Pharmaceutical composition and food composition for enhancing expression of WD and tetratricopeptide repeats 1 gene

Abstract

To provide a pharmaceutical composition for enhancing the expression of the WD and tetratricopeptide repeats 1 gene and a food composition for enhancing the expression of the WD and tetratricopeptide repeats 1 gene.SOLUTION: The present invention provides a pharmaceutical composition for enhancing the expression of the WD and tetratricopeptide repeats 1 gene and a food composition for enhancing the expression of the WD and tetratricopeptide repeats 1 gene, containing 5-acetyl-1-benzylpyrrolidine-2-one as an active ingredient.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a pharmaceutical composition and a food composition for enhancing the expression of the WD and tetratricopeptide repeats 1 (hereinafter simply referred to as "WDTC1") gene. [Background technology]

[0002] 5-Acetyl-1-benzylpyrrolidin-2-one, the active ingredient of the pharmaceutical composition and food composition of the present invention, is a compound in which an acetyl group is attached to the carbon at the 5-position of pyrrolidine, a benzyl group is attached to the nitrogen at the 1-position, and an oxygen double bond is attached to the carbon at the 2-position.

[0003] This 5-acetyl-1-benzylpyrrolidin-2-one is suggested as an example of a synthetic compound in the following Non-Patent Document 1, but its existence is merely suggested, and no specific attributes are disclosed or suggested.

[0004] Furthermore, as shown in the following Patent Documents 1 to 5, the present inventors have already discovered that 5-acetyl-1-benzylpyrrolidin-2-one has PDE5 inhibitory effects, estradiol production promoting effects, muscle hypertrophy promoting effects, xanthine oxidase inhibitory effects, and 5-aminolevulinic acid production promoting effects, but have not discovered its effect of enhancing the expression of the WDTC1 gene. [Prior art documents] [Non-patent literature]

[0005] [Non-Patent Document 1] DESKUS, et al., "SYNTHESIS OF 5S-(1-OXOALKYL AND ARYL)-2-PYRROLIDINONE DERIVATIVES", SYNTHETIC COMMUNICATIONS, USA, Marcel Dekker, Inc., May 1998, Vol. 28, No. 9, pp. 1649-1659 [Patent documents]

[0006] [Patent Document 1] Patent No. 6537689 [Patent Document 2] Patent No. 6578046 [Patent Document 3] Patent No. 6962630 [Patent Document 4] Patent No. 7134541 [Patent Document 5] Patent No. 7253301 Summary of the Invention [Problem to be solved by the invention]

[0007] As mentioned above, there is no literature that discloses or suggests that 5-acetyl-1-benzylpyrrolidin-2-one has the effect of enhancing the expression of the WDTC1 gene. [Means for solving the problem]

[0008] As a result of intensive research, the present inventors have found that 5-acetyl-1-benzylpyrrolidin-2-one has the effect of enhancing the expression of the WDTC1 gene, and have thus completed the present invention.

[0009] That is, the present invention relates to a pharmaceutical composition or a food composition for enhancing the expression of the WDTC1 gene, which comprises 5-acetyl-1-benzylpyrrolidin-2-one as an active ingredient. Effect of the Invention

[0010] The pharmaceutical composition and food composition for enhancing WDTC1 gene expression of the present invention enhance the expression of the WDTC1 gene, and as a result, are expected to have effects such as preventing and improving metabolic syndrome, enhancing insulin sensitivity, and improving energy metabolism. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0011] The present invention relates to a pharmaceutical composition for enhancing WDTC1 gene expression, comprising 5-acetyl-1-benzylpyrrolidin-2-one as an active ingredient. The pharmaceutical composition according to the present invention contributes to the prevention and improvement of metabolic syndrome, enhancement of insulin sensitivity, and improvement of energy metabolism by enhancing the expression of the WDTC1 gene.

[0012] 5-acetyl-1-benzylpyrrolidin-2-one is a compound in which an acetyl group is attached to the carbon at the 5th position of pyrrolidine, a benzyl group is attached to the nitrogen at the 1st position, and an oxygen double bond is attached to the carbon at the 2nd position. The structural formula is shown in Chemical formula 1 below. The molecular formula is C 13 H 15 NO 2 It is.

