WO2007132893A1 - Mcp-1の発現抑制剤、それを用いた炎症性疾患の改善剤、医薬品、サプリメント、食品、飲料および食品添加剤 - Google Patents
Mcp-1の発現抑制剤、それを用いた炎症性疾患の改善剤、医薬品、サプリメント、食品、飲料および食品添加剤 Download PDFInfo
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- WO2007132893A1 WO2007132893A1 PCT/JP2007/060044 JP2007060044W WO2007132893A1 WO 2007132893 A1 WO2007132893 A1 WO 2007132893A1 JP 2007060044 W JP2007060044 W JP 2007060044W WO 2007132893 A1 WO2007132893 A1 WO 2007132893A1
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- mcp
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- aurapten
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- food
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/75—Rutaceae (Rue family)
- A61K36/752—Citrus, e.g. lime, orange or lemon
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- 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
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
- A61P3/06—Antihyperlipidemics
-
- 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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
Definitions
- MCP-1 expression inhibitor inflammatory disease remedy, pharmaceuticals, supplements, foods, beverages and food additives
- the present invention relates to an expression inhibitor of MCP-1, an inflammatory disease ameliorating agent, a pharmaceutical, a supplement, a food, a beverage, and a food additive using the same.
- MCP-1 monocyte chemoattractant protein-1
- monocyte chemoattractant protein-1 is a type of chemokine. It is secreted mainly by monocytes, macrophages, fibroblasts, vascular endothelial cells, etc., and has functions such as monocyte and T cell migration activity, induction of site force-in production, and expression of adhesion molecules.
- the receptor for MCP-1 is CCR2. Recent research has shown that adipose tissue is an organ that secretes MCP-1, and that the amount of MCP-1 secretion increases in the adipose tissue of obese people.
- Non-patent Document 1 MCP-1 force infections, autoimmune diseases, rheumatoid arthritis, multiple sclerosis, transplant rejection, inflammatory diseases such as atherosclerosis and cancer metastasis, insulin resistance, etc.
- inflammatory diseases including obesity and insulin resistance are closely related to lifestyle habits, so it is necessary to improve exercise and eating habits. Therefore, suppressing the expression of MCP-1 in daily life such as meals is considered to be a force for preventing or treating inflammatory diseases.
- chemically synthesized drugs are difficult to take for a long time due to side effects as described above.
- chemically synthesized pharmaceuticals often have a unique flavor, there is a problem that, when taken with food, for example, the original flavor of the food is impaired. Therefore, chemically synthesized pharmaceuticals, for example, may not be useful in treatment under the guidance of doctors, but they have safety issues and should be applied to foods, beverages, supplements, etc. Cannot be applied. There is a problem of being narrow.
- Non-Patent Document 1 “Obesity Research” Vol. 11 No. 3 2005 27 (267)-32 (272)
- Patent Document 1 JP 2005-187451 A
- an object of the present invention is to provide an expression inhibitor of MCP-1 that is excellent in safety and can be widely applied to foods and the like.
- the MCP-1 expression inhibitor of the present invention contains aurapten.
- the inflammatory disease improving agent of the present invention contains the MCP-1 expression inhibitor of the present invention.
- the present invention is a pharmaceutical product for preventing or treating inflammatory diseases, and includes the inflammatory disease improving agent of the present invention.
- the present invention is a supplement, food, beverage, or food additive for preventing or ameliorating inflammatory diseases, including the inflammatory disease improving agent of the present invention.
- the present invention is a method for suppressing the expression of MCP-1, and includes the step of administering aurapten.
- the present invention is also a method for preventing or treating inflammatory diseases, comprising the step of administering an olapten.
- the present invention is the use of aurapten for suppressing the expression of MCP-1 or for preventing or treating inflammatory diseases.
- the present inventor has conducted a series of studies on substances that suppress the expression of MCP-1, focusing on natural products.
- the aurapten contained in citrus suppresses the expression of MCP-1 and led to the present invention.
- Citrus containing aurapten has been used as food for many years and there is no problem with its safety.
- aurapten has no or little unique flavor, even when applied to food, beverages, etc., the flavor does not deteriorate.
