CN110959851A - Application of agaricus bisporus gallic acid in functional food - Google Patents
Application of agaricus bisporus gallic acid in functional food Download PDFInfo
- Publication number
- CN110959851A CN110959851A CN201911125259.8A CN201911125259A CN110959851A CN 110959851 A CN110959851 A CN 110959851A CN 201911125259 A CN201911125259 A CN 201911125259A CN 110959851 A CN110959851 A CN 110959851A
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- CN
- China
- Prior art keywords
- gallic acid
- ethanol
- active ingredient
- compound
- agaricus
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 229940074391 gallic acid Drugs 0.000 title claims abstract description 70
- 235000004515 gallic acid Nutrition 0.000 title claims abstract description 70
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- 241000222519 Agaricus bisporus Species 0.000 title claims abstract description 32
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- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 40
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- 238000000034 method Methods 0.000 claims abstract description 8
- 238000002791 soaking Methods 0.000 claims abstract description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 29
- 240000007440 Agaricus campestris Species 0.000 claims description 24
- 235000004570 Agaricus campestris Nutrition 0.000 claims description 24
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/42—Separation; Purification; Stabilisation; Use of additives
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
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- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Abstract
The invention discloses application of active ingredient gallic acid in round spore mushroom, and the round spore mushroom gallic acid is preferably prepared by the following method: the preparation method comprises the steps of taking the agaricus bisporus as a raw material, slicing, soaking and extracting the agaricus bisporus by using 90-95% and 60-65% of ethanol in sequence to obtain a concentrated solution, concentrating the concentrated solution to obtain an extract, combining the ethanol extracts, finally combining the extracts, extracting the combined extract by using an organic solvent to obtain an extract, and separating and purifying the extract by using a chromatographic column to obtain gallic acid and other active ingredients, wherein the agaricus bisporus gallic acid has the effect of regulating a tumor microenvironment and can be used for preparing functional food with the effect of assisting in inhibiting esophagus cancer tumors.
Description
Technical Field
The invention belongs to the technical field of functional foods, relates to application of agaricus bisporus gallic acid in functional foods, and more particularly relates to application of agaricus bisporus gallic acid in preparation of functional foods with the effect of assisting in inhibiting esophagus cancer.
Background
Malignant tumor is a serious disease endangering human health at present, chemotherapy is one of the main methods applied to the whole body treatment of malignant tumor, but most of anti-tumor chemical drugs can kill tumor cells and damage normal cells seriously, so that the search for high-efficiency and low-toxicity anti-tumor drugs has important significance. In recent years, researches show that various natural product extracts have obvious antitumor activity and relatively small toxic and side effects on human bodies, and the research on the biological activity of the natural product extracts becomes a hot spot for the research of experts and scholars at home and abroad in the medical field.
Chemical composition research of Agaricus (Agaricaceae) of Agaricus in the last century began, and it was found that the chemical compositions of fungi of this genus mainly include volatile oils, Agarbilazeispirol, sterols, A-1 (sodium pyrrolidone carboxylate), flavones, etc. May contain ceramide components, daucosterol, diterpenes, triterpenes, physcion, apigenin-7-4' -dimethyl ether, guaiacyl glycerol, butenolide, etc.
Agaricus is called "Pleurotus Cineraricus" belonging to Agaricales of Agaricus. The obtained product has good flavor and taste. The young plenilla is milk white, and then gradually changes from pink to black brown, and the single plenilla weighs 58-350g and can reach 2-5kg at most. The soil can grow in 20-70cm soil under irrigated sandy land and lake reed, and can be opened under the ground to grow single, scattered or clustered, and mostly grow in the west and southwest regions of Xinjiang. Since the nineties of the last century, active ingredients of agaricus blazei murill of the same genus and various activities thereof have been found. However, the chemical composition and related activity of Agaricus blazei in the same genus are still blank. In order to develop and utilize this resource, a more systematic study on the small molecular chemical components of the sporozoite has been carried out.
Gallic acid, also known as gallic acid or gallic acid, is an organic acid found in plants such as Galla chinensis, Rhus verniciflua Stokes, Camellia sinensis, etc. Chemical formula C6H2(OH)3COOH. Gallic acid is readily soluble in water, alcohols and ethers; has the properties of phenol (which is easy to be oxidized and generates blue-black precipitate by ferric trichloride aqueous solution) and carboxylic acid (which loses carbon dioxide to form pyrogallic acid when being heated). Gallic acid can be used as developer, and its alkaline bismuth salt can be used as antiseptic, and also used in pharmaceutical industry.
The gallic acid has the inhibition effect on staphylococcus aureus, sarcina, α -type streptococcus, neisseria, pseudomonas aeruginosa, dysentery bacillus freudenreichii, typhoid bacillus Hd, paratyphoid bacillus A and the like in vitro in the aspect of antibiosis and antivirus, the inhibition concentration is 5mg/ml, the gallic acid has the inhibition effect on 17 fungi in vitro at the concentration of 3 percent, and has a certain inhibition effect on influenza virus.
Disclosure of Invention
The invention aims to provide application of agaricus bisporus gallic acid in preparation of functional food with the effect of assisting in inhibiting esophagus cancer.
The effect of assisting in inhibiting the esophageal cancer refers to the effect of adjusting a tumor microenvironment by inhibiting tumor angiogenesis, immunosuppression, oxidation resistance, inhibition of growth of esophageal cancer fibroblasts and the like, so that the effect of assisting in inhibiting the esophageal cancer tumor is achieved.
As an embodiment of the present invention, the agaricus bisporus gallic acid in the present invention is preferably prepared by the following method: the preparation method comprises the steps of taking the agaricus bisporus as a raw material, slicing, soaking and extracting the agaricus bisporus by using 90-95% and 60-65% of ethanol in sequence to obtain a concentrated solution, concentrating the concentrated solution to obtain an extract, combining the ethanol extracts, finally combining the extracts, extracting the extract by using an organic solvent to obtain an extract, and separating and purifying the extract by using a chromatographic column to obtain gallic acid and other active ingredients, wherein the agaricus bisporus gallic acid has the effect of regulating a tumor microenvironment.
As a preferred embodiment of the present invention, the agaricus bisporus gallic acid according to the present invention is specifically prepared by the following method: slicing fresh and undamaged sporophore of Agaricus campestris, soaking in 90-95% ethanol for one week, filtering to obtain filtrate, recovering solvent under reduced pressure, adding 90-95% ethanol into the residue, ultrasonic extracting for 3-5 times (each time for 1-5 hr), and concentrating under reduced pressure to obtain 90-95% ethanol extract; performing the same operation with 60-65% ethanol, and concentrating under reduced pressure to obtain 60-65% ethanol extract; adding distilled water into the alcohol-extracted agaricus bisporus filter residue, performing ultrasonic extraction for three times, extracting for 1-3h each time, and concentrating under reduced pressure to obtain a water extract.
