JP7133306B2 - Acyl steryl glucoside, method for producing acyl steryl glucoside, composition, antioxidant, blood lipid-lowering agent, anti-obesity agent, anti-tumor agent, and prophylactic or therapeutic agent for atherosclerosis - Google Patents

Description

Application of Article 30, Paragraph 2 of the Patent Act June 3, 2017, 19th Marine Biotechnology Society Sendai Conference Website

Application of Article 30, Paragraph 2 of the Patent Law Jun. 3, 2017, 19th Annual Meeting of the Society of Marine Biotechnology, Sendai Abstracts of Abstracts No. PA-12

Application of Patent Law Article 30, Paragraph 2 June 3, 2017, 19th Marine Biotechnology Society Sendai Convention PA-12 Poster

Application of Article 30, Paragraph 2 of the Patent Act July 8, 2017, 4th Labyrinthula Symposium Website

Application of Article 30, Paragraph 2 of the Patent Act July 8, 2017, 4th Labyrinthula Symposium Program

Application of Article 30, Paragraph 2 of the Patent Law July 8, 2017, 4th Labyrinthula Symposium P11 poster

The present invention relates to an acylsteryl glucoside, a method for producing the acyl steryl glucoside, a composition, an antioxidant , a blood lipid-lowering agent, an anti-obesity agent, an anti-tumor agent, and a prophylactic or therapeutic agent for atherosclerosis.

Labyrinthulids are eukaryotic microorganisms that live in the ocean. Labyrinthula taxonomically, they belong to protists and form a large phylogenetic group called Stramenoviridae together with Oomycetes and the like. Labyrinthulids are composed of Labyrinthulaceae and Thraustochytrium in a narrow sense, and the former is classified into 1 genus Labyrinthula, and the latter is classified into 11 genera such as Aurantiochytrium, Thraustochytrium, and Paeritichytrium. It is

Labyrinthula are excellent in producing highly unsaturated fatty acids such as DHA, saturated fatty acids such as palmitic acid, hydrocarbons such as squalene, and lipids such as sphingolipids. can be stored in Therefore, it is of great industrial interest as a production source for pharmaceuticals, functional foods, and bioenergy (Patent Document 1).

For example, Aurantiochytrium, a species of Labyrinthula, is attracting attention as an alga that produces oil, and is being developed as an alternative production source for n-3 polyunsaturated fatty acids, which are industrially produced from bluefish. is underway.

As a glycolipid contained in Labyrinthula, steryl glucoside (SG) in which glucose is bound to sterol has been identified. For example, four substances have been identified as steryl glucosides in the A. limacinum mh0186 strain isolated from the coastal seawater of Hateruma Island, Okinawa Prefecture. Specifically, GL-A (3-O-b-D-glucopyranosyl-stigmasta-5,7,22-triene) and GL-B (3-O-b-D-glucopyranosyl-4-a-methyl-stigmasta-7,22-diene) The structures of two steryl glucosides (SG) were determined by two-dimensional NMR, and GL-C (3-O-b-D-glucopyranosyl-stigmasta-7,22 -diene) and cholesteryl glucoside (CG) (Fig. 1).

Steryl glucoside (sterol glycoside) and acyl steryl glucoside (sterol glycoside ester) are contained in oils and fats as natural oil components, and their uses include, for example, hair growth and restoration (Patent Document 2). , lowering of blood lipids (Patent Document 3), and prevention of obesity (Patent Document 4).

Although steryl glucoside and acyl steryl glucoside are useful ingredients with high demand, they are rare in the natural world and their supply sources are limited. In addition, it was not previously known that Labyrinthulas contain acylsteryl glucosides.

Japanese Patent Application Laid-Open No. 2010-200690 JP-A-7-101835 JP-A-7-118159 JP-A-7-107939

The present invention has been made in view of the above problems, and an object of the present invention is to provide a method for producing a novel acylsteryl glucoside using Labyrinthulas as a starting material.
Another object of the present invention is to provide compositions such as food compositions, pharmaceutical compositions and cosmetic compositions containing acylsteryl glucosides derived from Labyrinthula.
Still another object of the present invention is to provide an anti-oxidant , blood lipid-lowering agent, anti-obesity agent, anti-tumor agent and anti-atherosclerosis agent containing as an active ingredient an acylsteryl glucoside derived from labyrinthula. It is to provide a preventive or therapeutic agent.

As a result of intensive studies aimed at solving the above problems, the present inventors have found that Labyrinthula contain glycolipids of unknown structure in addition to sterylglucosides, and have completed the present invention.

Therefore, according to the present invention, the above object is solved by an acylsteryl glucoside represented by the following structural formula (I), structural formula (II) or structural formula (III).

Further, according to the present invention, the above-mentioned problems are achieved by a labyrintula preparation step of preparing labyrintula, a separation step of separating an acylsteryl glucoside fraction containing acyl steryl glucoside from the labyrintula, and the separation step and a purification step of purifying the acyl steryl glucoside from the acyl steryl glucoside fraction separated in .
At this time, the acyl steryl glucoside is preferably one or more represented by the following structural formula (I), structural formula (II), or structural formula (III).

Moreover, according to the present invention, the above object is solved by a composition containing an acylsteryl glucoside derived from Labyrinthula and selected from food compositions, pharmaceutical compositions and cosmetic compositions .
At this time, the acylsteryl glucoside is preferably one or more represented by the following structural formula (I), structural formula (II), or structural formula (III).

At this time, the composition is preferably a food composition.
At this time, the composition is preferably a pharmaceutical composition.
At this time, the composition is preferably a cosmetic composition.

In addition, according to the antioxidant of the present invention, the antioxidant contains Labyrinthula-derived acyl steryl glucoside as an active ingredient, and the acyl steryl glucoside has the following structural formula (I) and structural formula (II) or one or more represented by Structural Formula (III) .
Further , according to the blood lipid-lowering agent of the present invention, an acylsteryl glucoside derived from Labyrinthula is contained as an active ingredient, and the acyl steryl glucoside is represented by the following structural formula (I) and structural formula (II) or one or more represented by Structural Formula (III) .
Further, according to the anti-obesity agent of the present invention, the acyl steryl glucoside derived from Labyrinthula is contained as an active ingredient, and the acyl steryl glucoside has the following structural formula (I) and structural formula (II) or one or more represented by Structural Formula (III) .
Further, according to the antitumor agent of the present invention, the acylsteryl glucoside derived from Labyrinthula is contained as an active ingredient, and the acyl steryl glucoside has the following structural formula (I) and structural formula (II) or one or more represented by Structural Formula (III) .
In addition, according to the preventive or therapeutic agent for atherosclerosis of the present invention, the above-mentioned problem is achieved by containing an acylsteryl glucoside derived from Labyrinthula as an active ingredient, and the acyl steryl glucoside is represented by the following structural formula (I ), Structural Formula (II) or Structural Formula (III) .

