Agent for inhibiting inflammation in glycated cells

The use of bilberry extract and Rosa multiflora var. cathayensis extract in a composition that inhibits NFκB nuclear translocation addresses the challenge of suppressing glycated cell inflammation, effectively reducing inflammatory responses and cell damage.

JP2025089970APending Publication Date: 2025-06-16ROHTO PHARM CO LTD
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Patent Information

Application Number
JP2023204984
Authority / Receiving Office
JP · JP
Patent Type
Applications
Current Assignee / Owner
Filing Date
2023-12-04
Publication Date
2025-06-16

AI Technical Summary

Technical Problem

Current solutions for suppressing glycated cell inflammation, such as AGE degrading agents, have not been sufficiently studied and do not effectively address the mechanism by which advanced glycosylation end products (AGEs) promote inflammatory responses.

Method used

A composition containing bilberry extract and Rosa multiflora var. cathayensis extract, which inhibits the nuclear translocation of NFκB, thereby suppressing glycated cell inflammation.

Benefits of technology

The composition effectively suppresses glycated cell inflammation by preventing the nuclear translocation of NFκB, thereby reducing the expression of inflammatory cytokines and alleviating cell inflammation associated with aging.

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Abstract

To provide an agent for inhibiting inflammation in glycated cells.SOLUTION: The present invention provides an agent for inhibiting inflammation in glycated cells that comprises at least one selected from the group consisting of bilberry extract and Rosa roxburghii extract.SELECTED DRAWING: None
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Description

Technical Field

[0001] The present invention relates to an agent for suppressing glycated cell inflammation and a product for suppressing glycated cell inflammation.

Background Art

[0002] In the bodies of mammals including humans, it is known that cells cause inflammation due to various stimuli and invasions.

[0003] It is known that advanced glycosylation end products (AGEs) generated by glycation promote inflammation by binding to cytokines that induce inflammation. An AGE degrading agent containing jaboticaba extract (Patent Document 1) has been proposed for splitting AGEs, but it has not been sufficiently studied.

[0004] Although AGEs are known to activate the inflammatory response by stimulating the receptor RAGE, the mechanism by which it promotes the inflammatory response has not been clarified. Topical products and oral products that suppress cell inflammation caused by glycation are desired in order to suppress the decline in quality of life and live healthier for a longer time.

Prior Art Documents

Patent Documents

[0005]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0006] An object of the present invention is to provide an agent for suppressing glycated cell inflammation containing one or more selected from the group consisting of bilberry extract and Rosa multiflora var. cathayensis extract, and an inhibitor of nuclear translocation of NFκB.

Means for Solving the Problems

[0007] The inventors have surprisingly found that a composition containing one or more selected from the group consisting of bilberry extract and Rosa multiflora var. cathayensis extract suppresses the nuclear translocation of NFκB in glycated cells and has an inhibitory effect on glycated cell inflammation. The present invention is based on this finding and provides the following inventions.

[0008] [1] An inhibitor for glycated cell inflammation containing, as an active ingredient, one or more selected from the group consisting of bilberry extract and Rosa multiflora var. cathayensis extract. [2] The inhibitor for glycated cell inflammation according to [1], which suppresses inflammation by suppressing the nuclear translocation of NFκB. [3] An external composition for suppressing glycated cell inflammation containing, as an active ingredient, one or more selected from the group consisting of bilberry extract and Rosa multiflora var. cathayensis extract. [4] A food or drink composition for suppressing glycated cell inflammation containing, as an active ingredient, one or more selected from the group consisting of bilberry extract and Rosa multiflora var. cathayensis extract. [5] An inhibitor for suppressing the nuclear translocation of NFκB containing, as an active ingredient, one or more selected from the group consisting of bilberry extract and Rosa multiflora var. cathayensis extract. [Effect of the Invention]

[0009] Since the inhibitor for glycated cell inflammation of the present invention contains one or more selected from the group consisting of bilberry extract and Rosa multiflora var. cathayensis extract, it can suppress the inflammation of glycated cells. [Brief Description of the Drawings]

[0010]

Figure 1

[0011] Hereinafter, modes for carrying out the present invention will be described in detail. However, the present invention is not limited to the following embodiments.

[0012] 〔1. Agent for Inhibiting Glycated Cell Inflammation〕 The agent for inhibiting glycated cell inflammation according to this embodiment contains one or more selected from the group consisting of bilberry extract and rose leaf extract. Here, the "glycated cell" referred to in the agent for inhibiting glycated cell inflammation of the present invention means a cell in which a glycation phenomenon has occurred. The "inhibition of glycated cell inflammation" of the present invention means preventing inflammation in glycated cells and suppressing the exacerbation of inflammation.