Wherein the ratio of the sporophore of the Agaricus campestris to the ethanol is 0.5-1:1-5, and the sporophore of the Agaricus campestris is completely soaked in the ethanol.
Wherein the reduced pressure recovery condition is 0.1-0.5MPA and the temperature is 25-40 ℃; the ultrasonic extraction condition is 200-800HZ, the ultrasonic treatment is carried out for 30-45min, and the temperature is 30-50 ℃.
Mixing the two ethanol extracts, kneading and dispersing the mixed extracts in pure water, adding petroleum ether (water to petroleum ether ratio is 1:1-0.5) into a separating funnel, adding the extract dispersion into the separating funnel, extracting for 5 times, mixing the extracts, and concentrating to obtain petroleum ether fraction. Adding ethyl acetate (water to ethyl acetate ratio of 0.5-1:1) into the separating funnel, extracting for 6 times, mixing the extractive solutions, and concentrating to obtain ethyl acetate fraction. Adding n-butanol (water to n-butanol ratio of 0.4-1:1) into separating funnel, extracting for 5 times, mixing extractive solutions, and concentrating to obtain n-butanol fraction.
Wherein, the extraction conditions are as follows: the extraction pressure is 20MPa to 40MPa, the extraction temperature is 30 ℃ to 50 ℃, and the extraction time is 0.8h to 2.5 h.
Separating the petroleum ether part by medium-pressure silica gel column flash chromatography, carrying out gradient elution by a petroleum ether-ethyl acetate system (100: 0-0: 100), detecting eluent by thin-layer chromatography, merging similar fractions, and recovering a solvent to obtain 9 components A-I. And carrying out medium-pressure silica gel chromatographic separation on the component D to obtain D1 and D2. D1 is recrystallized to obtain the needle compound 3. D2 was subjected to multiple medium pressure silica gel chromatography and Sephadex LH-20 column chromatography to obtain white solid compound 2. And (3) performing combined separation on the component E by multiple medium-pressure silica gel chromatographies and Sephadex LH-20 column chromatographies to obtain a yellowish green oily solid compound 1.
Wherein, the separation conditions of the medium-pressure silica gel column in the petroleum ether part are as follows: the silica gel column is prepared by using 120-type 160 mu m chromatographic silica gel as silica gel, the diameter-height ratio of the silica gel is 1:5-1:10, and the flow rate is 30-90 ml/min.
Wherein, the chromatographic separation conditions of the Sephadex LH-20 column are as follows: using acidified methanol as eluent, with concentration of 20-40% (Ph regulated at 3-4) and flow rate of 0.2-1.0 ml/min.
Subjecting the ethyl acetate fraction obtained above to medium pressure reverse phase C18The column fast chromatographic separation, gradient elution in water-methanol solvent system (5-100%), combination of eluents in the same gradient, and solvent recovery to obtain 6 components I-VI. After the high performance liquid chromatography test, the components I to IV are found to be common components in the n-butanol phase, so that the components are merged to the n-butanol phase. The V component is subjected to medium-pressure reverse phase C18After separation, use C18Semi-preparative column separation) to give compounds 4,5 and 24. Compound 4 is a yellow particulate solid; compound 24 is a yellow particulate solid; compound 5 was a red particulate solid.
Wherein the above-mentioned inverse phase C18The conditions for column chromatography separation were: gradient elution is carried out by a water-methanol solvent system (5-100%); flow rate: 1.0-3.5ml/min, column temperature: 25-30 ℃.
Wherein, the above-mentioned C18The semi-preparative column separation conditions were mobile phase a: 1ml/L phosphoric acid aqueous solution (0.2% triethylamine, pH2.0 adjusted with phosphoric acid), mobile phase B: acetonitrile; filtering the mobile phase A, B, and performing ultrasonic treatment for 10 min; mobile phase ratio: mobile phase A: mobile phase B90: 10; flow rate: 1.0ml/min, column temperature: at 30 ℃.
And adding ethanol into the obtained n-butanol part, precipitating crystals on the container wall during precipitation, repeating the operation for multiple times, and recrystallizing for multiple times to obtain the compound 23. The n-butanol fraction is reversed phase C under medium pressure18Separating, gradient eluting with water-methanol solution (5-100%), merging the eluates, and vacuum recovering solvent to obtain 6 components Z-I-Z-VI. The Z-II component is separated by MCI resin and is washed by water-methanol solution (0-100 percent) in a gradient wayRemoving and using C18Separating and purifying with semi-preparative column to obtain compound 7, compound 8, compound 9 and compound 10. And separating and purifying the Z-IV component by using a C18 semi-preparative column to obtain a compound 6. The Z-I component, namely the pure water elution part of the MCI resin, is separated and cut into sections by an Agilent Zorbax SB-CN full preparative column, and is isocratically eluted byA water-methanol solution (5 percent) to obtain 4 components of Z-A-Z-D.
Wherein the above-mentioned inverse phase C18The conditions for column chromatography separation were: gradient elution is carried out by a water-methanol solvent system (5-100%); flow rate: 1.0-3.5ml/min, column temperature: 25-30 ℃.
Wherein, the MCI resin separation condition is gradient elution of a water-methanol solvent system (0-100 percent); flow rate: 1.0-3.5ml/min, column temperature: 25-30 ℃.
Wherein, the separation and purification conditions of the C18 semi-preparative column are as follows: mobile phase A: 1ml/L phosphoric acid aqueous solution (0.2% triethylamine, pH2.0 adjusted with phosphoric acid), mobile phase B: acetonitrile; filtering the mobile phase A, B, and performing ultrasonic treatment for 10 min; mobile phase ratio: mobile phase A: mobile phase B90: 10; flow rate: 1.0-3.5ml/min, column temperature: 20-30 ℃.
And separating and purifying the Z-A component by an Agilent Zorbax SB-CN semi-preparative column to obtainA compound 13,A compound 14,A compound 16,A compound 17,A compound 19, compounds 20 and 21. Compounds 14, 16, 17, 20 and 21 were all white particles, compound 13 was a white gum; compound 19 was obtained as a purified crystal, a transparent needle crystal. Separating and purifying the Z-B component by an AgilentZorbax SB-CN semi-preparative column to obtain compounds 11 and 12, wherein the compounds 11 and 12 are white particles. And separating and purifying the Z-C component by an Agilent Zorbax SB-CN semi-preparative column to obtain a compound 18 and a compound 22, wherein the compounds 18 and 22 are white powder. And separating and purifying the Z-D component by an Agilent Zorbax SB-CN semi-preparative column to obtain a compound 15, wherein the compound 15 is white powder.
