Classifications

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Definitions

• the present invention relates to a composition for activating TGR5.
• the present invention also relates to a method for activating TGR5 and the like.
• TGR5 Transmembrane G protein-coupled receptor 5
• TGR5 Transmembrane G protein-coupled receptor 5
• Bile acids are known as in vivo ligands for TGR5. Bile acids in blood activate intracellular signals through binding to TGR5, and exert anti-obesity, hypoglycemic effects, and the like.
• Patent Document 1 describes that soybean saponin and the like have a TGR5 activating effect.
• Agonist compounds of the receptor are desired to be highly selective for the target receptor. This is because when the selectivity is low, it is easy to bind to a receptor other than the target, so that it is difficult to obtain a desired effect sufficiently, and side effects are likely to occur.
• TGR5 a substance having a TGR5 activating action and high selectivity for TGR5 is required. In Patent Document 1, the selectivity of the TGR5 activator to TGR5 has not been examined.
• soyasapogenols have a TGR5 activating effect and are highly selective for TGR5.
• the present invention is not limited to this, but the present invention relates to the following TGR5 activation composition and the like.
• a composition for activating TGR5 containing at least one of soyasapogenols as an active ingredient.
• the TGR5 activation composition according to the above [1] or [2] which is a food or drink, a cosmetic or a quasi drug.
• the present invention provides a composition for activating TGR5 or the like, which contains a substance having a TGR5 activating action and high selectivity for TGR5 as an active ingredient.
• the composition for activating TGR5 of the present invention has a TGR5 activating effect and is highly selective for TGR5 by containing one or more of soyasapogenols as an active ingredient.
• the soyasapogenols used in the present invention are components that have been ingested as foods and drinks for a long time, and are also advantageous in that they are highly safe and can be continuously ingested. Further, according to the present invention, it is possible to provide a method for activating TGR5 using a substance having high selectivity for TGR5.
• the composition for activating TGR5 of the present invention contains one or more of soyasapogenols as an active ingredient.
• the TGR5 Transmembrane G protein-coupled receptor 5
• the TGR5 is preferably a human TGR5 (hTGR5).
• Soyasapogenols (which can also be referred to as soyasapogenol compounds) have an action (agonist action) of activating TGR5.
• Soyasapogenols have the effect of activating TGR5 and increasing the intracellular cAMP concentration.
• Soya sapogenols are characterized by high selectivity for TGR5.
• Soyasapogenols are compounds contained in legumes such as soybean (scientific name: Glycine max). Soyasapogenols are a type of triterpenoid. In the present invention, as one or more kinds of soyasapogenol, only one kind of compound may be used, or two or more kinds of compounds may be used. In one aspect, the composition for activating TGR5 of the present invention may contain only one or more of soyasapogenols as an active ingredient.
• soyasapogenols examples include soyasapogenol A, soyasapogenol B, soyasapogenol C and the like.
• soyasapogenols soyasapogenol A and / or soyasapogenol B is preferable.
• Soyasapogenol B is preferable from the viewpoint of high selectivity for TGR5.
• Soyasapogenol A and Soyasapogenol B are used as the Soyasapogenols
• their ratios are not particularly limited.
• Soyasapogenol A: Soyasapogenol B (weight ratio) may be, for example, 1:99 to 99: 1, 10:90 to 90:10 or 10:90 to 30:70.
• Soybeans particularly soybean seeds (soybeans)
• azuki beans particularly soybean seeds (soybeans)
• Vigna angularis particularly azuki seeds (red beans)
• kudzu roots etc.
• Soyasapogenols can be extracted and purified from these plants by a known method to prepare them.
• Soyasapogenols can also be obtained by hydrolyzing soyasaponins by a known method.
• Commercially available products can also be used as soyasapogenols.
• a plant-derived raw material containing abundantly one or more of soyasapogenols may be contained in the composition of the present invention as long as the effects of the present invention are exhibited.
• plant-derived raw materials rich in one or more soyasapogenols include soybean seeds raw or dried by freeze-drying, and soybean seeds extracted with hot water or an organic solvent (extract). Can be used after concentrating or freeze-drying the soybean, or by purifying the dried product of the extract with a column or the like and purifying soybean sapogenols to a high degree.
