[go: up one dir, main page]

WO2010089874A1 - Amplificateur de l'expression du ppar-γ, amplificateur de la production d'adiponectine, activateur de l'ucp et préparation pharmaceutique, aliment ou boisson renfermant l'un quelconque de ces agents - Google Patents

Amplificateur de l'expression du ppar-γ, amplificateur de la production d'adiponectine, activateur de l'ucp et préparation pharmaceutique, aliment ou boisson renfermant l'un quelconque de ces agents Download PDF

Info

Publication number
WO2010089874A1
WO2010089874A1 PCT/JP2009/051985 JP2009051985W WO2010089874A1 WO 2010089874 A1 WO2010089874 A1 WO 2010089874A1 JP 2009051985 W JP2009051985 W JP 2009051985W WO 2010089874 A1 WO2010089874 A1 WO 2010089874A1
Authority
WO
WIPO (PCT)
Prior art keywords
ucp
ppar
agent
adiponectin
expression
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/JP2009/051985
Other languages
English (en)
Japanese (ja)
Inventor
文男 難波
吉田　正
千秋 伊藤
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Fujicco Co Ltd
Original Assignee
Fujicco Co Ltd
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 Fujicco Co Ltd filed Critical Fujicco Co Ltd
Priority to PCT/JP2009/051985 priority Critical patent/WO2010089874A1/fr
Publication of WO2010089874A1 publication Critical patent/WO2010089874A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Images

