CN114438133B - Inulin ferment, preparation method thereof and application thereof in preventing and treating animal colon cancer - Google Patents
Inulin ferment, preparation method thereof and application thereof in preventing and treating animal colon cancer Download PDFInfo
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- CN114438133B CN114438133B CN202210140311.2A CN202210140311A CN114438133B CN 114438133 B CN114438133 B CN 114438133B CN 202210140311 A CN202210140311 A CN 202210140311A CN 114438133 B CN114438133 B CN 114438133B
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- inulin
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- colon cancer
- bacteroides ovatus
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- JYJIGFIDKWBXDU-MNNPPOADSA-N inulin Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)OC[C@]1(OC[C@]2(OC[C@]3(OC[C@]4(OC[C@]5(OC[C@]6(OC[C@]7(OC[C@]8(OC[C@]9(OC[C@]%10(OC[C@]%11(OC[C@]%12(OC[C@]%13(OC[C@]%14(OC[C@]%15(OC[C@]%16(OC[C@]%17(OC[C@]%18(OC[C@]%19(OC[C@]%20(OC[C@]%21(OC[C@]%22(OC[C@]%23(OC[C@]%24(OC[C@]%25(OC[C@]%26(OC[C@]%27(OC[C@]%28(OC[C@]%29(OC[C@]%30(OC[C@]%31(OC[C@]%32(OC[C@]%33(OC[C@]%34(OC[C@]%35(OC[C@]%36(O[C@@H]%37[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O%37)O)[C@H]([C@H](O)[C@@H](CO)O%36)O)[C@H]([C@H](O)[C@@H](CO)O%35)O)[C@H]([C@H](O)[C@@H](CO)O%34)O)[C@H]([C@H](O)[C@@H](CO)O%33)O)[C@H]([C@H](O)[C@@H](CO)O%32)O)[C@H]([C@H](O)[C@@H](CO)O%31)O)[C@H]([C@H](O)[C@@H](CO)O%30)O)[C@H]([C@H](O)[C@@H](CO)O%29)O)[C@H]([C@H](O)[C@@H](CO)O%28)O)[C@H]([C@H](O)[C@@H](CO)O%27)O)[C@H]([C@H](O)[C@@H](CO)O%26)O)[C@H]([C@H](O)[C@@H](CO)O%25)O)[C@H]([C@H](O)[C@@H](CO)O%24)O)[C@H]([C@H](O)[C@@H](CO)O%23)O)[C@H]([C@H](O)[C@@H](CO)O%22)O)[C@H]([C@H](O)[C@@H](CO)O%21)O)[C@H]([C@H](O)[C@@H](CO)O%20)O)[C@H]([C@H](O)[C@@H](CO)O%19)O)[C@H]([C@H](O)[C@@H](CO)O%18)O)[C@H]([C@H](O)[C@@H](CO)O%17)O)[C@H]([C@H](O)[C@@H](CO)O%16)O)[C@H]([C@H](O)[C@@H](CO)O%15)O)[C@H]([C@H](O)[C@@H](CO)O%14)O)[C@H]([C@H](O)[C@@H](CO)O%13)O)[C@H]([C@H](O)[C@@H](CO)O%12)O)[C@H]([C@H](O)[C@@H](CO)O%11)O)[C@H]([C@H](O)[C@@H](CO)O%10)O)[C@H]([C@H](O)[C@@H](CO)O9)O)[C@H]([C@H](O)[C@@H](CO)O8)O)[C@H]([C@H](O)[C@@H](CO)O7)O)[C@H]([C@H](O)[C@@H](CO)O6)O)[C@H]([C@H](O)[C@@H](CO)O5)O)[C@H]([C@H](O)[C@@H](CO)O4)O)[C@H]([C@H](O)[C@@H](CO)O3)O)[C@H]([C@H](O)[C@@H](CO)O2)O)[C@@H](O)[C@H](O)[C@@H](CO)O1 JYJIGFIDKWBXDU-MNNPPOADSA-N 0.000 title claims abstract description 106
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- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P1/00—Preparation of compounds or compositions, not provided for in groups C12P3/00 - C12P39/00, by using microorganisms or enzymes
- C12P1/04—Preparation of compounds or compositions, not provided for in groups C12P3/00 - C12P39/00, by using microorganisms or enzymes by using bacteria
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/733—Fructosans, e.g. inulin
-
- 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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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P19/00—Preparation of compounds containing saccharide radicals
- C12P19/04—Polysaccharides, i.e. compounds containing more than five saccharide radicals attached to each other by glycosidic bonds
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P7/00—Preparation of oxygen-containing organic compounds
- C12P7/40—Preparation of oxygen-containing organic compounds containing a carboxyl group including Peroxycarboxylic acids
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P7/00—Preparation of oxygen-containing organic compounds
- C12P7/40—Preparation of oxygen-containing organic compounds containing a carboxyl group including Peroxycarboxylic acids
- C12P7/52—Propionic acid; Butyric acids
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P7/00—Preparation of oxygen-containing organic compounds
- C12P7/40—Preparation of oxygen-containing organic compounds containing a carboxyl group including Peroxycarboxylic acids
- C12P7/56—Lactic acid