- Aurapten also has calories. Because it is low, there is no problem in this point even if people who need calorie restriction such as obese and diabetics take it for a long time. Therefore, the MCP-1 expression inhibitor of the present invention is excellent in safety, can be widely applied to foods, etc., and can be ingested for a long time.
- FIG. 1 is a graph showing the effect of suppressing the expression of MCP-1 at the gene level in one example of the present invention.
- FIG. 2 is a graph showing the effect of suppressing the expression of MCP-1 at the protein level in the Example.
- the suppression of MCP-1 expression is at least one of suppression of expression at the gene level and suppression of expression at the protein level.
- the suppression of expression at the gene level includes suppression of transcription into mRNA.
- the suppression of expression at the protein level includes, for example, suppression in translation, and when modified after translation, includes suppression of the modification.
- the aurapten is preferably derived from citrus fruits.
- Citrus-derived auraptens may be derived from any part of the citrus fruits, for example, those derived from fruit juice, those derived from pulp, and those derived from skin.
- the citrus fruits are not particularly limited.
- Amatsuka scientific name Citrus natsudaidai HAYATA
- Yawata scientific name Citrus hassaku Hort. Ex TANAKA
- Summer tangerine scientific name Citrus natsudaidai HA YATA variant
- Grapefruit scientific name Citrus paradisi
- the aurapten described above may be used, for example, by isolating and purifying citrus fruits, or in a crude state including all or part of citrus fruits.
- Aurapten may be a synthetic product or a commercially available product.
- the MCP-1 expression inhibitor of the present invention is not limited in its configuration and form as long as it contains aurapten as described above. That is, in the present invention, the expression inhibitor of MCP-1 may be aurapten alone or may further contain other components, for example. The other components are not limited and can be appropriately determined depending on the use of the present invention. Various components exemplified in the above are listed.
- administering or ingesting the MCP-1 expression inhibitor of the present invention for example, the expression of MCP-1 can be suppressed at the gene level or protein level, for example.
- the expression inhibitor of the present invention is not limited, but is preferably administered or ingested to, for example, humans and mammals other than humans.
- the MCP-1 expression inhibitor of the present invention can be applied to, for example, an inflammatory disease ameliorating agent, a pharmaceutical product, a supplement, a food, a beverage, a food additive, and the like.
- an inflammatory disease ameliorating agent for example, a pharmaceutical product, a supplement, a food, a beverage, a food additive, and the like.
- the structure and form are not restrict
- the inflammatory disease improving agent of the present invention contains the MCP-1 expression inhibitor of the present invention.
- the inflammatory disease include metabolic syndrome, allergy, kidney disease, infectious disease, autoimmune disease, rheumatoid arthritis, multiple sclerosis, transplanted organ rejection, and cancer transition.
- the metabolic syndrome include insulin resistance, hyperinsulinemia, type 2 diabetes, hyperlipidemia, arteriosclerosis, hypertension, obesity and visceral fat obesity.
- the administration target is not limited, and examples thereof include humans and mammals excluding humans.
- the dose or intake of aurapten is not limited. Further, administration or ingestion of olapten may be performed once a day or may be divided into several times a day.
- the pharmaceutical product of the present invention is a pharmaceutical product for preventing or treating inflammatory diseases, and includes the inflammatory disease improving agent of the present invention.
- the pharmaceutical of the present invention for example, insulin resistance, hyperinsulinemia, type 2 diabetes, hyperlipidemia, arteriosclerosis, hypertension, obesity and visceral fat type obesity, etc., allergy, It can prevent or treat diseases such as kidney disease, infectious disease, autoimmune disease, rheumatoid arthritis, multiple sclerosis, transplant organ rejection and cancer metastasis.
- the subject to which the pharmaceutical of the present invention is administered is not limited, and examples thereof include humans and mammals other than humans.
- the pharmaceutical product of the present invention may contain, for example, other MCP-1 expression-suppressing ingredients, pharmaceutically acceptable additives and the like in addition to the improver of the present invention.
- specific dosage forms include, for example, tablets, fine granules (including powders), capsules, liquids ( Including syrup).