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
    • A61K31/33—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
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Preparation or treatment thereof
    • A23L2/52—Adding ingredients
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • the present invention relates to a PPAR- ⁇ [peroxisome proliferators-activated receptor ⁇ ] expression enhancer, adiponectin production promoter, UCP [uncoupling protein] activator and use thereof This is related to pharmaceuticals and foods.
  • Adiponectin (Acrp30, AdipoQ, GBP28) is an adipocytokine that improves insulin resistance.
  • Adiponectin is identified as a gene that is most abundantly expressed in human adipose tissue (Non-patent Document 1).
  • Non-patent Documents 2 to 6 Hypoadiponectinemia due to obesity and fat accumulation is considered to lead to insulin resistance syndrome such as diabetes and hyperlipidemia, systemic metabolic syndrome, arteriosclerosis and the like.
  • PPAR peroxisome-proliferators-activated receptor
  • RXR retinoid X receptor
  • PPRE PPAR response element
  • PPAR- ⁇ is known to control adipocyte differentiation and hypertrophy.
  • Studies using PPAR- ⁇ hetero-deficient mice have revealed that PPAR- ⁇ mediates obesity and insulin resistance. Suppressing hypertrophic adipogenesis by suppressing the intrinsic activity of PPAR- ⁇ is considered to be useful as an anti-obesity / anti-diabetic treatment (Non-patent Document 7).
  • PPAR and adiponectin act as insulin resistance improving substances, it is considered effective for the prevention and treatment of obesity and diabetes.
  • Appropriate dietary management is fundamental in the prevention and treatment of diabetes. Therefore, if a food that can activate and enhance production of PPAR and adiponectin is developed, it can be an effective means for preventing and treating diabetes. Furthermore, it can be expected to be effective against other diseases based on insulin resistance.
  • UCP uncoupling protein
  • UCP-2 is expressed in a wide variety of tissues, and by activating UCP-2, energy consumption can be increased without exercising, so it is an effective means of preventing and treating obesity. sell. UCP-2 is also thought to be involved in the response to infectious diseases such as diabetes and colds.
  • composition for promoting the secretion of adiponectin and the composition for promoting adiponectin containing proanthocyanidins contained in the grape extract as an active ingredient are derived from plants conventionally used as food, and are used for daily foods and drinks. It can be said that the safety is high in application (see Patent Documents 1 to 3).
  • adiponectin secretion-promoting compositions disclosed in Patent Documents 1 to 3 are actually not so high in adiponectin secretion-promoting performance and are compared with the performance of troglitazone (thiazolidinedione-based antidiabetic agent), which is a chemical. And quite inferior. Therefore, further improvement of the performance is expected by further research.
  • troglitazone thiazolidinedione-based antidiabetic agent
  • UCP activator development of a drug excellent in PPAR- ⁇ expression enhancement and UCP activity ability is expected with no side effects even if it is included in daily foods and drinks. Has been.
  • the present invention has been made in view of such circumstances, and is gentle to the human body without causing side effects, and can provide a PPAR- ⁇ expression enhancing effect, an adiponectin production promoting effect, a UCP expression enhancing effect,
  • the purpose is to provide pharmaceuticals and foods and drinks that can be expected to improve obesity, diabetes, etc. due to their effects.
  • the first gist of the present invention is a PPAR- ⁇ expression enhancer containing procyanidin B2 as an active ingredient and having a PPAR- ⁇ expression enhancing action.
  • the second gist of the present invention is an adiponectin production promoter containing procyanidin B2 as an active ingredient and having an adiponectin production promoting action.
  • the third gist of the present invention is a UCP activator containing procyanidin B2 as an active ingredient and having a UCP expression enhancing action.
  • the fourth aspect of the present invention is an anti-diabetic agent, an anti-obesity agent, a visceral fat accumulation reducing agent, or a visceral fat accumulation inhibitor comprising the drugs of the first to third aspects.
  • the fifth aspect of the present invention is a food / beverage product containing the drugs of the first to fourth aspects.
  • Procyanidins are polymers of epicatechin, and there are polymers such as dimers, trimers, tetramers, pentamers, etc. Isomers also exist. These have different physiological effects. The inventors further advanced research on such procyanidins.
  • procyanidin B2 which is a kind of procyanidin dimer is used as an active ingredient in the effect of enhancing the expression of PPAR- ⁇ , the effect of promoting the production of adiponectin, and the effect of enhancing the expression of UCP, it is extremely effective compared to other procyanidins. It was newly confirmed by experiment that this is recognized.
  • an improvement effect such as obesity / diabetes can be obtained, and therefore anti-diabetic agents, anti-obesity agents, visceral accumulated fat reducing agents, visceral fat accumulation inhibiting agents It was found that it can also be applied to the use of pharmaceuticals such as Furthermore, since procyanidin B2 does not cause side effects, it is highly safe and can be suitable for inclusion in daily foods and drinks, and it has been found that the intended purpose can be achieved. Reached.
  • the PPAR- ⁇ expression enhancer of the present invention contains procyanidin B2 as an active ingredient and has a PPAR- ⁇ expression enhancing action.
