CN117342970A - Wheat germ oil ceramide and synthesis method and application thereof - Google Patents

Wheat germ oil ceramide and synthesis method and application thereof Download PDF

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CN117342970A
CN117342970A CN202310186333.7A CN202310186333A CN117342970A CN 117342970 A CN117342970 A CN 117342970A CN 202310186333 A CN202310186333 A CN 202310186333A CN 117342970 A CN117342970 A CN 117342970A
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ceramide
wheat germ
germ oil
acid
weight percent
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杨超文
叶柳
李青
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Shenzhen Dikeman Biotechnology Co ltd
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Shenzhen Dikeman Biotechnology Co ltd
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Abstract

The invention belongs to the technical field of biological medicines, and discloses wheat germ oil ceramide which is obtained by reacting wheat germ oil fatty acid with a sphingosine compound, wherein the sphingosine compound is selected from sphingosine, phytosphingosine and dihydrosphingosine. The wheat germ oil ceramide has excellent performances in the aspects of repairing natural skin barriers, anti-inflammatory, tissue healing, anti-aging and the like, and has wide application prospects in the fields of cosmetics, health-care products, biological medicines and the like.

Description

Wheat germ oil ceramide and synthesis method and application thereof
Technical Field
The invention belongs to the technical field of biological medicines, and particularly relates to wheat germ oil ceramide and a synthesis method and application thereof.
Background
Ceramides (ceramides, also known as molecular nails) naturally occur in the skin and are very important components of the skin barrier (stratum corneum), in amounts of up to 40-50 wt.%, ceramides are a class of sphingolipids consisting of long-chain bases of sphingosine and fatty acids, in which the carbon chain length, unsaturation and number of hydroxyl groups of the sphingosine moiety, fatty acid moiety are all variable, and ceramides represent a class of compounds. Ceramide has excellent properties in regulating skin barrier function, recovering skin moisture, enhancing adhesion between skin keratinocytes, and the like.
Because of the importance of ceramides, many cosmetic and pharmaceutical companies are researching and developing corresponding products. The natural plant-derived ceramide can form an effective skin barrier to prevent water loss and resist external damage due to the more sustainable and more environment-friendly raw material source and the characteristics similar to the skin ceramide components, and can become a next-generation environment-friendly, safe and reliable ceramide product.
The wheat germ oil is a cereal germ oil prepared by taking wheat malt as a raw material, is rich in fatty acid necessary for human body, and has the content of more than 80wt%, wherein the content of linoleic acid is more than 50 wt%; the wheat germ oil also contains fatty acids such as oleic acid, palmitic acid, etc. The vitamin E content in the wheat germ oil is located in the crown of the vegetable oil, is recognized as a functional oil with nutrition and health care effects, can regulate blood fat, soften blood vessels, and has the effects of preventing arteriosclerosis, hypertension and stroke. The wheat germ oil contains a small amount of various physiologically active components such as octacosanol, sitosterol, lecithin, allantoin, arginine, amylase, maltase, protease, vitamin B, phytolectin and the like, so that the production of lipid peroxide can be reduced, the skin moisturizing function can be promoted, the skin is moist, and the aging is delayed. Wheat germ oil is also ideal cosmetic base oil, is praised as a cosmetic which can strengthen connective tissue of skin, promote blood circulation and keep skin elasticity, promote metabolism and skin update, resist wrinkles and wrinkles, prevent skin aging and eliminate scars; has good effect on regulating dry skin and black spot.
Disclosure of Invention
The invention aims to provide ceramide synthesized by utilizing wheat germ oil fatty acid of a plant source.
Another object of the present invention is to provide a method for synthesizing wheat germ oil ceramide, which uses wheat germ oil fat or wheat germ oil fatty acid which is natural plant source and is easy to obtain as raw material.
It is another object of the present invention to provide the use of wheat germ oil ceramide.
In order to achieve one of the above purposes, the present invention adopts the following technical scheme:
in a first aspect of the invention, wheat germ oil ceramide is obtained by reacting a wheat germ oil fatty acid with a sphingosine compound selected from the group consisting of sphingosine, phytosphingosine, and sphinganine.
The reaction can be chemical synthesis reaction (as detailed below), or microbial fermentation method, i.e. using Pichia pastoris or Saccharomyces cerevisiae, fermenting under certain environment to obtain sphingosine compound, and adding fatty acid to obtain ceramide; or taking wheat germ oil as a raw material, selecting a proper strain, and fermenting to obtain the wheat germ oil ceramide.
Sphingosine refers to 2-amino-4-octadecene-1, 3-diol, phytosphingosine refers to 2-amino-octadecane-1, 3, 4-triol, and dihydrosphingosine refers to 2-amino-octadecane-1, 3-diol.