Wherein, the conditions for separating and purifying the Agilent Zorbax SB-CN semi-preparative column are as follows: mobile phase A: using 10-30mM Na2HPO4-NaH2PO4 buffer solution or K2HPO4-KH2PO4 buffer solution or Tris-HCl buffer solution as eluent A (0.2% triethylamine, pH2.0 adjusted by phosphoric acid), mobile phase B: acetonitrile; filtering the mobile phase A, B, and performing ultrasonic treatment for 10 min; mobile phase ratio: mobile phase A: mobile phase B90: 10; flow rate: 1.0-3.5ml/min, column temperature: 20-30 ℃.
The agaricus bisporus gallic acid can be directly orally taken, can also be prepared into various dosage forms in pharmaceutics, such as capsules, tablets, powder, granules or oral liquid and the like, and has the effect of assisting in inhibiting esophagus cancer tumors after being eaten.
Therefore, the dosage form of the functional food of the present invention is preferably capsule type, tablet, powder, granule, oral liquid, or the like.
Compared with the prior art, the invention has the following advantages:
(1) the agaricus bisporus gallic acid has high purity and activity, can regulate a tumor microenvironment through the ways of inhibiting tumor angiogenesis, inhibiting the growth of esophageal cancer cells and the like, and has a good effect of assisting in inhibiting esophageal cancer tumors;
(2) the preparation method of the agaricus bisporus gallic acid has the advantages of simple, stable and efficient process, suitability for industrial production and low cost;
(3) the agaricus bisporus gallic acid can be used for preparing functional food with the effect of assisting in inhibiting esophagus cancer tumors.
Drawings
FIG. 1 is the activity of Agaricus campestris Gallic acid in inhibiting BMP 2-induced luciferase with BRE reporter gene in example 4 of the present invention;
FIG. 2 shows that the agaricus bisporus gallic acid inhibits TGF β -induced activity of the reporter gene SMAD2/3/4 in example 5 of the present invention;
FIG. 3 is a graph showing that Agaricus campestris gallic acid inhibits the activity of luciferase having NF- к B reporter gene in example 6 of the present invention;
FIG. 4 shows that Agaricus campestris Gallic acid inhibits Cocl 2-induced luciferase activity with HRE reporter gene in example 7 of the present invention;
FIG. 5 shows that the agaricus bisporus gallic acid can inhibit the growth of esophageal cancer cells in example 8 of the present invention.
Detailed Description
The invention is further illustrated, but not limited in any way, by the following examples in connection with the accompanying drawings.
The raw materials used in the following examples are all commercially available products unless otherwise specified.
Example 1 preparation of crude extracts of active ingredients of Agaricus campestris
Collecting fresh and undamaged sporocarp 10kg of sporocarp of the sporocarp. Concentrating under reduced pressure to obtain 95% ethanol extract. The 65% ethanol is used for the same operation, and the 65% ethanol extract is obtained by decompression and concentration. Adding 30L distilled water into alcohol extracted Agaricus campestris residue, and ultrasonic extracting at 1800HZ for three times, each time for 2 hr. Concentrating under reduced pressure to obtain 538g of water extract.
Wherein the reduced pressure recovery condition is 0.25MPA and the temperature is 30 ℃; the ultrasonic extraction conditions are 800HZ, ultrasonic extraction is 45min, and the temperature is 30 ℃.
Mixing the two ethanol extracts to obtain 84.5g, kneading and dispersing 84.5g of the mixed extract in 500ml of pure water, adding petroleum ether (the ratio of water to petroleum ether is 1:1) into a 2000ml separating funnel, adding the extract dispersion into the separating funnel, extracting for 5 times, mixing the extracts, and concentrating to obtain 10.0g of petroleum ether part. Then, ethyl acetate (the ratio of water to ethyl acetate is 1:1) was added to the above separatory funnel, extraction was performed for 6 times, and the extracts were combined and concentrated to obtain 6.0g of an ethyl acetate fraction. Adding n-butanol (water to n-butanol ratio of 1:1) into the separating funnel, extracting for 5 times, mixing extractive solutions, and concentrating to obtain n-butanol fraction 60.0 g.
Wherein, the extraction conditions are as follows: the extraction pressure is 40MPa, the extraction temperature is 35 ℃, and the extraction time is 2 h.
Example 2
60.0g of the n-butanol fraction obtained in example 1 was added to ethanol, and during precipitation, crystals were precipitated on the container wall, and the operation was repeated several times to obtain 30mg of compound 23 by repeated recrystallization. The n-butanol fraction is reversed phase C under medium pressure18The water-methanol solution (5-100 percent) for separation) Gradient elution, merging the eluates according to the same gradient, and decompressing and recovering the solvent to obtain 6 components of Z-I-Z-VI. The Z-II component is separated by MCI resin, and is eluted by water-methanol solution (0-100 percent) in a gradient way, and is added with C18Separating and purifying by semi-preparative column to obtain 4mg of compound 7, 5mg of compound 8, 4mg of compound 9 and 5mg of compound 10. The Z-IV fraction was separated and purified by C18 semi-preparative column to give 5mg of Compound 6. The Z-I component, namely the pure water elution part of the MCI resin, is separated and cut into sections by an Agilent ZorbaxSB-CN full preparative column, and is isocratically eluted byA water-methanol solution (5 percent) to obtain 4 components of Z-A-Z-D.
Wherein the above-mentioned inverse phase C18The conditions for column chromatography separation were: gradient elution is carried out by a water-methanol solvent system (5-100%); flow rate: 1.5ml/min, column temperature: at 30 ℃.
Wherein, the MCI resin separation condition is gradient elution of a water-methanol solvent system (0-100 percent); flow rate: 1.5ml/min, column temperature: at 30 ℃.
Wherein, the separation and purification conditions of the C18 semi-preparative column are as follows: mobile phase A: 1ml/L phosphoric acid aqueous solution (0.2% triethylamine, pH2.0 adjusted with phosphoric acid), mobile phase B: acetonitrile; filtering the mobile phase A, B, and performing ultrasonic treatment for 10 min; mobile phase ratio: mobile phase A: mobile phase B90: 10; flow rate: 1.5ml/min, column temperature: at 30 ℃.