- suitable additives and base materials can be used as appropriate, and can be produced according to the usual methods described in the Japanese Pharmacopoeia.
- the administration route is not particularly limited, and examples thereof include oral administration and parenteral administration. Examples of the parenteral administration include intraoral administration, intratracheal administration, rectal administration, subcutaneous administration, intramuscular administration, intravenous administration and the like.
- the supplement of the present invention is a supplement for preventing or ameliorating inflammatory diseases, and includes the inflammatory disease improving agent of the present invention.
- the supplement of the present invention for example, insulin resistance, hyperinsulinemia, type 2 diabetes, hyperlipidemia, arteriosclerosis, hypertension, obesity and visceral fat type obesity, etc., allergy, kidney It is possible to prevent or improve diseases such as diseases, infectious diseases, autoimmune diseases, rheumatoid arthritis, multiple sclerosis, transplanted organ rejection and cancer metastasis.
- the supplement of the present invention is not limited, but it is preferably taken by humans or mammals other than humans as described above.
- the supplement of the present invention may contain, for example, various additives and other supplements in addition to the improving agent of the present invention.
- Examples of other components include other MCP1 expression-suppressing components, various vitamins such as vitamin C, amino acids, oligosaccharides, and the like.
- the form of the supplement of the present invention is not particularly limited, and examples thereof include tablets, fine granules (including powder), capsules, liquids (including syrup) and the like.
- the food of the present invention is a food for preventing or ameliorating inflammatory diseases, and contains the inflammatory disease improving agent of the present invention.
- the food of the present invention for example, insulin resistance, hyperinsulinemia, type 2 diabetes, hyperlipidemia, arteriosclerosis, hypertension, metabolic syndrome such as obesity and visceral fat obesity, allergy, kidney It is possible to prevent or improve diseases such as diseases, infectious diseases, autoimmune diseases, rheumatoid arthritis, multiple sclerosis, transplant organ rejection and cancer metastasis.
- the food of the present invention is not limited, but for example, it is preferably taken by mammals other than humans.
- the food of the present invention may contain, for example, various components in addition to the improving agent.
- the food includes, for example, both general foods and functional foods.
- the form of the food is not limited, and for example, cereals, potatoes, confectionery, soup, meat, fish There are shellfish, seaweed, vegetables, fruits, beans, various processed products, dried foods, frozen foods, salmon products, canned foods, bottled foods, and retort foods.
- the beverage of the present invention is a beverage for preventing or ameliorating inflammatory diseases, and contains the inflammatory disease improving agent of the present invention.
- metabolic syndrome such as insulin resistance, hyperinsulinemia, type 2 diabetes, hyperlipidemia, arteriosclerosis, hypertension, obesity and visceral fat type obesity, allergy, It can prevent or improve diseases such as kidney disease, infectious disease, autoimmune disease, rheumatoid arthritis, multiple sclerosis, transplant organ rejection and cancer metastasis.
- the beverage of the present invention is not limited, but for example, it is preferably taken by mammals other than humans.
- the beverage of the present invention may contain various components in addition to the improver, for example.
- the beverage includes, for example, both general beverages and functional beverages.
- the form of the beverage is not limited, and examples thereof include soft drinks such as juice, carbonated drinks, coffee, black tea, green tea, and mineral water.
- the food additive of the present invention is, for example, a food additive for preventing or improving inflammatory diseases, and includes the inflammatory disease improving agent of the present invention.
- metabolic syndrome such as insulin resistance, hyperinsulinemia, type 2 diabetes, hyperlipidemia, arteriosclerosis, hypertension, obesity and visceral fat type obesity
- diseases such as allergies, kidney diseases, infectious diseases, autoimmune diseases, rheumatoid arthritis, multiple sclerosis, transplanted organ rejection, and cancer metastasis.
- the food additive of the present invention is not limited, but it is preferably taken by, for example, mammals other than humans.
- the food additive of the present invention may contain various components in addition to the improving agent, for example.
- the form of the food additive of the present invention is not limited, and examples thereof include liquid, powder, flakes, and granules.
- the food additive of the present invention includes, for example, a food additive for beverages in addition to food.