Further, the wheat germ oil fatty acid is obtained by hydrolyzing wheat germ oil grease.
Further, the wheat germ oil fatty acid contains 50-75wt% linoleic acid.
Further, the wheat germ oil fatty acid contains 15-45 wt% oleic acid.
Further, the wheat germ oil fatty acid contains 2 to 10wt% of palmitic acid.
Further, the wheat germ oil fatty acid contains 1-8wt% linolenic acid.
Further, the wheat germ oil fatty acid contains 0.1 to 1wt% of arachidonic acid.
In addition, the wheat germ oil fatty acid also contains 0 to 0.5 weight percent of stearic acid and 0 to 0.5 weight percent of arachidic acid.
The composition of the wheat germ oil fatty acid is as follows: 50 to 75 weight percent of linoleic acid, 15 to 45 weight percent of oleic acid, 2 to 10 weight percent of palmitic acid, 1 to 8 weight percent of linolenic acid, 0.1 to 1 weight percent of arachidonic acid, 0 to 0.5 weight percent of stearic acid and 0 to 0.5 weight percent of arachidic acid.
The main component of the wheat germ oil fatty acid is linoleic acid, other fatty acids comprise oleic acid, palmitic acid, linolenic acid and arachidonic acid, which are essential components, and are influenced by plant varieties, soil, climate, production place, picking season and extraction process, the content of each component is different, and stearic acid and arachidic acid are not necessarily contained, and are optional components or unnecessary components.
Wheat germ oil ceramide comprises the following components: linoleic acid ceramide, oleic acid ceramide, palmitic acid ceramide, linolenic acid ceramide, arachidonic acid ceramide; because fatty acids all participate in the same reaction, the mass ratio of ceramide after the reaction is not greatly changed, so the composition of the ceramide of the wheat germ oil is similar to that of the fatty acid of the wheat germ oil, and the composition of the ceramide of the wheat germ oil is as follows: 50 to 75 weight percent of linoleic acid ceramide, 15 to 45 weight percent of oleic acid ceramide, 2 to 10 weight percent of palmitic acid ceramide, 1 to 8 weight percent of linolenic acid ceramide and 0.1 to 1 weight percent of arachidonic acid ceramide. The content of each component is different due to the different content of each fatty acid in the wheat germ oil fatty acid or fat. In addition, the wheat germ oil ceramide also comprises ceramide obtained by reacting one or more of stearic acid and arachidic acid with sphingosine compounds, namely 0 to 0.5 weight percent of stearic acid ceramide and 0 to 0.5 weight percent of arachidic acid ceramide. Wheat germ oil ceramides also include compounds that are present in wheat germ oil fatty acids but do not react with sphingosine compounds, such as vitamin a, vitamin B, vitamin D, vitamin E, beta-carotene, gamma-oryzanol, sitosterol, lecithin, allantoin, arginine, amylase, maltase, protease, phytolectin, and the like.
Wheat germ oil ceramide comprises the following components: linoleic acid ceramide, oleic acid ceramide, palmitic acid ceramide; 50-75wt% of linoleic acid ceramide, 15-45wt% of oleic acid ceramide and 2-10wt% of palmitic acid ceramide.
Further, the wheat germ oil ceramide comprises linolenic acid ceramide, and the linolenic acid ceramide accounts for 1-8wt%.
Further, the wheat germ oil ceramide comprises arachidonic acid ceramide, and the content of the arachidonic acid ceramide is 0.1-1 wt%.
Further, the wheat germ oil ceramide comprises not more than 0.5wt% of stearic acid ceramide and not more than 0.5wt% of arachidic acid ceramide, especially 0.1 to 0.5wt% of stearic acid ceramide and 0.1 to 0.5wt% of arachidic acid ceramide.
The linoleic acid ceramide is obtained by condensation reaction of linoleic acid and sphingosine compounds, and comprises linoleic acid phytosphingosine ceramide, linoleic acid sphingosine ceramide and linoleic acid dihydrosphingosine ceramide; oleic acid ceramide is obtained by condensation reaction of oleic acid and sphingosine compounds, and comprises oleic acid phytosphingosine ceramide, oleic acid sphingosine ceramide and oleic acid dihydrosphingosine ceramide; the palmitic acid ceramide is obtained by condensation reaction of palmitic acid and sphingosine compounds, and comprises palmitic acid phytosphingosine ceramide, palmitic acid sphingosine ceramide and palmitic acid dihydrosphingosine ceramide; linolenic acid ceramide, arachidonic acid ceramide, stearic acid ceramide, arachidic acid ceramide, and the like, and so forth.
