JP2021091715A - Cell adhesion factor expression inhibitor - Google Patents

Abstract

To discover, among natural components, one having the action of inhibiting the expression of a cell adhesion factor, and provide a cell adhesion factor expression inhibitor containing such a component as an active ingredient, and a food and drink for inhibiting cell adhesion factor expression that contains the component.SOLUTION: A cell adhesion factor expression inhibitor contains digalactosyl diacylglycerol as an active ingredient. A food and drink for inhibiting cell adhesion factor expression contains digalactosyl diacylglycerol.SELECTED DRAWING: Figure 2

Description

The present invention relates to a cell adhesion factor expression inhibitor and a food or drink for suppressing cell adhesion factor expression.

According to the Vital Statistics of the Ministry of Health, Labor and Welfare (2015), the causes of death in Japanese are malignant neoplasms, heart disease, pneumonia, and cerebrovascular disease in that order. Cerebrovascular disease ranks high. In addition, heart disease and cerebrovascular disease have strong sequelae and are often forced to lie down for a long period of time. Therefore, prevention, treatment or improvement of arteriosclerosis is extremely important.

Arteriosclerosis, especially atherosclerosis, which accounts for a major proportion of it, is thought to be caused by risk factors such as dyslipidemia, diabetes, hypertension, and smoking, eventually blocking arterial blood flow and causing myocardial infarction. It causes heart diseases such as cerebral infarction and cerebrovascular diseases such as cerebral infarction.

For the treatment of atherosclerosis, antihyperlipidemic drugs such as statins and antihypertensive drugs such as angiotensin receptor blockers are generally used. However, since various factors are complicatedly involved in the development and progression of atherosclerosis, an atherosclerosis inhibitor having a different mechanism of action from these is required.

Atherosclerosis is thought to progress from the stage where vascular endothelial cells are damaged and activated, and monocytes in the blood adhere to these endothelial cells. Monocytes adhered to vascular endothelial cells invade between the endothelial cells, differentiate into macrophages, and further take up fatty substances such as cholesterol and change into foam cells. It is thought that these foam cells secrete various cytokines and growth factors to promote the progression of atherosclerotic lesions.

Here, in the adhesion of monospheres to vascular endothelial cells, which is the initial stage of arteriosclerosis, cell adhesion factors on the cell surface, such as ICAM-1 (intercellular adhesion molecule-1), are activated by activating the vascular endothelial cells. , VCAM-1 (vascular cell adhesion molecule-1) and the like are induced, and it is known that these cell adhesion factors contribute to adhesion to monospheres. Therefore, if the expression of cell adhesion factors such as ICAM-1 and VCAM-1 can be suppressed, it is considered that the progression of arteriosclerosis can be suppressed.

As a component that suppresses the expression of cell adhesion factor, an antibody that binds to digoxin (Patent Document 1), Kumazasa extract that has been stabilized with copper sulfate (Patent Document 2), and the like are known.

Special Table 2009-542682 Japanese Unexamined Patent Publication No. 2011-219434

The present invention has found a component derived from a natural product that has an action of suppressing the expression of a cell adhesion factor, a cell adhesion factor expression inhibitor containing the same as an active ingredient, and a cell adhesion factor expression containing the component. The purpose is to provide food and drink for suppression.

In order to solve the above problems, the cell adhesion molecule expression inhibitor according to the present invention is characterized by containing digalactosyldiacylglycerol as an active ingredient. Further, the food or drink for suppressing the expression of cell adhesion factor according to the present invention is characterized by containing digalactosyldiacylglycerol.

According to the present invention, by containing digalactosyldiacylglycerol as an active ingredient, it is possible to provide an agent for suppressing the expression of cell adhesion factor having excellent action and effect. Furthermore, by blending digalactosyldiacylglycerol, it is possible to provide a food or drink for suppressing the expression of cell adhesion factor excellent in the above-mentioned action.