According to the present invention, novel acylsteryl glucosides can be provided.
According to the method for producing acyl steryl glucoside of the present invention, it is possible to produce acyl steryl glucoside, which is a useful substance, using Labyrinthula, which is an algal biomass that can be mass-cultivated.
In addition, Labyrinthula-derived acylsteryl glucosides can be used as compositions such as food compositions, pharmaceutical compositions, and cosmetic compositions.
Further, according to the present invention, an antioxidant, hair growth or hair restorer, blood lipid-lowering agent, anti-obesity agent, anti-tumor agent, or atherosclerosis containing as an active ingredient an acylsteryl glucoside derived from Labyrinthula. A prophylactic or therapeutic agent for disease can be provided.

FIG. 2 shows steryl glucoside contained in A. limacinum mh0186 strain. 1 is a flowchart showing a method for producing an acylsteryl glucoside of this embodiment. FIG. 1 is a photograph showing the results of thin layer chromatography (TLC) in Test 1. FIG. Unknown glycolipids are indicated by arrows. Sitosteryl glucoside and acyl steryl glucoside were used as samples, and 2 mg of lipid extracted from dried cells was tested in one lane. Chloroform/methanol/water=65/25/4 was used as a developing solvent, and bands were detected with orcinol sulfuric acid. 2 shows the results of high-performance liquid chromatography-mass spectrometry (LC-MS) in Test 2. FIG. Figure 2 shows the structure of an acylsteryl glucoside identified in Study 2 (DHA-GL-A, Structural Formula (I)). 2 shows the results of high-performance liquid chromatography-mass spectrometry (LC-MS) in Test 2. FIG. Figure 2 shows the structure of the acylsteryl glucoside identified in Test 2 (DHA-CG, Structural Formula (II)). 2 is a graph showing the results of gas chromatography (GC) analysis of the composition of fatty acids bound to acylsteryl glucoside (ASG) in Test 3. FIG. 2 is a graph showing the results of analysis of a combination of steryl glucoside (SG) and fatty acid in acyl steryl glucoside (ASG) in Test 4 using a high-performance liquid chromatography-mass spectrometer (LC-MS). FIG. 10 is an explanatory diagram showing the flow of binding analysis (weak allial digestion and β-glucosidase (EGCrP2) treatment) performed in Test 5; FIG. 10 is a photograph of thin layer chromatography (TLC) showing the results of analysis of binding between ASG fatty acid and sugar in Test 5. FIG. A. in test 6. 1 is a graph showing growth curves of cells of Limacinum mh0186. 10 is a graph showing changes over time in the concentration of glucose contained in the culture solution in Test 6. FIG. The A.I. 1 is a graph showing changes over time in the amount of steryl glucoside (SG) contained in cells of Limacinum mh0186. The A.I. 1 is a graph showing changes over time in the amount of acylsteryl glucoside (ASG) contained in cells of limacinum mh0186. FIG. 4 is an explanatory diagram showing an estimated ASG synthesis process; (a) Hypothesis 1: TG lipase transfers fatty acids to SG. (b) Hypothesis 2: Phospholipases transfer fatty acids to SGs. Changes in SG and ASG amounts due to addition of oleic acid. (a) amount of EG (ergosteryl glucoside), (b) amount of AEG (acyl ergosteryl glucoside), (c) total AEG amount. Mean±SE (n=3), n.p. d means not detected. FIG. 2 is an illustration of the structures of novel acylsteryl glucosides (ASG) contained in Labyrinthula identified from Studies 1-6. FIG. 2 shows that acylsteryl glucoside (ASG), neutral lipids, and phospholipids act as reservoirs for DHA accumulation in Labyrinthula. 4 is a photograph showing the results of thin layer chromatography (TLC) measured in Test 8. FIG. 4 is a graph showing the results of high-performance liquid chromatography-mass spectrometry (LC-MS) measured in Test 8. FIG. 10 is a graph showing the results of oxidation measurement of DHA-SG and DHA examined in Test 9. FIG.

An embodiment (this embodiment) of the present invention will be described below with reference to FIGS.
This embodiment provides an acylsteryl glucoside, a method for producing an acyl steryl glucoside, a composition, an antioxidant, a hair growth or hair restorer, a blood lipid-lowering agent, an anti-obesity agent, an anti-tumor agent, and atherosclerosis. It relates to a prophylactic or therapeutic agent.

Abbreviations used herein are as follows.
ASG: acyl steryl gluoside
DCW: dry cell weight
DHA: docosahexaenoic acid
EG: ergosteryl glucoside
LC-MS: liquid chromatography-mass spectrometry
LPC: lysophosphatidyl choline
LPE: lysophosphatidyl ethanolamine
PC: phosphatidyl choline
PE: phosphatidyl ethanolamine
SE: sterol ester
SG: steryl glucoside
TG: triacylglycerol
TLC: thin layer chromatography

<Labyrinthula>
The acylsteryl glucoside of the present embodiment can be obtained by culturing, separating, and purifying Labyrinthula, which are marine eukaryotic microorganisms.
In the present embodiment, the term "Labyrinthula" includes all microorganisms classified as Labyrinthula in zoological and botanical classification, variants thereof, and variants thereof.

Labyrinthulas include the genus Labyrinthula, Althornia, Aplanochytrium, Japonochytrium, Labyrinthuloides, Schizochytrium, Thraustochytrium, Oblongichytrium, Parietichytrium, or Ulkenia, Aurantiochytrium, preferably Aurantiochytrium Among these microorganisms, Aurantiochytrium limacinum is particularly preferred. These may be strains distributed from preservation institutions or subculture strains thereof. The limacinum mh0186 strain is exemplified.

Labyrinthulas A. The limacinum mh0186 strain (accession number FERM P-19755) is isolated on the coast of Hateruma Island, Okinawa Prefecture, and can grow at a wide range of culture temperatures from 10 to 35 ° C. Therefore, the acylsteryl glucoside of the present embodiment. It can be suitably used for the manufacturing method.

Labyrinthulas are widely distributed in the ocean, especially in coastal seawater areas and brackish water areas such as estuaries. kind can be used.
Labyrinthulids include all variants thereof. These mutant strains also include those obtained by genetic methods such as recombination, transduction, and transformation.

