抑制、肌肉合成促進或骨密度降低抑制的上述化合物之使用，但並未限定於此等。又，該使用為人類或非人類動物之使用，亦可為治療的使用或非治療的使用。其中，所謂「非治療的」表示未含有醫療行為，即未含有藉由治療而對人體進行的處理行為之概念。The use of the present invention includes, but is not limited to, the use of the above-mentioned compounds for inhibiting muscle atrophy, promoting muscle synthesis, or inhibiting bone density reduction. The use is for use by humans or non-human animals, and may also be used for treatment or non-treatment. Among them, "non-therapeutic" means that there is no concept of medical behavior, that is, the concept of processing behavior performed on the human body by treatment.

(阻礙FOXO1活性之方法) 　　本發明之一態樣為，使用選自由查耳酮類、三萜烯類、黃酮類、單萜類化合物類、木脂素類、香豆素類及植物化學物質類所成群的至少一種化合物的阻礙FOXO1活性之方法。又，有關該方法之其他態樣為，含有對於以FOXO1活性的阻礙作為必要之對象，將上述化合物作為有效成分而投與治療有效量的阻礙FOXO1活性之方法。(Method for inhibiting FOXO1 activity) One aspect of the present invention is to use a substance selected from the group consisting of chalcones, triterpenes, flavones, monoterpenes, lignans, coumarins, and phytochemicals. A method for blocking FOXO1 activity by grouping at least one compound. In another aspect of this method, a method for inhibiting FOXO1 activity is required, and a method of administering the compound as an active ingredient to a therapeutically effective amount of inhibiting FOXO1 activity is included.

對於本發明之方法，可使用上述具體化合物。對於本發明之方法，作為查耳酮類而適用的化合物為4-羥基查耳酮、trans-查耳酮及2,3-二甲氧基-2'-羥基查耳酮。For the method of the present invention, the above-mentioned specific compounds can be used. For the method of the present invention, compounds suitable as chalcones are 4-hydroxychalcone, trans-chalcone, and 2,3-dimethoxy-2'-hydroxychalcone.

對於本發明之方法，作為三萜烯類而適用的化合物為科羅索酸。For the method of the present invention, a compound suitable as a triterpene is corosolic acid.

對於本發明之方法，作為黃酮類而適用的化合物為6,7-二羥基黃酮、6-甲基黃酮、5-甲氧基黃酮、7,8-二羥基黃酮、白楊素及皂草苷。For the method of the present invention, compounds suitable as flavones are 6,7-dihydroxyflavones, 6-methylflavones, 5-methoxyflavones, 7,8-dihydroxyflavones, chrysin and saponin.

對於本發明之方法，作為單萜類化合物類而適用的化合物為(±)異薄荷酮。In the method of the present invention, a compound suitable as a monoterpenoid is (±) isomentholone.

對於本發明之方法，作為香豆素類而適用的化合物為3,4-二氫香豆素。For the method of the present invention, a compound suitable as a coumarin is 3,4-dihydrocoumarin.

對於本發明之方法，作為植物化學物質類而適用的化合物為苦杏苷(amarogentin)。In the method of the present invention, a compound suitable as a phytochemical is amarogentin.

對於上述方法，所謂將FOXO1活性的阻礙作為必要的對象為與本發明之組成物的前述適用對象相同。又，所謂本說明書中之治療有效量，在將本發明之組成物投與於上述對象時，與不投與的對象做比較時，該FOXO1活性受到阻礙之量。作為具體有效量可藉由投與形態、投與方法、使用目的及對象年齡、體重、症狀等做適時設定，並非一定。Regarding the above-mentioned method, the object to which the inhibition of FOXO1 activity is necessary is the same as that of the aforementioned application of the composition of the present invention. The therapeutically effective amount in the present specification is an amount in which the activity of FOXO1 is inhibited when the composition of the present invention is administered to the above-mentioned subject and compared with a subject not administered. The specific effective amount can be set in a timely manner by the form of administration, the method of administration, the purpose of use, the age, weight, and symptoms of the subject, and is not necessarily fixed.

對於本發明之方法，將上述化合物以如前述治療有效量，直接投與或作為與含有上述化合物的組成物而投與。In the method of the present invention, the compound is administered in a therapeutically effective amount as described above, or as a composition containing the compound.

依據本發明之方法，可無副作用產生之下阻礙FOXO1活性。 [實施例]According to the method of the present invention, FOXO1 activity can be inhibited without causing side effects. [Example]

以下將本發明藉由實施例做更詳細說明，但藉此未能限定本發明之範圍。斯業者可將本發明之方法經種種變更、修飾後使用，這些皆含於本發明之範圍中。且，下述實施例皆在靜岡縣立大學中實施。Hereinafter, the present invention will be described in more detail through examples, but the scope of the present invention is not limited by this. A person skilled in the art can use the method of the present invention after various changes and modifications, and these are all included in the scope of the present invention. In addition, the following examples are all implemented in Shizuoka Prefecture University.