[0013] [ka]

[0014] The WDTC1 gene is a gene that encodes WDTC1 and is the human ortholog of the Adipose gene, which is known as the adipose gene. It is known that overexpression of WDTC1 suppresses fat accumulation and reduces body weight, enhances insulin sensitivity, and improves energy metabolism.

[0015] The pharmaceutical composition of the present invention enhances the expression of this WDTC1 gene, thereby contributing to the prevention and amelioration of metabolic syndrome, enhancement of insulin sensitivity, improvement of energy metabolism, and the like.

[0016] The pharmaceutical composition according to the present invention can be used as a drug or quasi-drug and can be in various forms. These drugs or quasi-drugs can be in dosage forms suitable for oral administration, such as powders, pills, tablets (e.g., coated tablets, sugar-coated tablets, chewable tablets, etc.), capsules (e.g., hard or soft gelatin capsules, etc.), granules, and oral liquids (e.g., emulsions, suspensions, syrups, etc.).

[0017] In addition, the compound may be in a dosage form suitable for rectal administration such as a suppository; a dosage form suitable for intravascular administration such as an injection or infusion, intramuscular administration, subcutaneous administration or intradermal administration such as an ointment, cream, gel, or liquid (including eye drops, eyewash, etc.); i.e., a dosage form suitable for parenteral administration, but oral administration is preferred.

[0018] When the pharmaceutical composition of the present invention is used in the form of tablets, granules, capsules, or chewable tablets, known carriers such as tableting aids, granule processing aids, capsule processing aids, etc. can be used.

[0019] Examples of tableting aids include granulated sugar, white sugar, powdered sugar, reduced maltose syrup powder, lactose, glucose, pullulan, erythritol, starch, dextrin, and other sugars, crystalline cellulose, gum arabic, soybean curd, and other dietary fibers, corn protein, calcium phosphate, and other food calcium, food extracts, dried food powders, natural fruit juice powders, surfactants such as sucrose fatty acid esters, powdered oils and fats, glycerin, fatty acid esters, and other oils and fats, and various sweeteners, various acidulants, and various flavors used in chewable tablets, and shellac, corn protein, yeast cell walls, starch, reduced maltose syrup, sugarless sugar coating, maltitol, glycerin, sorbitol, HPMC, HPC, and the like, as coating materials. However, there are no particular limitations as long as the effects of the present invention are not impaired.

[0020] Furthermore, there are no particular limitations on the granule processing aid as long as it does not impair the effects of the present invention, and examples include all sugars such as granulated sugar, white sugar, powdered sugar, reduced maltose syrup powder, lactose, glucose, pullulan, erythritol, starch, dextrin, and the like, dietary fibers such as crystalline cellulose and gum arabic, corn protein, food calcium such as calcium phosphate, food extracts, dried food powders, natural fruit juice powders, and the like.

[0021] Furthermore, there are no particular limitations on the capsule processing aids as long as they do not impair the effects of the present invention. Examples of such aids include all sugars, such as granulated sugar, white sugar, powdered sugar, reduced maltose syrup powder, lactose, glucose, pullulan, erythritol, starch, dextrin, and other sugars, dietary fibers, such as crystalline cellulose and gum arabic, corn protein, food calcium, such as calcium phosphate, food extracts, dried food powders, and natural fruit juice powders, for preparing hard capsules, and content viscosity adjusters, such as edible oils and fats, beeswax, and glycerin fatty acid esters, for preparing soft capsules.

[0022] Tablets can usually be prepared using a tablet press, but they can also be made into chewable tablets by blending flavoring materials into the tablets, or the tablet surface can be coated using an automatic coating machine, a spray granulator, or a hand pan. Granules can be formed using various granulators, such as spray granulator type, kneading (extrusion) type, or high-speed agitator granulator type. Capsules can be prepared using capsule filling machines (hard and soft types) by mixing capsule assistants.

[0023] The present invention also relates to a food composition for enhancing WDTC1 gene expression, comprising 5-acetyl-1-benzylpyrrolidin-2-one as an active ingredient. The food composition according to the present invention is expected to have effects such as preventing and improving metabolic syndrome, enhancing insulin sensitivity, and improving energy metabolism by enhancing WDTC1 gene expression.

