Application of agaricus bisporus polysaccharide in preparation of medicine for preventing and / or treating ulcerative colitis

Abstract

The invention discloses an application of agaricus bisporus polysaccharide MP and two agaricus bisporus polysaccharide components MP-1 and MP-2 in preparation of a medicine for preventing and / or treating ulcerative colitis. Animal experiments prove that the agaricus bisporus polysaccharide, especially the agaricus bisporus polysaccharide purified by a specific process, has the effects of improving colon pathological injury, restoring intestinal barrier function, resisting inflammation, relieving intestinal flora imbalance, and relieving weight loss and colonic atrophy, so that the effect of preventing and treating ulcerative colitis is achieved. The application of the agaricus bisporus polysaccharide to prevention and / or treatment of ulcerative colitis has a wide prospect.

Description

Technical Field

[0001] The present invention specifically relates to the use of Agaricus bisporus polysaccharide MP and two Agaricus bisporus polysaccharide components MP-1 and MP-2 in preparing medicines for preventing and / or treating ulcerative colitis. Background Art

[0002] The lesions of ulcerative colitis (UC) are mostly located in the colon and rectum, and the main symptoms include abdominal pain, diarrhea with bloody stools, and weight loss. Conventional treatments for ulcerative colitis include steroid anti-inflammatory agents, immunomodulators, and aminosalicylates, such as 5-aminosalicylic acid (5-ASA). However, these conventional drugs also have a series of disadvantages, such as large side effects, long treatment cycles, and even lead to decreased immunity and increased incidence of other diseases such as cataracts and osteoporosis. Therefore, there is an urgent need to find other new treatment options.

[0003] Agaricus bisporus, also known as white mushroom, is a healthy food that is popular in the global food market. Agaricus bisporus is delicious and has multiple health benefits. Agaricus bisporus polysaccharide is one of the most important active ingredients of Agaricus bisporus. It is a polydisperse polymer, and different parts of it can show different biological activities. So far, there are no reports on the efficacy of Agaricus bisporus polysaccharide and its purified components in relieving ulcerative colitis. Summary of the invention

[0004] In order to solve the above problems, the present invention provides the use of Agaricus bisporus polysaccharide MP and two Agaricus bisporus polysaccharide components MP-1 and MP-2 in the preparation of a drug for preventing and / or treating ulcerative colitis.

[0005] Furthermore, the Agaricus bisporus polysaccharide MP is obtained by extracting Agaricus bisporus with water and precipitating with alcohol, re-dissolving the precipitate with water, and then dialyzing and drying.

[0006] The Agaricus bisporus polysaccharide component MP-1 is prepared by re-dissolving crude polysaccharide MP through alcohol precipitation and then drying.

[0007] The Agaricus bisporus polysaccharide component MP-2 is prepared by alcohol precipitation of the supernatant of crude polysaccharide MP, re-alcohol precipitation, re-dissolving the precipitate with water, and ultrafiltration.

[0008] Furthermore, the Agaricus bisporus polysaccharide MP is a crude polysaccharide obtained by extracting Agaricus bisporus powder with water and precipitating with alcohol, dissolving it with water, and then dialyzing and freeze-drying it.

[0009] Furthermore, the crude polysaccharide is re-dissolved in alcohol and then centrifuged, the precipitate is re-dissolved in water and then freeze-dried to obtain component MP-1; the re-dissolution is to an alcohol concentration of 38%.

[0010] Furthermore, the supernatant after the centrifugation is added with alcohol, centrifuged, dissolved, and ultrafiltered to obtain component MP-2; the alcohol is added to an alcohol concentration of 68%; and the molar mass cutoff value of the ultrafiltration is 100 kDa.

[0011] Furthermore, the amount of water used for the water extraction and alcohol precipitation is 40 times that of Agaricus bisporus, the amount of alcohol used is 4 times the volume of water, the water temperature is 95° C., and the mixed extraction is performed for 60 minutes; the molar mass cutoff value of the dialysis is 3.5 kDa; and the molar mass cutoff value of the ultrafiltration is 100 kDa.

