JP2018100227A - Cell adhesion factor expression inhibitor - Google Patents

Abstract

PROBLEM TO BE SOLVED: 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 inhibiting cell adhesion factor expression.

  According to the Ministry of Health, Labor and Welfare's demographic statistics (2015), Japanese causes of death are malignant neoplasms, heart disease, pneumonia, and cerebrovascular disease. Cerebrovascular disease occupies the top. In addition, heart disease and cerebrovascular disease have strong sequelae and are often forced into long-term bedrock. Therefore, prevention, treatment or improvement of arteriosclerosis is extremely important.

  Atherosclerosis, particularly 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, arterial blood flow is blocked and myocardial infarction is blocked. Cause cardiovascular diseases such as cerebral infarction and the like.

  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 involved in the occurrence and progression of atherosclerosis in a complicated manner, there is a demand for an atherosclerosis inhibitor having a different mechanism of action from these factors.

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

  Here, for adhesion of monocytes to vascular endothelial cells, which is the initial stage of arteriosclerosis, cell adhesion factors such as ICAM-1 (intercellular adhesion molecule-1) on the cell surface are activated by activating vascular endothelial cells. It is known that expression of VCAM-1 (vascular cell adhesion molecule-1) and the like is induced, and these cell adhesion factors contribute to adhesion to monocytes. 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), a Kumazasa extract stabilized with copper sulfate (Patent Document 2), and the like are known.

Special table 2009-542682 gazette JP 2011-219434 A

  The present invention finds a substance having an action of suppressing the expression of a cell adhesion factor among components derived from natural products, a cell adhesion factor expression inhibitor containing the same as an active ingredient, and a cell adhesion factor expression containing the component It aims at providing food and drink for control.

  In order to solve the above-mentioned problems, the cell adhesion factor expression inhibitor according to the present invention is characterized by containing digalactosyl diacylglycerol as an active ingredient. Moreover, the food-drinks for cell adhesion factor expression suppression which concern on this invention mix | blended digalactosyl diacylglycerol.

  ADVANTAGE OF THE INVENTION According to this invention, the cell adhesion factor expression inhibitor excellent in the effect can be provided by containing digalactosyl diacylglycerol as an active ingredient. Furthermore, by blending digalactosyldiacylglycerol, a food and drink for cell adhesion factor expression suppression excellent in the above action can be provided.

It is a graph showing the result of having evaluated the cytotoxicity of the digalactosyl diacylglycerol (DGDG) with respect to a human umbilical vein endothelial cell (HUVECs). It is a graph showing the result (RT-PCR method) which evaluated the effect | action of DGDG with respect to the expression of the cell adhesion factor and cytokine in HUVECs. It is a photograph showing the result (immunoblot method) which evaluated the effect | action of DGDG with respect to the expression of the cell adhesion factor in HUVECs. It is the graph which digitized the result of FIG. 3A. It is a microscope picture showing the result of having evaluated the effect | action of DGDG with respect to adhesion | attachment of a monocyte (THP-1) -vascular endothelial cell (HUVECs). It is a graph showing the result of having counted the number of adhered cells from the micrograph of FIG. 4A.

Embodiments of the present invention will be described below.
The cell adhesion factor expression inhibitor according to the present embodiment contains digalactosyl diacylglycerol (hereinafter sometimes referred to as “DGDG”) as an active ingredient. Moreover, the food and drink for cell adhesion factor expression suppression which concerns on this embodiment mix | blends digalactosyl diacylglycerol.

  DGDG can be produced by, for example, isolating and purifying from a plant extract containing DGDG. In this case, the plant extract containing such DGDG can be obtained by a method generally used for plant extraction. Examples of plants containing DGDG include spinach, pineapple, rice, wheat, potato, komatsuna, and garlic.

  The method for extracting, isolating and purifying DGDG from the plant is not particularly limited, and can be performed according to a conventional method. For example, the extraction treatment may be performed by drying the plant as an extraction raw material, pulverizing it as it is or using a crusher, and subjecting it 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, and examples thereof include water and hydrophilic organic solvents. These are used alone or in combination of two or more at room temperature or a temperature below the boiling point of the solvent. It is preferable.

  Examples of water that can be used as the extraction solvent include pure water, tap water, well water, mineral spring water, mineral water, hot spring water, spring water, fresh water, and the like, and those subjected to various treatments. Examples of the treatment applied to water include 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 this embodiment includes purified water, hot water, ion exchange water, physiological saline, phosphate buffer, phosphate buffered saline, and the like.