• a commercially available one may be used, or a plant such as soybean may be prepared by a known method.
• the intracellular cyclic AMP (cAMP) concentration increases. Through this increase in cAMP concentration, transcription of the target gene is activated and various actions are exerted. Activation of TGR5 can be confirmed by evaluation of activity by a reporter assay and analysis of gene expression downstream of the TGR5 signal.
• the TGR5 activation composition of the present invention can be used to increase intracellular cAMP concentration.
• TGR5 activation suppressed alcoholic fatty liver (Iracheta-Verve A et al., Hepatol Commun. 2018 Oct 15; 2 (11): 1379-1391).
• the composition for activating TGR5 of the present invention can be expected to exert the above-mentioned actions by activating TGR5.
• Soyasapogenols suppress, maintain, recover or increase muscle mass, suppress muscle loss, maintain, recover or improve, improve motor function, improve endurance, suppress fatigue, suppress locomotive syndrome and sarcopenia through activation of TGR5.
• TGR5 to exert effects such as prevention or improvement of obesity, hypoglycemia, promotion of heat production, improvement of energy metabolism, enhancement of gastrointestinal motility, prevention or improvement of alcoholic fatty liver, prevention or improvement of metabolic syndrome, etc.
• the composition for activating TGR5 of the present invention can be used, for example, to obtain the above-mentioned effects by activating TGR5.
• the TGR5 activating composition of the present invention is, for example, for suppressing, maintaining, recovering or increasing muscle mass; for suppressing, maintaining, recovering or improving muscle strength; for improving motor function or endurance. It can be used for improvement and the like.
• the TGR5 activation composition of the present invention comprises, for example, fatigue suppression, prevention or amelioration of locomotive syndrome or sarcopenia, prevention or amelioration of obesity, hypoglycemia, promotion of heat production, improvement of energy metabolism, gastrointestinal motility. It can be used for enhancement, prevention or improvement of alcoholic fatty liver, prevention or improvement of metabolic syndrome, and the like.
• prevention includes preventing the onset, delaying the onset, reducing the onset rate, reducing the risk of onset, and the like.
• Improvement of a condition or disease is to recover the subject from the condition or disease, reduce the symptoms of the condition or disease, improve the symptoms of the condition or disease, delay the progression of the condition or disease, or prevent it. Etc. are included.
• composition for activating TGR5 of the present invention can be applied to either therapeutic use (medical use) or non-therapeutic use (non-medical use).
• the composition for activating TGR5 of the present invention can be provided, for example, in the form of foods and drinks, cosmetics, pharmaceuticals, quasi-drugs, feeds, etc., but is not limited thereto.
• the composition for activating TGR5 of the present invention may itself be food or drink, cosmetics, pharmaceuticals, quasi-drugs, feeds, etc., and is a preparation or material of additives or the like used for these. May be good.
• the composition for activating TGR5 of the present invention can be provided in the form of an agent as an example, but is not limited to this form.
• the agent can be provided as it is as a composition or as a composition containing the agent.
• the TGR5 activation composition of the present invention may be an oral composition or a parenteral composition, but is preferably an oral composition.
• the oral composition include foods and drinks, oral medicines, quasi-drugs for oral use, and feeds, and foods and drinks are preferable.
• parenteral compositions include parenteral medicines, parenteral quasi-drugs, and cosmetics.
• composition for activating TGR5 of the present invention may contain any additive and any component in addition to the above-mentioned soyasapogenols, as long as the effects of the present invention are not impaired.
• additives and ingredients can be selected according to the form of the composition and the like, and generally, those that can be used for foods and drinks, cosmetics, pharmaceuticals, quasi-drugs, feeds and the like can be used. Any additive or component may be used alone or in combination of two or more.
• various amino acids such as branched chain amino acids (valine, leucine, isoleucine, etc.) and salts thereof; metabolites of amino acids (eg, ⁇ -hydroxy- ⁇ -methylbutyric acid (HMB, etc.)) and their salts. Salts (HMBCa, etc.); Milk-derived proteins (casein protein, whey protein, etc.), soybean-derived proteins, rice-derived proteins, fish meat-derived proteins, wheat-derived proteins, pea-derived proteins, collagen and other proteins; imidazole peptides, milk peptides, etc.