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- General Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Molecular Biology (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses application of inulin fermented product in preparing medicines for preventing and/or treating colorectal cancer. The inulin ferment is a product obtained by fermenting inulin serving as a substrate by using bacteroides ovatus. The inulin ferment has improved nutrition characteristics for human and mammals, has no intestinal side effect, can be used for regulating intestinal microorganism composition of human and mammals, has the effect of preventing colorectal cancer, and has remarkable inhibition effect on the growth of tumors, so that the inulin ferment can provide a new idea and selection for preventing and treating colorectal cancer, in particular for treating and/or preventing colonitis related colon cancer, and has wide application prospect.
Description
Technical Field
The invention particularly relates to an inulin ferment, a preparation method thereof and application thereof in preventing and treating animal colon cancer, belonging to the field of bioengineering.
Background
Colorectal cancer is a common malignant tumor in modern life, and the morbidity and mortality in the world are respectively located at the 3 rd-4 th sites of all malignant tumors, and the morbidity is in an increasing trend year by year. Colon cancer is often formed in the form of ulcers, polyps, etc. due to genetic, dietary, lifestyle and environmental factors. Currently known methods for treating colon cancer are mainly as follows 4 types: (1) surgical excision, direct excision of the lesion; (2) radiation therapy, killing cancer cells by radiation; (3) Drug therapy, mainly comprising chemical drugs and targeting drugs. However, these treatments have great toxic and side effects on the body, and damage normal cells while killing tumor cells, and destroy the immune system of the body. Therefore, the development of the medicine for treating colon cancer with small toxic and side effects has great significance.
Disclosure of Invention
The invention mainly aims to provide an inulin ferment for preventing and treating animal colon cancer, which overcomes the defects of the prior art.
It is another object of the present invention to provide a method for producing the inulin ferment.
It is a further object of the present invention to provide the use of the inulin ferment for controlling colon cancer in animals.
In order to achieve the aim of the invention, the invention adopts the following technical scheme:
the inulin ferment provided by one aspect of the invention is obtained by fermenting inulin by bacteroides ovatus.
Further, the bacteroides ovatus is Bacteroides ovatus ATCC 8343.
The preparation method of the inulin ferment provided by the other aspect of the invention comprises the following steps:
1) Mixing inulin with a sterilization culture medium according to the mass ratio of 1-10:100, and regulating the pH value to 6-7 to obtain an inulin fermentation culture medium;
2) Inoculating the bacteroides ovatus to the inulin fermentation medium, wherein the inoculum size of the bacteroides ovatus is 0.1-10%, and carrying out anaerobic fermentation for 12-36 h at 35-38 ℃ to obtain the inulin fermentation product.
In a preferred embodiment, the preparation method specifically includes:
1) Mixing inulin with a sterilization culture medium according to the mass ratio of 1:20, and regulating the pH value to 7 to obtain an inulin fermentation culture medium;
2) Inoculating Bacteroides ovatus to inulin fermentation medium, wherein the inoculum size of Bacteroides ovatus is 10%, and anaerobic fermenting at 37deg.C for 24 hr to obtain inulin ferment.
In one embodiment, the bacteroides ovatus is Bacteroides ovatus ATCC 8343.
In one embodiment, the sterilization medium comprises 1.5 parts by weight tryptone, 0.5 parts by weight soytone, 0.5 parts by weight sodium chloride, 0.5 parts by weight inulin, 1-10 parts by weight defibrinated sheep blood, and 100 parts by weight distilled water.
In one embodiment, the inulin ferment is an inulin fermentation broth.