  • the adiponectin production promoter of this invention contains procyanidin B2 as an active ingredient, and has an adiponectin production promotion effect.
  • the UCP activator of the present invention contains procyanidin B2 as an active ingredient and has a UCP expression enhancing action.
  • each of the above-mentioned drugs is gentle to the human body without causing side effects, and has an effect of enhancing PPAR- ⁇ expression, an effect of promoting adiponectin production, an effect of enhancing UCP expression, and various diseases related to the prevention and improvement Can be demonstrated.
  • the above drugs can be advantageously applied to pharmaceutical uses such as antidiabetic agents, antiobesity agents, visceral fat accumulation reducing agents, visceral fat accumulation inhibitors.
  • FIG. 3 is a graph showing differences in the gene expression level of PPAR- ⁇ caused by pretreatment of 3T3-L1 cells (pretreatment with samples 1 to 8).
  • FIG. 3 is a graph showing the difference in the gene expression level of adiponectin caused by pretreatment of 3T3-L1 cells (pretreatment with samples 1 to 8).
  • FIG. 3 is a graph showing the difference in UCP-2 gene expression level resulting from pretreatment of 3T3-L1 cells (pretreatment with samples 1 to 8).
  • FIG. 3 is a graph showing the difference in the gene expression level of PPAR- ⁇ caused by pretreatment of 3T3-L1 cells (pretreatment with samples a to g).
  • FIG. 3 is a graph showing the difference in the gene expression level of adiponectin caused by pretreatment of 3T3-L1 cells (pretreatment with samples a to g).
  • FIG. 6 is a graph showing the difference in UCP-2 gene expression level resulting from pretreatment of 3T3-L1 cells (pretreatment with samples a to g).
  • the PPAR- ⁇ expression enhancer of the present invention contains procyanidin B2 as an active ingredient and has a PPAR- ⁇ expression enhancing action.
  • the adiponectin production promoter of this invention contains procyanidin B2 as an active ingredient, and has an adiponectin production promotion effect.
  • the UCP activator of the present invention contains procyanidin B2 as an active ingredient and has a UCP expression enhancing action (particularly a UCP-2 expression enhancing action). These drugs are considered to be free of substances that inhibit their action, etc., so that their actions can be demonstrated effectively in their respective applications.
  • the content ratio of procyanidin B2, which is an active ingredient is defined so as to be able to do so.
  • the chemical structure (steric structure) of procyanidin B2 is as shown in the following chemical formula (1).
  • procyanidin B2 is what was refine
  • Procyanidin B2 is abundant in plants such as black soybean seed coat, apple, cacao, grape, cinnamon, mutamba, hawthorn, bunoki, carambola, mother wort, keclopia, cola (cola nut) and the like.
  • an extraction solvent for procyanidin B2 for example, water, or a water-soluble solvent such as methanol, ethanol, isopropanol, n-propanol, and acetone is used.
  • procyanidins of about 1 to 30 mer are contained, procyanidins with a high degree of polymerization are mixed when extracted with lower alcohol or acetone. Therefore, in this case, a 0.01 to 10% by weight sulfuric acid aqueous solution is preferably used as one capable of extracting procyanidin B2 with high purity. Moreover, it is preferable from the point of purity and stability that the extraction temperature by the said extraction solvent is 70 degrees C or less.
  • a fraction containing procyanidin B2 at a high purity is extracted from the extract thus obtained by adsorption treatment, resin purification treatment, gel filtration treatment, ion exchange treatment, membrane separation treatment, salt precipitation treatment, and the like. Then, by drying and concentrating it, the target procyanidin B2 can be obtained.
  • the PPAR- ⁇ expression enhancer of the present invention preferably has a procyanidin B2 content in the range of 0.01 to 100% by weight, more preferably from the viewpoint of the effectiveness of its PPAR- ⁇ expression enhancing action. It is in the range of 10 to 100% by weight.
  • the adiponectin production promoter of the present invention preferably has a procyanidin B2 content in the range of 0.01 to 100% by weight, more preferably 10 to 10% from the viewpoint of the effectiveness of the adiponectin production promoting action. It is in the range of 100% by weight.
  • the UCP activator of the present invention preferably has a procyanidin B2 content in the range of 0.01 to 100% by weight, more preferably 10 to 100, from the viewpoint of the effectiveness of its UCP expression enhancing action. It is in the range of wt%.
  • the amount of the PPAR- ⁇ expression enhancer of the present invention is preferably set so that the daily procyanidin B2 intake is in the range of 0.1 to 1000 mg, more preferably from the viewpoint of effectiveness. Is in the range of 5 to 500 mg.
  • the adiponectin production promoter of the present invention is preferably set in an amount such that the daily procyanidin B2 intake is in the range of 0.1 to 1000 mg, more preferably 5 to 500 mg. Range.
  • the UCP activator of the present invention is preferably set so that the daily procyanidin B2 intake is in the range of 0.1 to 1000 mg, more preferably 5 to 500 mg. It is a range.
  • an antidiabetic agent an antiobesity agent, a visceral accumulated fat reducing agent
  • a pharmaceutical such as a visceral fat accumulation inhibitor
  • the procyanidin B2 content and the daily procyanidin B2 intake are in accordance with the ratios defined for the respective drugs.
  • the above procyanidin B2 extract may be used directly, but generally, the above extract is dissolved or dispersed in a suitable liquid carrier, What was mixed with the powder carrier is used.