  Examples of hydrophilic organic solvents that can be used as extraction solvents 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 using the liquid mixture of 2 or more types of polar solvents as an extraction solvent, the mixing ratio can be adjusted suitably. For example, when a mixed liquid of water and lower aliphatic alcohol is used as an extraction solvent, the mixing ratio of water and lower aliphatic alcohol is preferably 9: 1 to 1: 9 (volume ratio), More preferably, it is 7: 3 to 2: 8 (capacity ratio). In addition, when a mixed liquid 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). When using the liquid mixture with a monohydric alcohol, it is preferable that the mixing ratio of water and a polyhydric alcohol is 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 performed according to a conventional method. For example, the extraction raw material is immersed in an extraction solvent 5 to 15 times (mass ratio) of the extraction raw material, the soluble components are extracted at room temperature or under reflux, and then filtered to remove the extraction residue. A liquid can be obtained. After removing chlorophyll from the obtained extract using activated carbon or the like as necessary, the solvent is distilled off to obtain a paste-like concentrate, and when this concentrate is further dried, a dried product is obtained.

  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 performed by a conventional method. . For example, the extract is dissolved in a developing solvent, and subjected to column chromatography using a porous material such as silica gel or alumina, a porous resin such as styrene-divinylbenzene copolymer or polymethacrylate, and the like, and contains DGDG. Examples include a method for 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 etc. are mentioned. Further, the fraction containing DGDG obtained by column chromatography is subjected to any organic phase such as reverse phase silica gel chromatography using ODS, recrystallization, liquid-liquid countercurrent extraction, column chromatography using ion exchange resin, and the like. You may refine | purify using a compound refinement | purification means.

[Cell adhesion factor expression inhibitor]
Since 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 factor expression inhibitor. The cell adhesion factor expression inhibitor according to this embodiment can be used for a wide range of applications such as pharmaceuticals, quasi drugs, and cosmetics.

  In this embodiment, cell adhesion factors whose expression is suppressed by DGDG are, for example, ICAM-1 (intercellular adhesion molecule-1), VCAM-1 (vascular cell adhesion molecule-1), PECAM-1 (platelet endothelial cellular adhesion). immunoglobulin-1 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 this embodiment is preferably the 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 cell adhesion factor.

  Moreover, you may use DGDG as an active ingredient of an ICAM-1 expression inhibitor or a VCAM-1 expression inhibitor using the ICAM-1 expression inhibitory action or the VCAM-1 expression inhibitory action.

  In the present embodiment, the cell adhesion factor that is subject to expression suppression is preferably a cell adhesion factor of vascular endothelial cells.

  In addition, you may use the composition containing DGDG instead of isolated DGDG as an active ingredient of the cell adhesion factor expression inhibitor which concerns on this embodiment. Here, the “composition containing DGDG” in the present embodiment includes an extract obtained from a plant containing DGDG as an extraction raw material. The “extract” includes an extract obtained by an extraction process, a diluted or concentrated solution of the extract, or a dried product obtained by drying the extract.

  When a composition containing DGDG is used as an active ingredient of the cell adhesion factor expression inhibitor according to this embodiment, it is preferable to use a composition that has been purified to increase the purity of DGDG. A cell adhesion factor expression inhibitor more excellent in action and effect can be obtained by using as an active ingredient a substance having a higher purity of DGDG.

  The cell adhesion factor expression inhibitor according to this embodiment may be composed 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, cyclodextrin, and any other auxiliary agent according to a conventional method, such as powder, granule, tablet, liquid, etc. Can be formulated into any dosage form. In this case, as an auxiliary agent, for example, an excipient, a binder, a disintegrant, a lubricant, a stabilizer, a flavoring / flavoring agent, and the like can be used. The cell adhesion factor expression inhibitor can be used in combination with other compositions (for example, food and beverage for cell adhesion factor expression inhibition 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 a composition containing DGDG is not particularly limited, and can be appropriately set according to the purpose.

  In addition, the cell adhesion factor expression inhibitor according to the present embodiment, if necessary, is blended with other natural extracts having a cell adhesion factor expression inhibitory action or the like together with DGDG or a composition containing DGDG as an active ingredient. Can be used as

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

  The cell adhesion factor expression inhibitor according to the present embodiment is a monocyte 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 of DGDG as an active ingredient. Can be prevented, treated or ameliorated, such as arteriosclerosis; ischemic heart disease caused by arteriosclerosis; cerebrovascular disease caused by arteriosclerosis such as cerebral hemorrhage or cerebral infarction. However, the cell adhesion factor expression inhibitor according to the present embodiment can be used for all purposes that are meaningful for exerting the cell adhesion factor expression inhibitory action in addition to these applications.