In the invention, inulin is also called inulin, is a fructosan widely existing in plants in nature, the structure of the inulin is formed by connecting D-fructofuranose with beta- (1, 2) glycosidic bond, each molecular terminal is connected with one glucose residue with alpha- (1, 2) glycosidic bond, the polymerization degree is usually 2-60 fructoses, and the average polymerization degree is 10 fructoses.
In the invention, the bacteroides ovatus (Bacteroides ovatus) is a common gram-negative anaerobic bacterium in bacteroides enterica, has a capsule, is free of spores and does not move, is sensitive to light, and can metabolize and utilize polysaccharide and participate in bile and cholesterol metabolism.
In a further aspect of the invention there is provided an inulin ferment produced by any one of the methods described above.
In a further aspect, the present invention provides the use of the inulin ferment for the manufacture of a medicament for the prophylaxis and/or treatment of colon cancer.
In one embodiment, the colon cancer is a colitis-associated colon cancer.
In one embodiment, the colitis-associated colon cancer is azoxymethane and sodium dextran drug (AOM/DSS) induced formation.
Wherein, the mechanism of the inulin ferment for preventing and/or treating animal colon cancer mainly comprises the following steps: inhibit the number of tumors, the expression of protooncogene (C-MYC) and the proliferation of cancer cells, and repair intestinal mucosa barrier and colon length.
Compared with the prior art, the invention has the following advantages:
(1) The inulin ferment is easy to prepare and has good stability, and compared with the product performance of the preparation containing single inulin and the bacteroides ovatus;
(2) The inulin ferment provided has improved nutrition characteristics for human and mammals, such as significantly increased micromolecular polysaccharide (xylose furanose) and organic acid (lactic acid, formic acid and butyric acid), has no intestinal side effect, can be used for regulating intestinal microorganism composition of human and mammals, effectively repairing intestinal barriers, has the effect of preventing colorectal cancer, and has remarkable inhibition effect on tumor growth, so that the inulin ferment can provide new ideas and choices for preventing and treating colorectal cancer, in particular for treating and/or preventing colonitis related colon cancer, and has wide application prospect.
Drawings
FIG. 1 is a metabonomics view of inulin ferment in an embodiment of the invention.
FIG. 2 is an anatomic view of colorectal of mice in the blank, model, inulin metabolism (fermentate) groups of examples of the present invention.
FIG. 3 shows the tumor numbers of mice in the blank, model, inulin, and inulin metabolic groups according to the present invention.
FIG. 4 shows colorectal length of mice in the blank, model, inulin-metabolizing group of the examples of the present invention.
Fig. 5 is a graph of intestinal mucosa HE staining of mice with a blank group, a model group, an inulin group, and an inulin metabolome in accordance with an embodiment of the present invention.
FIG. 6 is a plot of intestinal microbial abundance heat of mice in the blank, model, inulin, and inulin metabolome of the present invention.
FIG. 7 is a graph showing proliferation of colon cancer cells (HT 29) in the hollow white group, medium group, inulin metabolic group, inulin group according to the present invention.
FIG. 8 shows intracellular glucose content of colon cancer cells (HT 29) in the hollow white blood cells, medium cells, inulin metabolic cells, inulin groups according to the example of the invention.
FIG. 9 is a chart showing the oil red staining of colon cancer cells (HT 29) in the hollow white group, medium group, inulin metabolic group, inulin group, according to the example of the present invention.
FIG. 10 is a western blot diagram of protooncogene C-MYC proteins of the mouse colon of the hollow white group, the model group, the inulin group, and the inulin metabolic group according to an embodiment of the present invention.
FIGS. 11 a-11 b are western blot diagrams of protooncogene C-MYC and regulatory gene beta-catenin proteins of hollow white blood group, medium group, inulin metabolic group, inulin group colon cancer cell (HT 29) according to an embodiment of the present invention, respectively.
Detailed Description
The technical scheme of the invention is further described below with reference to the embodiment and the attached drawings. It should be noted that unless otherwise indicated, all types of reagents used in the examples below are available from commercial sources and that all types of production, testing equipment and methods used in the examples below are well known to those skilled in the art.