• branched chain amino acids valine, leucine, isoleucine, etc.
• metabolites of amino acids eg, ⁇ -hydroxy- ⁇ -methylbutyric acid (HMB, etc.)
• Salts HMBCa, etc.
• Milk-derived proteins casein protein, whey protein, etc.
• soybean-derived proteins soybean-derived proteins, rice-derived proteins, fish meat-derived proteins, wheat-derived proteins, pe
• Peptides such as soybean peptide and collagen peptide; mucopolysaccharide such as chondroitin sulfate and its salt, proteoglycan and its salt or shark cartilage extract containing these; vitamin D, vitamin B1, vitamin B6, vitamin B12, vitamin E, vitamin C and the like. Vitamins; Minerals such as calcium and magnesium; quercetin and its glycosides, procyanidin, Amakusa-derived polyphenols, walnut polyphenols, grape seed polyphenols, glucosamine and its salts, creatin, folic acid, citric acid, ⁇ -orizanol, etc. Be done.
• excipients as an example of any additive or ingredient, excipients, binders, emulsifiers, tonicity agents (isotonic agents), buffers, solubilizers, preservatives, stabilizers to be added in the formulation. , Antioxidants, colorants, coagulants, coating agents, fragrances and the like.
• a component that can be used in the food or drink for example, a food or drink material such as the above-mentioned optional component, if necessary, is used for one or more of soyasapogenols. Additives, etc.
• Foods and drinks are not particularly limited, and examples thereof include general foods and drinks, health foods, foods with functional claims, foods for specified health use, foods and drinks for the sick, food additives, dietary supplements, and raw materials thereof. ..
• the form of the food or drink is not particularly limited, and examples thereof include solid, semi-fluid, and fluid.
• Foods and drinks are oral solid preparations such as tablets, coated tablets, fine granules, granules, powders, pills, capsules, dry syrups and chewables; various forms of oral liquid preparations such as oral liquids and syrups. It can also be.
• TGR5 activation composition of the present invention When used as a cosmetic, a carrier, an additive or the like acceptable for the cosmetic can be blended with one or more of soyasapogenols.
• the product form of the cosmetic is not particularly limited.
• composition for activating TGR5 of the present invention When the composition for activating TGR5 of the present invention is used as a drug or a quasi-drug, various dosage forms of a drug or a drug or a quasi-drug may be prepared by blending one or more of soyasapogenols with a pharmacologically acceptable excipient or the like. It can be a quasi drug.
• the administration form of the drug or quasi-drug may be oral administration or parenteral administration. From the viewpoint of obtaining the effects of the present invention more sufficiently, the administration form is preferably oral administration.
• the dosage form may be a dosage form suitable for administration.
• an oral solid preparation such as a tablet, a coated tablet, a fine granule, a granule, a powder, a pill, a capsule, a dry syrup, or a chewable agent
• Oral liquid preparations such as syrups.
• Dosage forms of parenteral medicines or parenteral medicines include injections, infusions, ointments, lotions, patches, suppositories, nasal preparations, transpulmonary agents (inhalants), and the like. ..
• the drug may be a non-human veterinary drug.
• composition for activating TGR5 of the present invention When used as a feed, one or more of soyasapogenols may be mixed with components that can be used in the feed to prepare the feed.
• the feed include livestock feed used for cattle, pigs, chickens, sheep, horses, etc .; small animal feed used for rabbits, guinea pigs, rats, mice, etc .; pet food used for dogs, cats, small birds, etc. ..
• the production method thereof is not particularly limited, and one or more of soyasapogenols are generally used. It can be manufactured by a conventional method.
• a purified compound may be used as the soyasapogenols, or a plant-derived raw material rich in one or more of the above-mentioned soyasapogenols may be used. .. Soyasapogenols may be contained in the composition in the form of a plant-derived raw material containing the compound.
• TGR5 activation composition of the present invention one or two or more of the intended use, the type of active ingredient, the above-mentioned effect, the method of use (for example, ingestion method, administration method), etc. are indicated on the packaging, container, instruction manual, etc. You may.
• the composition for activating TGR5 of the present invention may be labeled as having a TGR5 activating action or an action based on this action.