  Moreover, since the cell adhesion factor expression inhibitor which concerns on this embodiment has the outstanding cell adhesion factor expression inhibitory effect, it can be utilized suitably also as a reagent for the research regarding these action mechanisms.

[Food and drink for cell adhesion factor expression suppression]
Since DGDG has an excellent cell adhesion factor expression inhibitory action, it is suitable for blending into food and drink for cell adhesion factor expression inhibition. In this case, DGDG may be blended as it is, or a cell adhesion factor expression inhibitor formulated from DGDG may be blended.

  Here, food and drink are those that are less likely to harm human health and that are taken by oral or gastrointestinal administration in normal social life. It is not limited to such categories. Therefore, “food and drink” in the present embodiment includes general foods that are taken orally, health foods (functional foods and drinks), health functional foods (special health foods, nutritional functional foods), quasi drugs, and pharmaceuticals. And so on.

  By blending DGDG or the above-mentioned cell adhesion factor expression inhibitor into food and drink, the cell adhesion factor expression inhibitory action, particularly the ICAM-1 expression inhibitory action or VCAM-1 expression inhibitory action can be imparted to the food and drink.

  When DGDG or a cell adhesion factor expression inhibitor formulated from DGDG is blended into a food or drink to make it a food or drink for cell adhesion factor expression suppression, the compounding amount of the active ingredient in them is the use purpose, symptom, sex, etc. Although it can be appropriately changed in consideration, it is preferable that the daily intake of the extract is about 1-1000 mg per adult in consideration of the general intake of food and drink to be added. . In addition, when the food / beverage products to be added are granular, tablet or capsule food / beverage products, the addition amount of DGDG or the cell adhesion factor expression inhibitor formulated from DGDG is usually 0. It is 1-100 mass%, Preferably it is 5-100 mass%.

  The cell-adhesive factor expression-suppressing food or drink according to this embodiment may be a food supplement that contains DGDG in any food or drink that does not impede its activity, and is a dietary supplement mainly composed of DGDG. May be.

  When producing a food or drink for cell adhesion factor expression suppression 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; Arbitrary auxiliaries such as polysaccharides such as cellulose and gum arabic; oils and fats such as soybean oil and medium chain fatty acid triglycerides can be added to make foods and drinks of any shape.

  Although the food and drink which can mix | blend DGDG is not specifically limited, As its specific examples, drinks, such as a soft drink, a carbonated drink, a nutritive drink, a fruit drink, and a lactic acid drink (The concentrated undiluted solution and powder for adjustment of these drinks are included.) Ice cream, ice sherbet, shaved ice and other frozen desserts; buckwheat noodles, udon, harusame, gyoza skin, sushi, Chinese noodles, instant noodles and other noodles; Sweets such as biscuits, jelly, jam, cream, baked confectionery; processed fishery and livestock products such as kamaboko, ham, sausage; dairy products such as processed milk, fermented milk; salad oil, tempura oil, margarine, mayonnaise, shortening, whipped Fats and oils and processed foods such as creams and dressings; Seasonings such as sauces and sauces; Soups Nursing, salads, prepared foods, pickles; various other forms of health and nutritional supplements; tablets, capsules, drinks, etc., and supplementary ingredients commonly used when DGDG is added to these foods and drinks And additives can be used in combination.

  In addition, although the cell adhesion factor expression inhibitor and the food and drink for cell adhesion factor expression suppression according to this embodiment are suitably applied to humans, as long as the respective effects are exhibited, other than humans The present invention can also be applied to other animals (eg, mouse, rat, hamster, dog, cat, cow, pig, monkey, etc.).

  Hereinafter, although a manufacture example, a test example, and a compounding example are shown and this invention is demonstrated concretely, this invention is not restrict | limited to each following example at all.

  In the test examples described later, lipopolysaccharide (LPS) and PKH26 Red Fluorescent Cell Linker Kit purchased from Sigma Aldrich were used. Anti-ICAM-1, anti-VCAM-1, and anti-β-actin antibodies were manufactured by Cell Signaling Technology. 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 were obtained by adding a growth factor EGM-2MV addition factor (attached to EBM-2) to an endothelial cell basal medium (EBM-2; manufactured by Lonza) under conditions of 37 ° C. and 5% CO _2. In culture. Human acute monocytic leukemia cells (THP-1) were purchased from JCRB cell bank, and RPMI1640 medium (Life technologies) was supplemented with 10% FBS and 1% antibiotics (both from Life technologies). Cultured.