[0012] Furthermore, the alcohol is ethanol; the concentration of ethanol is 95%.

[0013] Furthermore, the molecular weight range of the Agaricus bisporus polysaccharide component MP-1 is 8.0×10 6 -9.0×10 6 Da, monosaccharide composition type includes glucose, infrared spectrum signal includes pyranose ring and α configuration, the signal of the pyranose ring is located at 1079cm -1 The signal of the α configuration is located at 843 cm -1 or 925cm -1 .

[0014] Furthermore, the molecular weight range of the Agaricus bisporus polysaccharide component MP-2 is 1.5×10 4 -2.0×10 4 Da, monosaccharide composition types include glucose and galactose, infrared spectrum signals include pyranose ring and α configuration, the signal of the pyranose ring is located at 1079cm -1 The signal of the α configuration is located at 843 cm -1 or 925cm -1 .

[0015] Furthermore, the drug is a drug for alleviating weight loss and / or colon atrophy caused by ulcerative colitis.

[0016] Furthermore, the drug is a drug for improving colon pathological damage.

[0017] Furthermore, the drug is a drug for restoring intestinal barrier function.

[0018] Furthermore, the drug is a drug that regulates the level of inflammatory factors.

[0019] Furthermore, it regulates the levels of inflammatory factors mainly by downregulating tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1β and IL-17A and upregulating IL-10 to inhibit pathological inflammation caused by colitis.

[0020] Furthermore, the drug can regulate the composition of intestinal microbiota and has the effect of alleviating intestinal flora imbalance.

[0021] Furthermore, the drug can regulate metabolic pathways, specifically, by regulating bile secretion and tryptophan metabolic pathways or steroid hormone biosynthesis.

[0022] The use of Agaricus bisporus polysaccharide in the preparation of a drug for preventing and / or treating ulcerative colitis is proved by animal experiments that Agaricus bisporus polysaccharide, especially Agaricus bisporus polysaccharide purified by a specific process, has the effects of improving colon pathological damage, restoring intestinal barrier function, resisting inflammation and relieving intestinal flora imbalance, relieving weight loss and colon atrophy, thereby achieving the effect of preventing and treating ulcerative colitis, and showing excellent safety. The application of Agaricus bisporus polysaccharide in preventing and / or treating ulcerative colitis has broad prospects.

[0023] Obviously, according to the above contents of the present invention, in accordance with common technical knowledge and customary means in the art, without departing from the above basic technical ideas of the present invention, other various forms of modification, replacement or change may be made.

[0024] The above contents of the present invention are further described in detail below through specific implementation methods in the form of embodiments. However, this should not be understood as the scope of the above subject matter of the present invention being limited to the following examples. All technologies realized based on the above contents of the present invention belong to the scope of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 Figure 3. Effects of MP, MP-1 and MP-2 on alleviating DSS-induced ulcerative colitis after administration; (A) Schematic diagram of mouse modeling and administration time in animal experiment 1; six groups of C57BL / 6 mice drank water or water containing 2.5% DSS for 9 days, and were gavaged with MP, MP-1, MP-2 or 5-ASA (100 mg / kg) from the 2nd to the 9th day; (B) Body weight changes; (C) Pictures of representative colons; (D) Length of colon; (E) H&E staining of colon sections (200×); n=5, *p<0.05, **p<0.01, ***p<0.001, ns: not significant.

[0026] Figure 2 Effects of MP, MP-1 and MP-2 on FITC-dextran concentration in serum; n=3, *p<0.05, **p<0.01, ***p<0.001, ns: not significant.

[0027] Figure 3Effects of MP, MP-1 and MP-2 on intestinal inflammatory cytokine levels; (A) IL-10, (B) IFN-γ, (C) IL-6, (D) IL-1β and (E) IL-17A levels in the colon. n=5, *p<0.05, **p<0.01, ***p<0.001, ns: not significant.