The AA-A fraction was isolated and purified by Agilent Zorbax SB-CN semipreparative column to give 4mg of compound 13, 100mg of compound 14, 5mg of compound 16, 4mg of compound 17, 15mg of compound 19, 4mg of compound 20 and 3mg of compound 21. Compounds 14, 16, 17, 20 and 21 were all white particles, compound 13 was a white gum; compound 19 was obtained as a purified crystal, a transparent needle crystal. The Z-B component was separated and purified by Agilent Zorbax SB-CN semi-preparative column to give 4mg of compound 11, 5mg of compound 12, and the compounds 11, 12 were white particles. And separating and purifying the Z-C component by an Agilent Zorbax SB-CN semi-preparative column to obtain 5mg of compound 18 and 4mg of compound 22, wherein the compounds 18 and 22 are white powder. The Z-D fraction was isolated and purified by Agilent Zorbax SB-CN semipreparative column to give 4mg of Compound 15, Compound 15 being a white powder.
Wherein, the Agilent Zorbax SB-CN semi-preparative column is used for separationThe purification conditions were: mobile phase A: at 15mM Na2HPO4-NaH2PO4Buffer solution or K2HPO4-KH2PO4Buffer or Tris-HCl buffer as eluent a (0.2% triethylamine, PH2.0 adjusted with phosphoric acid), mobile phase B: acetonitrile; filtering the mobile phase A, B, and performing ultrasonic treatment for 10 min; mobile phase ratio: mobile phase A: mobile phase B90: 10; flow rate: 1.5ml/min, column temperature: at 30 ℃.
And (3) carrying out physical and chemical property identification on the separated and purified compound components by a conventional physical detection method: the detection method comprises the following steps: EIS-MS, H-NMR, C-NMR. The detection method is the same as that of the pharmacopoeia 2015 edition. The detection results are as follows:
A white powder; EI-MS M/z 428[ M-H ═ M2O],410[M-2H20],382[M-2H2O-CO].1H-N MR(CD3OD,500MHz):5.21(2Hm,H-22,23),5.05(1H,brs,H-7),3.88(2H,m,H-3,6)，1.05(3H,S,H-19),1.03(3H,d,J＝6.7Hz,H-21),0.93(3H,d,J＝6.9Hz,H-28),0.86(3H,d,J＝6.8Hz,H-27),0.84(3H,d,J＝6.8Hz,H-26),0.61(3H,S,H-18)。13The C-NMR (DEPT) spectrum gives a signal of 28 carbons, 6 methyl groups, 7 methylene groups, 10 methine groups and 5 quaternary carbons. The four carbon signals are at δ c78.6, 75.8, 71.2, 67.9, indicating that they are linked to oxygen. Four carbon signals at δ c143.3,137.0,133.3,122.0 indicate two double bonds. The above data are essentially consistent with ergosterol data, and compound 6 was identified as ergosterol.
Compound 7 Peroxyaergosterol (peroxy-ergosterol)
White powder.1H-NMR(500MHz,CDCl3)δ:6.50(1H,d,J＝8.5Hz,H-7),6.24(1H,d,J＝8.5Hz,H-6),5.22(1H,dd,J＝7.6,15.3Hz,H-23),5.14(1H,dd,J＝8.3,15.5Hz,H-22),3.92(1H,m,H-3),1.25(3H,s,Me-19),1.00(3H,d,J＝6.7,Me-21),0.91(3H,d,J＝6.9Hz,Me-28),0.88(3H,s,Me-18),0.83(3H,d,J＝6.8Hz,Me-26),0.82(3H,d,J＝6.8Hz,Me-27)。13C-NMR(125MHz,CDCl3) 34.7(t, C-1),30.1(t, C-2),66.4(d, C-3),36.9(t, C-4),82.2(s, C-5),135.4(d, C-6),130.7(d, C-7),79.4(s, C-8),51.1(d, C-9),36.9(s, C-10),23.4(t, C-11),39.4(t, C-12),44.6(s, C-13),51.8(d, C-14),20.6(t, C-15),28.6(t, C-16),56.2(d, C-17),12.9(q, C-18),18.2(q, C-19),39.4(d, C-20),20.9(q, C-21),135.2(d, C-22, 22.42, 132.42 (d, C-3), c-24),33.1(d, C-25),20.0(q, C-26),19.6(q, C-27),17.6(q, C-28); the above data are consistent with those of peroxyergosterol, and compound 7 was identified as peroxyergosterol.
Compound 8 Macrospelide A
White powder, ESI-MS M/z 365.2[ M + Na ]]+,341.2[M-H]-From this, it was concluded that the relative molecular mass was 342, and the molecular formula C was deduced from the combination of the hydrogen spectrum and the carbon spectrum16H22O8,1H-NMR(CDCl3):6.88(1H,dd,J＝15.6,1.5Hz,H-7),6.83(1H,dd,J＝15.6,1.5Hz,H-13),6.02(1H,dd,J＝15.6,1.5Hz,H-12),6.01(1H,dd,J＝15.6,1.5Hz,H-6),5.35(1H,m,H-3),4.93(1H,q,J＝6.3Hz,H-9),4.82(1H,q,J＝6.3Hz,H-15),4.18(1H,m,H-8),4.09(1H,m,H-14),3.57(2H,brs,8-OH,14-OH),2.58(2H,dd,J＝7.2,2.4Hz,2-H2),1.40(3H,d,J＝6.6Hz,9-CH3),1.33(3H,d,J＝6.3Hz,15-CH3),1.29(3H,d,J＝6.6Hz,3-CH3)；13C-NMR(CDCl3) 170.1(C-1),165.7(C-11),164.9(C-5),146.4(13-CH),145.6(7-CH),122.5(6-CH),122.1(12-CH),74.5(9-CH),74.4(8-CH),73.6(15-CH),72.8(14-CH),67.7(3-CH),40.9(2-CH2),19.6(3-CH3),17.8(9-CH3),17.7(15-CH 3); the above data are consistent with those of Macrosphalide A, and therefore Compound 8 was identified as Macrosphalide A.
Compound 9 adenosine (a-denosine)
White powder, mp.230-232 ℃;1H-NMR(DMSO-d6,500MHz)δ:3.58(1H,d,J＝10.8Hz,H-5′),3.67(1H,d,J＝11.4Hz,H-5′),5.88(1H,d,J＝9.6Hz,H-1′),7-33(2H,brs,J＝1.0Hz,NH2),8.14(1H,s,H-8),8.34(1H,s,H-2)；13CNM R(DMSO-d6125MHz) delta 152.3(C-2),149.0(C-4),119.3(C-5),156.1(C-6),139.9(C-8),87.9(C-1 '), 73.4 (C-2'), 70.6(C-3 '), 85,8 (C-4'), 61.6(C-5 '), 156.1 (C-6'), the spectral data and the physicochemical characteristics of which are consistent with those of adenosine, and thus, the compound 9 was identified as adenosine (a-denosine).