Labyrinthulids are cultured in a conventional solid medium, liquid medium, or the like by a conventional method. At this time, the medium used includes, for example, carbon sources such as glucose, fructose, saccharose, starch, and glycerin, and nitrogen sources such as yeast extract, corn steep liquor, polypeptone, sodium glutamate, urea, ammonium acetate, ammonium sulfate, ammonium nitrate, and chloride. It is a medium in which ammonium, sodium nitrate, etc., and potassium phosphate as an inorganic salt, and other necessary components are appropriately combined, and is not particularly limited as long as it is commonly used for culturing Labyrinthula, but is particularly preferred. A yeast extract-glucose medium (GY medium) is used. After preparation, the medium is adjusted to a pH within the range of 3.0 to 8.0, and then sterilized by an autoclave or the like before use. Cultivation may be performed at 10 to 40° C., preferably 15 to 35° C., for 1 to 14 days by aeration and stirring culture, shaking culture, or static culture.

Labyrinthula can be cultivated without irradiating light, but the open pond method, which directly uses sunlight, collects sunlight with a light collector, sends it through optical fibers, etc., and irradiates it in the culture tank for photosynthesis. It may be performed by a condensing method or the like used for the above.
Labyrinthula can be cultured using, for example, a feeding batch method, but flask culture, culture using a fermenter, batch culture method, semi-batch culture method (fed-batch culture method), continuous culture method ( Any liquid culture method such as perfusion culture method) may be used.
Separation of labyrinthulids is carried out, for example, by centrifugation, filtration or simple sedimentation of the broth.

<Steryl glucoside and acyl steryl glucoside>
(steryl glucoside)
A steryl glucoside (SG) is a type of glycolipid, and has a structure in which glucose is bonded to a sterol skeleton via α- or β-glucoside. It has been suggested that steryl glucoside may function as a lipid mediator in cell differentiation and stress response. In addition, steryl glucoside is known as an active ingredient of, for example, therapeutic agents for viral and bacterial infections, hair growth agents, hair growth agents, blood lipid-lowering agents, anti-obesity agents, anti-stress agents, nutrient absorption promoters, and the like. It is

(acyl steryl glucoside)
Acyl steryl glucoside (ASG) is a general term for substances in which fatty acids are ester-bonded to steryl glucoside (SG).
Here, in the acyl steryl glucoside of the present embodiment, docosahexaenoic acid (DHA) or palmitic acid is ester-bonded to steryl glucoside (SG).

The acyl steryl glucoside of the present embodiment has the following structural formula (I) (DHA-GL-A), structural formula (II) (DHA-CG), or structural formula ( III) is represented by (DHA-GL-C).

As a function of acylsteryl glucoside (ASG), it kills human breast cancer cell line (MCF7) better than steryl glucoside (SG) (Wimmerova et al, Improved enzyme-mediated synthesis and supramolecular self-assembly of naturally occurring conjugates of β-sitosterol, Steroids 117 (2017) 38-43), reducing elevated LDL cholesterol (Ito et al, Rice bran extract containing acylated steryl glucoside fraction decreases elevated blood LDL cholesterol level in obese Japanese men, The Journal of Medical Investigation, 62 (2015) 80-84), Nhung et al, Rice Bran Extract Reduces the Risk of Atherosclerosis in Post-Menopausal Vietnamese Women., Journal of Nutritional Science and Vitaminology, 62 (2016) 295-302) have been reported.

<Method for Producing Acylsteryl Glucoside>
The method for producing acyl steryl glucoside of the present embodiment includes a labyrintula preparation step of preparing labyrintula, a separation step of separating an acyl steryl glucoside fraction containing acyl steryl glucoside from the labyrintula, and the separation and a purification step of purifying the acyl steryl glucoside from the acyl steryl glucoside fraction separated in the step.
Each step will be described in detail below with reference to FIG.

(Labyrinthula preparation process)
In the labyrinthula preparing step, labyrinthula as a raw material for acylsteryl glucoside are prepared (step S1).
Labyrinthula used as a raw material is preferably a dried product of Labyrinthula cells from the viewpoint of separation and purification of acylsteryl glucoside, but is not limited to this. In the present embodiment, it is preferable to use, as a raw material, a dried body of Labyrinthula obtained by freeze-drying or spray-drying live Labyrinthula cells.

In addition, live Labyrinthula cells collected by centrifugation, filtration, sedimentation, or the like after culturing can also be used as a raw material. Live Labyrinthula cells can be used as they are after being harvested from the culture vessel, but are preferably washed with water or saline. Alternatively, the Labyrinthulula alga body may be used in the form of a dispersion in a liquid such as a culture solution or water.
Furthermore, a mechanically treated product of algal bodies obtained by subjecting Labyrinthula cells to ultrasonic irradiation treatment or mechanical treatment such as homogenization may be used as a raw material. Also, a dried mechanically processed product obtained by subjecting a mechanically processed product to a drying treatment may be used as a raw material.

(Separation process)
In the separation step, an acylsteryl glucoside fraction containing acyl steryl glucoside is separated from the labyrinthula prepared in the labyrinthula preparation step (step S2).
The method of separation (fractionation) is not particularly limited as long as the acylsteryl glucoside fraction can be separated. A method of fractionating a fraction with a high acylsteryl glucoside content by reverse-phase or normal-phase high performance liquid chromatography (HPLC, etc.), A method of filtering the extraction mixture, separating the extract and residue, concentrating the extract, and fractionating by liquid chromatography may be mentioned.

When a culture medium containing cultured Labyrinthuula is prepared in the Labyrinthulea preparation step, the Labyrinthulan algal body is recovered by a known method such as centrifugation of the culture medium, simple sedimentation, or membrane filtration, and the Labyrinthulan algal body is After washing, the dried alga body of Labyrinthula may be used in the separation step by drying by a known drying method (vacuum freeze drying, spray drying, heat vacuum drying, etc.).

Alternatively, the labyrinthula prepared in the labyrinthula preparation step may be pulverized by a known pulverization method such as an ultrasonic crusher.