In a second aspect of the invention, a method for synthesizing wheat germ oil ceramide comprises the following steps:
under the conditions of condensing agent and organic alkali, wheat germ oil fatty acid reacts with sphingosine compound, wherein the condensing agent is EDCI, and the organic alkali is Et 3 N。
Further, the wheat germ oil fatty acid, sphingosine compound, EDCI, et 3 The molar ratio of N is 1: (1-1.5): (1-2): (1-2), wherein the solvent for the reaction is at least one of dichloromethane, tetrahydrofuran, ethyl acetate and acetonitrile.
Wheat germ oil purchased on the market is generally in the form of oil and fat, and needs to be hydrolyzed into fatty acids of the wheat germ oil, and therefore, the method further comprises the following steps:
the wheat germ oil fat is hydrolyzed by saponification reaction to obtain wheat germ oil fatty acid.
Further, the saponification reaction is hydrolysis of wheat germ oil grease in potassium hydroxide solution.
Further, the mass ratio of the wheat germ oil grease to the potassium hydroxide is 1: (1-2).
In a third aspect of the invention, the use of wheat germ oil ceramide in cosmetics, pharmaceutical products, dietary or health care products.
Further, the wheat germ oil ceramide has at least one of skin barrier repair, tissue healing, anti-aging, anti-inflammatory, anti-photoaging, antioxidant, collagen synthesis promoting, elastin activity maintaining, and whitening effects.
A composition comprising wheat germ oil ceramide, said composition having at least one of skin barrier repair, tissue healing, anti-aging, anti-inflammatory, anti-photoaging, antioxidant, promoting collagen synthesis, maintaining elastin viability, whitening efficacy.
The composition contains acceptable auxiliary materials, including one or more of solubilizer, antiseptic, antioxidant, pH regulator, penetration enhancer, liposome, humectant, thickener, chelating agent, skin feel regulator, surfactant, emulsifier, essence and pigment; the composition is in the form of cream, emulsion, solution, film, aerosol or spray.
The invention has the following beneficial effects:
the wheat germ oil fatty acid belongs to naturally-formed fatty acid, the main component is unsaturated fatty acid-linoleic acid, oleic acid, palmitic acid, linolenic acid, arachidonic acid and the like are also contained, and the wheat germ oil ceramide is prepared by mild reaction with a sphingosine compound naturally existing in skin, has excellent performance in the aspects of repairing, resisting oxidation, resisting aging and the like of a natural skin barrier, and has wide application prospect in the fields of cosmetics, health-care products, biological medicines and the like.
1. Better results compared to ceramide alone. Different ceramides have different effects due to the structural differences, and ceramides with a single structure generally have difficulty in having comprehensive effects. The scheme is based on a bionic thought, and the wheat germ oil grease or fatty acid from natural sources is used as a raw material to synthesize the compound ceramide so as to make up the difference of different ceramide effects, and trace fatty acid in the wheat germ oil can form trace ceramide to play a role in efficacy supplement.
2. Compared with the compounded ceramide, the effect is better. Besides fatty acid (or grease), the wheat germ oil also contains vitamin A, vitamin B, vitamin D, vitamin E, beta-carotene, gamma-oryzanol, sitosterol, lecithin, allantoin, arginine, amylase, maltase, protease, phytolectin and the like, and the nutrients have the effects of regulating endocrine, resisting oxidation, resisting wrinkle, moisturizing and moisturizing skin, and the ceramide synthesized by the wheat germ oil has a synergistic effect with other active ingredients contained in the wheat germ oil, so that the ceramide compounded according to similar proportion has better effect.
3. The cost is lower. The method of the invention can rapidly obtain the composition compounded by various ceramides, and the wheat germ oil and fat or the fatty acid of the wheat germ oil and fat of plant sources has wide sources, is easy to obtain commercially, has lower cost, is more environment-friendly and economical, is different from the idea of mixing and compounding different single ceramides, has high raw material price of the fatty acid of single component, needs to separately produce different ceramides, and then is compounded, thereby increasing the preparation cost.
4. The synthesis method is simple. The method can adopt chemical synthesis to realize one-step preparation of various ceramides, and can also use a microbial fermentation method.
Drawings
FIG. 1 is a bar graph showing the results of the cell proliferation activity test of example 4;
FIG. 2 is the result of the cell migration ability test of example 5;
FIGS. 3 and 4 are bar graphs of elastase inhibition ratios of example 6;
FIG. 5 is a bar graph showing the detection of IL-6 factor expression level in anti-inflammatory repair efficacy in example 7;
FIGS. 6 and 7 are bar charts of MMP1 expression levels in the photo-aging test of example 8;
FIGS. 8 and 9 are bar graphs of DPPH radical scavenging rate for oxidation resistance test of example 9;
fig. 10 is a bar graph of the whitening activity test melanin content of example 10.