A colorless oil; it is easily soluble in acetone, chloroform and methanol, and is hardly soluble in water. ESIMS M/z 167[ M + H ]]+；1H-NMR (Me2CO-d,6,500Hz) δ 7.87(2H, d, J ═ 9.0Hz, H-2,6),6.90(2H, d, J ═ 9.0Hz, H-3,5),4.22(2H, q, J ═ 7.0Hz, H2-1 '), 1.31(3H, t, J ═ 7.0Hz, H3-2'). The data above are consistent with those for ethyl paraben, so compound 10 was identified as ethyl paraben.
Compound 12 p-hydroxybenzaldehyde (p-hydroxybenzaldehyde)
A colorless oil; easily soluble in acetone, chloroform and methanol, and hardly soluble in water; ESIMS M/z 123[ M + H ]]+；1H-NMR (Me2CO-d6,500hz,) δ 9.84(1H, s, H-7),7.79(2H, d, J ═ 9.0Hz, H-2,6),7.00(2H, d, J ═ 8.5Hz, H-3, 5). The above data are consistent with those for p-hydroxybenzaldehyde, so compound 12 was identified as p-hydroxybenzaldehyde.
Compound 134-hydroxy-3-methoxy-benzyl alcohol (4-hydroxy-3-methoxy-benzyl alcohol)
A white solid. Is easily soluble in acetone, chloroform and methanol and is insoluble in water; ESIMS M/z 155[ M + H ]]+；1H-NMR(Me2CO-,d,6,500Hz)δ:7.53(1H,s,4-OH),6.84(1H,d,J＝1.5H z,H-2),6.85(1H,d,J＝8.0Hz,H-5),6.75(1H,dd,J＝1.5,8.0Hz,H-6),4.47(2H,d,J＝6.5Hz,H2-7),4.03(1H,t,J＝6.5Hz,7-OH),3.80(3H,s,-OMe)；13C-NMR (Me2CO-, d,6,125Hz) delta 136.1(C-1),112.2(C-2),147.3 (C-or C-4),147.0 (C-or C-4),114.7(C-5),118.5(C-6),64.4(C-7),56.3 (-OMe). The above data are consistent with the data for 4-hydroxy-3-methoxy-benzyl alcohol, and compound 13 was identified as 4-hydroxy-3-methoxy-benzyl alcohol.
Compound 145 α,6 α -Epoxy- (22E,24R) -ergosta-8(14),22-diene-3 β,7 α -diol
A white powder;
HRESIMS:m/z＝451.3167[M+Na]+(calcd for C28H44NaO3,451.3183)；1H-NMR(600MHz,CDCl3)δ:5.21(2H,m,H-22,23),4.42(1H,d,J＝6.3Hz,H-7),3.91(1H,m,H-3),3.14(1H,d,J＝3.5Hz,H-6),1.02(3H,d,J＝6.7Hz,H-21),0.92(3H,d,J＝6.8Hz,H-28),0.87(6H,s,H-18,19),0.84(3H,d,J＝6.8Hz,H-27),0.82(3H,d,J＝6.8Hz,H-26)；13C-NMR(150MHz,CDCl3) Δ 152.75(C-14),135.41(C-22),132.44(C-23),125.38(C-8),68.87(C-3),67.92(C-5),65.25(C-7),61.49(C-6),57.02(C-17),43.15(C-13),43.01(C-24)39.78(C-20),39.39(C-4),38.92(C-9),36.78(C-12),36.01(C-10),33.27(C-25),32.38(C-1),31.31(C-2),27.31(C-16),25.13(C-15),21.40(C-21),19.82(C-27),19.17(C-26),18.24(C-11),17.77(C-18,28),16.70(C-19), the above data are consistent with those of Epdione 34, 6- (C-22),132, 3622-24), α - (Epdiose) and the above data are as for compounds identified as Epdiose (Epdiose) 22, 3926, 3-24, α, 367, 368, 3626, 368, 24-24, 3626, 368, 3626, and Epdiose,7α-diol。
Compound 15 p-hydroxybenzyl alcohol (p-hydroxybenzyl alcohol)
White needle crystals (methanol); is easily soluble in acetone, chloroform and methanol and is insoluble in water; (-) -ESIMS M/z 283[ M-H ]]-；1H-NMR (500MHz, DMSO-d6) δ 9.31(1H, s, OH),7.25(2H, d, J ═ 8.0Hz, H-2,6),6.89(2H, d, J ═ 8.0Hz, H-3,5),4.76(1H, s, OH),4.36(2H, s, H-7). The data above are essentially identical to the data control for p-hydroxybenzyl alcohol, so compound 15 was identified as p-hydroxybenzyl alcohol.
Compound 16 p-hydroxybenzoic acid (p-hydroxybenzoic acid)
White flaky crystal (acetone), easily soluble in chloroform and methanol, insoluble in water (-) -ESIMS M/z 137[ M-H ]]-；1H-NMR(500MHz,Me2CO-d6)δ:7.68(2H,d,J＝9.0Hz,H-2,6),6.79(2H,d,J＝9.0Hz,H-3,5)。13C-NMR (125MHz, Me2CO-d6) delta: 168.3(COOH),162.1(C-4),132.1(C-2,6),122.2(C-1),114.9(C-3, 5). The above data are consistent with those for parahydroxybenzoic acid, so compound 16 was identified as parahydroxybenzoic acid.
Compound 17 p-hydroxybenzyl methyl ether (p-hydroxybenzyl methyl ether)
White flaky crystals (acetone), which are easily soluble in chloroform and methanol and insoluble in water. (-) -ESIMS M/z 137[ M-H ]]-；1H-NMR (500MHz, DMSO-d6) δ 9.25(1H, OH),7.17(2H, d, J ═ 8.0Hz, H-2,6),6.69(2H, d, J ═ 8.0Hz, H-3,5),4.19(2H, s, H-7),3.18(3H, s, OM e). The above data are consistent with those for p-hydroxybenzyl methyl ether, so compound 17 was identified as p-hydroxybenzyl methyl ether.
Compound 18 p-hydroxybenzylethyl ether (p-hydroxybenzyl ethyl ether)
White flaky crystals (acetone), which are easily soluble in chloroform and methanol and insoluble in water; (+) -ESIMS M/z 153[ M + H ]]+；1H-NMR (300MHz, DMSO-d6) δ 9.29(1H, OH),7.09(2H, d, J ═ 8.4Hz, H-2,6),6.80(2H, d, J ═ 8.4Hz, H-3,5),4.31(2H, s, H-7),3.39(2H, q, J ═ 6.9Hz, OCH2CH3),1.11(3H, t, J ═ 6.9Hz, OCH2CH 3). The above data are consistent with those for p-hydroxybenzylether, so compound 18 was identified as p-hydroxybenzylether.