Example 1
1. The preparation method of the inulin ferment comprises the following steps: mixing tryptone 1.5g, soyase peptone 0.5g, sodium chloride 0.5g, inulin (inulin) (source leaf, S11143) 0.5g, adding 100mL distilled water to prepare a liquid culture medium, sterilizing at 120deg.C for 20min, cooling, adding 5% (Soy pal, TX 0030) defibrinated sheep blood), inoculating Bacteroides ovatus (Bacteroides ovatus), anaerobic culturing at 37deg.C for 48h, centrifuging at 5000r/min for 5min, and collecting supernatant as inulin metabolite (inulin fermentation liquid).
2. The preparation method of the bacterial culture medium solution comprises the following steps:
mixing tryptone 1.5g, soyase peptone 0.5g and sodium chloride 0.5g, adding 100mL distilled water to prepare a liquid culture medium, sterilizing at 120 ℃ for 20min, cooling, adding 5% (Soy pal, TX 0030) defibrinated sheep blood), inoculating bacteroides ovatus (Bacteroides ovatus), anaerobic culturing at 37 ℃ for 48h, centrifuging at 5000r/min for 5min, and taking the supernatant as a bacterial culture medium solution.
Example 2 induced colon cancer assay:
taking 72C 57 male mice, randomly dividing the weight of the mice into 4 groups of 18 mice, namely blank groups, respectively, wherein the weight of the mice is 19-23g, and the mice are selected from a model group, an inulin group and an inulin fermentation group. After pre-adaptation for 1 week, except for the normal saline and drinking normal drinking water, the mice in the blank groups were intraperitoneally injected with 10mg/kg Azoxymethane (AOM), drinking water containing 2.5% (wt%) DSS after one week was continuously drunk for 7 days, and normal drinking water was then given for 14 days, and the above 21 days were one cycle, and repeated for 3 cycles in total, to establish a colon cancer model related to colitis in mice. Dosing was performed on day 1 with 2.5% DSS consumed in the first cycle for 7 consecutive days, and after stopping consuming DSS, dosing was stopped, followed by 14 days of normal diet and drinking water, with a total of 3 cycles for 21 days. The administration mode of the inulin group is to add 5% of inulin into the feed, and the administration mode of the inulin metabolite group is to add 25% of the inulin metabolite obtained in example 1 into drinking water. The general state of life of the mice was observed.
Example 3 treatment of test animals:
after the end of the induced colon cancer test of example 2, each group of mice was first treated with CO 2 Anesthesia was performed, mice were then sacrificed, the abdominal cavity of the mice was exposed, the colorectal was dissected and measured for length, the inside and outside of the colorectal were washed with physiological saline, the colorectal was slowly turned over with forceps, the mucosal layer was turned outward, the formation of tumors in the colorectal was visually observed, and the number of tumors was recorded, after which a portion was fixed in 4% paraformaldehyde solution.
Example 4 conventional HE staining of the intestinal tract of mice:
the fixed tissue of example 3 was dehydrated, transparent, waxed, embedded, and then paraffin-sectioned into tissue samples, which were sequentially immersed in xylene I and xylene II to dewax. And carrying out hydration treatment by adopting a gradient alcohol mode. The hematoxylin is used for dyeing treatment, and the treatment time is 1-3min. Washing with double distilled water, differentiating with hydrochloric acid alcohol, and turning blue. And then dyeing for 1min by using eosin, dehydrating by adopting a gradient alcohol mode, and finally sealing by using neutral gum.
Example 5 fecal microorganism 16sRNA assay:
on the last day of the test to induce a model of colon cancer in mice in example 2, the feces of the mice of each group were collected using sterile EP tubes, facilitating a-80 ℃ refrigerator. The export company then performs 16sRNA gene sequencing to determine the type and abundance of microorganisms in the feces.
Example 6 colon cancer cell (HT 29) assay:
inoculating colon cancer cells into a 96-well plate, adding 1/3 PBS, a thallus culture medium solution, an inulin ferment and an inulin solution (10 mg/mL) into each group after 8 hours, culturing for 48 hours at 37 ℃, then washing for 2 times by using PBS, adding a DMEM culture medium containing 10% CCK8 reagent for 1 hour, and measuring absorbance at 450nm by using an enzyme-labeled instrument; measuring the glucose content in colon cancer cells by using a glucose detection kit (GOD-POD colorimetric method) (source leaves); fat of colon cancer cells was stained using an oil red staining kit.