  • pharmacologically acceptable carriers include excipients, lubricants, binders and disintegrants in solid preparations, or solvents, solubilizers, suspending agents, and isotonic agents in liquid preparations. , Buffering agents and soothing agents.
  • various components usually used for the preparation are arbitrarily used in the preparation.
  • examples thereof include starch, dextrin, lactose, corn starch, inorganic salts, and the like. Can be given.
  • Examples of the dosage form of the drug of the present invention include ampoules, tablets, capsules, granules, fine granules, powders, infusions, drinks and the like.
  • the drug of the present invention can be provided as a form in which it is associated with food and drink.
  • the foods and drinks include health foods (tablets, powders, granules, concentrated liquids), soft drinks, foods for specified health use, drinks, tea, milk, pudding, jelly, rice cake, gum, yogurt, chocolate, soup, cookies , Snacks, wine, shochu, sake, dressing, boiled beans, tofu, natto, soy milk, roasted beans, dried beans, miso, etc.
  • the obesity suppression effect comes to be obtained by eating and drinking these food and drink similarly to normal food and drink.
  • the drug of the present invention is friendly to the human body without causing side effects, and has a PPAR- ⁇ expression enhancing effect, an adiponectin production promoting effect, a UCP expression enhancing effect (particularly a UCP-2 expression enhancing effect), and various diseases related thereto (In particular, obesity and diabetes) can be prevented and improved.
  • the above-mentioned effects can be obtained not only in humans but also in animals such as pets and livestock, and the dose is determined based on conditions such as differences in organisms to be administered, sex, weight, age, etc. It is set appropriately according to And as above-mentioned, since the chemical
  • ⁇ Experiment method> Mouse-derived preadipocytes 3T3-L1 were cultured in a DME medium (Dulbecco's modified Eagle medium; hereinafter referred to as “basic medium”) containing 10% by volume of fetal bovine serum using a 24-well plate at 37 ° C., 5 The culture was performed in a volume% CO 2 atmosphere environment. Then, after this culture, 3T3-L1 cells reached 100% confluence, and then, in the basic medium, three types of reagents, dexamethasone, methylisobutylxanthine, and insulin, respectively, dexamethasone 1 ⁇ mol / l, and methylisobutylxanthine 0.1%.
  • DME medium Dulbecco's modified Eagle medium
  • Differentiation induction treatment was performed by adding 25 ⁇ mol / l insulin to a concentration of 2 ⁇ mol / l, and the 3T3-L1 cells were differentiated into adipocytes.
  • the differentiation induction treatment is continued for 3 days, and then the 3T3-L1 cells are cultured for about 1 week by adding only insulin to the basic medium (insulin concentration: 2 ⁇ mol / l) to mature the adipocytes. It was.
  • insulin concentration insulin concentration: 2 ⁇ mol / l
  • the pre-processing by the difference of the said sample was performed on the same conditions under the same environment.
  • the medium is removed, the cells are washed with a phosphate buffer, and then the cells are washed with a basic medium supplemented with 10 ng / ml of inflammation-inducing cytokine TNF- ⁇ . was again cultured for 12 hours (stress treatment).
  • the sample 4 shown in Table 1 is procyanidin B2, which is a kind of procyanidin dimer, and its chemical structure (steric structure) is as shown in the following chemical formula (1).
  • procyanidin C1 which is a kind of procyanidin trimer
  • its chemical structure stereostructure
  • the extent to which the pretreatment reduces the stress due to TNF- ⁇ was confirmed by the expression behavior of the gene. Specifically, this verification was performed by quantifying the expression level (Relative mRNA Levels) of each gene of PPAR- ⁇ , adiponectin, and UCP-2 in the above cDNA by real-time PCR using a light cycler (Roche). .
  • the primer sequences of each gene are as shown in Table 2 below.
  • SYBR Premix Ex Taq (manufactured by Takara Bio Inc.) is used as a reaction solution for this determination, and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is used as a gene for data correction (normalization). It was.
  • FIG. 1 is a graph showing the results.
  • sample 4 procyanidin B2
  • PPAR- ⁇ gene expression level of sample 4 was significantly different from the PPAR- ⁇ gene expression levels of all other samples at a risk rate of less than 5%.
  • FIG. 2 is a graph showing the results.
  • sample 4 procyanidin B2
  • example 8 a conventional diabetes therapeutic chemical. It was accepted to show.
  • the adiponectin gene expression level by the use of sample 4 was significantly different from the adiponectin gene expression level of all other samples except sample 8 at a risk rate of less than 5%.
  • FIG. 3 is a graph showing the results.
  • sample 4 procyanidin B2
  • sample 4 procyanidin B2
  • the gene expression level of UCP-2 due to the use of sample 4 is significantly different from the UCP-2 gene expression level of sample 1, sample 3, sample 5, sample 6, and sample 7 at a risk rate of less than 5%. Admitted.
  • procyanidin B2 (sample 4) has a high PPAR- ⁇ expression enhancing action and adiponectin production promoting action. Since the UCP-2 expression enhancing action was observed, in Example 2, a comparative experiment was conducted with the case where a compound (sample) closer to procyanidin B2 was used in terms of chemical structure, physical properties, and the like.
  • any of samples a to g shown in Table 6 below was used as a sample used for pretreatment of 3T3-L1 cells differentiated into mature adipocytes.