[0013] Bilberry means a plant of the Ericaceae family. Any part of the bilberry can be used in the bilberry extract of the present invention, and one or more parts can be selected and used. In particular, the leaf extract is preferred. The extraction method and extraction solvent of bilberry are not particularly limited, and known techniques can be used. The extract may be used as it is, or a powder or granule obtained by drying the extract may be used, or a decomposition product obtained by treating the extract using known techniques such as enzymatic decomposition may be used. Commercially available products may also be used.

[0014] Rose leaf means the leaf of a plant belonging to the Rosaceae family. Any part of the rose leaf can be used in the rose leaf extract of the present invention, and one or more parts can be selected and used. In particular, the fruit extract is preferred. The extraction method and extraction solvent of rose leaf are not particularly limited, and known techniques can be used. The extract may be used as it is, or a powder or granule obtained by drying the extract may be used, or a decomposition product obtained by treating the extract using known techniques such as enzymatic decomposition may be used. Commercially available products may also be used.

[0015] When obtaining an extract of bilberry and / or rose leaf using a solvent, any commonly used solvent may be used. For example, an extract obtained by extracting with one or more polar solvents such as ethanol and water, a powder obtained by drying the extract, a pulverized product, extract, dried product, etc. of these, which are purified by column or distribution between solutions to enhance the active ingredient, etc. can be used. Commercially available products may also be used.

[0016] The glycated cell inflammation inhibitor of the present invention has an effect of suppressing inflammation of glycated cells, and effects such as suppressing inflammation of glycated cells are expected. In particular, an effect of suppressing cell inflammation caused by the binding of AGEs to RAGE, which is a receptor, is expected. NF-κB, which is a protein complex that acts as a transcription factor in the cell nucleus, increases the expression of inflammatory cytokines when it translocates into the cell nucleus. Therefore, the glycated cell inflammation inhibitor of the present invention is expected to have an effect of suppressing and / or improving cell inflammation by suppressing the nuclear translocation of NF-κB. Since the expression rate of RAGE increases in the subcutaneous layer with aging, an effect of preventing and / or improving cell inflammation associated with aging is expected.

[0017] The contents of the bilberry extract and the Rosa multiflora var. thomsonii extract in the glycated cell inflammation inhibitor according to the present embodiment are not particularly limited as long as they have an effect of suppressing glycated cell inflammation, and are appropriately set according to the types and contents of other formulation components, the formulation form of the glycated cell inflammation inhibitor, and the like. From the viewpoint of more significantly exhibiting the effects of the present invention, for example, it is preferably 0.00001 to 5 w / v%, more preferably 0.00002 to 3 w / v%, still more preferably 0.00005 to 1 w / v%, and particularly preferably 0.0001 to 1 w / v%. The dosage for human administration is preferably 0.001 to 2000 mg per day, more preferably 0.01 to 1000 mg, still more preferably 0.1 to 500 mg, and particularly preferably 1 to 300 mg.

[0018] The glycated cell inflammation inhibitor according to the present embodiment may further contain excipients, thickeners, binders, disintegrants, dispersants, surfactants, suspending agents, emulsifiers, stabilizers, gelling agents, sweeteners, acidulants, umami agents, salt agents, bitter agents, coloring agents, ultraviolet protectants, antioxidants, preservatives, antibacterial agents, pH adjusters, buffers, chelating agents, vitamins, fragrances, minerals and other additives, amino acids or their salts, saccharides, humectants, organic acids or their salts, dietary fibers, animal tissue extracts, etc. These can be appropriately selected from known ones and used, and can be produced using conventional methods.

[0019] The dosage form of the saccharified cell inflammation inhibitor according to this embodiment can be used without being limited to specific products, properties, etc., and can be appropriately prepared by known methods for any dosage form such as liquid, gel, cream, paste, solid, aerosol or patch. Examples of liquid dosage forms include lotion, emulsion, essence, oral liquid, syrup, etc. Examples of solid dosage forms include stick, tablet, chewable, granule, powder, capsule, ointment, etc. In terms of the administration form, although it can be either an external preparation or an internal preparation, from the viewpoint of achieving the effects of the present invention, it is preferably an external preparation. The external preparation is not limited, whether it is a pharmaceutical or a cosmetic. These can be manufactured using conventional methods.

[0020] [2. External preparation for inhibiting saccharified cell inflammation] The external preparation according to this embodiment has the function of inhibiting the inflammation of saccharified cells. Therefore, as one embodiment of the present invention, there is provided an external preparation for inhibiting saccharified cell inflammation containing one or more selected from the group consisting of bilberry extract and Rosa multiflora var. cathayensis extract.

[0021] In addition, regarding the content of one or more selected from the group consisting of bilberry extract and Rosa multiflora var. cathayensis extract in this embodiment, the types and contents of other components, the formulation form and uses of the external preparation, etc., are as described in [1. Saccharified cell inflammation inhibitor].