Detailed Description
The invention will be further illustrated with reference to specific examples.
EDCI refers to 1-ethyl- (3-dimethylaminopropyl) carbodiimide, et 3 N refers to triethylamine. The silica gel column chromatography uses Qingdao ocean silica gel (particle size 0.040-0.063 mm). Thin Layer Chromatography (TLC) using 60F254 silica gel plates was performed using UV light (254 nm) or iodine.
Example 1
Synthesis of ceramide from wheat germ oil fatty acid and phytosphingosine
The first step: 50g of wheat germ oil is dissolved in 60mL of tetrahydrofuran, cooled in an ice bath, 110mL of potassium hydroxide (25 wt%) solution is added dropwise, and the mixture is cooled to room temperature for reaction after the dropwise addition until TLC detection is completed.
Post-treatment: adding dilute hydrochloric acid (3N) to adjust the pH value of the reaction system to 3, adding 120mL of ethyl acetate to extract a water phase, adding 80mL of saturated saline water for washing once, and adding anhydrous Na into an organic phase 2 SO 4 Drying, filtering and concentrating in vacuum to obtain 40g of wheat germ oil fatty acid.
And a second step of: mixing wheat germ oil fatty acid (50 mmol based on main component fatty acid), EDCI (80 mmol), et 3 N (80 mmol) was added to a 250mL round bottom flask, followed by 80mL dichloromethane, followed by stirring at room temperature for 1 hour, followed by phytosphingosine (75 mmol) added to the reaction system, stirred at room temperature until TLC detection was complete.
Post-treatment: adding water for quenching reaction, separating an organic layer, drying, filtering and concentrating in vacuum, washing by a solvent to obtain wheat germ oil ceramide, and analyzing a product by HPLC (high performance liquid chromatography) under the condition of HPLC chromatography: using an shimadzu high performance liquid chromatograph (LC-2030 c3d Plus), column temperature with Innoval ODS-2.6x250 mm,5 μm column: 30 ℃, sample injection volume: 10 μl, flow rate: 1.0mL/min, evaporation temperature: 40 ℃, carrier gas flow rate: 2.5L/min, mobile phase: 100% methanol.
The retention time of each component HPLC was: linolenic acid-phytosphingosine ceramide 8.3min, linoleic acid-phytosphingosine ceramide 9.5min, palmitic acid-phytosphingosine ceramide 10.7min, oleic acid-phytosphingosine ceramide 11.3min, arachidonic acid-phytosphingosine ceramide 12.9min, stearic acid-phytosphingosine ceramide 13.9min, and arachidic acid-phytosphingosine ceramide 16.5min.
The obtained products are analyzed by high performance liquid chromatography, the contents of linoleic acid-phytosphingosine ceramide, oleic acid-phytosphingosine ceramide, palmitic acid-phytosphingosine ceramide, linolenic acid-phytosphingosine ceramide, arachidonic acid-phytosphingosine ceramide, stearic acid-phytosphingosine ceramide and arachidic acid-phytosphingosine ceramide are 61%, 26%, 5%, 0.5% and 0.5% in sequence, and the rest are other components, and the contents are small.
Example 2
Synthesis of ceramide from fatty acid and sphingosine of wheat germ oil
The first step: 50g of wheat germ oil is dissolved in 60mL of tetrahydrofuran, cooled in an ice bath, 110mL of potassium hydroxide (25 wt%) solution is added dropwise, and the mixture is cooled to room temperature for reaction after the dropwise addition until TLC detection is completed.
Post-treatment: adding dilute hydrochloric acid (3N) to adjust the pH value of the reaction system to 3, adding 120mL of ethyl acetate to extract a water phase, adding 80mL of saturated saline water for washing once, and adding anhydrous Na into an organic phase 2 SO 4 Drying, filtering and concentrating in vacuum to obtain 39.5g of wheat germ oil fatty acid.
And a second step of: mixing wheat germ oil fatty acid (50 mmol based on main component fatty acid), EDCI (70 mmol), et 3 N (70 mmol) was added to a 250mL round bottom flask, followed by 100mL of dichloromethane, followed by stirring at room temperature for 1 hour, followed by sphingosine (65 mmol) added to the reaction system, and stirring at room temperature until TLC detection was complete.
Post-treatment: adding water for quenching reaction, separating an organic layer, drying, filtering and concentrating in vacuum, washing by a solvent to obtain wheat germ oil ceramide, and analyzing a product by HPLC (high performance liquid chromatography) under the condition of HPLC chromatography: using an shimadzu high performance liquid chromatograph (LC-2030 c3d Plus), column temperature with Innoval ODS-2.6x250 mm,5 μm column: 30 ℃, sample injection volume: 10 μl, flow rate: 1.0mL/min, evaporation temperature: 40 ℃, carrier gas flow rate: 2.5L/min, mobile phase: 100% methanol.
