Composition for improving metabolism

Abstract

To provide a material that suppresses metabolic abnormality caused by a high glucose load and is suitable for prevention or treatment of periodontitis.SOLUTION: A composition for the prevention or treatment of periodontitis contains a specific material capable of suppressing metabolic abnormality caused by a high glucose load.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present disclosure relates to a composition for improving metabolism. [Background technology]

[0002] It is known that high glucose loading enhances oxidative stress in cells and causes metabolic abnormalities. In particular, it is believed that high glucose loading in diabetic patients and prediabetic subjects leads to metabolic abnormalities and various symptoms. These symptoms may include symptoms in the oral cavity.

[0003] For example, it has been reported that the metabolic function of periodontal tissues is impaired in a diabetic state, and that activating the metabolic function of the gingiva of diabetic rats suppresses alveolar bone resorption. [Prior art documents] [Non-patent literature]

[0004] [Non-Patent Document 1] J Clin Periodontol 2017; 44: 463-471. IADR / PER General Session 2018; Presentation ID 1622 Summary of the Invention [Problem to be solved by the invention]

[0005] The present inventors have searched for components capable of suppressing metabolic abnormalities caused by high glucose loading. [Means for solving the problem]

[0006] The present inventors have found various components capable of suppressing metabolic abnormalities caused by high glucose load, and have further improved them.

[0007] The present disclosure includes, for example, the subject matter described in the following sections: Section 1. Contains at least one selected from the group consisting of components listed in the table below: An oral composition for preventing or treating periodontal disease.

[0008] [Table 1]

[0009] TIFF2024090914000002.tif231170

[0010] TIFF2024090914000003.tif231170

[0011] TIFF2024090914000004.tif111170

[0012] Section 2. Contains at least one selected from the group consisting of components listed in the table below: An oral composition for preventing or treating periodontal disease.

[0013] [Table 2]

[0014] Section 3. The composition according to item 1 or 2, for a subject having a metabolic disorder (preferably a glucose metabolic disorder). Section 4. Item 3. The composition according to item 1 or 2, which is a composition for improving metabolism (preferably improving sugar metabolism) in oral cells. Section 5. Item 3. The composition according to item 1 or 2, which is for improving ATP metabolic abnormalities caused by high glucose load in oral cells. Section 6. Item 3. The composition according to item 1 or 2, for use in suppressing inflammation caused by high glucose load in oral cells. Section 7. 7. The composition according to claim 4, wherein the oral cells are periodontal ligament cells. Section 8. Item 7. The composition according to any one of Items 1 to 6, which is a food composition. Effect of the Invention

[0015] It can suppress metabolic abnormalities caused by high glucose load. In particular, it can suppress metabolic abnormalities (particularly ATP metabolic abnormalities) and inflammation caused by high glucose load in cells in the oral cavity. This makes it possible to prevent or treat periodontal disease. More specifically, it is expected to suppress periodontitis accompanied by bone resorption, and thus to suppress tooth loss associated with the progression of periodontitis. [Brief description of the drawings]

[0016] [Figure 1] This paper outlines an experiment in which high glucose loading was administered to human periodontal ligament fibroblasts (HPDLFs) to examine how this affects ATP metabolism and gene expression levels of inflammatory cytokines. [Diagram 2] This is an outline of an experiment in which a test substance (sample) was first applied to human periodontal ligament fibroblasts, and then high glucose load was applied to examine how ATP metabolism and gene expression levels of inflammatory cytokines changed. [Diagram 3] The results of intracellular ATP measurement in the study shown in FIG. 1 (without application of test substance) are shown. 3d indicates the results after 3 days, 6d indicates the results after 6 days, and 9d indicates the results after 9 days. The bar graphs showing the results after each number of days show, from left to right, the relative values ​​when the control is taken as 100%, for the results of the control (L-glucose), D-glucose 25 mM, D-glucose 50 mM, and D-glucose 100 mM. The control for D-glucose 25 mM is L-glucose 25 mM, the control for D-glucose 50 mM is L-glucose 50 mM, and the control for D-glucose 100 mM is L-glucose 100 mM. [Figure 4]The results of measuring the expression level of MCP-1 gene in the study shown in Figure 1 (without application of the test substance) are shown after correction to the expression level of RPS18. 3d shows the results after 3 days, and 6d shows the results after 6 days. The bar graphs showing the results after each number of days show the relative values, from left to right, of the control (L-glucose), D-glucose 25 mM, D-glucose 50 mM, and D-glucose 100 mM, with the control set at 1. The control for D-glucose 25 mM is L-glucose 25 mM, the control for D-glucose 50 mM is L-glucose 50 mM, and the control for D-glucose 100 mM is L-glucose 100 mM. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0017] Each embodiment included in the present disclosure will be described in more detail below. The present disclosure preferably includes compositions for preventing or treating periodontal disease (particularly oral compositions), but is not limited thereto, and the present disclosure includes all that is disclosed in the present specification and that can be recognized by a person skilled in the art.