It is a graph which shows the result of having evaluated the cytotoxicity of digalactosyldiacylglycerol (DGDG) with respect to human umbilical vein endothelial cells (HUVECs). It is a graph which shows the result (RT-PCR method) which evaluated the effect of DGDG on the expression of cell adhesion factor and cytokine in HUVECs. It is a photograph showing the result (immunoblotting) of evaluating the effect of DGDG on the expression of cell adhesion factor in HUVECs. It is a graph which quantified the result of FIG. 3A. 6 is a photomicrograph showing the results of evaluating the effect of DGDG on the adhesion of monocytes (THP-1) -vascular endothelial cells (HUVECs). It is a graph which shows the result of counting the number of adhered cells from the micrograph of FIG. 4A.

Hereinafter, embodiments of the present invention will be described.
The cell adhesion molecule expression inhibitor according to the present embodiment contains digalactosyl diacylglycerol (hereinafter sometimes referred to as "DGDG") as an active ingredient. In addition, the food and drink for suppressing the expression of cell adhesion factor according to the present embodiment contains digalactosyldiacylglycerol.

DGDG can be produced, for example, by isolating and purifying from a plant extract containing DGDG. In this case, such a plant extract containing DGDG can be obtained by a method generally used for extracting plants. Examples of plants containing DGDG include spinach, pineapple, rice, wheat, potato, Japanese mustard spinach, and garland chrysanthemum.

The method for extracting, isolating, and purifying DGDG from the above plant is not particularly limited, and can be carried out according to a conventional method. For example, in the extraction treatment, the plant as an extraction raw material may be dried and then crushed as it is or by using a coarse crusher and subjected to extraction with an extraction solvent. Drying may be performed in the sun or using a commonly used dryer.

As the extraction solvent, it is preferable to use a polar solvent, for example, water, a hydrophilic organic solvent and the like, and these are used alone or in combination of two or more at room temperature or a temperature below the boiling point of the solvent. Is preferable.

Water that can be used as an extraction solvent includes pure water, tap water, well water, mineral spring water, mineral water, hot spring water, spring water, fresh water, and the like, as well as those subjected to various treatments. Treatments applied to water include, for example, purification, heating, sterilization, filtration, ion exchange, osmotic pressure adjustment, buffering and the like. Therefore, the water that can be used as the extraction solvent in the present embodiment includes purified water, hot water, ion-exchanged water, physiological saline, phosphate buffer, phosphate buffered saline and the like.

Hydrophilic organic solvents that can be used as the extraction solvent include lower aliphatic alcohols having 1 to 5 carbon atoms such as methanol, ethanol, propyl alcohol and isopropyl alcohol; lower aliphatic ketones such as acetone and methyl ethyl ketone; 1,3-butylene. Examples thereof include polyhydric alcohols having 2 to 5 carbon atoms such as glycol, propylene glycol and glycerin.

When a mixed solution of two or more polar solvents is used as the extraction solvent, the mixing ratio can be appropriately adjusted. For example, when a mixed solution of water and a lower fatty alcohol is used as an extraction solvent, the mixing ratio of water and the lower fatty alcohol is preferably 9: 1 to 1: 9 (volume ratio). It is more preferably 7: 3 to 2: 8 (volume ratio). When a mixed solution of water and a lower aliphatic ketone is used, the mixing ratio of water and the lower aliphatic ketone is preferably 9: 1 to 2: 8 (volume ratio), and water and a large amount are used. When a mixed solution with a valent alcohol is used, the mixing ratio of water and the polyhydric alcohol is preferably 5: 5 to 1: 9 (volume ratio).

The extraction treatment is not particularly limited as long as the soluble component contained in the extraction raw material can be eluted in the extraction solvent, and can be carried out according to a conventional method. For example, the extraction material is immersed in an extraction solvent 5 to 15 times the amount (mass ratio) of the extraction material, the soluble component is extracted at room temperature or under reflux heating, and then filtered to remove the extraction residue. The liquid can be obtained. Chlorophyll is removed from the obtained extract using activated carbon or the like, if necessary, and then the solvent is distilled off to obtain a paste-like concentrate, and the concentrate is further dried to obtain a dried product.