The retention time of each component HPLC was: linolenic acid-sphingosine ceramide 7.9min, linoleic acid-sphingosine ceramide 8.7min, oleic acid-sphingosine ceramide 10.2min, palmitic acid-sphingosine ceramide 10.4min, and arachidonic acid-sphingosine ceramide 12.8min.
The obtained product is analyzed by high performance liquid chromatography, the content of linoleic acid-sphingosine ceramide, oleic acid-sphingosine ceramide, palmitic acid-sphingosine ceramide, linolenic acid-sphingosine ceramide and arachidonic acid-sphingosine ceramide is 72%, 15%, 3%, 7% and 1% in sequence, and the rest is other components, and the content is less.
Example 3
Synthesis of ceramide from wheat germ oil fatty acid and sphinganine
The first step: 50g of wheat germ oil is dissolved in 60mL of tetrahydrofuran, cooled in an ice bath, 110mL of potassium hydroxide (25 wt%) solution is added dropwise, and the mixture is cooled to room temperature for reaction after the dropwise addition until TLC detection is completed.
Post-treatment: adding dilute hydrochloric acid (3N) to adjust the pH value of the reaction system to 3, adding 120mL of ethyl acetate to extract a water phase, adding 80mL of saturated saline water for washing once, and adding anhydrous Na into an organic phase 2 SO 4 Drying, filtering and concentrating in vacuum to obtain 39.8g of wheat germ oil fatty acid.
And a second step of: mixing wheat germ oil fatty acid (50 mmol based on main component fatty acid), EDCI (60 mmol), et 3 N (60 mmol) was added to a 250mL round bottom flask, followed by 100mL of dichloromethane, followed by stirring at room temperature for 1 hour, followed by addition of sphinganine (55 mmol) to the reaction system, stirring at room temperature, and detection by TLC was complete.
Post-treatment: adding water for quenching reaction, separating an organic layer, drying, filtering and concentrating in vacuum, washing by a solvent to obtain wheat germ oil ceramide, and analyzing a product by HPLC (high performance liquid chromatography) under the condition of HPLC chromatography: using an shimadzu high performance liquid chromatograph (LC-2030 c3d Plus), column temperature with Innoval ODS-2.6x250 mm,5 μm column: 30 ℃, sample injection volume: 10 μl, flow rate: 1.0mL/min, evaporation temperature: 40 ℃, carrier gas flow rate: 2.5L/min, mobile phase: 100% methanol.
The retention time of each component HPLC was: linolenic acid-dihydrosphingosine ceramide 8.3min, linoleic acid-dihydrosphingosine ceramide 9.5min, palmitic acid-dihydrosphingosine ceramide 10.6min, oleic acid-dihydrosphingosine ceramide 11.1min, stearic acid-dihydrosphingosine ceramide 13.5min, arachidonic acid-dihydrosphingosine ceramide 14.0min, and arachidic acid-dihydrosphingosine ceramide 16.0min.
The obtained products are analyzed by high performance liquid chromatography, the contents of linoleic acid-dihydrosphingosine ceramide, oleic acid-dihydrosphingosine ceramide, palmitic acid-dihydrosphingosine ceramide, linolenic acid-dihydrosphingosine ceramide, arachidonic acid-dihydrosphingosine ceramide, stearic acid-dihydrosphingosine ceramide and arachidic acid-dihydrosphingosine ceramide are 53%, 32%, 8%, 2.5%, 1%, 0.5% and 0.5% in sequence, and the rest are other components, and the contents are small.
Example 4
MTT method for detecting proliferation activity of compound on cell
HaCaT cells were grown at 1X 10 4 The density of individuals/wells was seeded in 96-well plates and the incubator was overnight. After 24h, the supernatant was discarded, 100. Mu.L of medium containing samples of different concentrations (product of example 1) was added, incubation was continued for 24h, medium was removed, 100. Mu.L of thiazole blue (MTT) was added to each well, absorbance at 450nm was measured, and cell viability = A was calculated Drug delivery hole /A Blank hole ×100％。
As a result, as shown in FIG. 1, wheat germ oil ceramide has an effect of promoting cell viability, and cell viability at concentrations of 3.90625, 7.8125, 15.625, 31.25, 62.5, 125, 250, 500, 1000mg/L was 85.71%, 81.67%, 88.48%, 90.32%, 101.10%, 94.93%, 114.64%, 126.05%, 129.46%, respectively. The composition has the effect of promoting cell proliferation at a higher concentration and has good tissue repair capability.