The results illustrate:
referring to fig. 2 showing the colon anatomy of the mice in the foregoing blank, model, inulin, and inulin metabolite groups, it was found that tumors developed in the mid-to-posterior segment of the colon in each group (except the blank) after induction of colon cancer with AOM/DSS, and that the number of tumors in the colon was reduced in the inulin-and inulin-metabolite-fed mice relative to the model, wherein the inulin-metabolite-fed group had statistical significance, as shown in fig. 3. By measuring the colon length of each group of mice, it was found that the colon length of the inulin group and inulin metabolite group mice was significantly higher than that of the model group, as shown in fig. 4. From the above, it can be concluded that inulin metabolites have a very pronounced effect on the prevention of colonic genesis.
As shown in fig. 5, which shows the HE staining results of the colon of each group of mice, it was found that the villus structure of the intestinal section of the mice in the model group had been completely damaged, the goblet cells disappeared, the inflammatory cell infiltration was severe, the crypt disappeared, and the epithelial mucus layer was almost disappeared, compared with the blank group. Whereas intestinal sections of the mice from the inulin group and the inulin metabolite group were much more complete than from the model group. The inulin group had only a small amount of goblet cell damage, the inflammatory cell infiltration degree was light, the crypt and epithelial mucus layer partially disappeared, but the goblet cells, crypt and epithelial mucus layer of the inulin metabolome section were very complete, no difference from the blank group. It can be concluded that the inulin metabolites effectively maintain the integrity of the colon of the mice, protecting the colon structure of the mice from damage by AOM/DSS.
As shown in fig. 6, which shows the abundance of intestinal microorganisms in each group of mice, it can be found that firmicutes and proteasomes are reduced in intestinal microorganisms in inulin ferment group relative to model group and inulin group, while bacteroides abundance is significantly increased, returning to similar level to control group. Indicating that feeding inulin ferments can remodel the intestinal microbial composition of mice.
As shown in fig. 7, which shows the proliferation test results of colon cancer cells of each group, it was found that inulin fermented product significantly reduced proliferation of colon cancer cells, while common cell culture medium and inulin solution did not have significant inhibitory effect. The glucose content of the inulin fermented material group and the cell culture broth group was found to be significantly increased as compared with the normal colon cancer cells and the inulin group colon cancer cells by measuring the glucose content in the colon cancer cells of each group, as shown in fig. 8. While fat accumulation of colon cancer cells of the inulin fermented product group and the cell culture broth group was found to be significantly increased as compared with normal colon cancer cells and inulin group colon cancer cells by oil red staining, as shown in fig. 9. This suggests that inulin fermentate can reduce the energy metabolism rate of colon cancer cells and increase fat accumulation, and reduce proliferation of colon cancer cells.
As shown in fig. 10 and 11 a-11 b, in model group mice and HT29 colon cancer cells, protooncogene C-MYC (MYC) and regulatory gene β -catenin are highly expressed, whereas protooncogene C-MYC (MYC) can regulate proliferation and metabolism of cells, β -catenin gene can activate protooncogene C-MYC (MYC), indicating that proliferation and metabolic genes in colon cancer cells are highly expressed; expression of protooncogene C-MYC (MYC) and regulatory gene beta-catenin can be significantly reduced by administration of inulin ferment, which suggests that inulin ferment can reduce expression of proliferation and metabolic genes in colon cancer cells by modulating Wnt/beta-catenin pathway.
In summary, according to the embodiment of the invention, the fermentation product is used for feeding mice which are inducing colon cancer through the anaerobic fermentation of the bacteroides ovatus, so that the inulin metabolite can be found to be capable of effectively improving the microbial composition in the intestinal tracts of mammals and preventing colonic cancer, and the tumor incidence of the mice fed with the inulin metabolite is greatly reduced, which indicates that the fermentation inulin metabolite also has a remarkable anti-tumor effect, and the mechanism is probably due to the fact that the inulin fermentation product changes the metabolism and accumulation of energy of colon cancer cells by regulating Wnt/beta-catenin channels.
The above description is only of the preferred embodiments of the present invention and is not intended to limit the present invention, and it should be noted that it is possible for those skilled in the art to make several improvements and modifications without departing from the technical principle of the present invention, and these improvements and modifications should also be regarded as the protection scope of the present invention.