將販賣的來自人類胚胎腎的HEK293T細胞放入60mm皿內之D-MEM(10%FBS+抗生物質(含有青黴素、鏈黴素及兩性黴素(Amphotericin)B)培養基中，在CO2 恆溫培養器內進行37℃、5%CO2 +95%air及濕度100%之條件下的傳代培養。自確認細胞密度變成70～90%合流後，將HEK293T細胞以PBS洗淨，其後以胰蛋白酶溶液(0.05% (w/v)胰蛋白酶、0.53mM EDTA･4Na)處理細胞，將剝離的細胞以1,200rpm進行離心分離處理並回收。將回收的細胞再次懸浮於D-MEM(含有10%FBS)，計算細胞數後使用於傳代培養及試驗上。The HEK293T cells from human embryo kidneys were placed in a D-MEM (10% FBS + antibiotic (containing penicillin, streptomycin, and amphotericin B)) medium in a 60 mm dish in a CO 2 incubator. Subculture was performed at 37 ° C, 5% CO 2 + 95% air, and 100% humidity. After confirming that the cell density became 70 to 90% confluence, HEK293T cells were washed with PBS, and then trypsinized The cells were treated with a solution (0.05% (w / v) trypsin, 0.53 mM EDTA ･ 4Na), and the detached cells were centrifuged at 1,200 rpm and recovered. The recovered cells were resuspended in D-MEM (containing 10% FBS) ), Calculate the number of cells and use it in subculture.

將結合來自酵母的GAL4DBD(GAL4-DNA Binding Domain)與來自老鼠的FOXO1的cDNA插入於表現質體中，製作成FOXO1質體。將該FOXO1質體與含有UAS鹼基序列之質體，及含有熒光素酶基因之內部標準質體導入於HEK293T細胞中。A GAL4-DBD (GAL4-DNA Binding Domain) derived from yeast and a FOXO1 derived from a mouse were inserted into a expression plastid to prepare a FOXO1 plastid. This FOXO1 plastid, a plastid containing a UAS base sequence, and an internal standard plastid containing a luciferase gene were introduced into HEK293T cells.

基因導入後之HEK293T細胞在CO2 恆溫培養器內以37℃、5%CO2 +95%air及濕度100%的條件下進行24小時培養後，溶解於水或DMSO至被驗物質的最終濃度成為1μg/mL或10μg/mL。After gene introduction, HEK293T cells are cultured in a CO 2 thermostat incubator at 37 ° C, 5% CO 2 + 95% air, and 100% humidity for 24 hours, and then dissolved in water or DMSO to the final concentration of the test substance. It was 1 μg / mL or 10 μg / mL.

自添加被驗物質經24小時後，測定熒光素酶(Luc)活性，將該測定値以內部標準的Luc活性測定値除的値作為FOXO1活性。又，欲評估被驗物質之FOXO1活性，將以水或DMSO作為被驗物質時的FOXO1活性作為100%，將所有的被驗物質之FOXO1活性以相對比例表示。該結果如下表所示。Twenty-four hours after the test substance was added, the luciferase (Luc) activity was measured, and this measurement was performed using the internal standard Luc activity measurement as the FOXO1 activity. In addition, to evaluate the FOXO1 activity of the test substance, let the FOXO1 activity when water or DMSO be used as the test substance be 100%, and express the FOXO1 activity of all test substances in relative proportions. The results are shown in the following table.

如上所述，將最終濃度設定在1μg/mL或10μg/mL，當測定値(相對比例)比60%小的化合物，皆表示具有FOXO1活性之阻礙能。且，試驗上述其他36種類之化合物，確認該化合物中未見到FOXO1活性之阻礙能。 [產業上可利用性]As described above, when the final concentration is set to 1 μg / mL or 10 μg / mL, when a compound whose tritium (relative ratio) is smaller than 60% is measured, it means that it has the blocking energy of FOXO1 activity. In addition, the other 36 types of compounds were tested, and it was confirmed that no inhibitory ability of FOXO1 activity was observed in the compounds. [Industrial availability]

本發明為提供一種將所定化合物作為有效成分而含有之具有FOXO1活性阻礙之有用組成物者。本發明為提供對肌肉萎縮抑制、肌肉合成促進及骨密度降低抑制上有貢獻的新穎方法者，故在產業上的利用性高。The present invention is to provide a useful composition containing a predetermined compound as an active ingredient and having FOXO1 activity inhibition. The present invention has a high industrial applicability because it provides a novel method that contributes to the inhibition of muscle atrophy, the promotion of muscle synthesis, and the suppression of reduction of bone density.