The method for isolating and purifying DGDG from the extract obtained as described above, the concentrate of the extract, or the dried product of the extract is not particularly limited, and can be carried out by a conventional method. .. For example, the extract is dissolved in a developing solvent and subjected to column chromatography using a porous substance such as silica gel or alumina, a porous resin such as a styrene-divinylbenzene copolymer or polymethacrylate, and contains DGDG. Examples include a method of collecting fractions. In this case, the developing solvent may be appropriately selected according to the stationary phase to be used. For example, when the extract is separated by normal phase chromatography using silica gel as the stationary phase, the developing solvent is chloroform: methanol: water = 40:10:0.1 and the like can be mentioned. Further, the fraction containing DGDG obtained by column chromatography can be subjected to any organic such as reverse phase silica gel chromatography using ODS, recrystallization, liquid-liquid countercurrent extraction, and column chromatography using an ion exchange resin. It may be purified by using a compound purification means.

[Cell adhesion factor expression inhibitor]
Since the DGDG obtained as described above has an excellent cell adhesion factor expression inhibitory action, it can be used as an active ingredient of a cell adhesion molecule expression inhibitor. The cell adhesion molecule expression inhibitor according to this embodiment can be used in a wide range of applications such as pharmaceuticals, quasi-drugs, and cosmetics.

In the present embodiment, the cell adhesion factor whose expression is suppressed by DGDG is, for example, ICAM-1 (intercellular adhesion molecule-1), VCAM-1 (vascular cell adhesion molecule-1), PECAM-1 (platelet endothelial cellular adhesion molecule-1). Immunoglobulin superfamily such as molecule-1); integrin family such as LFA-1 and VLA4; selectin family such as E-selectin and P-selectin; and the like. Among these, the cell adhesion factor whose expression is suppressed in the present embodiment is preferably an immunoglobulin superfamily, and particularly preferably ICAM-1 and / or VCAM-1. However, the cell adhesion factor whose expression is suppressed by DGDG is not limited to the above cell adhesion factor.

In addition, DGDG may be used as an active ingredient of an ICAM-1 expression-suppressing agent or a VCAM-1 expression-suppressing agent by utilizing its ICAM-1 expression-suppressing action or VCAM-1 expression-suppressing action.

In the present embodiment, the cell adhesion factor whose expression is to be suppressed is preferably a cell adhesion factor of vascular endothelial cells.

As the active ingredient of the cell adhesion molecule expression inhibitor according to the present embodiment, a composition containing DGDG may be used instead of the isolated DGDG. Here, the "composition containing DGDG" in the present embodiment includes an extract obtained by using a plant containing DGDG as an extraction raw material. Further, the "extract" includes an extract obtained by an extraction treatment, a diluted solution or a concentrated solution of the extract, or a dried product obtained by drying the extract.

When a composition containing DGDG is used as the active ingredient of the cell adhesion factor expression inhibitor according to the present embodiment, it is preferable to use one that has been purified to increase the purity of DGDG. By using a substance having an increased purity of DGDG as an active ingredient, it is possible to obtain a cell adhesion factor expression inhibitor having an even more excellent action and effect.

The cell adhesion factor expression inhibitor according to the present embodiment may consist only of a composition containing DGDG or DGDG, or may be a formulation of a composition containing DGDG or DGDG.

The cell adhesion factor expression inhibitor according to the present embodiment uses a pharmaceutically acceptable carrier such as dextrin or cyclodextrin or any other auxiliary agent, and is powdery, granular, tablet-like, liquid or the like according to a conventional method. It can be formulated into any dosage form of. At this time, as the auxiliary agent, for example, an excipient, a binder, a disintegrant, a lubricant, a stabilizer, a flavoring / odorant, and the like can be used. The cell adhesion factor expression inhibitor can be used by blending with other compositions (for example, foods and drinks for suppressing cell adhesion factor expression described later), and can also be used as tablets, capsules and the like.