Claims (6)
1. Use of inulin ferment for the manufacture of a medicament for the prevention and/or treatment of colon cancer, characterized in that: the inulin ferment is inulin ferment liquid obtained by fermenting inulin with Bacteroides ovatus, wherein the Bacteroides ovatus isBacteroides ovatus ATCC 8343。
2. The use according to claim 1, characterized in that the preparation method of the inulin ferment comprises:
1) Inulin and a sterilization culture medium are mixed according to the mass ratio of 1-10: 100, and regulating the pH value to 6-7 to obtain an inulin fermentation medium;
2) Inoculating the bacteroides ovatus to the inulin fermentation medium, wherein the inoculum size of the bacteroides ovatus is 0.1-10% and the inoculum size is 35-38% o Anaerobic fermentation under the condition C for 12-36 h to obtainObtaining inulin ferment.
3. The use according to claim 2, wherein the preparation method comprises:
1) Inulin and a sterilization culture medium are mixed according to the mass ratio of 1:20, and regulating the pH value to 7 to obtain an inulin fermentation medium;
2) Inoculating Bacteroides ovatus to inulin fermentation medium, wherein the inoculating amount of Bacteroides ovatus is 10%, at 37 o Anaerobic fermentation is carried out for 24 hours under the condition C, and inulin ferment is obtained.
4. Use according to any one of claims 2-3, characterized in that: the sterilization culture medium comprises 1.5 parts by weight of tryptone, 0.5 part by weight of soybean peptone, 0.5 part by weight of sodium chloride, 0.5 part by weight of inulin, 1-10 parts by weight of defibrinated sheep blood and 100 parts by weight of distilled water.
5. Use according to claim 1, characterized in that: the colon cancer is colonitis-related colon cancer.
6. Use according to claim 5, characterized in that: the colonic cancer related to colonitis is formed by the induction of azoxymethane and sodium dextran.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104955466A (en) * | 2012-11-23 | 2015-09-30 | 赛里斯治疗公司 | Synergistic bacterial compositions and methods of production and use thereof |
| CN108220200A (en) * | 2018-02-08 | 2018-06-29 | 中国人民解放军军事科学院军事医学研究院 | For treating micro- anaerobic bacteria of colitis and its application |
| KR20180104834A (en) * | 2017-03-14 | 2018-09-27 | 연세대학교 원주산학협력단 | Producing method of colorectal cancer animal model induced without Azoxymethane |
| GB2581531A (en) * | 2019-02-25 | 2020-08-26 | Akromaa Afolabi Bene | Deoxycholic - bound inulin |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20150246081A1 (en) * | 2014-03-03 | 2015-09-03 | Shayne Kenneth Morris | Probiotics with methods for growth and use separately and in combination |
| US20210353697A1 (en) * | 2018-10-05 | 2021-11-18 | Korea Food Research Institute | Composition comprising molokhia extract as active ingredient for improving gut microbiome or for alleviating, preventing, or treating intestinal inflammation, leaky gut syndrome, obesity, or metabolic disease |
-
2022
- 2022-02-15 CN CN202210140311.2A patent/CN114438133B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104955466A (en) * | 2012-11-23 | 2015-09-30 | 赛里斯治疗公司 | Synergistic bacterial compositions and methods of production and use thereof |
| KR20180104834A (en) * | 2017-03-14 | 2018-09-27 | 연세대학교 원주산학협력단 | Producing method of colorectal cancer animal model induced without Azoxymethane |
| CN108220200A (en) * | 2018-02-08 | 2018-06-29 | 中国人民解放军军事科学院军事医学研究院 | For treating micro- anaerobic bacteria of colitis and its application |
| GB2581531A (en) * | 2019-02-25 | 2020-08-26 | Akromaa Afolabi Bene | Deoxycholic - bound inulin |
Non-Patent Citations (4)
| Title |
|---|
| The evolution of cooperation within the gut microbiota;Seth Rakoff-Nahoum et al.;Nature;第533卷(第7602期);255-259 * |
| Unraveling the Metabolic Requirements of the Gut Commensal Bacteroides ovatus;Robert Fultz et al.;Frontiers in Microbiology;第12卷;第2页左栏第3段，第4页左栏第2段，图1E * |
| 养阴化瘀解毒方对结肠炎相关性结肠癌前病变及细胞凋亡的影响;严小军等;中国实验方剂学杂志;19(05);258-261 * |
| 小麦***木聚糖的益生功能及对肠道微生态的调节;赵萌菲等;中国食物与营养;第25卷(第04期);12-16 * |
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