[0018] The compositions for preventing or treating periodontal disease included in the present disclosure contain the specific components listed in the following table, either singly or in combination of two or more. The compositions for preventing or treating periodontal disease included in the present disclosure may be referred to as the compositions of the present disclosure. In addition, the components with these characteristics may be referred to as the components of the present disclosure.

[0019] [Table 3]

[0020] TIFF2024090914000007.tif231170

[0021] TIFF2024090914000008.tif231170

[0022] TIFF2024090914000009.tif111170

[0023] Among these components, the components listed in the following table are more preferred.

[0024] [Table 4]

[0025] The content of the components of the present disclosure in the composition of the present disclosure is not particularly limited as long as the effects are not impaired, and may be, for example, about 0.01 to 99.99% by mass.

[0026] The intake form of the composition of the present disclosure is not particularly limited, but is preferably oral intake. That is, the composition of the present disclosure is preferably an oral composition. By orally ingesting the composition of the present disclosure, the effect of suppressing metabolic abnormalities caused by high glucose load in cells (particularly cells in the oral cavity) can be preferably achieved. The composition of the present disclosure is preferably, for example, an oral pharmaceutical composition or a food composition (including a beverage composition and a food additive composition).

[0027] The composition of the present disclosure includes the above-mentioned components and may further include other components. The other components may be appropriately selected depending on the field in which the composition is used. For example, a medicamentically or food hygienically acceptable carrier may be used.

[0028] When used as a pharmaceutical composition, other components include pharma- ceutically acceptable bases, carriers, and / or additives (e.g., solvents, dispersants, emulsifiers, buffers, stabilizers, excipients, binders, disintegrants, lubricants, etc.), etc. The form of the pharmaceutical composition is not particularly limited, and examples thereof include tablets, pills, powders, liquids, suspensions, emulsions, granules, capsules, creams, and poultices.

[0029] When used as a food composition, other ingredients include bases, carriers, additives that are acceptable from the viewpoint of food hygiene, and other ingredients and materials that can be used as foods. The form of the food composition is not particularly limited, and examples thereof include processed foods, health foods (nutritional supplements, nutritional functional foods, foods for the sick, foods for specified health uses, functional products, etc.), supplements, foods for the sick (hospital food, sick food, nursing food, etc.). These can be prepared by conventional methods. In particular, when preparing a food composition as a health food (nutritional supplements, nutritional functional foods, foods for the sick, foods for specified health uses, functional products, etc.) or supplements, it is preferable to prepare it in the form of, for example, granules, capsules, tablets (including chewable agents, etc.), beverages (drink powders, drinks, smoothies, etc.) so that it is easy to take continuously, and among them, the forms of capsules, tablets, tablets, drink powders, drinks, jellies, and gummies are preferable from the viewpoint of ease of intake, but are not particularly limited thereto. When the food composition is used as a food additive composition, the food composition may be in the form of, for example, liquid, powder, flake, granule, or paste.

[0030] From the viewpoint that the effect can be preferably achieved, the subject of taking the composition of the present disclosure is preferably a subject with metabolic abnormality, more specifically, a subject with metabolic abnormality caused by, for example, high glucose load. More specifically, metabolic abnormality caused by high glucose load includes, for example, ATP metabolic abnormality caused by high glucose load, and inflammation that can be caused by the metabolic abnormality (inflammation caused by high glucose load). In addition, a subject with gingival inflammation is preferred. Although not particularly limited, inflammation in which the expression level of inflammatory cytokines is increased is preferred, and in particular inflammation in which the expression level of at least one inflammatory cytokine selected from the group consisting of MCP-1 (Monocyte chemoattractant protein-1), IL-8 (Interleukin-8), and MMP1 (Matrix metallopeptidase 1) is increased is preferred.

[0031] The timing of taking the composition of the present disclosure is not particularly limited, but it may be taken, for example, before or after taking a meal containing carbohydrates (particularly carbohydrates that can become glucose when absorbed into the body). It may also be preferably used, for example, during or after treatment for periodontal disease to prevent recurrence.

[0032] Furthermore, although not particularly limited, the cells in which metabolic abnormalities can be suppressed by ingestion of the composition of the present disclosure are preferably cells in the oral cavity, and among them, gingival cells and periodontal ligament cells (particularly gingival fibroblasts and periodontal ligament fibroblasts) are preferred. Periodontal ligament cells are known to be strongly involved in immune responses, inflammatory responses, and alveolar bone resorption in periodontal disease, and are therefore most preferred.

[0033] In addition, in this specification, the term "comprising" includes "consisting essentially of" and "consisting of." In addition, the present disclosure includes any combination of the constituent elements described in this specification.