When the cell adhesion factor expression inhibitor according to the present embodiment is formulated, the content of DGDG or the composition containing DGDG is not particularly limited and can be appropriately set according to the intended purpose.

The cell adhesion factor expression inhibitor according to the present embodiment is an active ingredient in which, if necessary, another natural extract or the like having a cell adhesion factor expression inhibitory action is blended together with DGDG or a composition containing DGDG. Can be used as.

Examples of the administration method of the cell adhesion molecule expression inhibitor according to the present embodiment to patients include oral administration and intravenous administration, and a method suitable for prevention or treatment thereof is appropriately selected according to the type of disease. do it. In addition, the dose of the cell adhesion molecule expression inhibitor according to the present embodiment may be appropriately increased or decreased depending on the type and severity of the disease, individual differences of patients, administration method, administration period and the like.

The cell adhesion factor expression inhibitor according to the present embodiment is a monosphere to vascular endothelial cells through the cell adhesion factor expression inhibitory action, particularly the ICAM-1 expression inhibitory action or the VCAM-1 expression inhibitory action, which the active ingredient DGDG has. It is possible to prevent, treat or improve arteriosclerosis; ischemic heart disease caused by arteriosclerosis; cerebrovascular disease caused by arteriosclerosis such as cerebral hemorrhage and cerebral infarction. However, the cell adhesion factor expression inhibitor according to the present embodiment can be used for all uses other than these uses, which are significant in exerting the cell adhesion factor expression inhibitory action.

Further, since the cell adhesion factor expression inhibitor according to the present embodiment has an excellent cell adhesion factor expression inhibitory action, it can be suitably used as a reagent for research on these action mechanisms.

[Food and drink for suppressing cell adhesion factor expression]
Since DGDG has an excellent cell adhesion factor expression inhibitory action, it is suitable for blending in foods and drinks for suppressing cell adhesion molecule expression. In this case, DGDG may be blended as it is, or a cell adhesion molecule expression inhibitor formulated from DGDG may be blended.

Here, foods and drinks are those that are less likely to harm human health and are ingested by oral or gastrointestinal administration in normal social life, and are foods, pharmaceuticals, quasi-drugs under administrative divisions. It is not limited to such categories. Therefore, the "food and drink" in the present embodiment includes general foods, health foods (functional foods and drinks), health functional foods (foods for specified health use, nutritional functional foods), quasi-drugs, and pharmaceuticals that are orally ingested. Etc. are widely included.

By blending DGDG or the above-mentioned cell adhesion factor expression inhibitor into a food or drink, it is possible to impart a cell adhesion factor expression inhibitory effect, particularly an ICAM-1 expression inhibitory effect or a VCAM-1 expression inhibitory effect, to the food or drink.

When DGDG or a cell adhesion factor expression inhibitor formulated from DGDG is added to foods and drinks to prepare foods and drinks for suppressing cell adhesion factor expression, the amount of the active ingredient in them depends on the purpose of use, symptoms, gender, etc. Although it can be changed as appropriate in consideration, it is preferable that the daily intake of the extract for adults is about 1 to 1000 mg in consideration of the general intake of foods and drinks to be added. .. When the food or drink to be added is a granular, tablet-shaped or capsule-shaped food or drink, the amount of the cell adhesion factor expression inhibitor formulated from DGDG or DGDG is usually 0. It is 1 to 100% by mass, preferably 5 to 100% by mass.

The food or drink for suppressing the expression of cell adhesion factor according to the present embodiment may be a food or drink containing DGDG in any food or drink that does not interfere with its activity, or is a dietary supplement containing DGDG as a main component. You may.