[0028] Figure 4 Antibiotics eliminated the therapeutic effects of MP, MP-1 and MP-2 on DSS-induced ulcerative colitis mice; (A) Schematic diagram of mouse modeling and drug administration time in animal experiment 2; All mice received a broad-spectrum oral antibiotic (Abs) mixture (vancomycin 30 mg / kg, neomycin sulfate 60 mg / kg, metronidazole 60 mg / kg and ampicillin 60 mg / kg) on ​​days 0-4 and 8-10, and then 2.5% DSS (m / V) was administered on days 4-8 and 10-12. (B) Body weight changes. (C) Representative colon images; (D) Length of colon; (E) H&E staining of colon sections (100×); (F) FITC-dextran concentration in serum, n=3; (G) IL-10, (H) IL-6, (I) IL-1β, (J) IL-17A levels in colon tissue, n=5. *p<0.05, **p<0.01, ***p<0.001, ns: not significant.

[0029] Figure 5 Effect diagram of MP, MP-1 and MP-2 on the diversity and structure of intestinal microbiota; (A) Shannon index; (B) Simpson index; (C) PCoA analysis at the OTU level; n = 3; *p < 0.05, **p < 0.01, ***p < 0.001, ns: not significant.

[0030] Figure 6 KEGG pathway enrichment map based on differential metabolites in the MP-2 group compared with the Model group; *p<0.05, **p<0.01, ***p<0.001.

[0031] Figure 7 KEGG pathway enrichment map based on differential metabolites in the MP-1 group compared with the Model group; *p<0.05, **p<0.01, ***p<0.001.

[0032] Figure 8 Safety evaluation results of MP, MP-1 and MP-2; H&E staining of heart, liver, spleen, lung and kidney (100×). DETAILED DESCRIPTION

[0033] The raw materials and equipment used in the specific implementation manner can be obtained by commercial purchase, wherein Agaricus bisporus polysaccharide MP and two purified polysaccharide components MP-1 and MP-2 are prepared according to patent CN202210390434.1, as follows:

[0034] Take 250g of Agaricus bisporus powder and mix it with 10.0L of deionized water, extract it at 95℃ for 1h, extract it twice continuously, combine the supernatant and precipitate it with ethanol. Filter, retain the precipitate and add water to dissolve it, then dialyze it (molar mass cutoff value is 3.5kDa), and freeze-dry it to obtain crude polysaccharide (MP). Take MP and add ethanol to dissolve it, stir it, so that the final ethanol concentration reaches 38vt%, centrifuge it after 2h, and collect the precipitate and supernatant respectively. The precipitate is reconstituted with ultrapure water, and the sample obtained after freeze-drying is coded as MP-1; add ethanol (95%, v / v) to the supernatant, so that the final ethanol concentration reaches 68vt%, stand it and centrifuge it, retain the precipitate, add water to dissolve it, and use ultrafiltration (molar mass cutoff: 100kDa) to remove relatively large molecular weight components to obtain MP-2.

[0035] The structural characteristics of Agaricus bisporus polysaccharide MP and two purified polysaccharide components MP-1 and MP-2 obtained by the preparation method are consistent with those described in CN202210390434.1, wherein the molecular weight range of component MP-1 is 8.0×10 6 -9.0×10 6 Da, monosaccharide composition types include glucose, infrared spectrum signals include pyranose ring and α configuration, and the signal of pyranose ring is located at 1079cm -1 The signal of α configuration is located at 843 cm -1 or 925cm -1 ; The molecular weight range of component MP-2 is 1.5×10 4 -2.0×10 4 Da, monosaccharide composition types include glucose and galactose, infrared spectrum signals include pyranose ring and α configuration, and the signal of pyranose ring is located at 1079cm -1 The signal of α configuration is located at 843 cm -1 or 925cm -1 .