• the TGR5 activation composition of the present invention includes, for example, “muscle loss suppression”, “muscle maintenance”, “muscle gain”, “muscle improvement”, “muscle weakness suppression”, “muscle strength maintenance”, “Increase muscle strength”, “Improve muscle strength”, “Support muscle building power”, “Improve walking function”, “Maintain walking function”, “Improve motor function”, “Maintain motor function”, “Decrease with aging”
• One or two or more indications such as “maintenance of muscle” and “maintenance of muscle strength that declines with aging” may be attached.
• the TGR5 activation composition of the present invention includes, for example, "anti-obesity”, “prevention of obesity”, “improvement of obesity”, “reduction of waist circumference”, “maintenance of waist circumference”. , “Maintaining a slim body”, “Suppressing the accumulation of body fat”, “Reducing body fat”, “Suppressing the accumulation of visceral fat”, “Reducing visceral fat”, “Suppressing the accumulation of fat in the liver” , “Reducing fat in the liver", “Weight loss”, “Weight loss”, “Diet”, “Adipose burning”, “Adipose consumption”, “Lipid metabolism”, “Military function", “Thermal production”, " One or two or more functions such as “basic metabolism”, “metabolic function”, “metabolic power”, “prevention of metabolic syndrome", and “improvement of metabolic syndrome” may be indicated.
• the TGR5 activation composition of the present invention includes, for example, “suppressing the rise in blood glucose level after meals”, “moderating the rise in blood glucose level after meals”, and “lowering the blood glucose level after meals”. , “For those who are concerned about blood sugar level”, “For those who are concerned about blood sugar level after meals”, “Improving the constitution that blood sugar level tends to rise”, etc. May be good.
• the content of soyasapogenols in the TGR5 activation composition of the present invention can be appropriately set according to the form of the composition and the like.
• the total content of soyasapogenols may be 0.0001 to 95% by weight, 0.001 to 90% by weight or 0.01 to 90% by weight in the composition.
• the total content of soyasapogenols is 0.01 weight by weight in the composition. % Or more is preferable, 0.2% by weight or more is more preferable, 20% by weight or less is preferable, and 10% by weight or less is more preferable.
• the total content of soyasapogenols is preferably 0.01 to 20% by weight, more preferably 0.2 to 10% by weight in the TGR5 activation composition of the present invention.
• the total content is the total amount of two or more soyasapogenol compounds when they are contained.
• the content of soyasapogenols can be measured according to a known method, and for example, an HPLC method or the like can be used.
• the composition for activating TGR5 of the present invention can be ingested or administered by an appropriate method according to its form.
• the composition for activating TGR5 of the present invention is preferably orally administered or orally ingested.
• the ingestion amount (which can also be referred to as the dose) of the TGR5 activation composition of the present invention is not particularly limited, and may be an amount (effective amount) that can obtain the TGR5 activation effect, and the administration form and administration method. , It may be set appropriately according to the weight and the like.
• the total intake of soyasapogenols is preferably 5 mg or more, more preferably 10 mg or more, further preferably 20 mg or more, and 500 mg per day.
• the following is preferable, 200 mg or less is more preferable, and 100 mg or less is further preferable.
• the total intake of soyasapogenols is preferably 5 to 500 mg, more preferably 10 to 200 mg, and further 20 to 100 mg per day. preferable. It is preferable that the above amount is orally administered or ingested, for example, once a day or divided into 2 to 3 times.
• composition for activating TGR5 of the present invention When the composition for activating TGR5 of the present invention is ingested for the purpose of obtaining the TGR5 activating effect in humans (adults), the total intake of soyasapogenols is within the above range per 60 kg of body weight per day. As such, it is preferred that the composition of the present invention be orally ingested or administered to a subject.
• the TGR5 activation composition of the present invention contains, in consideration of its form, administration method, etc., an amount such that the desired effect of the present invention can be obtained, that is, an effective amount of the above-mentioned soyasapogenols. Is preferable.
• the TGR5 activation composition of the present invention is an oral composition such as a food or drink, an oral drug, etc., during the intake of the composition per 60 kg of body weight per adult per day.