When producing foods and drinks for suppressing the expression of cell adhesion factors according to the present embodiment, for example, saccharides such as dextrin and starch; proteins such as gelatin, soybean protein and corn protein; amino acids such as alanine, glutamine and isoleucine; Polysaccharides such as cellulose and arabic rubber; any auxiliary agent such as oils and fats such as soybean oil and medium-chain amino acid triglyceride can be added to prepare foods and drinks having any shape.

The foods and drinks that can contain DGDG are not particularly limited, and specific examples thereof include beverages such as soft drinks, carbonated beverages, nutritional beverages, fruit beverages, and lactic acid beverages (including concentrated stock solutions and adjustment powders of these beverages). Cold confectionery such as ice cream, ice sherbet, shaved ice; noodles such as buckwheat, udon, harusame, gyoza skin, sushi skin, Chinese noodles, instant noodles; candy, chewing gum, candy, gum, chocolate, tablet confectionery, snack confectionery, Confectionery such as biscuits, jellies, jams, creams, baked goods; marine and livestock processed foods such as kamaboko, ham, sausage; dairy products such as processed milk and fermented milk; salad oil, tempura oil, margarine, mayonnaise, shortening, whipping Fats and oils such as creams and dressings and processed fats and oils; Seasonings such as sauces and sauces; Soups, stews, salads, prepared foods, pickles; Other various forms of health and nutritional supplements; Tablets, capsules, drinks, etc. Therefore, when DGDG is added to these foods and drinks, commonly used auxiliary raw materials and additives can be used in combination.

The cell adhesion factor expression inhibitor and the food and drink for suppressing cell adhesion factor expression according to the present embodiment are preferably applied to humans, but as long as their respective actions and effects are exhibited, they are not humans. It can also be applied to animals (eg, mice, rats, hamsters, dogs, cats, cows, pigs, monkeys, etc.).

Hereinafter, the present invention will be specifically described with reference to Production Examples, Test Examples and Formulation Examples, but the present invention is not limited to the following examples.

In the test examples described later, lipopolysaccharide (LPS) and PKH26 Red Fluorescent Cell Linker Kit purchased from Sigma Aldrich were used. As the anti-ICAM-1, anti-VCAM-1, and anti-β-actin antibodies, those manufactured by Cell Signaling Technology were used. HRP-labeled anti-rabbit IgG antibody and enhanced chemiluminescence (ECL) system were purchased from GE Healthcare.

Human umbilical vein endothelial cells (HUVECs) were purchased from Cambrex Bio Science Walkersville. HUVECs are medium in which EGM-2MV addition factor (supplied with EBM-2), which is a growth factor, is added to endothelial cell basal medium (EBM-2; manufactured by Lonza) _{under 37 ° C. and 5% CO 2} conditions. Was cultured in. Human acute monocytic leukemia cells (THP-1) were purchased from JCRB Cell Bank and used in RPMI1640 medium (manufactured by Life technologies) supplemented with 10% FBS and 1% antibiotics (both manufactured by Life technologies). It was cultured.

[Production Example] Production of DGDG Dried spinach (200 g) was reflux-extracted with 70% ethanol (2 L) for 2 hours. After filtration, activated carbon was added to the extract, and the mixture was stirred under reflux for 1 hour and then filtered. The obtained filtrate was concentrated under reduced pressure to obtain a glycolipid mixture (48.7 g). The glycolipid mixture (47.5 g) was subjected to column chromatography (carrier: Diaion HP-20, manufactured by Mitsubishi Chemical Corporation) and eluted in the order of 70% ethanol, 95% ethanol, and chloroform, and the chloroform-eluting part (2). .7 g) was obtained. The chloroform-eluting part (2.6 g) was subjected to normal phase silica gel column chromatography (carrier: Silica gel 60, manufactured by Merck), fractionated with chloroform-methanol-water (40:10: 0.1), and sugar was added. A lipid fraction (425 mg) was obtained. Glycolipid fraction (425 mg), recycled HPLC (solvent: methanol, column: JAIGEL GS310 connected in two (500 x 20 mm id) (manufactured by Nippon Analytical Industry Co., Ltd.), equipment used: YMC LC-forte / R Purification with (manufactured by the company)) to obtain a purified product (303 mg, 0.15%). The obtained purified product ^{was analyzed by 1} H-NMR, ¹³ C-NMR and DEPT, and it was confirmed that it was DGDG (Sample 1).