Compound 19 p-methoxybenzoic acid (p-hydroxybenzoic acid)
White flaky crystals (acetone), which are readily soluble in chloroform and methanol and poorly soluble in water. (-) -ESIMS M/z 151[ M-H ═ M]-；1H-NMR (500MHz, DMSO-d6) δ 7.87(2H, d, J ═ 8.5Hz, H-2,6),6.77(2H, d, J ═ 8.5Hz, H-3,5),3.74(3H, s, OMe). The above data are consistent with those for p-methoxybenzoic acid, so compound 19 was identified as p-methoxybenzoic acid.
Compound 208-methoxy-1-naphthol (8-Methoyynapthhalene-1-ol)
White powder, ESI-MS M/z 175[ M + H ]]+.1H-NMR(CDC13,500MHz)δ:9.31(1H,s,1-OH),7.41(1H,d,J＝8.3Hz,H-4),7.36～7.28(3H,m,H-3,H-5,H-6)6.87(1H,d,J＝7.5Hz,,H-7),6.78(1H,d,J＝7.7Hz,H-2)4.06(3H,s,8-OCH3)；13C-NMR(CDCl3125MHz) delta 156.2(C-8)154.5(C-1)136.8(C-4a)127.7(C-3)125.6(C-6),121.9(C-5)118.8(C-4)115.1(C-8a)110.4(C-2)103.9(C-7),56.1(8-OCH 3). The data above are essentially consistent with 8-methoxy-1-naphthol, and compound 20 was identified as 8-methoxy-1-naphthol.
Compound 22 Gallic acid (gallic acid)
White needle crystal; EI-MS M/z (%). 171[ M + H ] +; 1H-NMR (500MHz, CDCl3) 7.15(2H, s, H-2,6),7.60(2H, s,3,5-OH),7.28(1H, s,4-OH),12.10(1H, s,1-CO OH); 13C-NMR (100MHz, CDCl3) 123.1(s, C-1),114.3(d, C-2,6),146.0(s, C-3,5),139.4(s, C-4),170.6(s, COOH). The data are essentially identical to those of gallic acid, and compound 22 was identified as gallic acid.
White amorphous powder (methanol). 1H-NMR (CD3OD,500MHz) delta (ppm) 9.55(1H, s, -CHO),7.27(2H, s, H-2, 6); 13C-NMR (CD3OD,100MHz) delta (ppm) 192.8(-CH O),149.9(C-3,5),145.2(C-4),128.0(C-1),108.3(C-2, 6). The above data are consistent with 3,4, 5-trihydroxy-benzaldehyde, so compound 23 was identified as 3,4, 5-trihydroxy-benzaldehyde.
Example 4 Agaricus campestris Gallic acid can inhibit BMP 2-induced luciferase Activity with BRE reporter Gene
The C2C12 cell line was purchased from the cell bank of the Chinese academy of sciences, and the C2C12-pGF1-BRE cell line was purchased from Shanghai pharmaceutical research institute of Chinese academy of sciences and stored in liquid nitrogen. The C2C12-pGF1-BRE cells are cultured in DMEM medium containing 10% Gibco fetal bovine serum and placed at 37 ℃ in saturated humidity and containing 5% CO2Cultured in an incubator of 1X 104The density of cells/well was seeded in 96-well plates at 100. mu.L per well. After 24h of adherence, 60. mu.L of the medium was aspirated, 50. mu.L of the prepared sample (agaricus bisporus gallic acid in example 1) with corresponding concentrations were added to the medium to obtain final concentrations of 1.5mg/mL, 1mg/mL and 0.5mg/mL, respectively, and 10. mu.L of BMP2 was adjusted to obtain a final concentration of 200 ng/mL. Blank and BMP2 controls were also set. After 16h of administration the medium was aspirated, 20. mu.L of Reporter Lysis1XBuffer was added and 20. mu.L of lysed cell lysate was transferred toAdd 40. mu.L of luciferase substrate to the plates, read the plates within 3 minutes, and read the RLU values. Statistical processing was performed using SPSS statistical software. Data are expressed as mean ± standard deviation (. x ± s), independent sample t test is adopted for comparison between two groups, and one-factor analysis of variance is adopted for comparison between multiple groups.
As shown in fig. 1, the agaricus bisporus gallic acid has the activity of inhibiting BMP 2-induced luciferase with BRE reporter gene at a low concentration of 0.5mg/mL, and the activity is significantly increased with the increase in the concentration of gallic acid, indicating that gallic acid has a dose dependence in the activity. Tumor neovascularization is known to play a key role in the development of tumors, while the BMP2 signaling pathway plays a key role in tumor neovascularization. The gallic acid can remarkably inhibit a BMP2 signal path, and shows that the gallic acid has the effects of potentially inhibiting tumor angiogenesis and regulating a tumor microenvironment.
Example 5 Agaricus campestris Gallic acid can inhibit TGF β -induced activity of reporter gene with SMAD2/3/4
The HEK293T cell line was purchased from cell bank of Chinese academy of sciences, and the HEK293T-pGF1-SMAD2/3/4 cell line was purchased from Shanghai pharmaceutical research institute of Chinese academy of sciences, and stored in liquid nitrogen. HEK293T-pGF1-SMAD2/3/4 cells were cultured in DMEM medium containing 10% Gibco fetal bovine serum and placed at 37 ℃ in saturated humidity and containing 5% CO2Cultured in an incubator at 2X 104The density of cells/well is inoculated in a 96-well plate, 100 μ L of each well, 60 μ L of culture medium is aspirated after 24h adherence, 50 μ L of sample (agaricus bisporus gallic acid in example 2) with corresponding concentration is added, the final concentration is 1.5mg/mL, 1mg/mL, 0.5mg/mL, 10 μ L TGF β 1 is adjusted to 50ng/mL, blank group and TGF β 1 group are set for comparison at the same time, the culture medium is aspirated after 16h administration, 20 μ L LReporter lysine 1XBuffer is added, 20 μ L of dissolved cell lysate is transferred to a white board, 40 μ L luciferase substrate is added, the board is read within 3 min, RLU value is read, SPSS statistical processing software is adopted, data are expressed by mean number plus or minus standard deviation (x plus or minus s), two-group comparison adopts independent sample t test, and multiple-group comparison adopts single factor analysis.