The extraction solvent used in the separation step is not particularly limited as long as it can extract the acyl steryl glucoside and facilitates subsequent purification. Examples include methanol, ethanol, propanol, isopropanol, butanol, propylene glycol, Alcohols such as butylene glycol, methyl acetate, ethyl acetate, acetone, chloroform, toluene, pentane, hexane, cyclohexane, and the like can be used alone or in combination of two or more.
In particular, it is preferable to extract the acylsteryl glucoside using a mixed solvent of chloroform/methanol. At this time, the mixing ratio of the solvent may be set arbitrarily, but it is preferable to use a solvent of chloroform: methanol = 50 vol%: 50 vol% to 90 vol%: 10 vol%, chloroform: methanol = 60 vol%: 40 vol% to 70 vol%. %:30 vol % solvent is more preferred, and it is particularly preferred to use a solvent with a Folch distribution, ie chloroform:methanol=2:1 (volume ratio).

(Refining process)
In the purification step, the acylsterylglucoside is purified from the acylsterylglucoside fraction separated in the separation step (step S3).
The purification method is not particularly limited as long as it can purify the desired acyl steryl glucoside, but examples include a method of purifying the acyl steryl glucoside by a suitable separation column or recrystallization.

<Application>
Labyrinthula-derived acyl steryl glucoside can be used for various purposes by utilizing its functionality, like other steryl glucosides (SG) and acyl steryl glucosides (ASG).

(antioxidant)
Polyunsaturated fatty acids such as docosahexaenoic acid (DHA) have antioxidant effects, and acyl steryl glucoside derived from Labyrinthula, in which docosahexaenoic acid (DHA) is ester-bonded to steryl glucoside (SG), is an anti-oxidant. It can be used as an oxidizing agent.

(hair growth agent, hair restorer)
Labyrinthula-derived acylsteryl glucoside can be used as a hair growth agent or a hair restorer (JP-A-7-101835).

(Blood lipid-lowering agent)
Labyrinthula-derived acylsteryl glucoside can be used as a blood lipid-lowering agent that is used to lower lipids such as cholesterol, neutral lipids and phospholipids in the blood (JP-A-7-118159). Bulletin, Ito et al, The Journal of Medical Investigation, 62 (2015) 80-84).

(anti-obesity agent)
Labyrinthula-derived acylsteryl glucosides can be used as anti-obesity agents for the treatment and prevention of obesity (JP-A-7-107939).

(antitumor agent)
Labyrinthula-derived acylsteryl glucoside has a cancer cell-killing effect and can be used as an anti-tumor agent (anti-breast cancer agent) for treating cancer by suppressing tumor growth. (Wimmerova et al, Steroids 117 (2017) 38-43).

(Prophylactic or therapeutic agent for atherosclerosis)
Labyrinthula-derived acyl steryl glucoside has the effect of reducing the risk of atherosclerosis, and is used as a prophylactic or therapeutic agent for atherosclerosis to prevent or treat atherosclerosis. (Nhung et al, Journal of Nutritional Science and Vitaminology, 62 (2016) 295-302).

<Composition>
Antioxidant, hair growth or hair growth agent, blood lipid-lowering agent, anti-obesity agent, anti-tumor agent, and prevention of atherosclerosis containing Labyrinthula-derived acylsteryl glucoside according to the present embodiment as an active ingredient Alternatively, the therapeutic agent is configured as a food composition such as a health food, a pharmaceutical composition, or a cosmetic composition and administered to a living body.

(Food composition)
The labyrinthula-derived acylsteryl glucoside of the present embodiment can also be used in foods.
In the field of foods, the food composition of the present embodiment has an effective amount of Labyrinthula-derived acylsteryl glucoside that can effectively exhibit various actions as a food material, and is added to various foods. A food composition can be provided.
It is also possible to provide a food composition by combining a Labyrinthula-derived acylsteryl glucoside with a food for specified health uses, a food with nutrient function claims, a food with functional claims, a food for hospital patients, a supplement, or the like.
Examples of the food composition include seasonings, processed meat products, processed agricultural products, beverages (soft drinks, alcoholic drinks, carbonated drinks, milk drinks, fruit juice drinks, tea, coffee, nutritional drinks, etc.), powdered drinks (powder juices, powdered soups, etc.), concentrated beverages, confectionery (candies, cookies, biscuits, gums, gummies, chocolates, etc.), breads, cereals and the like. In the case of food for specified health uses, food with nutrient function claims, food with function claims, etc., the shape may be capsule, troche, syrup, granule, powder, or the like.

Foods for Specified Health Uses are foods that contain functional health ingredients that affect physiological functions, etc., and can be labeled as suitable for specific health uses with the permission of the Director-General of the Consumer Affairs Agency. be.

A food with nutrient function claims is a food that is used to supplement nutritional ingredients (vitamins and minerals), and the functions of the nutritional ingredients are indicated. In order to be sold as a food with nutrient function claims, the amount of nutrients contained in the recommended daily intake must be within the specified upper and lower limits. also need to
Foods with function claims are foods labeled with functionalities based on scientific evidence under the responsibility of the business operator. Information on the grounds for safety and functionality was submitted to the Commissioner of the Consumer Affairs Agency before sales.

In the food composition according to the present embodiment, in addition to Labyrinthula-derived acylsteryl glucoside, one or more components that can be used in ordinary food compositions can be freely selected and blended. is. For example, all additives that can be commonly used in the food field, such as various seasonings, preservatives, emulsifiers, stabilizers, fragrances, coloring agents, preservatives, and pH adjusters, can be included.

To the food composition according to the present embodiment, it is also possible to add one or more other substances known to have various actions to the Labyrinthula-derived acylsteryl glucoside.

(Pharmaceutical composition)
The labyrinthula-derived acylsteryl glucoside of the present embodiment can be used as a pharmaceutical composition.
The pharmaceutical composition of the present embodiment is a pharmaceutical composition having an effect by blending a pharmaceutically acceptable carrier and an additive with an acylsteryl glucoside derived from Labyrinthula in an amount that can effectively exhibit various effects. goods are provided. The pharmaceutical composition may be a drug or a quasi-drug.
The pharmaceutical composition may be applied topically or internally. Therefore, the pharmaceutical composition is used in formulation forms such as oral preparations, injections such as subcutaneous injections, intravenous injections, intradermal injections, intramuscular injections and/or intraperitoneal injections, transmucosal applications, transdermal applications, and the like. be able to.
The dosage form of the pharmaceutical composition can be appropriately set depending on the form of application. Examples include solid formulations such as capsules, powders, and powders.

The pharmaceutical composition according to this embodiment can contain one or more pharmaceutically acceptable additives by freely selecting them.
For example, when the pharmaceutical composition according to this embodiment is applied to an oral formulation, for example, excipients, binders, disintegrants, surfactants, preservatives, coloring agents, flavoring agents, fragrances, stabilizers, preservatives All additives that can be commonly used in the field of pharmaceutical formulations, such as agents, antioxidants, etc., can be contained. In addition, a drug delivery system (DDS) can be used to prepare a sustained-release preparation or the like.