Claims (13)

一種FOXO1活性阻礙用組成物，其特徵為含有選自由查耳酮類、三萜烯類、黃酮類、單萜類化合物類、木脂素類、香豆素類及植物化學類所成群的至少一種化合物。A composition for inhibiting the activity of FOXO1, comprising a group selected from the group consisting of chalcones, triterpenes, flavones, monoterpenes, lignans, coumarins, and phytochemicals. At least one compound. 如請求項1之組成物，其中查耳酮類為選自由4-羥基查耳酮、trans-查耳酮及2,3-二甲氧基-2'-羥基查耳酮所成群的至少一種化合物。The composition of claim 1, wherein the chalcones are at least one member selected from the group consisting of 4-hydroxychalcone, trans-chalcone, and 2,3-dimethoxy-2'-hydroxychalcone A compound. 如請求項1或2之組成物，其中三萜烯類為科羅索酸。The composition of claim 1 or 2, wherein the triterpene is corosolic acid. 如請求項1～3中任一項之組成物，其中黃酮類為選自由6,7-二羥基黃酮、6-甲基黃酮、5-甲氧基黃酮、7,8-二羥基黃酮、白楊素及皂草苷所成群的至少一種化合物。The composition according to any one of claims 1 to 3, wherein the flavones are selected from the group consisting of 6,7-dihydroxyflavones, 6-methylflavones, 5-methoxyflavones, 7,8-dihydroxyflavones, and poplars. At least one compound in a group of serotonin and saponin. 如請求項1～4中任一項1項之組成物，其中單萜類為(±)異薄荷酮。The composition according to any one of claims 1 to 4, wherein the monoterpenes are (±) isomentone. 如請求項1～5中任一項1項之組成物，其中木脂素類為腸內二醇及/或絡石甙元(trachelogenin)。The composition according to any one of claims 1 to 5, wherein the lignans are intestinal diols and / or trachelogenin. 如請求項1～6中任一項1項之組成物，其中香豆素類為3,4-二氫香豆素。The composition according to any one of claims 1 to 6, wherein the coumarins are 3,4-dihydrocoumarin. 如請求項1～7中任一項1項之組成物，其中植物化學類為苦杏苷(amarogentin)。The composition according to any one of claims 1 to 7, wherein the phytochemical is amarogentin. 如請求項1～8中任一項1項之組成物，其為使用於肌肉萎縮抑制、肌肉合成促進，或骨密度降低抑制上。The composition according to any one of claims 1 to 8, which is used for inhibiting muscle atrophy, promoting muscle synthesis, or inhibiting bone density reduction. 如請求項1～9中任一項1項之組成物，其中附有藉由FOXO1活性之阻礙而發揮的功能表示。The composition according to any one of claims 1 to 9, which is accompanied by a function indication exerted by the hindrance of FOXO1 activity. 如請求項10之組成物，其中功能表示為選自由「維持肌肉」、「抑制肌肉萎縮」、「防止肌肉減少」、「抑制肌肉減少」、「防止肌肉衰退」、「抑制肌肉衰退」、「賦予肌肉」、「增加肌肉」、「製作肌肉」、「支持肌肉」、「維持骨密度」、「防止骨密度之降低」、「抑制骨密度的降低」、「支持骨格」、「維持強健的骨格」、「維持骨格的健康」及「對骨骼的健康有利」所成群者。For example, the composition of claim 10, wherein the function is selected from the group consisting of "maintain muscle", "inhibit muscle atrophy", "prevent muscle loss", "inhibit muscle loss", "prevent muscle loss", "inhibit muscle decline", " "Make Muscle", "Make Muscle", "Make Muscle", "Support Muscle", "Maintain Bone Mineral Density", "Prevent Bone Density Decrease", "Suppress Bone Density Decrease", "Support Bone Marrow", "Maintain Strong "Bone", "maintaining bone health" and "beneficial to bone health". 一種使用於阻礙FOXO1活性之選自由查耳酮類、三萜烯類、黃酮類、單萜類化合物類、木脂素類、香豆素類及植物化學類所成群的至少一種化合物之使用。Use of at least one compound selected from the group consisting of chalcones, triterpenes, flavones, monoterpenes, lignans, coumarins, and phytochemicals to inhibit FOXO1 activity . 一種阻礙FOXO1活性的方法，其特徵為使用選自由查耳酮類、三萜烯類、黃酮類、單萜類化合物類、木脂素類、香豆素類、及植物化學類所成群的至少一種化合物。A method for inhibiting FOXO1 activity, which is characterized by using a group selected from the group consisting of chalcones, triterpenes, flavones, monoterpenes, lignans, coumarins, and phytochemicals. At least one compound.
TW106137248A 2016-10-27 2017-10-27 Composition for inhibiting foxo1 activity TW201831173A (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2016211109 2016-10-27
JP2016-211109 2016-10-27