- the present invention is a method for suppressing the expression of MCP-1, which comprises the step of administering the aurapten.
- the subject to which aurapten is administered is not limited, and may be, for example, a living body or a cell isolated from a living body. Examples of the living body include, but are not limited to, humans and mammals including humans.
- the form of the aurapten to be administered is not limited, and for example, the same form as the above-described MCP-1 expression inhibitor, inflammatory ameliorating agent, pharmaceuticals, supplements, foods, beverages, food additives, etc. of the present invention. Can be given.
- the administration method is not limited, and examples thereof include oral administration and parenteral administration in the case of a living body.
- parenteral administration include intraoral administration, intratracheal administration, rectal administration, subcutaneous administration, intramuscular administration, intravenous administration and the like.
- a method of culturing by adding aurapten to the medium can be mentioned.
- the present invention is a method for preventing or treating an inflammatory disease, comprising the step of administering the expression inhibitor of MCP-1 of the present invention.
- the form of the MCP-1 expression inhibitor of the present invention is not limited and is the same as described above.
- the MCP-1 expression inhibitor may be administered, for example, as an inflammatory improver, pharmaceutical, supplement, food, beverage, or food additive as described above.
- the administration method is not limited, and examples thereof include oral administration and parenteral administration.
- Examples of the parenteral administration include oral administration, intratracheal administration, rectal administration, subcutaneous administration, intramuscular administration, intravenous administration and the like.
- the subject to which the MCP-1 expression inhibitor of the present invention is administered is not limited, and examples thereof include humans and mammals including humans.
- the aurapten in the present invention is preferably produced using citrus fruits as a raw material as described above.
- An example of this manufacturing method Japanese Patent Laid-Open No. 11-29565) is shown below.
- a citrus peel is immersed in water at room temperature, and then centrifuged to obtain a peel oil.
- pericarp fruit, pulp and fruit juice may be used, but it is preferable to use pericarp because of the high content of aurapten.
- the peel oil is adsorbed on an adsorbent.
- adsorbent for example, a porous adsorbent that is electrically neutral and has a large specific surface area is preferably used. Sucking like this Examples of the adsorbent include rosin containing a copolymer of styrene and dibutenebenzene. Further, from the viewpoint of efficiently purifying aurapten by increasing the amount of adsorption, it is preferable to use the resin used as the adsorbent in a dry state.
- the adsorbent adsorbing the peel oil is washed with an aqueous alcohol solution. Thereby, impurities adsorbed on the adsorbent are removed.
- the alcohol concentration of the aqueous alcohol solution is, for example, less than 50% (volume ratio), preferably 10% to 45%, more preferably 35% to 45%.
- the alcohol include ethanol and isopropyl alcohol.
- the amount of the aqueous alcohol solution is not limited, but for example, it is preferably about 14 times (volume ratio) that of an auraptene-containing liquid (eg, peel oil) adsorbed on an adsorbent.
- the aurapten is eluted from the adsorbent using an aqueous alcohol solution. Since this eluate contains aurapten, it may be used as it is, or it may be concentrated or dried. The aurapten thus obtained is almost white, tasteless and odorless.
- the alcohol concentration of the alcohol aqueous solution for elution is, for example, 50% or more and 95% or less, preferably 60% or more and 90% or less, and more preferably 75% or more and 85% or less.
- the amount of the alcohol aqueous solution and the amount of the additive are, for example, the same as described above.
- This example shows the MCP at the gene level and protein level by aurapten.
- a differentiation induction medium a differentiation promotion medium.
- DMEM fetal serum
- FBS usi fetal serum
- a differentiation induction medium was prepared by adding MIX (3-Isobutyl-1-methylxanthine) (manufactured by Nacalai) to the required amount of the medium so as to be 0.5 mM. Since MIX is very difficult to dissolve, it was first dissolved in a small amount of 99.5% ethanol and then added to DMEM containing 10% FBS. At this time, the final concentration of 99.5% ethanol was not allowed to exceed 1% in the induction medium.
- MIX 3-Isobutyl-1-methylxanthine
- composition DMEMZ aurapten containing 5ug / mL insulin Z10% FBS
- the frozen cultured preadipocytes 3T3-L1 were thawed and seeded in a 100 mm dish containing the medium, and cultured until 3T3-L1 reached about 80% confluence.