  • the pre-processing by the difference of the said sample was performed on the same conditions under the same environment. Otherwise, the experiment was carried out in the same manner as in the experimental method of Example 1, RNA extraction after stress treatment with TNF- ⁇ following the above pretreatment and its reverse transcription reaction, and further, each gene expression level (PPAR) by real-time PCR Quantification of - ⁇ , adiponectin and UCP-2 gene expression levels) was also performed in the same manner as in Example 1.
  • PPAR gene expression level
  • procyanidin B1 which is a kind of procyanidin dimer
  • its chemical structure stereostructure
  • FIG. 4 is a graph showing the results.
  • sample b procyanidin B2
  • PPAR- ⁇ gene expression level in sample b was significantly different from the PPAR- ⁇ gene expression level in all other samples except sample f at a risk rate of less than 5%.
  • FIG. 5 is a graph showing the results.
  • the sample b (procyanidin B2) as an example product has a high adiponectin production promotion effect next to troglitazone (sample g), which is a conventional chemical for treating diabetes. It was accepted to show.
  • the adiponectin gene expression level by using sample b was significantly different from the adiponectin gene expression level by sample a, sample d, sample e, and sample f at a risk rate of less than 5%.
  • FIG. 6 is a graph showing the results.
  • sample b procyanidin B2
  • the gene expression level of UCP-2 by using sample b is significantly different from the gene expression level of UCP-2 by sample a, sample c, sample d, sample e, and sample f at a risk rate of less than 5%. Admitted.
  • the PPAR- ⁇ expression enhancing action, adiponectin production promoting action, and UCP expression enhancing action are closely related to the prevention and improvement of obesity, diabetes and the like, it contains procyanidin B2, which is the product of this example, as an active ingredient.
  • procyanidin B2 which is the product of this example.
  • a drug capable of exerting each of the above-mentioned effects will have advantageous effects even when used as an anti-diabetic agent, anti-obesity agent, visceral fat accumulation reducing agent, or visceral fat accumulation inhibitor. Is done.
  • medical agents do not show a side effect substantially, they can also be contained in food-drinks.
  • the drug of the present invention contains procyanidin B2 as an active ingredient and has a PPAR- ⁇ expression enhancing action, adiponectin production promoting action or UCP expression enhancing action, and exhibits these effects without showing any side effects. Is effective, so that it is excellent in safety and industrially useful. Further, based on these actions, it can be used as an antidiabetic agent, an antiobesity agent, a visceral accumulated fat reducing agent, a visceral fat accumulation inhibiting agent, or the like. Moreover, since the food / beverage products containing the said chemical
  • medical agent can be applied to all food / beverage products, it is industrially useful also in the meaning which gives a functional added value to food / beverage products. Furthermore, application to livestock and pet feed is also possible.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Diabetes (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Obesity (AREA)
  • Hematology (AREA)
  • Nutrition Science (AREA)
  • Food Science & Technology (AREA)
  • Polymers & Plastics (AREA)
  • Endocrinology (AREA)
  • Emergency Medicine (AREA)
  • Botany (AREA)
  • Mycology (AREA)
  • Child & Adolescent Psychology (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne un amplificateur de l'expression du PPAR-γ qui comprend de la procyanidine B2 en tant que principe actif et qui possède une activité d'amplification de l'expression du PPAR-γ ; un agent favorisant la production d'adiponectine qui comprend de la procyanidine B2 en tant que principe actif et qui possède une activité favorisant la production d'adiponectine ; un activateur de l'UCP qui comprend de la procyanidine B2 en tant que principe actif et qui possède une activité d'amplification de l'expression de l'UCP ; un antidiabétique, un agent anti-obésité, un réducteur de l'accumulation de graisse viscérale ou un inhibiteur de l'accumulation de graisse viscérale, qui comprend un agent quelconque parmi l'amplificateur de l'expression du PPAR-γ, l'agent favorisant la production d'adiponectine et l'activateur de l'UCP ; et un aliment ou une boisson, qui comprend un agent quelconque parmi l'amplificateur de l'expression du PPAR-γ, l'agent favorisant la production d'adiponectine et l'activateur de l'UCP. Il devient possible de procurer une préparation pharmaceutique, un aliment ou une boisson qui ne provoque aucun effet secondaire indésirable, qui est sans danger pour le corps humain et qui est supposé présenter un effet d'amplification de l'expression du PPAR-γ, un effet favorisant la production d'adiponectine, un effet d'amplification de l'expression de l'UCP, un effet d'amélioration de l'obésité, du diabète ou analogues qui est induit par l'effet d'amplification de l'expression du PPAR-γ, l'effet favorisant la production d'adiponectine ou l'effet d'amplification de l'expression de l'UCP, ou analogues.
PCT/JP2009/051985 2009-02-05 2009-02-05 Amplificateur de l'expression du ppar-γ, amplificateur de la production d'adiponectine, activateur de l'ucp et préparation pharmaceutique, aliment ou boisson renfermant l'un quelconque de ces agents Ceased WO2010089874A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/JP2009/051985 WO2010089874A1 (fr) 2009-02-05 2009-02-05 Amplificateur de l'expression du ppar-γ, amplificateur de la production d'adiponectine, activateur de l'ucp et préparation pharmaceutique, aliment ou boisson renfermant l'un quelconque de ces agents