• the total content of soyasapogenols is preferably 5 to 500 mg, more preferably 10 to 200 mg, still more preferably 20 to 100 mg.
• the subject to which the composition for activating TGR5 of the present invention is administered or ingested is preferably a mammal (human or non-human mammal), and more preferably a human.
• an administration target in the present invention a target that requires or desires TGR5 activation is preferable.
• the subject to be administered in the present invention is a subject who needs or desires to suppress, maintain or recover muscle mass; a subject who needs or desires to suppress, maintain or improve muscle strength. There are also subjects who need or desire to improve their motor function or endurance.
• the present invention also includes the following method of activating TGR5, use for activating TGR5.
• the above method may be a therapeutic method or a non-therapeutic method.
• the above uses may be therapeutic or non-therapeutic.
• TGR5 can be activated in the subject.
• Soyasapogenols can be used to activate TGR5 in a subject.
• an amount of soyasapogenols that can obtain a desired effect (which can also be called an effective amount) may be used.
• soyasapogenols are the same as those of the above-mentioned composition for activating TGR5.
• Soyasapogenols may be administered as they are, or may be administered as a composition containing the same.
• the composition for activating TGR5 of the present invention described above may be administered.
• the present invention also includes the use of one or more soyasapogenols for producing a composition for activating TGR5.
• the composition for activating TGR5 and a preferred embodiment thereof are the same as described above. All academic and patent documents described herein are incorporated herein by reference.
• Example 1 The TGR5 activating effect of the test substance was evaluated by a luciferase assay.
• This evaluation system determines the activation of human TGR5 (hTGR5) by transcriptional activation of cAMP response element binding protein (CREB), which is a signal downstream of TGR5.
• CREB cAMP response element binding protein
• hTGR5 in addition to the cells forcibly expressing hTGR5 (also referred to as hTGR5 forcible expression cells), a glucagon-like peptide which is a G protein-coupled receptor like hTGR5- A luciferase assay was performed on cells in which 1 (GLP-1) receptor (GLP1R) was forcibly expressed in place of hTGR5 (also referred to as hGLP1R forcible expression cells). The hGLP1R forced expression cells do not express hTGR5. Both GLP1R and TGR5 are G protein-coupled receptors, and when GLP1R is activated, intracellular cAMP increases.
• the luciferase activity is increased in the cells forcibly expressing hTGR5 by the addition of the test substance, it is judged that the substance has a TGR5 activating effect. Further, when the test substance was added to the hTGR5 forced expression cells and the hGLP1R forced expression cells, the greater the increase in luciferase activity in the hTGR5 forced expression cells with respect to the increase in the luciferase activity in the hGLP1R forced expression cells, the more the test substance became TGR5. It can be said that the selectivity is high.
• the hTGR expression vector (pTGR5) was prepared by the following procedure. As the base sequence of the human-derived TGR5 gene, NM_001077191 was referred to, an artificial gene encoding human TGR5 was designed, and DNA was synthesized.
• the hTGR expression vector (plasmid) was obtained by inserting the synthesized DNA into the eukaryotic expression vector pcDNA3.1 (+) (Invitrogen®, Thermo Fisher Scientific) using the cloning sites BamHI and EcoRI of the vector. ) was prepared. The host of transformation is E.I. A plasmid was prepared using colli K12 (dam + dcm + tonA).
• the constructed hTGR expression vector was named pTGR5.
• CRE-reactive luciferase expression vector pCRE / Luc
• pGL4.29 [luc2P / CRE / Hygro] manufactured by Promega Co., Ltd. was used.
• This plasmid is a vector carrying a luciferase gene linked to cAMP response element (CRE).
• the purified plasmid is treated with multiple restriction enzymes together with the plasmid used for transformation, and the enzyme-treated fragments are compared by electrophoresis and the same pattern is confirmed, so that the purified plasmid is different from the original vector. It was confirmed that the same structure was maintained (results not shown). In the following experiments, the plasmid purified above was used.
• DMEM High-glucose
• PBS Phosphate Buffered Salts
• HEK293 cells human fetal kidney cell line, ATCC: CRL-2828
• FBS fetal bovine serum
• the medium was removed and the cells were washed with 10 mL of PBS ( ⁇ ) solution.