In addition to Labyrinthula-derived acylsteryl glucoside, one or more other substances known to have various actions can be added to the pharmaceutical composition according to the present embodiment.

(Cosmetic composition)
The labyrinthula-derived acylsteryl glucoside of the present embodiment can be suitably used in cosmetic compositions by utilizing various actions.
The cosmetic composition can be applied to any form of cosmetics. For example, it can be applied to skin care cosmetics such as lotions, milky lotions, creams and serums, makeup cosmetics such as foundations, concealers, makeup bases, lipsticks, blushers, eye shadows and eyeliners, and sunscreen cosmetics. .

In the cosmetic composition according to the present embodiment, in addition to Labyrinthula-derived acylsteryl glucoside, one or more components that can be used in ordinary cosmetic compositions are freely selected and blended. is possible.
For example, base materials, preservatives, emulsifiers, coloring agents, preservatives, surfactants, ultraviolet absorbers, antioxidants, moisturizing agents, ultraviolet absorbers, fragrances, antiseptic antifungal agents, extender pigments, coloring pigments, alcohols, All additives that can normally be used in the cosmetic field, such as water, can be included.

In the cosmetic composition according to the present embodiment, the content of the labyrinthula-derived acylsteryl glucoside is not particularly limited, and can be freely set according to the purpose.

EXAMPLES The present invention will be specifically described below based on specific examples, but the present invention is not limited to these.
In the following examples, unknown glycolipids were isolated from the total lipid fraction of Aurantiochytrium limacinum mh0186 strain, which is a labyrinthula, using a Sep-pak plus silica column, and the structure was clarified by mass spectrometry, weak alkaline decomposition, and β-glucosidase treatment. Analyzed. Glycolipids were quantified with a liquid chromatograph-mass spectrometer (LC-MS).

<Material>
SG and ASG were purchased from Matreya LCC. TG(12:0/12:0/12:0), PC(11:0/11:0), LPC(13:0), PE(12:0/12:0), LPE(13:0) , SE (16:0-d7 cholesterol), d7 cholesterol were purchased from Avanti Polar Lipids. Artificial seawater (SEALIFE) was purchased from Nihonkaisui. Organic solvents used for LC-MS analysis were purchased from Wako Pure Chemical Industries.

<Test 1 Isolation and purification of unknown glycolipid>
(Culture of A. limacinum mh0186)
A. limacinum mh0186 strain was used as Labyrinthulas. Cells pre-cultured in 3ml of GY medium containing 0.1% vitamin mixture and 0.2% element solution (3.1% (w/v) D-glucose, 1.0% (w/v) Yeast Extract, 1.75% (w/v) SEALIFE) 100 μl of this was added to 100 ml of GY medium (300 ml Erlenmeyer flask, containing 0.1% vitamin mixture, 0.2% element solution) and cultured with shaking for 3 days (150 rpm, 25° C.). Here, the composition of the vitamin mixture is 0.2% (w/v) vitamin _B1 , 0.001% (w/v) vitamin B2, 0.001% ₍ w/v) vitamin _B12 . The composition of the element solution is 3% (w/v) EDTA do-sodium, 0.145% (w/v) FeCl ₃ 6H ₂ O, 3.42% (w/v) H ₃ BO ₃ , 0.43% (w/v ) _MnCl2.4H2O , _0.1355 % ₍ w/v) _ZnSO4.7H2O , 0.013% ₍ w/v) _CoCl2.6H2O , 0.01% ₍ w/v) _CuSO4.5H2O . be.

(lipid extraction)
100 ml of culture solution cultured for 3 days was centrifuged (4° C., 3,000×g, 5 min) to remove the supernatant. After washing with 1.75% SEA LIFE, the cells were collected by centrifugation again and freeze-dried to obtain dry cells. The weight of the dried cells obtained was measured, and an equal volume of water and 200-fold volume of chloroform (C)/methanol (M) = 2/1 were added, and lipids were extracted with ultrasonic waves. After concentration and drying, C/M/water(W)=8/4/3 was added and centrifuged (600×g, 5 min), and the lower layer was recovered and dried to obtain total lipid.

(Isolation and purification of unknown glycolipids)
A Sep-Pak plus silica cartridge (manufactured by Waters) was conditioned by sequentially passing methanol, acetone, and chloroform. The collected total lipid was dissolved in 3 ml of chloroform, and the whole amount was applied to a Sep-Pak plus silica column. After eluting neutral lipids with 10 ml of chloroform, elution was performed with C/acetone(A)=80:20 (vol%).

(Thin layer chromatography (TLC) analysis)
After drying the eluate fractionated on a Sep-Pak plus silica column, it was dissolved in C/M=2/1, and 2 mg DCW of lipid was applied to a TLC plate (TLC Silica Gel 60, Merck).
C/M/W=65/25/4 (v/v/v) was used as a developing solvent, and color was developed with orcinol-sulfuric acid (0.2% orcinol, 11.4% sulfuric acid).

(Results of Test 1)
When the total lipids of A. limacinum mh0186 were detected by TLC, the bands of unknown glycolipids were very close in mobility to the bands of neutral lipids. Therefore, a Sep-Pak plus silica column was used to separate neutral lipids, glycolipids, and phospholipids from the total lipids of A. limacinum mh0186. As a result, it was detected in the acetone fraction together with SG. Next, a method for isolating unknown glycolipids containing no SG was investigated using a Sep-Pak plus silica column, and as a result, unknown glycolipids could be isolated by elution with chloroform/acetone = 80/20 (Fig. 3). Also, this band coincided with the Rf value of the standard ASG.

<Test 2 LC-MS analysis of unknown glycolipid>
(Scraping of unknown glycolipid from silica)
An unknown glycolipid was applied to a TLC plate (2 mg DCW x 7 lanes), developed under the same conditions as Test 1, and bands were detected. The detected band was scraped off with a spatula.

(Removal of silica using spin column)
C/M/W=65/25/4 (v/v/v) was added to the scraped silica and lipids were extracted by sonication. After centrifugation (600×g, 5 min), the supernatant was collected and dried. 400 μl of C/M=1/2 and 800 μl of M/0.45% NaCl=1/1 were added and suspended, and subjected to MonoSpin C18 FF (manufactured by GL Sciences). Centrifugation (1,000×g, 1 min) was performed to remove the waste liquid, and this operation was repeated three times. 200 μl of ultrapure water was added to the column and centrifuged (1,000×g, 1 min) to remove the waste liquid. 100 μl of methanol was added to the column and centrifuged (1,000×g, 1 min) to obtain an eluate.