The experimental result is shown in figure 2, the agaricus bisporus gallic acid has an SMAD2/3/4 signal channel for inhibiting TGF β induction at a low concentration of 0.5mg/mL, and the activity is remarkably increased along with the increase of the concentration of the agaricus bisporus gallic acid, which indicates that the gallic acid has dose dependence on the activity.
Example 6 Agaricus campestris Gallic acid can inhibit the activity of luciferase with NF- к B reporter gene
THP-1 cell strain is purchased from cell bank of Chinese academy of sciences, THP-1/pGF1-NF- к B cell strain is purchased from Shanghai pharmaceutical research institute of Chinese academy of sciences, and is stored in liquid nitrogen, THP-1/pGF1-NF- к B cell is cultured with RPMI-1640 medium containing 10% fetal bovine serum, and is placed at 37 ℃ in saturated humidity and 5% CO2Cultured in an incubator of 5X 104The density of cells/well was seeded in 96-well plates at a volume of 50. mu.L per well. The test sample (50. mu.L of the Neurospora gallic acid in example 3) was added to the sample at final concentrations of 1.5mg/mL, 1mg/mL, and 0.5mg/mL, respectively, while a blank group and an LPS control group were established. Adding LPS solution 10 μ L to a final concentration of 1 μ g/mL, and standing at 37 deg.C saturated humidity and containing 5% CO2Was incubated overnight in an incubator. After overnight incubation, 100. mu.L of LBright-GloTMLuciferase assay System substrate was added to each well and the RLU values were read by plate reader.
Statistical processing was performed using SPSS statistical software. Data are expressed as mean ± standard deviation (. x ± s), independent sample t test is adopted for comparison between two groups, and one-factor analysis of variance is adopted for comparison between multiple groups.
The experimental results are shown in figure 3, and the gallic acid has better activity of inhibiting an NF- к B signal channel under the low concentration of 0.5mg/mL, NF- к B is known to be a key nuclear transcription factor involved in the regulation and control of a series of gene expression, has important functions in the origin, development, angiogenesis and metastasis of cancer and is closely related to the generation of cancer drug resistance, NF- к B is involved in the processes through different pathways after being activated, and the effect of blocking NF- к B can inhibit the generation of the cancer, so the gallic acid can play a potential role in inhibiting the tumor activity by inhibiting the NF- к B signal channel.
Example 7 Cocl is inhibited by Marasmius sporogenes Gallic acid2Induced luciferase Activity with HRE reporter Gene
The HEK293T cell line was purchased from cell bank of Chinese academy of sciences, and the HEK293T-pGF1-HRE cell line was purchased from Shanghai pharmaceutical institute of Chinese academy of sciences, stored in liquid nitrogen, and cultured in DMEM medium containing 10% Gibco fetal bovine serum. HEK293T-pGF1-HRE cells at 2X 104The density of cells/well was seeded in 96-well plates at 100. mu.L per well. After 24h of adherence, 60. mu.L of the culture medium was aspirated off, and 50. mu.L of the prepared sample (agaricus bisporus gallic acid in example 2) with corresponding concentrations were added to the culture medium to obtain final concentrations of 1.5mg/mL, 1mg/mL, 0.5mg/mL, and 10. mu.L of LCocl2Adjusted to a final concentration of 250. mu.M. Setting blank group and Cocl simultaneously2Group control. After 16h of administration the medium was aspirated, 20. mu.L reporterLysis1XBuffer was added and frozen at-80 ℃ in a freezer until the plate was read. The plate to be tested was removed from the-80 ℃ freezer, 20. mu.L of lysed cell lysate was transferred to a white plate, 40. mu.L of luciferase substrate was added, the plate was read within 3 minutes and the RLU value was read. Statistical processing was performed using SPSS statistical software. Data are expressed as mean ± standard deviation (. x ± s), independent sample t test is adopted for comparison between two groups, and one-factor analysis of variance is adopted for comparison between multiple groups.
FIG. 4 shows that the activity of the agaricus bisporus gallic acid is possible to inhibit Cocl at a concentration of 0.5mg/mL2The activity of the induced luciferase with HRE reporter gene proves that the luciferase has potential antioxidant activity.
Example 8 Gallic acid of Agaricus campestris inhibits the growth of human esophageal cancer cells
The human esophageal cancer cell line EC9706 was purchased from the institute of biophysics of the Chinese academy of sciences. Cells were seeded in 96-well plates at a cell density of 1X 104Cells/well. Will carry outThe agaricus bisporus gallic acid of example 1 was dissolved in DMEM +/+ medium to a concentration of 1.0 mg/mL. After culturing for 4 days, the growth state of the cells was measured using a CCK assay kit (Beijing Jiang alliance Biotech). The amount of each polysaccharide sample was 3.
The experimental result is shown in figure 5, the agaricus bisporus gallic acid can obviously inhibit the growth of a human esophageal cancer cell line EC9706 under the concentration of 1.0mg/mL, and has certain dose dependence. EC9706 plays an important regulatory role in esophageal cancer. The polysaccharide can inhibit the growth of human esophageal cancer cell line EC9706, and has effect of regulating esophageal cancer microenvironment.
The experiments show that the agaricus bisporus gallic acid can regulate a tumor microenvironment through multiple ways of inhibiting tumor angiogenesis, immunosuppression, oxidation resistance, esophagus cancer cell growth and the like, and further exert potential esophagus cancer tumor resistance activity, so that the agaricus bisporus gallic acid can be prepared into various dosage forms in pharmaceutics through a conventional process, and can be used for preparing functional food with the effect of assisting in inhibiting the esophagus cancer, and the dosage form of the functional food can be capsule type, tablets, powder, granules, oral liquid and the like.
The above examples are only intended to illustrate the technical solution of the present invention, but not to limit it; although the present invention has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: the technical solutions described in the foregoing embodiments may still be modified, or some technical features may be equivalently replaced; and such modifications or substitutions do not depart from the spirit and scope of the corresponding technical solutions of the embodiments of the present invention.
Claims (10)
1. The application of the active ingredient gallic acid in the sporotrichum mushroom is characterized in that: application of gallic acid in preparing functional food with effect of assisting in inhibiting esophageal cancer is provided.
2. The use of gallic acid as an active ingredient in a Agaricus campestris according to claim 2, wherein: gallic acid can inhibit tumor angiogenesis, immunosuppression, oxidation, and esophageal cancer cell growth.
3. The use of gallic acid as an active ingredient in a Agaricus campestris according to claim 2, wherein: the gallic acid can be directly orally taken, and also can be made into various dosage forms in pharmaceutics, such as capsules, tablets, powder, granules or oral liquid and the like.