- One dish of 3T3—L1 that reached about 80% confluence was transferred to one 6-well plate.
- the medium was replaced with a differentiation-inducing medium for induction.
- the medium was replaced with a differentiation promoting medium. Then, the medium for promoting differentiation was changed every two days thereafter.
- the medium was removed from the 6-well plate, 1 mL of Sepasol RNA I super (manufactured by Nacalai) was added to each well, and the cells were dispersed by repeating pipetting several times. This cell dispersion was transferred to a 1.5 mL tube and allowed to stand at room temperature for 5 minutes. After standing, 200 L of black mouth form was placed in the tube, stirred well with Vortex, and left at room temperature for 3 minutes. The tube was cooled to 4 ° C. and centrifuged at 12000 ⁇ g for 15 minutes to separate a phenol layer (lower layer, yellow) and an aqueous layer (upper layer, colorless).
- RNA sample Z primer mixture was incubated at 70 ° C for 10 minutes in the hernal Cycler to The next structure was destroyed, moved to ice and left for more than 1 minute.
- 11 L of the RNA sample Z primer mixture, 5 ⁇ L of 5 X reverse transcription buffer, RNase inhibitor 1 L, 2.5 mM dNTP Mix 5 L, and Nuclease Free water 2 L were sequentially added ( Total 24 L).
- a plasmid containing a fragment of the target gene (MCP-1 gene or 36B4 gene) whose expression level was to be measured was prepared by a conventionally known method. Add 5 L of this plasmid solution to a 0.665 mL tube, add 45 L of water supplied with Light Cycler (registered trademark) DNA Master SYBR Green (trade name), and add the plasmid 10 times. Dilute to This operation was repeated to prepare 10 2 , 10 3 , 10 4 , 10 5 , 10 6 , 10 7 and 10 8 times each diluted solution of the plasmid.
- the relative ratio calculated with the measured value of the untreated control (control) as 100 with respect to the measured value of the secretion amount of MCP-1 by ELISA is shown in the following Table 2 and the graph of FIG.
- the aurapten concentrations in Table 2 and Fig. 2 below are the final concentrations in the differentiation promoting medium.
- AUR represents aurapten
- Ctrl represents an untreated control (control).
- the abscissa indicates the amount of auraptene (AUR) added M)
- the ordinate indicates the protein mass of MCP-1 relative to the untreated control (control) ( Secretion amount) (%).
- the MCP-1 expression inhibitor of the present invention which contains aurapten, is excellent in safety and can suppress the expression of MCP-1 that is not a problem even when ingested for a long period of time. . Moreover, since there is no problem of flavor, for example, even if it is applied to foods, the flavor is not impaired. Therefore, the expression inhibitor of MCP-1 of the present invention can be applied to various products such as pharmaceuticals, supplements, foods, beverages, food additives and the like, and its uses are not limited and are wide.