[0034] In addition, the various characteristics (properties, structures, functions, etc.) described in each embodiment of the present disclosure above may be combined in any way to specify the subject matter included in the present disclosure. In other words, the present disclosure includes all subject matter consisting of all combinations of each combinable characteristic described in this specification. EXAMPLES

[0035] Hereinafter, the embodiments of the present disclosure will be described more specifically with reference to examples, but the embodiments of the present disclosure are not limited to the following examples.

[0036] Examination of high glucose loading in periodontal ligament cells We applied high glucose to human periodontal ligament fibroblasts (HPDLFs) to examine how ATP metabolism and gene expression levels of inflammatory cytokines would change as a result (Figure 1). Furthermore, we applied a test substance (sample) to human periodontal ligament fibroblasts in advance, and then examined how ATP metabolism and gene expression levels of inflammatory cytokines would change when high glucose was applied (Figure 2). More specifically, we performed the study as follows. The following detailed explanation is for the study shown in Figure 2 (with test substance), but the study shown in Figure 1 was also performed in the same way, except that the test substance was not applied and the D-glucose concentration was changed.

[0037] [Measurement of intracellular ATP concentration] Intracellular ATP was measured using a Luminescent ATP detection assay kit (ab113849; Abcam). Human periodontal ligament fibroblasts (HPDLF) were cultured at 0.12 × 10 5 The cells were seeded in a 48-well plate at a density of cells / 100 μL / well and cultured for 48 hours. The cells were pretreated with each test substance (sample) (1 μg / mL) for 24 hours, and then treated with 50 mM D-glucose (Sigma Aldrich) for 72 hours. The same concentration of L-glucose was used as a control. Then, 50 μL of cell lysis solution was added for 5 minutes to lyse the cells and stabilize ATP. Furthermore, D-luciferase reagent was added and incubated for 10 minutes in the dark. Chemiluminescence due to the luciferase reaction was measured using a Cytation 5 plate reader (BioTek Instruments), and ATP concentration (μM) was measured using a standard curve. The ATP reduction improvement rate (%) when each test substance (sample) was applied was calculated using the following formula.

[0038]

number

[0039] In other words, the ATP decrease improvement rate (%) indicates the percentage obtained by subtracting the chemiluminescence value when only D-glucose was treated from the chemiluminescence value when D-glucose was treated after sample treatment, divided by the value obtained by subtracting the chemiluminescence value when only D-glucose was treated from the chemiluminescence value when only L-glucose was treated.

[0040] [Gene expression of MCP-1, IL-8, and MMP-1] Human periodontal ligament fibroblasts (HPDLF) were cultured at 0.45 × 10 5 The cells were seeded in 12-well plates at a density of cells / 1 mL / well and cultured for 72 hours. The cells were pretreated with each sample (1 μg / mL) for 24 hours, and then treated with 50 mM D-glucose (Sigma Aldrich) for 72 hours. The same concentration of L-glucose was used as a control. Total RNA was extracted using RNeasy Mini Kit (Qiagen). Single-stranded cDNA was synthesized from 0.5 μg of total RNA using PrimeScript RT reagent Kit (Takara Bio). The expression of each gene was quantified using the 7500 Fast real-time PCR system (Applied Biosystems) with specific primers and the intercalator method using TB Green Fast qPCR Mix (Takara Bio). The expression level of each gene was corrected by the expression level of ribosomal protein S18 (RPS18), and the relative value was calculated with the expression level after treatment with L-glucose set to 1. The gene expression inhibition rate (%) when each test substance (sample) was applied was calculated using the following formula.

[0041]

number

[0042] In other words, the gene expression inhibition rate (%) is the percentage obtained by subtracting the relative value when D-glucose was treated after sample treatment from the relative value when D-glucose was treated only, divided by the relative value when L-glucose was treated only from the relative value when D-glucose was treated only.

[0043] The results of the study shown in Figure 1 (without application of the test substance) are shown in Figure 3 (measurement results of intracellular ATP concentration) and Figure 4 (measurement results of MCP-1 gene expression level: relative value). Figure 3 confirmed that intracellular ATP production decreased in a D-glucose concentration-dependent manner (i.e., ATP metabolism decreased). Figure 4 also showed that the gene expression level of the inflammatory cytokine (MCP-1) increased in a D-glucose concentration-dependent manner.

[0044] The results of the study shown in Figure 2 (with application of the test substance) are shown in the following table. Specifically, the following table shows the ATP reduction improvement rate (%) and the inflammatory cytokine gene expression inhibition rate (%) obtained as described above.

[0045] [Table 5]

[0046] TIFF2024090914000014.tif232170

[0047] TIFF2024090914000015.tif232170

[0048] TIFF2024090914000016.tif232170

[0049] TIFF2024090914000017.tif232170

[0050] TIFF2024090914000018.tif232170

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