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/JP2009/051985 WO2010089874A1 (fr) 2009-02-05 2009-02-05 Amplificateur de l'expression du ppar-γ, amplificateur de la production d'adiponectine, activateur de l'ucp et préparation pharmaceutique, aliment ou boisson renfermant l'un quelconque de ces agents

Publications (1)

Publication Number Publication Date
WO2010089874A1 true WO2010089874A1 (fr) 2010-08-12

Family

ID=42541796

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2009/051985 Ceased WO2010089874A1 (fr) 2009-02-05 2009-02-05 Amplificateur de l'expression du ppar-γ, amplificateur de la production d'adiponectine, activateur de l'ucp et préparation pharmaceutique, aliment ou boisson renfermant l'un quelconque de ces agents

Country Status (1)

Country Link
WO (1) WO2010089874A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2012158553A (ja) * 2011-02-01 2012-08-23 Gunze Ltd 内臓脂肪蓄積抑制剤
JP2014527506A (ja) * 2011-06-02 2014-10-16 ユリエヴィッチ レシコフ，セルゲイ 糖尿病治療のための組み合わせ
WO2022029029A1 (fr) * 2020-08-07 2022-02-10 Universitat Rovira I Virgili Composition et méthode pour moduler la prise alimentaire

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005082390A1 (fr) * 2004-03-02 2005-09-09 Asahi Breweries, Ltd. Inhibiteurs d’accumulation de graisse
JP2006182706A (ja) * 2004-12-28 2006-07-13 Kikkoman Corp 血中アディポネクチン量増加剤
CN101125139A (zh) * 2007-09-28 2008-02-20 天津市尖峰天然产物研究开发有限公司 原花青素b2在制备防治糖尿病及血管并发症药物的应用

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005082390A1 (fr) * 2004-03-02 2005-09-09 Asahi Breweries, Ltd. Inhibiteurs d’accumulation de graisse
JP2006182706A (ja) * 2004-12-28 2006-07-13 Kikkoman Corp 血中アディポネクチン量増加剤
CN101125139A (zh) * 2007-09-28 2008-02-20 天津市尖峰天然产物研究开发有限公司 原花青素b2在制备防治糖尿病及血管并发症药物的应用

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
CHEN, D. ET AL.: "Inhibitory effects of procyanidin B(2) dimer on lipid-laden macrophage formation", JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, vol. 48, no. 2, 2006, pages 54 - 70 *
JORGE M. RICARDO DA SILVA ET AL.: "Procyanidin dimers and trimers from grape seeds", PHYTOCHEMISTRY, vol. 30, no. 4, 1991, pages 1259 - 1264 *
MA, L. ET AL.: "Grape seed proanthocyanidin extracts inhibit vascular cell adhesion molecule expression induced by advanced glycation end products through activation of peroxisome proliferators-activated receptor y", JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, vol. 49, no. 5, 2007, pages 293 - 298 *
PENG, X. ET AL.: "Cinnamon Bark Proanthocyanidins as Reactive Carbonyl Scavengers To Prevent the Formation of Advanced Glycation Endproducts", JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, vol. 56, no. 6, 2008, pages 1907 - 1911 *
YUTAKA OTA ET AL.: "Ringo Polyphenol ni yoru Ihimansei Rat no Shishitsu Taisha Oyobi Insulin Hi Izonsei no Kaizen", JOURNAL OF THE JAPANESE SOCIETY FOR FOOD SCIENCE AND TECHNOLOGY, vol. 54, no. 6, 2007, pages 287 - 294 *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2012158553A (ja) * 2011-02-01 2012-08-23 Gunze Ltd 内臓脂肪蓄積抑制剤
JP2014527506A (ja) * 2011-06-02 2014-10-16 ユリエヴィッチ レシコフ，セルゲイ 糖尿病治療のための組み合わせ
WO2022029029A1 (fr) * 2020-08-07 2022-02-10 Universitat Rovira I Virgili Composition et méthode pour moduler la prise alimentaire