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Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP07743479A EP2019098A4 (en) | 2006-05-17 | 2007-05-16 | SUPPRESSOR OF THE EXPRESSION OF MCP-1 AND RELYING MEDICAMENT FOR INFLAMMATORY DISEASE, PHARMACEUTICAL, COMPLEMENTARY AGENT, FOOD, BEVERAGE OR FOOD SUPPLEMENT USING THE SUPPRESSOR |
US12/299,993 US20090118361A1 (en) | 2006-05-17 | 2007-05-16 | Suppressor of expression of mcp-1, and ameliorating agent for inflammatory disease, pharmaceutical, supplement, food, beverage or food additive using the suppressor |
JP2008515591A JPWO2007132893A1 (ja) | 2006-05-17 | 2007-05-16 | Mcp−1の発現抑制剤、それを用いた炎症性疾患の改善剤、医薬品、サプリメント、食品、飲料および食品添加剤 |
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JP2006137223 | 2006-05-17 | ||
JP2006-137223 | 2006-05-17 |
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WO2007132893A1 true WO2007132893A1 (ja) | 2007-11-22 |
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PCT/JP2007/060044 WO2007132893A1 (ja) | 2006-05-17 | 2007-05-16 | Mcp-1の発現抑制剤、それを用いた炎症性疾患の改善剤、医薬品、サプリメント、食品、飲料および食品添加剤 |
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EP (1) | EP2019098A4 (ja) |
JP (1) | JPWO2007132893A1 (ja) |
CN (1) | CN101448813A (ja) |
WO (1) | WO2007132893A1 (ja) |
Cited By (6)
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US8729279B2 (en) | 2010-03-03 | 2014-05-20 | Erina Co., Inc. | Agent for promoting osteoblast differentiation, pharmaceutical composition for promoting bone formation, and food for special dietary use containing auraptene analog as active ingredient |
KR101491493B1 (ko) | 2013-04-04 | 2015-02-09 | 한국식품연구원 | 감귤 과피 및 구아바 추출물을 포함하는 항염증 약학 조성물 |
KR101491492B1 (ko) | 2013-04-04 | 2015-02-09 | 한국식품연구원 | 항염증 활성 증진을 위한 팔삭 과피의 추출방법 |
WO2017043612A1 (ja) * | 2015-09-10 | 2017-03-16 | 株式会社Lttバイオファーマ | ドライアイ改善剤 |
WO2019065718A1 (ja) * | 2017-09-26 | 2019-04-04 | 学校法人東洋大学 | 熱中症の予防、軽減及び/又は治療のための組成物 |
JP2019131488A (ja) * | 2018-01-29 | 2019-08-08 | 静岡県公立大学法人 | Vcam−1発現抑制剤、mcp−1発現抑制剤、炎症性疾患改善用組成物、加工食品又は飲料 |
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KR101416191B1 (ko) | 2012-01-19 | 2014-07-08 | 경희대학교 산학협력단 | 제주 재래 감귤인 팔삭, 당유자 또는 이예감 추출물을 유효성분으로 함유하는 암 예방 또는 치료용 약학조성물 |
KR101643347B1 (ko) * | 2015-03-25 | 2016-07-28 | 충남대학교산학협력단 | 아우랍텐을 포함하는 신장암의 예방 또는 치료용 조성물 |
WO2024108386A1 (zh) * | 2022-11-22 | 2024-05-30 | 中国科学院深圳先进技术研究院 | 抗mcp1中和抗体在制备治疗神经退行性疾病引起的系统性炎症药物中的应用 |
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Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8729279B2 (en) | 2010-03-03 | 2014-05-20 | Erina Co., Inc. | Agent for promoting osteoblast differentiation, pharmaceutical composition for promoting bone formation, and food for special dietary use containing auraptene analog as active ingredient |
KR101491493B1 (ko) | 2013-04-04 | 2015-02-09 | 한국식품연구원 | 감귤 과피 및 구아바 추출물을 포함하는 항염증 약학 조성물 |
KR101491492B1 (ko) | 2013-04-04 | 2015-02-09 | 한국식품연구원 | 항염증 활성 증진을 위한 팔삭 과피의 추출방법 |
WO2017043612A1 (ja) * | 2015-09-10 | 2017-03-16 | 株式会社Lttバイオファーマ | ドライアイ改善剤 |
WO2019065718A1 (ja) * | 2017-09-26 | 2019-04-04 | 学校法人東洋大学 | 熱中症の予防、軽減及び/又は治療のための組成物 |
JP6557893B1 (ja) * | 2017-09-26 | 2019-08-14 | 学校法人 東洋大学 | 熱中症の予防、軽減及び/又は治療のための組成物 |
JP2019131488A (ja) * | 2018-01-29 | 2019-08-08 | 静岡県公立大学法人 | Vcam−1発現抑制剤、mcp−1発現抑制剤、炎症性疾患改善用組成物、加工食品又は飲料 |
Also Published As
Publication number | Publication date |
---|---|
EP2019098A4 (en) | 2012-10-31 |
EP2019098A1 (en) | 2009-01-28 |
JPWO2007132893A1 (ja) | 2009-09-24 |
US20090118361A1 (en) | 2009-05-07 |
CN101448813A (zh) | 2009-06-03 |
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