(LC-MS analysis)
The structures of unknown glycolipids were analyzed by LC-MS (3200 Q TRAP, manufactured by AB SCIEX). Phospholipids, neutral lipids and glycolipids were separated using InertSustain C18 (2.1×150 mm, 5 μl, manufactured by GL Science) in a column at a flow rate of 200 μl/min. The eluent was A (acetonitrile/Methanol/H ₂ O=19/19/2(v/v/v), 0.1% Formic acid, 0.028% Ammonia) and buffer B (IPA, 0.1% Formic acid, 0.028% Ammonia). It was used. The gradient conditions were 3% B for 3 minutes, then 40% B for 21 minutes, 70% B for 1 minute, 70% B for 7 minutes, and finally back to 3% B for 7 minutes. did. A: 100%, B: 0% (3min) → A: 60%, B: 40% (21min) → A: 30%, B: 70% (1min) → A: 30%, B: 70% (7min ).

(Results of test 2)
The results are shown in Figures 4A and 5A. For both unknown glycolipids, a value consistent with the mass number of the sterol skeleton portion was detected. As a result of further MS/MS/MS analysis, a value consistent with the mass number of the characteristic portion of each sterol skeleton was detected. From these results, A. limacinum mh0186 contains GL-A (3-ObD-glucopyranosyl-stigmasta-5,7,22-triene) and acylsteryl glucoside (ASG), which is CG (cholesteryl glucoside) with DHA attached. It was found to be present (Fig. 4B, Fig. 5B). Specifically, DHA-GL-A in which DHA is attached to GL-A (Fig. 4B, structural formula (I)) and DHA-CG in which DHA is attached to CG (Fig. 5B, structural formula (II)) found to exist.

<Test 3 Gas Chromatography (GC) Analysis of ASG Fatty Acids>
The composition of fatty acids bound to acyl steryl glucoside (ASG) was analyzed by gas chromatography (GC).

(Results of Test 3)
The results are shown in FIG. DHA (C22:6) and palmitic acid (C16:0) were found to be abundant in unknown glycolipids.

<Test 4 molecular species analysis of ASG>
The combination of steryl glucoside (SG) and fatty acid in acyl steryl glucoside (ASG) was analyzed by LC-MS.

(Results of test 4)
The results are shown in FIG. DHA-added ASG was the most abundant, and DHA-CG (Fig. 5B) and DHA-GL-A (Fig. 4B) were particularly abundant. DHA-GL-C (structural formula (III)) was also present. In addition, many SGs existed in the order of GL-A, GL-B, GL-C, and CG.
DHA-attached acylsteryl glucoside (ASG) is a novel structure that has never been reported before.

<Test 5 ASG Fatty Acid and Sugar Binding Analysis>
From the LC-MS analysis results, the unknown glycolipid was considered to be acylsteryl glucoside (ASG) in which a fatty acid is bound to SG. In plants, ASG has been reported to have a structure in which a fatty acid is ester-bonded to the carbon at the 6-position of glucose. Therefore, ASG of A. limacinum mh0186 was also subjected to mild alkali hydrolysis and treatment with β-glucosidase (EGCrP2) to clarify whether or not the structure of A. limacinum mh0186 is similarly ester-bonded with fatty acid (Fig. 8).

(weak alkaline decomposition)
90 μl of C/M=1/2 and 10 μl of NaOH were added to the purified unknown glycolipid (4 mg lyophilized cell weight) and incubated at 37°C. After 2 hours, the mixture was returned to room temperature, neutralized by adding 6 μl of 10-fold diluted acetic acid with methanol, and then dried under nitrogen.

(Purification of unknown glycolipid)
The dried unknown glycolipid after the reaction was dissolved in 200 μl of C/M=1/2 and desalted in the same manner as in Test 2. The extract was dried with nitrogen.

(β-glucosidase treatment)
50 mM Acetate buffer (pH 5.0), 0.025% Sodium Cholate and 500 ng of recombinant EGCrP2 were added to the weakly alkaline digested unknown glycolipid to a total volume of 20 μl, and the mixture was allowed to react at 37° C. for 24 hours. As a negative control, boiled EGCrP2 was also prepared and reacted under the same conditions. After completion of the reaction, it was evaporated to dryness.

(TLC analysis)
The dried lipid was dissolved in 5 μl of C/M=2/1 and the total amount was applied to the TLC plate. C/M/W=65/25/4 was developed as a developing solvent and colored with orcinol sulfuric acid.

(Results of Test 5)
As a result of weak alkaline digestion and β-glucosidase treatment, the unknown glycolipid was resistant to EGCrP2, but was degraded by EGCrP2 by weak alkaline degradation (Fig. 9). From the results of this test, it was found that the unknown glycolipid was acyl steryl glucoside (ASG) in which a fatty acid is ester-bonded to steryl glucoside (SG).

<Test 6: Comparison of SG/ASG amounts during culture period>
In Test 6, changes in the amounts of SG and ASG during the culture period of A. limacinum mh0186 were analyzed by LC-MS.

(Culturing of A. limacinum mh0186 and preparation of growth curve)
Cells pre-cultured in 3ml GY medium (0.1% vitamin mixture, 0.2% element solution) were added to 100ml GY medium (300ml Erlenmeyer flask, 0.1% vitamin mixture, 0.2% element solution) at an initial concentration of OD ₆₀₀ = 0.02 (containing element solution) and cultured with shaking (150 rpm, 25°C). _OD600 was measured every 24 hours.

(Measurement of glucose concentration)
1 ml of the culture medium was collected every 24 hours and centrifuged (4°C, 3,000 xg, 5 min) to collect the supernatant. With ultrapure water, 100 times the supernatant on the 1st day of culture, 50 times the supernatant on the 2nd and 3rd days, 10 times the supernatant on the 4th day, 5 times the supernatant on the 5th to 9th days. Diluted twice. In addition, a 2-fold dilution series of a glucose standard solution (200 mg/dL) was prepared for preparation of a standard curve, and 10 μl of each was dispensed.
10 μl of diluted culture medium and coloring reagent (glucose CII test, Wako) were added to each well of a 96-well plate, incubated at room temperature for 15 minutes, and then OD ₄₉₂ was measured with MULTISKAN FC (manufactured by Thermo SCIENTIFIC).