Example 5
Assessment of skin barrier repair by cell migration
Principle of: when the cells grow to be fused into a single-layer state, a scratch tool is manufactured on the fused single-layer cells, the cells in the blank area are removed by mechanical force, the migration condition of the cells to the cell-free area is observed through a period of culture, and the migration capability of the cells is reflected by measuring the migration distance of the cells.
The operation steps are as follows:
1. the culture plate is streaked. Firstly, a Marker pen is used for uniformly scribing transverse lines by comparing with a straight ruler, and the transverse lines are crossed through the through holes at intervals of about 0.5 cm to 1cm, and each hole at least passes through 5 lines, so that attention lines are not too thick when scribing.
2. And (5) paving cells. About 5X 10 is added to the well 5 Individual cells (different cell numbers)The amount is different, and the inoculation principle is that the fusion rate reaches 100% after overnight according to the growth speed of cells.
3. Cell streaking. The next day the tip is used to scratch the cell layer along the line marked on the back of the plate on the first day, perpendicular to the cell plane (the same tip is preferably used between the different wells).
4. Washing cells. After the streaking was completed, cells were washed 3 times with sterile PBS, cells that did not adhere to the wall, i.e., streaked cells at streaking, and the gap left after streaking was clearly visible, followed by replacement of fresh serum-free medium.
5. And (5) culturing and observing the cells. After the sample (product of example 1, ceramide 3B) was diluted with the medium (product of example 1, concentration of ceramide 3B was 50mg/L, concentration of ceramide 3B was 100 mg/L), the cells were placed in a cell culture dish, and the cells were placed in 5wt% CO at 37 ℃C 2 Incubator culture, after 24 hours, cells were removed, observed with a microscope and the width of scratches was measured, and photographed, and the healing rate was calculated using Image J software.
The results are shown in fig. 2, and the scratch width of the experimental group is narrower than that of the solvent control group, which indicates that the wheat germ oil ceramide has better tissue healing capacity. The healing rate of the solvent control group after 24 hours is 36.85%, the healing rate of the wheat germ oil ceramide after 24 hours is 85.36%, and the healing rate of the ceramide 3B after 24 hours is 59.32%. The compound obviously improves the cell healing rate, has good skin tissue repair activity and has better effect than ceramide 3B.
Example 6
Elastase inhibition experiment tests anti-aging effect
Elastase inhibition method: 2mg/mL elastase solution (product of example 1) is taken, samples with different concentrations (2 mL) are added, vortex mixing is carried out fully, shaking is carried out for 20min at 37 ℃ by a 400r/min shaking table, 5mL of 0.5mol/L phosphate buffer solution with pH of 6.0 is added immediately, vortex mixing is carried out, a proper amount of mixed solution is taken into a 2mL centrifuge tube, centrifugation is carried out for 10min at 9 391×g, 200 mu L of supernatant is sucked into a 96-well plate precisely, absorbance is measured by an enzyme-labeled instrument at a wavelength of 495nm, and spectrum scanning at 400-800 nm is carried out simultaneously.
The substrate enzyme adding solution is used as a blank control group, the substrate enzyme adding and sample solution is used as an enzyme inhibition group, and the substrate enzyme adding and sample solution is used as a background. Each group is provided with 3 multiple holes. Inhibition ratio (%) = [1- (An-An ')/(A0-A0') ] ×100%, where A0 is absorbance with no enzyme added to the sample, A0 'is absorbance with no enzyme added to the substrate and no sample added to the enzyme, an is absorbance with only sample solution, an' is absorbance with no enzyme added to the sample. When An ' > An, the effect is expressed as acceleration, and the acceleration rate (%) = [1- (An ' -An)/(A0-A0 ') ] ×100%.
As shown in FIG. 3, wheat germ oil ceramide has excellent inhibitory effects on elastase at various concentrations, specifically, 17.47% at a concentration of 0.25g/L, 35.00% at a concentration of 0.5g/L, 46.93% at a concentration of 1.0g/L, and 58.67% at a concentration of 2.0 g/L.
The inhibitory activities of ceramide 4 on elastase were measured in the same manner, and as a result, as shown in FIG. 4, the elastase inhibition rates at concentrations of 0.25, 0.5, 1.0 and 2.0g/L were 10.12%, 18.06%, 28.84% and 19.78%, respectively, which were not as good as those of wheat germ oil ceramide at the same concentrations.
Example 7
LPS induced cell method for detecting anti-inflammatory repair efficacy
B16 mouse melanoma cells were grown at a density of 1X 10 4 The cells/wells were seeded in 96-well plates, placed in an incubator overnight, the supernatant was discarded after 24 hours, 100. Mu.L of samples of different concentrations diluted with DMEM medium (product of example 1) were added, the negative control group was DMEM medium without samples, 3 wells per group, and mixed with CO at 5 wt.% 2 Incubate at 37 ℃. Lipopolysaccharide model group and experimental group were added with 10 μg/mL LPS and incubated together for 24h 2h after dosing. After the reaction, 50. Mu.L of the cell supernatant was collected, and the intracellular IL-6 gene expression was detected using an IL-6ELISA kit.