[Test Example 1] Evaluation of cytotoxicity against HUVECs The cytotoxicity against human umbilical vein endothelial cells (HUVECs) was examined using the Premix WST-1 Cell Proliferation Assay System (manufactured by Takara Bio Co., Ltd.) according to the test method attached to the product. It was. Specifically, HUVECs were pre-cultured in the above-mentioned medium at 37 ° C. and 5% CO ₂ ^{, 1 × 10 3} cells were seeded in each well of a 96-well plate, and after culturing for 4 hours, a test sample (sample). 1. The final concentration was shown in Fig. 1), and the cells were further cultured for 24 hours. After culturing, Premix WST-1 solution (manufactured by Takara Bio Inc.) was added and incubated for 30 minutes, and the absorbance at a wavelength of 440 nm was measured using a microplate reader (Multiscan FC, manufactured by Thermo Fisher Scientific). Each of the obtained data is shown as mean ± standard deviation.

The results are shown in FIG. As is clear from FIG. 1, DGDG (Sample 1) showed no cytotoxicity to vascular endothelial cells (HUVECs) at the tested concentrations.

[Test Example 2] Evaluation of expression inhibitory effect of cell adhesion factor and cytokine (RT-PCR method)
HUVECs were precultured and cells were harvested by trypsin treatment. The collected cells were ^{diluted with the same medium as the preculture so that the cell density was 2.4 × 10 4} cells / mL, and then 2 mL each was seeded in a 35 mm petri dish (manufactured by FALCON) at 37 ° C. and 5% CO _2. Was cultured for 48 hours.

After culturing, the medium was removed, and 2 mL of the medium containing the test sample (sample 1,5 μg / mL) and lipopolysaccharide (LPS, 1 μg / mL) was added to each petri dish to 37 ° C. and 5% CO ₂ . Was cultured for 2 hours. The control cells were similarly cultured in the sample and medium without LPS, and the expression-inducing cells were cultured in the medium without sample and LPS. After culturing, the medium was removed, and total RNA was extracted with ISOGEN (manufactured by Nippon Gene).

Using 1 μg of this total RNA as a template, a reverse transcription reaction was carried out using a random primer and MMLV reverse transcriptase (ReverTra Ace, manufactured by Toyobo Co., Ltd.). Then, using a PCR device (LightCycler480 system, manufactured by Roche Diagnostics) and QuantiTect SYBR Green PCR kit (manufactured by QIAGEN), quantitative real-time PCR was performed to obtain mRNA for ICAM-1, VCAM-1, and the internal standard GAPDH. The expression level was measured.

The results are shown in FIG. Induction of expression of ICAM-1 and VCAM-1 mRNA by LPS was suppressed by DGDG (Sample 1).

[Test Example 3] Evaluation of expression inhibitory effect of cell adhesion factor (immunoblot method)
HUVECs were precultured and cells were harvested by trypsin treatment. The collected cells were ^{diluted with the same medium as the preculture so that the cell density was 2.4 × 10 4} cells / mL, and then 2 mL each was seeded in a 35 mm petri dish (manufactured by FALCON) at 37 ° C. and 5% CO _2. Was cultured for 48 hours.