Publications (1)

Publication Number Publication Date
TW201831173A true TW201831173A (en) 2018-09-01

Family

ID=62025199

Family Applications (1)

Application Number Title Priority Date Filing Date
TW106137248A TW201831173A (en) 2016-10-27 2017-10-27 Composition for inhibiting foxo1 activity

Country Status (4)

Country Link
JP (2) JPWO2018079715A1 (en)
CN (1) CN109890378A (en)
TW (1) TW201831173A (en)
WO (1) WO2018079715A1 (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TWI828123B (en) * 2021-09-07 2024-01-01 旭富製藥科技股份有限公司 Method for purification of terpenoid amino alcohol derivatives

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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
KR102210502B1 (en) * 2019-06-19 2021-02-01 영남대학교 산학협력단 Composition for preventing or treating muscular diseases
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
WO2023019147A1 (en) * 2021-08-09 2023-02-16 Ergo Health Llc Methods for extending the lifespan of cells and organisms
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

Family Cites Families (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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
CA2529510A1 (en) * 2003-07-01 2005-01-13 President And Fellows Of Harvard College Compositions for manipulating the lifespan and stress response of cells and organisms
US20070160698A1 (en) * 2004-02-10 2007-07-12 Toshiaki Waga Muscular strength enhancing agent
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
JPWO2011108499A1 (en) * 2010-03-03 2013-06-27 株式会社エリナ Osteoblast differentiation-promoting agent, pharmaceutical composition for promoting bone formation, and functional food for health, containing aurapten-related compounds as active ingredients
JP5808797B2 (en) * 2010-05-20 2015-11-10 ユニバーシティ オブ アイオワ リサーチ ファウンデーション 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

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TWI828123B (en) * 2021-09-07 2024-01-01 旭富製藥科技股份有限公司 Method for purification of terpenoid amino alcohol derivatives

Also Published As

Publication number Publication date
JP2022130618A (en) 2022-09-06
JPWO2018079715A1 (en) 2019-09-19
CN109890378A (en) 2019-06-14
WO2018079715A1 (en) 2018-05-03

Similar Documents

Publication Publication Date Title
TWI747984B (en) PGC-1α activation composition
TW201831173A (en) Composition for inhibiting foxo1 activity
Chen et al. Modifications of dietary flavonoids towards improved bioactivity: An update on structure–activity relationship
Khan et al. Evidence and prospective of plant derived flavonoids as antiplatelet agents: Strong candidates to be drugs of future
Twilley et al. A review on traditionally used South African medicinal plants, their secondary metabolites and their potential development into anticancer agents
Zhu et al. Flavonoids possess neuroprotective effects on cultured pheochromocytoma PC12 cells: a comparison of different flavonoids in activating estrogenic effect and in preventing β-amyloid-induced cell death
Hwang et al. Neuroprotective effects of citrus flavonoids
Morris et al. Flavonoid–drug interactions: effects of flavonoids on ABC transporters
Augusti et al. Bioactivity, bioavailability, and gut microbiota transformations of dietary phenolic compounds: Implications for COVID-19
Menezes et al. Bioactivity of natural biflavonoids in metabolism-related disease and cancer therapies
US20220257561A1 (en) Compositions and methods for improving wellness
AU2012316001A1 (en) Selective metabolic approach to increasing oral bioavailability of phenylephrine and other phenolic bioactives
Ahmad et al. Mechanisms of action for the anti-obesogenic activities of phytochemicals
Kulkarni et al. Diabetes, diabetic complications, and flavonoids
Li et al. BaZiBuShen alleviates cognitive deficits and regulates Sirt6/NRF2/HO-1 and Sirt6/P53-PGC-1α-TERT signaling pathways in aging mice
Obakan-Yerlikaya et al. Breast cancer and flavonoids as treatment strategy
TW201733619A (en) Composition for inhibiting carnosine dipeptidase
Walker et al. The use of bergamot-derived polyphenol fraction in cardiometabolic risk prevention and its possible mechanisms of action
CA3215173A1 (en) Polyphenol compositions having improved bioavailability
Xue et al. Mechanism of flavonoids inhibiting xanthine oxidase and alleviating hyperuricemia from structure–activity relationship and animal experiments: A review
Kushwah et al. Cardioprotective activity of Cassia fistula L. bark extract in isoproterenol-induced myocardial infarction rat model
Jain et al. Comprehensive review on pharmacological effects and mechanism of actions of taxifolin: A bioactive flavonoid
Chand et al. Flavonoids: As omnipotent candidates for cancer management
Mukherjee et al. Bioactive flavonoid apigenin and its nanoformulations: a promising hope for diabetes and cancer
KR20170023910A (en) Pharmaceutical Compositions for Prevention or Treatment of nonalcoholic fatty liver disease Comprising Quercetin-3-O-glucoside