[Production Example] Production of DGDG Dry spinach (200 g) was subjected to reflux extraction with 70% ethanol (2 L) for 2 hours. After filtration, activated carbon was added to the extract, and the mixture was stirred for 1 hour under reflux 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 elution part (2 0.7 g) was obtained. The chloroform eluate (2.6 g) was subjected to normal phase silica gel column chromatography (carrier: Silica gel 60, manufactured by Merck & Co., Inc.) and fractionated with chloroform-methanol-water (40: 10: 0.1) to give sugar. A lipid fraction (425 mg) was obtained. Glycolipid fraction (425 mg), recycle HPLC (solvent: methanol, column: two JAIGEL GS310 linked (500 x 20 mm id) (manufactured by Nihon Analytical Industrial Co., Ltd.), equipment used: YMC LC-forte / R )) 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 confirmed to be DGDG (Sample 1).

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

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

[Test Example 2] Evaluation of cell adhesion factor and cytokine expression inhibitory action (RT-PCR method)
HUVECs were pre-cultured and cells were collected by trypsinization. The collected cells are diluted with the same medium as the preculture so as to have a cell density of 2.4 × 10 ⁴ cells / mL, and then seeded at 2 mL in a 35 mm petri dish (manufactured by FALCON) at 37 ° C., 5% CO _2. For 48 hours.

After culturing, the medium was removed, and 2 mL of the medium to which the test sample (sample 1, 5 μg / mL) and lipopolysaccharide (LPS, 1 μg / mL) were added was added to each petri dish at 37 ° C. and 5% CO ₂ . For 2 hours. The control cells were cultured in the same manner in the sample and the medium not containing LPS, and the expression-inducing cells were cultured in the same manner in the medium without the sample and LPS. After culture, the medium was removed, and total RNA was extracted with ISOGEN (Nippon Gene).

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

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

[Test Example 3] Evaluation of cell adhesion factor expression inhibitory action (immunoblot method)
HUVECs were pre-cultured and cells were collected by trypsinization. The collected cells are diluted with the same medium as the preculture so as to have a cell density of 2.4 × 10 ⁴ cells / mL, and then seeded at 2 mL in a 35 mm petri dish (manufactured by FALCON) at 37 ° C., 5% CO _2. For 48 hours.

After culturing, the medium was removed, and 2 mL of the medium to which the test sample (sample 1, 5 μg / mL) and lipopolysaccharide (LPS, 1 μg / mL) were added was added to each petri dish at 37 ° C. and 5% CO ₂ . For 4 hours. In addition, it culture | cultivated similarly about the culture medium (For the test sample density | concentration, refer FIG. 3A and FIG. 3B) without LPS as a comparison object. After culturing, the medium was removed and dissolved in RIPA solution (ThermoFisher Scientific), and the obtained sample was subjected to immunoblotting. An anti-ICAM-1, anti-VCAM-1, and anti-β-actin primary antibody (all manufactured by Cell Signaling Technology) and an anti-rabbit IgG antibody labeled with HRP as a secondary antibody were used, and an enhanced chemiluminescence (ECL) system It was detected at. Based on the obtained results, the signal intensity was digitized using Image-J, which is image analysis software.

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

[Test Example 4] Evaluation of monocyte adhesion inhibitory action on HUVECs HUVECs were pre-cultured and cells were collected by trypsin treatment. The collected cells were seeded at 5 × 10 ⁴ cells in each well of a 24-well plate and cultured for 24 hours, and then treated with a PBS buffer solution with or without lipopolysaccharide (LPS, 1 μg / mL) added for 24 hours. . To the thus treated HUVECs, 2 × 10 ⁵ cells of human acute monocytic leukemia cells (THP-1) labeled with PKH26 Red were added, and a test sample (sample 1, ⁵ μg / mL) or a control ( DMSO) for 1 hour. Thereafter, the cells that did not adhere were washed with PBS buffer, and then the cultured cells were fixed with 4% paraformaldehyde for 10 minutes and washed with PBS buffer. Adhered THP-1 cells with red fluorescence were counted using a fluorescence microscope (EVOS FL cell imaging system, ThermoFisher Scientific). Adherent cells were counted from 5 fields randomly selected from duplicate 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 monocytes (THP-1) to vascular endothelial cells (HUVECs) induced by LPS was suppressed by DGDG (Sample 1).

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

[Formulation Example 2]
By an ordinary method, an oral liquid preparation for suppressing expression of cell adhesion factor having the following composition was produced.
<Composition in one ampoule (one 100 mL)>
DGDG 0.3% by mass
Sorbit 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)

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

  Cell adhesion factor expression inhibitor and food / drink for cell adhesion factor expression suppression 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 contribute greatly.

Claims (3)

  A cell adhesion factor expression inhibitor comprising digalactosyl diacylglycerol 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 and drink for suppressing the expression of cell adhesion factor, characterized in that it contains digalactosyldiacylglycerol.