After culturing, the medium was removed, and 2 mL of the medium containing the test sample (sample 1,5 μg / mL) and lipopolysaccharide (LPS, 1 μg / mL) was added to each petri dish to 37 ° C. and 5% CO ₂ . Was cultured for 4 hours. For comparison, a medium without LPS added (see FIGS. 3A and 3B for the test sample concentration) was also cultured in the same manner. After culturing, the medium was removed, dissolved in a RIPA lysate (manufactured by Thermo Fisher Scientific), and the obtained sample was subjected to immunoblot. An enhanced chemiluminescence (ECL) system using anti-ICAM-1, anti-VCAM-1, and anti-β-actin primary antibodies (all manufactured by Cell Signaling Technology) and HRP-labeled anti-rabbit IgG antibodies as secondary antibodies. Detected in. Based on the obtained results, the signal intensity was quantified using Image-J, an image analysis software.

The results are shown in FIGS. 3A and 3B. DGDG (Sample 1) suppressed the induction of expression of ICAM-1 and VCAM-1.

[Test Example 4] Evaluation of monocyte adhesion inhibitory effect on HUVECs HUVECs were pre-cultured and cells were collected by trypsin treatment. The collected cells were seeded in each well of a 24-well plate by 5 × 10 ⁴ cells and cultured for 24 hours, and then treated with PBS buffer containing or without lipopolysaccharide (LPS, 1 μg / mL) for 24 hours. .. To treated HUVECs Thus, the addition of labeled human acute monocytic leukemia cells (THP-1) 2 × 10 5 cells at PKH26 Red, further test sample (Sample 1,5μg / mL) or control ( Incubated in DMSO) for 1 hour. Then, the cells that did not adhere were washed with PBS buffer, the cultured cells were fixed with 4% paraformaldehyde for 10 minutes, and washed with PBS buffer. THP-1 cells having adhered red fluorescence were counted using a fluorescence microscope (EVOS FL cell imaging system, manufactured by Thermo Fisher Scientific). Adhered cells were counted from 5 fields randomly selected from 2 wells and each test was repeated 4 times.

The results are shown in FIG. 4A (micrograph) and FIG. 4B (graph of counting results). Adhesion of LPS-induced monocytes (THP-1) to vascular endothelial cells (HUVECs) was suppressed by DGDG (Sample 1).

[Formulation Example 1]
A tablet for suppressing cell adhesion factor expression having the following composition was produced by a conventional method.
DGDG 5.0 mg
Dolomite (containing 20% calcium and 10% magnesium) 83.4 mg
Casein phosphopeptide 16.7 mg
Vitamin C 33.4 mg
Maltitol 136.8 mg
Collagen 12.7 mg
Sucrose fatty acid ester 12.0 mg

[Formulation Example 2]
An oral liquid preparation for suppressing the expression of cell adhesion factor having the following composition was produced by a conventional method.
<Composition in 1 ampoule (100 mL per ampoule)>
DGDG 0.3% by mass
Sorbitol 12.0% by mass
Sodium benzoate 0.1% by mass
Fragrance 1.0% by mass
Calcium sulfate 0.5% by mass
Purified water balance (100% by mass)

[Formulation Example 3]
A coffee beverage having the following composition was produced by a conventional method.
DGDG 0.1 part by mass Coffee extract (L (brightness) = 20, Brix = 3) 40 parts by mass Maltitol 2 parts by mass Fragrance Appropriate amount Water balance (100 parts by mass)

The cell adhesion factor expression inhibitor and the food and drink for suppressing cell adhesion factor expression according to the present invention include arteriosclerosis; ischemic heart disease caused by arteriosclerosis; cerebrovascular disease caused by arteriosclerosis such as cerebral hemorrhage and cerebral infarction; Can greatly contribute to.

Claims (3)

A cell adhesion molecule expression inhibitor characterized by containing digalactosyldiacylglycerol as an active ingredient. The cell adhesion factor expression inhibitor according to claim 1, wherein the cell adhesion factor is ICAM-1 and / or VCAM-1. A food or drink for suppressing the expression of cell adhesion factor, which is characterized by containing digalactosyldiacylglycerol.

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