(Cell recovery and lipid extraction)
1 ml of culture medium was collected every 24 hours and centrifuged (4° C., 3,000×g, 5 min) to remove the supernatant. Lyophilized cells were obtained after washing with 1.75% SEALIFE. 4 mg of dried cells was weighed out and added to 300 μl of internal standard (20 μM EG, 10 μM ASG (18:0-sitosteryl glucoside), TG (12:0/12:0/12:0), PC (11:0/ 11:0), LPC (13:0), PE (12:0/12:0), LPE (13:0), SE (16:0-d7 cholesterol), d7 cholesterol) C/M=2/ 1 was added and lipids were extracted with ultrasonic waves for 10 minutes. After centrifuging (4°C, 15,000 rpm, 5 min) and collecting the supernatant, 75 µl of ultrapure water was added, followed by centrifugation (4°C, 15,000 rpm, 5 min) to collect the lower layer.

(LC-MS analysis)
100 μl of the collected lower layer was added to an autosampler vial containing 900 μl of 2-propanol, and 5 μl was subjected to LC-MS. LC-MS conditions are similar to test 2.

(Results of test 6)
The results are shown in Figures 10-13. FIG. 10 is a cell growth curve, FIG. 11 is a time-dependent change in the glucose concentration contained in the culture medium, FIG. 12 is a time-dependent change in the amount of steryl glucoside (SG), and FIG. Shows change over time.

Acyl steryl glucoside (ASG) increased during the logarithmic growth phase and decreased after the stationary phase, while steryl glucoside (SG) tended to increase after the stationary phase.
These results indicate that DHA binds to SG and accumulates in the body when carbon sources are sufficient, but when glucose is depleted and nutrients are depleted, DHA bound to SG is released and used as an energy source. It was thought that Therefore, it was suggested that acyl steryl glucoside (ASG) may act as a reservoir for steryl glucoside (SG).

<Test 7 Search for ASG synthase in budding yeast>
Regarding ASG synthase, two hypotheses are proposed: TG lipase transfers fatty acid to SG (hypothesis 1, FIG. 14(a)) or phospholipase transfers fatty acid to SG (hypothesis 2, FIG. 14(b)). Thought. Hypothesis 1 of the two hypotheses was verified using Saccharomyces cerevisiae.

(Comparison of SG and ASG amounts by adding oleic acid in budding yeast)
Saccharomyces cerevisiae produces large oil droplets by adding oleic acid to the medium. Therefore, we added oleic acid to the medium to increase the amount of TG in budding yeast by making large oil droplets, and analyzed the changes in SG and ASG amounts by LC-MS. In addition, since wild strains of budding yeast have almost no SG, in this test, Ugt51, which synthesizes ergosteryl glucoside (EG) by transferring Glc from UDP-Glc to ergosterol, a major sterol of budding yeast, was used. An overexpressed EG-overaccumulating strain was used.
(Culture of budding yeast UGT51OE/egh1KO strain)
Using the UGT51OE/egh1KO strain, precultured cells in 3 ml of YPD medium (2.0% (w/v) D-glucose, 1.0% (w/v) Polypeptone, 1.0% (w/v) Yeast Extract) Added to 3 ml of YPD medium at a concentration of OD ₆₀₀ =0.2. 3 μl of 1 μg/μl oleic acid dissolved in ethanol was added to the YPD medium and cultured with shaking for 24 hours (150 rpm, 30° C.). As a negative control, 3 µl of ethanol alone was also prepared and cultured under the same conditions.

(Cell recovery and lipid extraction)
After culturing for 24 hours, 3 ml of the culture medium was centrifuged (4°C, 3,000 xg, 5 min) to remove the supernatant. After washing with a PBS solution, the cells were collected by centrifugation again and freeze-dried to obtain dry cells. 4 mg of dried cells was weighed out and added to 300 μl of internal standard (20 μM CG, 10 μM ASG (18:0-sitosteryl glucoside), TG (12:0/12:0/12:0), PC (11:0/11 :0), LPC (13:0), PE (12:0/12:0), LPE (13:0), SE (16:0-d7 cholesterol), d7 cholesterol) C/M=2/1 was added and sonicated for 10 minutes. Centrifugation (
4°C, 15,000 rpm, 5 min) and the supernatant was collected. 75 μl of ultrapure water was added and centrifuged (4° C., 15,000 rpm, 5 min) to collect the lower layer.

(Measurement of SG/ASG amount by LC-MS analysis)
The entire bottom layer collected was placed in an autosampler vial and 5 μl was subjected to LC-MS. LC-MS conditions are similar to test 2.

(Measurement of SG and ASG amounts in TG lipase (tgl3, 4, 5)-deficient strains)
TG lipase (tgl3, tgl4, tgl5)-deficient strains were used. Cells precultured in 3 ml of YPD medium were added to 3 ml of YPD medium to an initial concentration of OD ₆₀₀ =0.02, and cultured with shaking (150 rpm, 30° C.) for 24 hours. Lipid extraction was performed by the method described above, and the content of SG and ASG was analyzed by LC-MS.

(AEG amount analysis in TG lipase-deficient strain)
If TG lipase is an AEG synthase, it was thought that deficiency of TG lipase would reduce the amount of AEG. Since Saccharomyces cerevisiae has Tgl3, Tgl4, and Tgl5 as major TG lipases, we measured the amount of ASG in tgl3, tgl4, and tgl5-deficient strains.

(Results of Test 7)
The results are shown in FIG. As a result of LC-MS analysis, EG and acyl EG (AEG) in which a fatty acid was added to EG were not detected in the wild type, but both EG and AEG were detected in the EG overaccumulation strain (Fig. 15(a)). ). The fatty acid types of AEG were 16:0, 16:1, 18:0 and 18:1 (Fig. 15(b)). In addition, in the EG-overaccumulating strain, EG hardly changed depending on the presence or absence of oleic acid (Fig. 15(a)), but AEG tended to increase with the addition of oleic acid (Fig. 15(b)). These results suggested that the increase in TG content in Saccharomyces cerevisiae was related to the increase in AEG content, and that Saccharomyces cerevisiae possessed AEG synthase.

Further, as a result of LC-MS analysis, the amount of AEG tended to decrease when tgl3, tgl4, and tgl5 were deficient (Fig. 15(c)). This result supported hypothesis 1 that TG lipase transfers fatty acids to SG.