[0022] [3. Food and beverage products for inhibiting saccharified cell inflammation] The food and beverage products according to this embodiment have the function of inhibiting the inflammation of saccharified cells. Therefore, as one embodiment of the present invention, there is provided a food and beverage product for inhibiting saccharified cell inflammation containing one or more selected from the group consisting of bilberry extract and Rosa multiflora var. cathayensis extract.

[0023] In addition, regarding the content of one or more selected from the group consisting of bilberry extract and Rosa multiflora var. cathayensis extract in this embodiment, the types and contents of other components, the formulation form and uses of the external preparation, etc., are as described in [1. Saccharified cell inflammation inhibitor].

Examples

[0024] Hereinafter, the present invention will be specifically described based on test examples, but the present invention is not limited thereto. In addition, the blending amounts in the following test examples and the like indicate mass% unless otherwise specified. Note that the test conditions such as the culture conditions in each test example were made the same except for the difference in the plant extracts to be added, unless otherwise specified. Also, for each test, a control without adding the plant extract was provided to accurately evaluate the effect of the plant extract of the present invention.

[0025] 〔Test Example 1: Glycated Cell Inflammation Inhibition Test 1〕 The glycated cell inflammation inhibition test was conducted by the following method. After waking up normal human epidermal keratinocytes (NHEK: Normal Human Epidermal Keratinocytes, manufactured by Kurabo Industries Ltd.), they were seeded in a 75 cm 2 culture flask (manufactured by Corning) so as to be 187,500 cells / 15 mL, and cultured for 4 days under the conditions of 37 ° C and 5% CO2. Then, the cells were collected using 0.025% Trypsin-EDTA (manufactured by Kurabo Industries Ltd.). NHEK was seeded in a 96-well plate (manufactured by Corning) so as to be 12,000 cells / 0.2 mL / well. After 6 hours of seeding, 0.2 mL / well of bilberry extract and izayoi rose extract were added so that the final concentrations were each 0.01%, and cultured under the conditions of 37 ° C and 5% CO2 (Day 1 of the test). After 24 hours of seeding, the medium was removed, and bilberry extract and Japanese rose extract were added so that their final concentrations were 0.01% each. Furthermore, Glyoxal was added at 0.1 mL / well so that its final concentration was 5 mM, and the cells were cultured at 37 °C under 5% CO2 conditions for 2 hours (glycation treatment). Then, the medium was removed, 0.1 mL of 100% methanol was added, and the cells were fixed by allowing them to stand at -30 °C for 15 minutes. Then the cells were washed with 0.2 mL of phosphate buffer (PBS), 0.1 mL of blocking solution (PBS containing 5% BSA and 0.3% Triton X-100) was added, and the cells were allowed to stand at room temperature for 60 minutes, and then the cells were washed again with 0.2 mL of PBS. Then, 0.05 mL of the primary antibody of NF-κB p65 (manufactured by Cell Signaling Technology) diluted 1000-fold with the antibody dilution solution (PBS containing 1% BSA and 0.3% Triton X-100) was added, and the cells were allowed to stand overnight at 4 °C (day 2 of the test). On the next day, the antibody dilution solution was removed, the cells were washed with 0.2 mL of PBS, then 0.05 mL of the secondary antibody (manufactured by Abcam) and Hoechst (manufactured by Tongrentang) diluted 1000-fold with the antibody dilution solution were added, and the reaction was carried out on a shaker at room temperature for 1 hour. Then, the antibody dilution solution was removed, the cells were washed with 0.2 mL of PBS, then 0.15 mL of PBS was added, and the ratio of NF-κB p65 positive cells was quantified using Image Xpress (MOLECULAR DEVICES) (day 3 of the test). The case where the same test conditions were used except that bilberry extract and Japanese rose extract were not added was used as a control. The ratio of positive cells in the case where bilberry extract and Japanese rose extract were added (test solution 1) was calculated with the positive cells of the control taken as 100%. The results are shown in Figure 1.

[0026] As shown in Figure 1, when bilberry extract and Japanese rose extract were added, the ratio of NF-κB p65 positive cells decreased compared to the control. Bilberry extract and Japanese rose extract prevented and suppressed the nuclear translocation of NFκB in cells induced by glycation. To prevent and suppress the nuclear translocation of NFκB, cell inflammation caused by glycation was prevented and suppressed.

Claims

1. A glycated cell inflammation inhibitor containing, as an active ingredient, one or more selected from the group consisting of bilberry extract and Rosa multiflora var. cathayensis extract.

2. The glycated cell inflammation inhibitor according to Claim 1, which suppresses inflammation by suppressing the nuclear translocation of NFκB.

3. An NFκB nuclear translocation inhibitor containing, as an active ingredient, one or more selected from the group consisting of bilberry extract and Rosa multiflora var. cathayensis extract.

Citation Information

Patent Citations

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