[0024] The food composition for enhancing WDTC1 gene expression of the present invention can be used as a food, beverage, or animal feed, for example, as a health food, functional food, food for specified health uses, beauty food, or nutritional supplement (supplement). These foods, beverages, and animal feeds may be in the form of known foods such as ice cream, jelly, candy, chocolate, and chewing gum, or drinking water such as tea and juice. They may also be in the form of liquids, powders, granules, capsules, tablets, or the like.

[0025] The intake amount of the pharmaceutical composition for enhancing WDTC1 gene expression and the food composition for enhancing WDTC1 gene expression according to the present invention is not particularly limited, and can be appropriately selected depending on the age, weight, symptoms, etc. of the user or patient or animal that takes the composition, and the dosage form. In addition, the intake period can be determined arbitrarily depending on the age and symptoms of the user or animal that takes the composition. EXAMPLES

[0026] Next, the present invention will be described in more detail with reference to examples. However, the present invention is not limited to the following examples as long as it does not depart from the gist of the present invention.

[0027] Measurement of WDTC1 gene expression using DNA microarray In this test, human adrenal cortex-derived cells H295R were cultured in the presence of 5-acetyl-1-benzylpyrrolidin-2-one, and then DNA microarray analysis was performed to confirm whether or not there was an effect of enhancing WDTC1 gene expression.

[0028] <Adrenal cortex-derived cells> Human adrenal cortical adenocarcinoma line (H295R) Obtained from American Type Culture Collection (ATCC).

[0029] Sample Preparation 1) 10 mg of 5-acetyl-1-benzylpyrrolidin-2-one was dissolved in 100 μL of DMSO, and the test substance was serially diluted with DMSO to a concentration of 50 mM. 2) The test substance was further diluted with cell culture medium to a concentration of 50 μM.

[0030] <method> Preparation of H295R cells 1) 2 x 10 H295R cells 5 The cells were seeded in a 6 cm dish at a concentration of 50 cells / mL, 5 mL at a time. 2) 24 hours after seeding, adhesion was confirmed, the cell culture medium was removed, and 5 mL of fresh cell culture medium containing the test substance (final concentration 50 μM) was added to each well. 3) After addition, the cells were cultured for 24 hours, the cell culture medium was removed, and the adherent cells were washed with PBS. The obtained cells were then used for RNA extraction and DNA microarray analysis as described below.

[0031] RNA Extraction 1) RNA was extracted from the cells obtained by the above cell preparation using RNAiso plus and purified using the RNeasy MinElute Cleanup Kit.

[0032] DNA microarray analysis 1) cDNA was synthesized from the RNA sample using the Low Input Quick Amp Labeling Kit (Agilent), and Cy3-labeled cRNA was synthesized and purified. 2) Using the Gene Expression Hybridization Kit (Agilent), each labeled cRNA was fragmented and applied to a Whole Human Genome Microarray Ver2.0 (Agilent), followed by hybridization at 65°C for 17 hours. 3) The array slide was washed using Gene Expression Wash Buffer 1 and 2 (Agilent). 4) Array images scanned with a microarray scanner (GenePix 4000B, Molecular Devices) were digitized using array analysis software GenePix Pro (Molecular Devices). Fluorescence intensity values ​​were normalized, and the ratio of the test substance group to the control was calculated.

[0033] <result> The expression of the WDTC1 gene was increased 1.51-fold in the presence of 5-acetyl-1-benzylpyrrolidin-2-one in adrenal cortex-derived cells (H295R). Therefore, 5-acetyl-1-benzylpyrrolidin-2-one enhances the expression of the WDTC1 gene.

Claims

1. A pharmaceutical composition for enhancing expression of WD and tetratricopeptide repeats 1 genes, comprising 5-acetyl-1-benzylpyrrolidin-2-one as an active ingredient.

2. A food composition for enhancing expression of WD and tetratricopeptide repeats 1 genes, comprising 5-acetyl-1-benzylpyrrolidin-2-one as an active ingredient.

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