[0036] Example 1 Study on the application of Agaricus bisporus polysaccharide in treating ulcerative colitis

[0037] 1. Methods

[0038] 1. Animals, grouping and modeling

[0039] Male SPF-grade C57BL / 6 mice, weighing 17–24 g, were randomly divided into six groups (Control, Model, 5-ASA, MP, MP-1, and MP-2). The 10-day intervention schedule was as follows: Figure 1 As shown in A. Briefly, the Control group was given normal drinking water from day 0 to day 10. For the other five groups, ulcerative colitis was induced by giving drinking water containing 2.5% DSS from day 0 to day 9. From day 9 to day 10, all animals had free access to water. In addition, from day 2 to day 9, mice in the 5-ASA, MP, ABP-1, and MP-2 groups were gavaged with 5-ASA (100 mg / kg), MP (100 mg / kg), MP-1 (100 mg / kg), and MP-2 (100 mg / kg), respectively. The mice in the Control and Model groups were given normal saline accordingly. The body weights of all mice were recorded every day. Blood was collected from the eyeballs on day 10. After determining the colon length, colon tissues were collected for further analysis. Fecal samples were collected for microbiota composition analysis and non-targeted metabolomics analysis.

[0040] 2. Histopathological analysis

[0041] About 5 mm of mouse colon tissue was taken, fixed in 4% paraformaldehyde fixative, embedded in paraffin, and sliced. The colon tissue samples were then stained with hematoxylin / eosin (H&E).

[0042] 3. Intestinal permeability measurement

[0043] The fluorescein isothiocyanate (FITC)-dextran experiment was used to evaluate changes in intestinal permeability in mice. In brief, after 4 hours of water and food deprivation, each mouse was gavaged with 4kDa FITC-dextran (Sigma-Aldrich) (44mg / 100g). After 4 hours, blood was collected by enucleation, allowed to stand, centrifuged, and serum was collected. In a 96-well plate, the fluorescence of the serum was measured under the conditions of excitation / emission wavelengths of 485 / 528nm, respectively. The FITC-dextran concentration in mouse serum was then calculated using a standard curve.

[0044] 4. Determination of inflammatory factor levels

[0045] The colon tissues of mice were collected and homogenized, and then the contents of IL-10, IFN-γ, IL-6, IL-1β and IL-17A in the colon tissues of mice were determined using specific ELISA kits provided by Biolegend (California, USA).

[0046] 5. Antibiotic treatment to confirm whether Agaricus bisporus polysaccharides MP, MP-1 and MP-2 can relieve symptoms of ulcerative colitis by regulating intestinal flora

[0047] To confirm whether Agaricus bisporus polysaccharides MP, MP-1 and MP-2 relieve ulcerative colitis symptoms by regulating intestinal flora, mice were provided with an antibiotic mixture (Abs: vancomycin 30 mg / kg, neomycin sulfate 60 mg / kg, metronidazole 60 mg / kg and ampicillin 60 mg / kg). Specifically, the mice were randomly divided into five groups and administered antibiotics on days 0-4 and 8-10 to eliminate intestinal microbiota. Except for the Abs+Control group, mice were administered 2.5% DSS (m / V) in drinking water on days 4-8 and 10-12.

[0048] For the polysaccharide administration group, mice were gavaged with MP, MP-1, and MP-2 on days 4 to 12. The specific treatments of the five groups of mice, Abs+Control, Abs+Model, Abs+MP, Abs+MP-1, and Abs+MP-2, are as follows: Figure 4 As shown in A, and the body weight was recorded every day. H&E staining of colon tissue, FITC-dextran test in serum and analysis of inflammatory factors in colon tissue were as described above (2. Histopathological analysis, 3. Intestinal permeability determination, 4. Determination of inflammatory factor levels).

[0049] 6. Intestinal flora analysis

[0050] For intestinal microbial analysis, fecal samples of mice in the Control, Model, 5-ASA, MP, MP-1, and MP-2 groups were collected for total DNA extraction, amplification, and 16SrRNA gene sequencing. The effects of polysaccharides on intestinal flora were evaluated using alpha diversity (Shannon index and Simpson index) and beta diversity (PCoA analysis).