The results are shown in FIG. 5, where IL-6 levels were 10.97 times the basal levels at a working concentration of 10. Mu.g/mL of LPS stimulation. Under the action of wheat germ oil ceramide with the concentration of 50mg/L, 100mg/L, 200mg/L and 400mg/L respectively, the IL-6 factor level is obviously reduced and is 0.95 times, 0.88 times, 0.91 times and 0.57 times of that of an LPS model group respectively, and the wheat germ oil ceramide is dose-dependent, so that the wheat germ oil ceramide has good anti-inflammatory effect and can promote the repair of inflammatory damaged skin.
Example 8
MMP1 is also called interstitial collagenase and matrix metalloproteinase, belongs to matrix metalloproteinase family, and its main acting substrate is fibrous collagen, which can degrade collagen fiber and gelatin in extracellular matrix and change microenvironment of cells. MMP1 plays an important role in elastin, inhibiting MMP1 can improve the synthesis of fibroblast collagen and elastin, and reducing MMP activity can increase the collagen synthesis speed.
HaCaT cells were grown at 1X 10 5 The density of individuals/wells was seeded in 96-well plates and the incubator was overnight. After 24h, the supernatant was discarded, 100. Mu.L of medium containing samples of different concentrations (product of example 1) was added, no samples were added to the model group, the negative control group was DMEM medium without samples, 3 wells per group, and the mass fraction was 5% CO 2 After incubation for 2h at 37℃either UVA or UVB ultraviolet radiation is irradiated. The distance between the ultraviolet radiation source and the cells was 15cm, and the UVA intensity was 200mJ/cm 2 The irradiation time was 2 hours, and the UVB intensity was 50mJ/cm 2 The irradiation time was 1h. After the end of irradiation, incubation was continued for 12h in the incubator. Intracellular MMP-1 gene expression was detected using an MMP-1ELISA kit. Inhibition = 1- (experimental group MMP1 expression level/model group MMP1 expression level) ×100%.
As shown in fig. 6 and 7, the expression level of MMP1 in the negative control group was 1, the expression level in the model group was 1.90, and the inhibition ratio of MMP1 expression in the model group was 38%, 61%, 67% at the concentrations of 125, 250, 400mg/L of wheat germ oil ceramide; for UVB, the MMP1 expression level of the negative control group was 1, the expression level of the model group was 2.33, and the inhibition ratios of the MMP1 expression of the wheat germ oil ceramide at the concentrations of 125, 250 and 400mg/L were 43%, 48% and 68% relative to the model group.
After UVA uv radiation, keratinocytes promote elevated expression of MMP1 by fibroblasts, thereby causing degradation of the extracellular matrix of the skin and collagen of the skin, leading to photoaging of the skin. The results show that the wheat germ oil ceramide can inhibit the fibroblast from producing MMP1 caused by ultraviolet radiation, and has a certain effect on preventing skin photoaging.
Example 9
DPPH free radical scavenging detection of antioxidant performance
DPPH is 1, 1-diphenyl-2-trinitrophenylhydrazine, and can be used for antioxidant experiments.
Samples (product of example 1) at corresponding concentrations (50, 100, 200, 400, 800 mg/L) were mixed with 0.1mol/L DPPH, absolute ethanol solution at a ratio of 1:1, and DPPH and absolute ethyl alcohol 1:1, and the absorbance at 517 nm. The absorbance of the sample and the reaction solution of DPPH was designated as A1, the absorbance of the sample and the reaction solution of absolute ethyl alcohol was designated as A2, the absorbance of the reaction solution of DPPH and absolute ethyl alcohol was designated as A3, and the clearance rate of DPPH of the sample was = [1- (A1-A2)/A3 ]. Times.100%.
As a result, as shown in FIG. 8, the DPPH radical scavengers at concentrations of 50, 100, 200, 400 and 800mg/L were 11.09%, 24.91%, 30.44%, 35.07% and 40.58%, respectively, and excellent antioxidant effects were exhibited. The antioxidant effect of ceramide 3B (i.e., oleic acid ceramide) was measured in the same manner, and the result was shown in FIG. 9, in which DPPH radical scavenging rate was 7.76%, 12.82%, 24.10%, 29.60% and 33.16% at concentrations of 50, 100, 200, 400 and 800 mg/L. The clearance rate of the wheat germ oil ceramide to DPPH is higher than that of ceramide 3B, and the wheat germ oil ceramide has better antioxidation effect.