Similar Documents

Publication Publication Date Title
Wan et al. Molecular mechanism underlying the ability of caffeic acid to decrease uric acid levels in hyperuricemia rats
JP2011178728A (ja) Ａｍｐｋ活性化剤、ｇｌｕｔ４活性化剤、およびそれらを用いた医薬品・飲食品
JP5389434B2 (ja) アディポネクチン発現低下抑制剤及びその用途
Cai et al. Effect of yeast-derived peptides on skeletal muscle function and exercise-induced fatigue in c2c12 myotube cells and icr mice
WO2010089874A1 (fr) Amplificateur de l'expression du ppar-γ, amplificateur de la production d'adiponectine, activateur de l'ucp et préparation pharmaceutique, aliment ou boisson renfermant l'un quelconque de ces agents
KR20100032670A (ko) ＰＰＡＲ의 작용에 의해 조절되는 질환을 예방 또는 치료하기 위한 약학 조성물, ＰＰＡＲγ 작용제, ＰＰＡＲα 작용제, ＰＰＡＲ의 작용에 의해 조절되는 질환을 예방 또는 개선하기 위한 건강식품 및 약학 조성물의 제조 방법
JP5403942B2 (ja) グルタチオン産生促進剤およびグルタチオンの欠乏に起因する疾患の予防・治療剤
JP2005350375A (ja) 血中尿酸値低下剤
EP2351559B1 (fr) Nouvelle utilisation d'un dérivé de panduratine ou d'un extrait de boesenbergia pandurata
JP2008115163A (ja) アディポネクチン産生増強・促進剤
JP2013107852A (ja) メイラード反応阻害剤
JP2015214501A (ja) ウイルスの細胞内増殖抑制剤、Ｍｎ−ＳＯＤ活性化剤および抗ウイルス剤
Li et al. Anti-hypoxia effects of ginseng (Panax Ginseng CA Meyer) oligopeptides in mice
JP2008231080A (ja) 脂肪細胞からのレプチン分泌促進剤
Parjapath et al. Hydroxycitric Acid‑Induced Activation of Peroxisome Proliferator‑Activated Receptors in 3T3‑L1 Adipocyte Cells
JP7610209B2 (ja) ミトコンドリア活性向上用組成物
JP5061282B2 (ja) ナリンゲニン誘導体、それを含有するグルコース取込み促進剤及び血糖値上昇抑制剤
JP2014019648A (ja) ＰＰＡＲδ活性化剤
JP5877731B2 (ja) Ｕｃｐ−３発現促進剤
JP2007039367A (ja) 細胞の分化を促進する組成物およびその利用
KR102168228B1 (ko) 신규한 2-하이드록시-4-메틸벤조산 무수물 및 이를 유효성분으로 함유하는 신경염증질환의 예방 또는 치료용 조성물
Choi et al. Gelidium elegans Extract Ameliorates Type 2 Diabetes Mellitus through Negative Regulation of MAPK Signaling Pathway by PI3K/Akt Activation
Lu et al. Effect of the essential oil from the ripe fruit pericarp of Zanthoxylum bungeanum Maxim. on glucose metabolism in diabetic mice induced by streptozotocin.
US20180296522A1 (en) ENHANCED EXPRESSION OF mTOR AND INHIBITED EXPRESSION OF MYOSTATIN IN SKELETAL MUSCLE CELLS
JP2024060271A (ja) 抗肥満用組成物

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 09839651

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 09839651

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: JP