• Add 1 mL of trypsin solution (0.25% trypsin-EDTA (Nacalitesk Co., Ltd.) diluted 10-fold with PBS solution) to the cells, leave for about 30 seconds, peel off the cells, and then add 10 mL of medium.
• the cells were collected.
• the collected cells were transferred to a 50 mL centrifuge tube and centrifuged at room temperature 1000 rpm for 3 minutes.
• the obtained pellets were loosened with 2 mL of medium, a part thereof was diluted 10-fold with 0.2% trypan blue, and the number of cells was counted using a hemocytometer.
• an incubator 37 ° C., 5% CO 2
• the plasmid was introduced into HEK293 cells according to the following procedure. Take 45 ⁇ L of X-tremeGENE (registered trademark) (Roche) in a 1.5 mL tube, add 705 ⁇ L of OptiMEM (registered trademark) I Reduced Serum Medium (Thermo Fisher Scientific) at room temperature, mix immediately, and mix the solution twice. Was spun down to obtain an X-tremeGENE diluent.
• X-tremeGENE registered trademark
• OptiMEM registered trademark
• I Reduced Serum Medium Thermo Fisher Scientific
• plasmid hTGR5 expression vector (pTGR) (5 ⁇ g) and CRE-reactive luciferase expression vector (pCRE / Luc) (5 ⁇ g)
• pTGR hTGR5 expression vector
• pCRE / Luc CRE-reactive luciferase expression vector
• the collected cells were transferred to a 50 mL centrifuge tube and centrifuged at room temperature 1000 rpm for 3 minutes. The obtained pellets were loosened with 2 mL of medium, a part thereof was diluted 10-fold with 0.2% trypan blue, and the number of cells was counted using a hemocytometer.
• Cells were suspended in seed medium (DMEM (FBS-free, penicillin / streptomycin (Fujifilm Wako Pure Chemical Industries, Ltd.) included)), and 96-well white clear plate (Corning, Corning 96-well white transparent bottom) at 75 ⁇ L / well.
• Flat-bottom cell culture surface-treated polystyrene microplate was seeded and cultured in an incubator (37 ° C., 5% CO 2 ) to obtain hTGR forced expression cells.
• hGLP1 forced expression cells A vector expressing the human GLP1 receptor (hGLP1R) gene was introduced into HEK293 cells to prepare cells in which hGLP1R was forcibly expressed.
• GLP1R NM_002062
• ORIGENE Human United Clone
• the hGLP1R expression vector was introduced into HEK293 cells in the same manner as above except that the above hGLP1R expression vector was used instead of the hTGR5 expression vector (pSTW01) to obtain hGLP1R forced expression cells.
• Soyasapogenol A and Soyasapogenol B were used as the test substance.
• soybean saponin (Saponin B-50 manufactured by J-Oil Mills Co., Ltd.) was used. Soyasapogenol A and Soyasapogenol B were prepared by the following methods. A 20-fold amount of saponin B-50 (manufactured by J-Oil Mills Co., Ltd.) was reacted with a 2N hydrochloric acid aqueous solution at 100 ° C. for 2 hours to cleave the sugar chain of saponin. After completion of the reaction, the reaction solution was cooled to room temperature and neutralized with an aqueous sodium hydroxide solution.
• the reaction solution was suction-filtered, and the residue was washed with a large amount of distilled water and suction-filtered repeatedly. It was confirmed that there was no residual sodium hydroxide, and the mixture was dried. Total) was obtained.
• This crude soyasapogenol fraction was further purified by column chromatography using a mixed solution of silica gel, hexane and ethyl acetate to obtain soyasapogenol A (purity 99% or more) and soyasapogenol B (purity 99% or more), respectively. The obtained soyasapogenol A and soyasapogenol B were used.
• test substance was added (final concentration: 20 ⁇ g / mL), and the cells were further cultured for 5 hours.
• the test substance (soyasapogenol A, soyasapogenol B or soybean saponin) was dissolved in dimethyl sulfoxide (DMSO) and added.
• DMSO dimethyl sulfoxide
• Dual-Glo Luciferase Assay Reagent attached to the Dual-Glo® Luciferase Assay System (Promega) at 75 ⁇ L / well, and incubate at room temperature for 10 minutes, and then incubate at room temperature for 10 minutes.