[0051] 7. Identification of KEGG pathway enrichment in MP-1 and MP-2 groups

[0052] Liquid chromatography-mass spectrometry (LC-MS) was used to perform non-targeted metabolomics analysis of fecal samples. KEGG pathway enrichment analysis was used to evaluate changes in metabolic pathways in feces of MP-1 and MP-2 mice.

[0053] 8. Safety evaluation of MP, MP-1 and MP-2

[0054] The mouse viscera (heart, liver, spleen, lung, and kidney) were removed and fixed in 4% paraformaldehyde fixative, embedded in paraffin, and sliced, and then stained with hematoxylin / eosin (H&E).

[0055] 2. Results

[0056] 1. MP, MP-1 and MP-2 can alleviate the symptoms of DSS-induced ulcerative colitis, including weight loss, colonic atrophy and colonic pathological damage.

[0057] (1) Mouse weight record

[0058] In general, weight loss is a typical feature of ulcerative colitis. Figure 1 As shown in B, the weight of the mice in the Model group treated with DSS alone was significantly reduced, but after the administration of MP, MP-1 and MP-2, the symptoms of weight loss in the mice were alleviated.

[0059] (2) Determination of mouse colon length

[0060] By comparing the length of the mouse colon ( Figure 1 C and Figure 1 D), it was found that the administration of the three polysaccharides and 5-ASA alleviated the colon shortening caused by DSS, especially the MP and MP-2 groups showed better recovery effects than MP-1. The results showed that DSS successfully established a mouse ulcerative colitis model, and the three polysaccharides could alleviate colon atrophy to a certain extent.

[0061] (3) Pathological changes in mouse colon tissue

[0062] like Figure 1 As shown in E, the results showed that the severity of ulcerative colitis in the Model group mice was significantly increased compared with other groups, such as goblet cell reduction and inflammatory infiltration, and the symptoms were relieved after the administration of MP, MP-1 and MP-2. The administration of three kinds of Agaricus bisporus polysaccharides can effectively improve the colon pathological damage of mice. In short, MP, MP-1 and MP-2 showed good therapeutic effects on alleviating DSS-induced ulcerative colitis.

[0063] 2. MP, MP-1 and MP-2 can restore intestinal barrier function

[0064] FITC-dextran was used to analyze and quantify the extent of intestinal barrier integrity disruption. The intestinal permeability results of the six groups of mice are shown in Figure 2 As shown. The results showed that the serum FITC-dextran level in the Model group was significantly higher than that in the Control group. Then, the intestinal permeability of mice in the MP, MP-1, and MP-2 administration groups was significantly reduced. In summary, the FITC-dextran experiment showed that all three Agaricus bisporus polysaccharides can partially restore the functional intestinal barrier of mice with ulcerative colitis.

[0065] 3. MP, MP-1 and MP-2 affect the levels of intestinal inflammatory factors

[0066] To further evaluate the effects of the three polysaccharides on ulcerative colitis mice, the levels of inflammatory factors in colon tissues were analyzed. Figure 3 AE showed the effects of three Agaricus bisporus polysaccharides, MP, MP-1 and MP-2, on the expression of IL-10, IFN-γ, IL-6, IL-1β and IL-17A levels in colon tissue. Figure 3 As shown in A, compared with the Control group, the IL-10 level in the Model group was significantly reduced, but after the administration of MP, MP-1 and MP-2, the IL-10 level was significantly increased. The expression of IFN-γ, IL-6, IL-1β, and IL-17A in the Model group was significantly increased, which was 2.51, 2.91, 2.51, and 2.61 times that of the Control group, respectively ( Figure 3 BE).