<Summary of Tests 1 to 7>
(1. Structure determination of unknown glycolipid)
Unknown glycolipids were eluted with chloroform:acetone=80:20.
As a result of analyzing the unknown glycolipid by LC-MS, weak alkali digestion, and β-glucosidase treatment, the unknown glycolipid was acylsterylglucoside (ASG )Met.
Acyl steryl glucoside (ASG) in which DHA was attached to steryl glucoside (SG) was a novel structure (Fig. 16).

(2. Comparison of SG/ASG amount during culture period)
Acylsteryl glucoside (ASG) increased during the exponential growth phase and decreased after the stationary phase. On the other hand, steryl glucoside (SG) tended to increase after glucose depletion.
It was suggested that acylsteryl glucoside (ASG), like neutral lipids and phospholipids, acts as a reservoir for DHA accumulation (Fig. 17).

<Consideration of test>
Structural determination and biological function elucidation of SG have progressed with respect to labyrinthulid glycolipids. However, in addition to SG, Labyrinthulids contain an unknown glycolipid of unknown structure, and the purpose of this study was to determine the structure of this unknown glycolipid and to elucidate the synthase.

As a result of determining the structure of the unknown glycolipid, the unknown glycolipid was ASG in which DHA or palmitic acid was added to SG (Figs. 4B, 5B, 6 and 7). ASG has never been reported in Labyrinthulids, and the DHA-attached structure is a novel structure that has never been reported in other organisms.

Labyrinthula are characterized by accumulating polyunsaturated fatty acids such as DHA as TG and SE in oil droplets. As a result of measuring the amount of SG and ASG during the culture period in this test, there was almost no change in the amount of SG depending on the culture period, whereas ASG increased during the logarithmic growth phase and decreased after entering the stationary phase. (Figs. 12 and 13). This suggests that ASG, like TG and SE, may act as a reservoir of DHA.

DHA is known to have anti-inflammatory effects, and it has been reported that ASG contained in rice bran extract oil has a role in lowering elevated blood LDL-cholesterol. ASG combined with DHA can be applied to humans as health foods and supplements, taking advantage of both the functionality of DHA and that of ASG.

There are at least four types of Labyrinthulid SGs (Fig. 1). It has been reported that SGs in fungi and human fibroblasts are increased by heat stress. SGs are also increased by heat stress in Labyrinthuleas, suggesting that SGs play an important role in the development of the environmental adaptation mechanism of Labyrinthuleas. Possibility of having a function is conceivable.

<Test 8 A. Limacinum-derived DHA-GL-C degradation by lipase>
(Method of Test 8)
DHA-GL-C and 25 U of porcine pancreatic lipase were mixed, reacted with a thermomixer at 37° C. and 750 rpm, and C/M=2:1 was added to terminate the reaction.
(A) Decomposition product reacted with lipase for 28 hours was placed on TLC, developed with C/M/W = 65/16/2, and treated with copper sulfate reagent (3% copper sulfate dissolved in 15% phosphoric acid solution). Color was developed (boxed lanes in Figure 18). As a control, triacylglycerol (TG) was degraded with the same amount of lipase (right two lanes).
(B) After timed reaction, the reactants were quantified by LC-MS.

(Results of Test 8)
The results are shown in Figures 18 and 19.
(A) DHA-GL-C was degraded by lipase, and DHA and SG (GL-C) were released (Fig. 18, +: lipase added, -: no addition).
(B) Degradation of DHA-GL-C by lipase was dependent on the reaction time. DHA-GL-C decreased and free SG (GL-C) increased with the lapse of reaction time (Fig. 19).

<Test 9 A. Limacinum-derived DHA-GL-C and oxidation measurement of DHA>
(Method of Test 9)
Add 100 μl of 50 mM phosphate buffer pH 7.3 to DHA-GL-C or DHA (5 nmol) purified from 1 mg dry cell weight, and with the lid of the container open, expose it to UV irradiation (254 nm, 51 μW/cm ² , from the lamp). 35 cm to the sample, 23°C).
After completion of irradiation, 200 μl of C/M=2/1 was added to extract lipids, and DHA-GL-C and DHA were quantified by LC-MS.

(Results of Test 9)
The results are shown in FIG. About 50% of DHA was oxidized after 1 hour of UV irradiation, but DHA-GL-C was not oxidized at all even after 3 hours of irradiation. Therefore, DHA-GL-C was shown to be more resistant to oxidation than DHA.

As a result of oxidation test by UV irradiation, ASG with DHA ester-bonded exists in a stable form in the body, and when degraded by lipase, it is converted into functional metabolites such as resolvin and protectin in the same way as free DHA. It turned out to be possible.

Claims (11)

An acyl steryl glucoside represented by the following structural formula (I), structural formula (II) or structural formula (III).

a labyrintula preparation step of preparing a labyrintula;
A separation step of separating an acyl steryl glucoside fraction containing acyl steryl glucosides from the labyrinthula;
A purification step of purifying the acyl steryl glucoside from the acyl steryl glucoside fraction separated in the separation step;
and
A method for producing acyl steryl glucoside, wherein the acyl steryl glucoside is one or more types represented by the following structural formula (I), structural formula (II), or structural formula (III) .

containing an acylsteryl glucoside derived from Labyrintura,
The acyl steryl glucoside is one or more represented by the following structural formula (I), structural formula (II) or structural formula (III),
A composition characterized by being a composition selected from a food composition, a pharmaceutical composition, and a cosmetic composition.

4. The composition of claim 3 , wherein said composition is a food composition. 4. The composition of claim 3 , wherein said composition is a pharmaceutical composition. 4. The composition of claim 3 , wherein said composition is a cosmetic composition. Contains acyl steryl glucoside derived from Labyrinthula as an active ingredient ,
The acylsteryl glucoside is one or more antioxidants represented by the following structural formula (I), structural formula (II), or structural formula (III) .

Contains acyl steryl glucoside derived from Labyrinthula as an active ingredient ,
The acylsteryl glucoside is one or more types represented by the following structural formula (I), structural formula (II), or structural formula (III) .

Contains acyl steryl glucoside derived from Labyrinthula as an active ingredient ,
The acyl steryl glucoside is one or more kinds represented by the following structural formula (I), structural formula (II) or structural formula (III) .

Contains acyl steryl glucoside derived from Labyrinthula as an active ingredient ,
The acylsteryl glucoside is one or more types of antitumor agents represented by the following structural formula (I), structural formula (II), or structural formula (III) .

Contains acyl steryl glucoside derived from Labyrinthula as an active ingredient ,
The acylsteryl glucoside is one or more of the following structural formula (I), structural formula (II), or structural formula (III), and is a prophylactic or therapeutic agent for atherosclerosis.

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