• the emission intensity was measured using DEVICES).
• the luminescence intensity was defined as luciferase activity.
• sea shiitake luciferase is used as an internal standard.
• lithocholic acid (Tokyo Chemical Industry Co., Ltd.) was dissolved in DMSO as a positive control and added to hTGR5 forced expression cells and hGLP1R forced expression cells (final concentration 3.3 ⁇ M), and the luminescence intensity was increased by the above method.
• DMSO DMSO
• Taurolithoholic Acid Sodium Salt (Fujifilm Wako Pure Chemical Industries, Ltd.) was lysed in DMSO and added to hTGR5 compulsory expression cells and hGLP1R compulsory expression cells (final concentration 3.3 ⁇ M) by the above method. The emission intensity was measured. It was confirmed that in the hTGR5 forced expression cells and the hGLP1R forced expression cells, the luminescence intensity was stronger as compared with the negative control (DMSO) when either positive control was added.
• DMSO negative control
• TGR5 activation action The hTGR5 forced expression cells supplemented with soyasapogenol A, soyasapogenol B or soybean saponin all had significantly stronger luminescence intensity than the negative control, indicating that soyasapogenol A, soyasapogenol B and soybean saponin had an hTGR5 activating effect.
• the ratio of the luminescence intensity of the hTGR5 forced expression cells to which the test substance was added when the luminescence intensity of the negative control to which DMSO was added to the hTGR5 forced expression cells was set to 1 (the luminescence intensity of the cells to which the test substance was added / the emission of the negative control). Intensity) was defined as luciferase activity (Luc-hTGR5) in hTGR5 forced expression cells to which the test substance was added.
• the ratio of the luminescence intensity of the hGLP1R forced expression cells to which the test substance was added when the luminescence intensity of the negative control to which DMSO was added to the hGLP1R forced expression cells was set to 1 (the luminescence intensity of the cells to which the test substance was added / the emission of the negative control). Intensity) was defined as luciferase activity (Luc-hGLP1R) in hGLP1R forced expression cells to which the test substance was added.
• the ratio of the luciferase activity (Luc-hTGR5) in the hTGR5 forced expression cells to the luciferase activity (Luc-hGLP1R) in the hGLP1R forced expression cells to which the test substance was added (Luc-hTGR5 / It was evaluated by Luc-hGLP1R).
• Table 1 shows the ratio (Luc-hTGR5 / Luc-hGLP1R) of the luciferase activity (Luc-hTGR5) in the hTGR5 forced expression cells to the luciferase activity (Luc-hGLP1R) in the hGLP1R forced expression cells to which the test substance was added.
• Soyasapogenol A and Soyasapogenol B have a TGR5 activating effect.
• the ratio of luciferase activity (Luc-hTGR5 / Luc-hGLP1R) was significantly higher in soyasapogenol A and soyasapogenol B than in soybean saponin. Therefore, it was shown that soyasapogenol A and soyasapogenol B have higher selectivity for hTGR5 than soybean saponin.
• a formulation example for preparing the composition for activating TGR5 of the present invention is shown, but the present invention is not limited thereto.
• the soyasapogenol for example, a mixture of soyasapogenol A and soyasapogenol B, soyasapogenol A or soyasapogenol B and the like can be used.
• a mixture of Soyasapogenol A and Soyasapogenol B for example, a mixture having a weight ratio of Soyasapogenol A: Soyasapogenol B of 1: 99 to 99: 1 can be used.
• the following formulation example is an example, and it is possible to use another protein in place of the following protein, for example. Similarly, other peptides, amino acids, etc. can be used for the following peptides, amino acids, etc.
• ⁇ Prescription example 4> Drink DL-sodium tartrate 0.10 g Succinic acid 0.01g Liquid sugar 800.00g Citric acid 12.00g Vitamin C 10.00g Soyasa Pogenol 0.50g Collagen 40.00g Cyclodextrin 5.00g Emulsifier 5.00g Fragrance 15.00g Potassium chloride 1.00g Magnesium sulfate 0.50g Mix the above ingredients and add water to make 1 liter. Drink 100 mL or more of this drink at a time.

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• 2020
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