[0067] The results showed that DSS caused a severe inflammatory response in the colon tissue of mice, and may further cause the destruction of the intestinal barrier. After treatment with MP, MP-1 and MP-2, the levels of these proinflammatory factors were significantly reduced. Pharmacological studies have found that excessive proinflammatory cytokines can lead to immune response diseases and further lead to inflammation. Anti-inflammatory cytokines can reduce inflammation and promote healing. The cooperation of proinflammatory cytokines and anti-inflammatory cytokines is a key defense mechanism of the intestine. The results showed that MP, MP-1 and MP-2 can reduce the levels of proinflammatory cytokines and increase the levels of anti-inflammatory cytokines, thereby inhibiting inflammation in mice. Therefore, MP, MP-1 and MP-2 can inhibit pathological inflammation caused by colitis by downregulating TNF-α, IL-6, IL-1β and IL-17A and upregulating IL-10. In particular, as Figure 3 As shown in B and C, MP-2 showed a significantly better regulatory effect than MP and MP-1 on IFN-γ and IL-6, indicating that MP-2 has more significant anti-inflammatory activity.

[0068] 4. Antibiotics offset the effects of MP, MP-1, and MP-2 in alleviating inflammation in mice with ulcerative colitis

[0069] from Figure 4 BE showed that the effect of polysaccharide in reversing the symptoms of DSS-induced ulcerative colitis mice, such as weight loss, colon shortening, and histological damage, was almost abolished by antibiotics.

[0070] Depend on Figure 4 F shows that there is no significant difference in the FITC-dextran concentration in the serum of the four groups of mice: Abs+Model, Abs+MP, Abs+MP-1, and Abs+MP-2. That is, after antibiotic treatment, the administration of MP, MP-1, and MP-2 did not reverse the increased intestinal permeability of mice with ulcerative colitis.

[0071] In addition, after antibiotic treatment, DSS could still successfully induce the UC model and promote inflammatory response in mice, but MP, MP-1 and MP-2 could no longer significantly upregulate the content of IL-10 in the colon tissue of UC mice ( Figure 4 G), nor could it downregulate the levels of IL-6, IL-1β, and IL-17A ( Figure 4 HJ) to inhibit the expression of inflammation in mice. Therefore, the results of the antibiotic experiment indicate that the intestinal microbiota is very important for the anti-inflammatory effects of MP, MP-1, and MP-2 in mice with ulcerative colitis.

[0072] 5. MP, MP-1 and MP-2 relieve intestinal flora imbalance

[0073] like Figure 5 A and Figure 5 As shown in B, the community richness of intestinal flora was evaluated by Shannon index and Simpson index. The results showed that 5-ASA and three kinds of Agaricus bisporus polysaccharides could restore the changes of Shannon index and Simpson index caused by DSS. In addition, principal coordinate analysis (PCoA) ( Figure 5 C) showed that there were some differences between the intestinal flora of the Model group mice and the other five groups of mice.

[0074] 6. Identification of KEGG pathway enrichment in MP-1 and MP-2 groups

[0075] KEGG pathway enrichment analysis was performed based on the analysis of differential metabolites, and the results are as follows Figure 6 As shown, bile secretion and tryptophan metabolic pathways were enriched in the MP-2 group. In particular, bile secretion is an important metabolic pathway, and 6 metabolites are directly involved, which are significantly enriched after MP-2 administration compared with the Model group. Previous studies have shown that bile secretion disorders are closely related to acute experimental colitis, and bile can reduce the level of inflammation by inhibiting inflammasome activation, increasing the proliferation and differentiation of intestinal stem cells, and thus improving the intestinal barrier function of mice. Studies have also shown that increased tryptophan metabolism is associated with the relief of DSS-induced colitis.

[0076] In addition, the pathways enriched in the MP-1 group and the Model group were as follows Figure 7 As shown in Figure 4. Pathway enrichment analysis showed that the KEGG metabolic pathway for steroid hormone biosynthesis was significantly enriched after MP-1 treatment compared with the Model group. Similarly, the biosynthesis of steroid hormones may be disturbed in DSS-induced colitis mice.