Example 10
Whitening Activity test
Taking B16 cells in exponential growth phase, digesting with trypsin-EDTA with mass fraction of 0.25%, blowing uniformly, and mixing the cells according to 3×10 5 Density of individual/well was seeded in 12-well plates. At 37 ℃, the mass fraction of CO is 5 percent 2 Incubated overnight in the environment. The supernatant was discarded and the culture medium containing samples of different mass concentrations (product of example 1) was added toIncubating RPMI-1640 culture medium without sample as blank group, incubating with DMEM culture medium as model group, 3 multiple holes in each group, and mixing with CO at mass fraction of 5% 2 Incubation was carried out for 24h at 37 ℃. The culture medium in the well plate is discarded, and after washing with Phosphate Buffer (PBS) for one to two times, 1mL of NaOH solution (1 mol/L) containing 10% DMSO by mass fraction is added to lyse the cells, and the cells are kept at a constant temperature of 80℃or 100℃for 2 hours until the cells are completely lysed. The absorbance was measured at 405nm in a microplate reader. The melanin inhibition rate=1- (OD value per well/OD value of model group) ×100% was calculated.
As a result, as shown in FIG. 10, the melanin content of the blank group was 1, the melanin expression of the model group was 1.51, and the melanin inhibition rates of wheat germ oil ceramide were 4.16%, 12.52%, 17.79%, 16.73% and 22.84% at concentrations of 10, 20, 40, 80 and 100mg/L, respectively, and a good whitening effect was exhibited.
The foregoing is merely illustrative embodiments of the present invention, and the present invention is not limited thereto, and any changes or substitutions that may be easily contemplated by those skilled in the art within the scope of the present invention should be included in the scope of the present invention. Therefore, the protection scope of the present invention should be subject to the protection scope of the claims.

Claims (10)

1. Wheat germ oil ceramide is obtained by reacting wheat germ oil fatty acid with a sphingosine compound selected from the group consisting of sphingosine, phytosphingosine and dihydrosphingosine.
2. The wheat germ oil ceramide of claim 1, wherein the wheat germ oil fatty acid is obtained by hydrolyzing wheat germ oil.
3. The wheat germ oil ceramide of claim 1 or 2, wherein the wheat germ oil fatty acid comprises 50 to 75wt% linoleic acid, 15 to 45wt% oleic acid, 2 to 10wt% palmitic acid, 1 to 8wt% linolenic acid, 0.1 to 1wt% arachidonic acid.
4. Wheat germ oil ceramide comprises the following components: linoleic acid ceramide, oleic acid ceramide, palmitic acid ceramide, linolenic acid ceramide, arachidonic acid ceramide.
5. The wheat germ oil ceramide of claim 4, comprising the composition of: 50 to 75 weight percent of linoleic acid ceramide, 15 to 45 weight percent of oleic acid ceramide, 2 to 10 weight percent of palmitic acid ceramide, 1 to 8 weight percent of linolenic acid ceramide and 0.1 to 1 weight percent of arachidonic acid ceramide.
6. The wheat germ oil ceramide of claim 4 or 5, further comprising: 0 to 0.5 weight percent of stearic acid ceramide and 0 to 0.5 weight percent of arachidic acid ceramide.
7. The method for synthesizing wheat germ oil ceramide according to any one of claims 1 to 6, comprising the steps of:
under the conditions of condensing agent and organic alkali, wheat germ oil fatty acid reacts with sphingosine compound, wherein the condensing agent is EDCI, and the organic alkali is Et 3 N；
The wheat germ oil fatty acid, sphingosine compound, EDCI, et 3 The molar ratio of N is 1: (1-1.5): (1-2): (1-2), wherein the solvent for the reaction is at least one of dichloromethane, tetrahydrofuran, ethyl acetate and acetonitrile.
8. Use of the wheat germ oil ceramide of any one of claims 1 to 6 in cosmetics, pharmaceuticals, dietary or health care products.
9. The use according to claim 8, wherein said wheat germ oil ceramide has at least one of skin barrier repair, tissue healing, anti-aging, anti-inflammatory, anti-photoaging, antioxidant, promoting collagen synthesis, maintaining elastin viability, whitening efficacy.
10. A composition comprising the wheat germ oil ceramide of any one of claims 1-6, which has at least one of skin barrier repair, tissue healing, anti-aging, anti-inflammatory, anti-photoaging, antioxidant, promoting collagen synthesis, maintaining elastin viability, whitening efficacy.
CN202310186333.7A 2022-11-25 2023-03-01 Wheat germ oil ceramide and synthesis method and application thereof Pending CN117342970A (en)

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