4. The use of gallic acid as an active ingredient in Agaricus campestris according to claim 1, wherein: the method for extracting the gallic acid comprises the following steps: slicing fresh and undamaged sporophore of Agaricus campestris, soaking in 90-95% ethanol for one week, filtering to obtain filtrate, recovering solvent under reduced pressure, adding 90-95% ethanol into the residue, ultrasonic extracting for 3-5 times (each time for 1-5 hr), and concentrating under reduced pressure to obtain 90-95% ethanol extract; performing the same operation with 60-65% ethanol, and concentrating under reduced pressure to obtain 60-65% ethanol extract; adding distilled water into the alcohol-extracted agaricus bisporus filter residue, performing ultrasonic extraction for three times, extracting for 1-3h each time, and concentrating under reduced pressure to obtain a water extract;
mixing the two ethanol extracts, kneading and dispersing the mixed extracts in pure water, adding petroleum ether into a separating funnel, adding the extract dispersion liquid into the separating funnel, extracting for 5 times, mixing the extracts, and concentrating to obtain petroleum ether part; adding ethyl acetate into the separating funnel, extracting for 6 times, combining the extracts, and concentrating to obtain an ethyl acetate part; and adding n-butanol into the separating funnel again, extracting for 5 times, combining the extract solutions, and concentrating to obtain n-butanol fraction.
5. The use of gallic acid as an active ingredient in Agaricus campestris according to claim 4, wherein: the ratio of the above sporophore of Agaricus campestris to ethanol is 0.5-1:1-5, so that the sporophore of Agaricus campestris is completely soaked in ethanol.
6. The use of gallic acid as an active ingredient in Agaricus campestris according to claim 4, wherein: the reduced pressure recovery condition is 0.1-0.5MPA, and the temperature is 25-40 ℃; the ultrasonic extraction condition is 200-800HZ, the ultrasonic treatment is carried out for 30-45min, and the temperature is 30-50 ℃.
7. The use of gallic acid as an active ingredient in Agaricus campestris according to claim 4, wherein: adding petroleum ether into the separating funnel, wherein the ratio of water to petroleum ether is 1: 1-0.5.
8. The use of gallic acid as an active ingredient in Agaricus campestris according to claim 4, wherein: adding ethyl acetate into the separating funnel, wherein the ratio of water to ethyl acetate is 0.5-1: 1.
9. The use of gallic acid as an active ingredient in Agaricus campestris according to claim 4, wherein: adding n-butanol into the separating funnel, wherein the ratio of water to n-butanol is 0.4-1: 1.
10. The use of gallic acid as an active ingredient in Agaricus campestris according to claim 4, wherein: the extraction conditions of the extractum are as follows: the extraction pressure is 20MPa to 40MPa, the extraction temperature is 30 ℃ to 50 ℃, and the extraction time is 0.8h to 2.5 h.
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Citations (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001009373A2 (en) * | 1999-07-30 | 2001-02-08 | Basf Bioresearch Corporation | Native cdc25 substrates, compositions and uses related thereto |
| CN102895523A (en) * | 2011-07-26 | 2013-01-30 | 贵州大学 | Extraction method of Pseudobulbus Cremastrae seu Pleiones extracts |
| US20130345137A1 (en) * | 2012-06-20 | 2013-12-26 | Hiroko Itoh | Method of inhibiting angiogenesis and food/beverage composition for angiogenesis inhibition |
| CN106309511A (en) * | 2016-08-30 | 2017-01-11 | 青海民族大学 | Effective part of agaricus gennadii for inhibiting CDC25 enzyme as well as preparation method and application of effective part |
| CN106333969A (en) * | 2016-08-30 | 2017-01-18 | 青海民族大学 | Agaricus gennadii HDAC1 enzyme inhibition effective part and preparation method and application |
| CN106924242A (en) * | 2017-04-12 | 2017-07-07 | 中山大学 | The purposes of the composition comprising theaflavih digallate |
| US20170247706A1 (en) * | 2014-09-26 | 2017-08-31 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Cdc25a inhibitor for the treatment of drug resistant cancer or for the prevention of tumor relapse |
| CN108619214A (en) * | 2017-03-15 | 2018-10-09 | 王慎君 | A kind of drug for treating tumour |
| CN110423284A (en) * | 2019-08-14 | 2019-11-08 | 浙江万寿康药业有限公司 | Lucid ganoderma spore powder polysaccharide has effects that auxiliary inhibits the application in the functional food of colon cancer in preparation |
| CN110812479A (en) * | 2019-11-18 | 2020-02-21 | 青海晨菲制药有限公司 | Gallic acid and EGFR target antibody composition and application thereof in lung cancer |
-
2019
- 2019-11-18 CN CN201911125259.8A patent/CN110959851A/en active Pending
Patent Citations (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001009373A2 (en) * | 1999-07-30 | 2001-02-08 | Basf Bioresearch Corporation | Native cdc25 substrates, compositions and uses related thereto |
| CN102895523A (en) * | 2011-07-26 | 2013-01-30 | 贵州大学 | Extraction method of Pseudobulbus Cremastrae seu Pleiones extracts |
| US20130345137A1 (en) * | 2012-06-20 | 2013-12-26 | Hiroko Itoh | Method of inhibiting angiogenesis and food/beverage composition for angiogenesis inhibition |
| US20170247706A1 (en) * | 2014-09-26 | 2017-08-31 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Cdc25a inhibitor for the treatment of drug resistant cancer or for the prevention of tumor relapse |
| CN106309511A (en) * | 2016-08-30 | 2017-01-11 | 青海民族大学 | Effective part of agaricus gennadii for inhibiting CDC25 enzyme as well as preparation method and application of effective part |
| CN106333969A (en) * | 2016-08-30 | 2017-01-18 | 青海民族大学 | Agaricus gennadii HDAC1 enzyme inhibition effective part and preparation method and application |
| CN108619214A (en) * | 2017-03-15 | 2018-10-09 | 王慎君 | A kind of drug for treating tumour |
| CN106924242A (en) * | 2017-04-12 | 2017-07-07 | 中山大学 | The purposes of the composition comprising theaflavih digallate |
| CN110423284A (en) * | 2019-08-14 | 2019-11-08 | 浙江万寿康药业有限公司 | Lucid ganoderma spore powder polysaccharide has effects that auxiliary inhibits the application in the functional food of colon cancer in preparation |
| CN110812479A (en) * | 2019-11-18 | 2020-02-21 | 青海晨菲制药有限公司 | Gallic acid and EGFR target antibody composition and application thereof in lung cancer |
Non-Patent Citations (1)
| Title |
|---|
| 王怡等: "圆孢蘑菇中抑菌活性物质的提取分离与含量测定", 《湖南师范大学自然科学学报》 * |
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