[0077] 7. Safety evaluation of MP, MP-1 and MP-2

[0078] Safety evaluation is a very critical factor in the application of Agaricus bisporus polysaccharides in functional foods and biopharmaceuticals. The above results confirm that these three polysaccharides, especially MP-2, have a significant alleviating effect on mice with ulcerative colitis. However, before application, it is necessary to determine whether these three polysaccharides cause adverse side effects to the body during treatment. The safety of MP, MP-1 and MP-2 was evaluated by pathological examination of major organs, and the oral toxicity results were as follows: Figure 8 As shown. Figure 8 As shown in the figure, the H&E staining results of MP, MP-1 and MP-2 showed no obvious abnormal lesions in the heart, liver, spleen, lung and kidney of each group compared with the control group. Therefore, the three polysaccharides MP, MP-1 and MP-2 from Agaricus bisporus showed excellent safety in mice and can be used in functional foods and medicines.

[0079] In summary, the present invention proves through animal experiments that Agaricus bisporus polysaccharide, especially Agaricus bisporus polysaccharide purified by a specific process, has the effects of improving colon pathological damage, restoring intestinal barrier function, anti-inflammatory and relieving intestinal flora imbalance, relieving weight loss and colon atrophy, thereby achieving the effect of preventing and treating ulcerative colitis, and showing excellent safety. The application of Agaricus bisporus polysaccharide in the prevention and / or treatment of ulcerative colitis has broad prospects.

Claims

1. Use of Agaricus bisporus polysaccharide MP and two Agaricus bisporus polysaccharide components MP-1 and MP-2 in the preparation of a medicament for preventing and / or treating ulcerative colitis, characterized in that: The medicine is a medicine for alleviating weight loss, colon atrophy and / or colon pathological damage caused by ulcerative colitis.

2. The use according to claim 1, characterized in that: The Agaricus bisporus polysaccharide MP is prepared by extracting Agaricus bisporus with water and precipitating with alcohol, re-dissolving the precipitate with water, and then dialyzing and drying. The Agaricus bisporus polysaccharide component MP-1 is prepared by re-dissolving crude polysaccharide MP with water after alcohol precipitation and then drying; The Agaricus bisporus polysaccharide component MP-2 is prepared by alcohol precipitation of the supernatant of crude polysaccharide MP, re-alcohol precipitation, re-dissolving the precipitate with water, and ultrafiltration.

3. The use according to claim 1 or 2, characterized in that: The molecular weight range of the Agaricus bisporus polysaccharide component MP-1 is 8.0×10 6 -9.0×10 6 Da, monosaccharide composition type includes glucose, infrared spectrum signal includes pyranose ring and α configuration, the signal of the pyranose ring is located at 1079cm -1 The signal of the α configuration is located at 843 cm -1 or 925cm -1 .

4. The use according to claim 1 or 2, characterized in that: The molecular weight range of the Agaricus bisporus polysaccharide component MP-2 is 1.5×10 4 -2.0×10 4 Da, monosaccharide composition types include glucose and galactose, infrared spectrum signals include pyranose ring and α configuration, the signal of the pyranose ring is located at 1079cm -1 The signal of the α configuration is located at 843 cm -1 or 925cm -1 .

5. The use according to claim 1, characterized in that: The drug is a drug for restoring the intestinal barrier function.

6. The use according to claim 1, characterized in that: The drug is a drug that regulates the level of inflammatory factors.

7. The use according to claim 6, characterized in that: Modulates downregulation of TNF-α, IL-6, IL-1β and IL-17A, and / or upregulation of IL-10.

8. The use according to claim 1, characterized in that: The drug is a drug that relieves intestinal flora imbalance by regulating the composition of intestinal microbiota.

9. The use according to claim 1, characterized in that: The drug is a drug that regulates bile secretion, tryptophan metabolic pathway or steroid hormone biosynthesis by regulating metabolic pathways.

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