Application of pachymaran in regulating intestinal bacteria metabolism and relieving chronic obstructive pulmonary disease

Abstract

The invention relates to the field of medicines, in particular to application of pachymaran in regulating intestinal bacteria metabolism and relieving chronic obstructive pulmonary diseases. The pachymaran has remarkable curative effects of improving lung tissue lesions of chronic obstructive pulmonary diseases, improving lung functions and slowing down the development process of the chronic obstructive pulmonary diseases for the first time, and the pachymaran can improve intestinal mucosal immunity by improving intestinal flora, so that the lung mucosal immunity is improved, and the purposes of preventing infection, preventing diseases and treating chronic obstructive pulmonary diseases are achieved. The acute attack frequency of the chronic obstructive pulmonary disease is reduced. The discovery has great influence on research and treatment of chronic obstructive pulmonary diseases, and has clinical practical value.

Description

Technical Field

[0001] The present invention relates to the field of medicine, and in particular to the application of pachymaran in regulating intestinal bacteria metabolism and alleviating chronic obstructive pulmonary disease. Background Art

[0002] Chronic obstructive pulmonary disease (COPD) is a heterogeneous lung condition characterized by chronic respiratory symptoms (dyspnea, cough, sputum) and persistent (often progressive) airflow obstruction caused by airway abnormalities (bronchitis, bronchiolitis) and / or alveolar abnormalities (emphysema). COPD is a chronic inflammatory disease of lung tissue caused by damaging factors such as smoke and pathogens. The main risk factor is smoking. The pathogenesis is complex and is related to inflammatory-immune imbalance, oxidative stress, protease-antiprotease imbalance, airway mucus hypersecretion and cell apoptosis.

[0003] Inflammation-immune imbalance is the key lesion and mechanism of COPD. The lesions involve the lung parenchyma and interstitium, and are mainly manifested as airway inflammation, airway remodeling, emphysema, pulmonary vascular remodeling and interstitial fibrosis. The continuous occurrence of these lesions leads to repeated damage, inflammation and repair of lung tissue, damage to the gas-blood barrier, and persistent airflow limitation, which eventually causes the patient's lung function to continue to decline. At present, there is no specific drug for the treatment of chronic obstructive pulmonary disease. The focus of prevention and treatment is to alleviate or prevent the decline of lung function, alleviate symptoms, improve the quality of life of patients, and reduce the mortality rate of the disease. Commonly used drugs include anticholinergic drugs, theophylline, β2 receptor blockers, glucocorticoids, etc. The above drugs have obvious limitations and adverse reactions. Long-term use will reduce patient tolerance. Therefore, based on literature surveys and the research accumulation of the research group, this study conducted relevant research on the regulation of intestinal mucosal immunity by Poria cocos polysaccharide and the improvement of lung mucosal immune function, which is of great significance for further understanding the action pathway of Poria cocos polysaccharide and drug development. Summary of the invention

[0004] In view of the shortcomings of the prior art, the present invention takes Poria cocos polysaccharide as the research object and studies its biological activity. It is found that it can increase the ratio of Firmicutes / Bacteroidetes in COPD mice, improve the immune function of the lung mucosa by regulating intestinal mucosal immunity, prevent infection, and reduce the frequency of acute attacks of COPD, thereby improving COPD lung tissue lesions and lung function, and slowing down the progression of COPD lesions.

[0005] One of the purposes of the present invention is to provide an application of Poria cocos polysaccharide in medicines, foods or health products for treating and / or alleviating chronic obstructive pulmonary disease.

[0006] The second purpose of the present invention is to provide an application of pachymaran in regulating intestinal bacteria metabolism drugs.

[0007] The following applications are also within the scope of protection of the present invention:

[0008] Furthermore, the drug action mechanism is manifested in reducing the expression levels of IL-1β, IL-6, IL-8, and TNF-a, and increasing the expression level of IL-10.

[0009] Furthermore, the drug action mechanism is manifested in increasing the content of sIgA, pIgR, β-DF, and a-DF.

[0010] Furthermore, the drug uses Poria cocos polysaccharide as an active ingredient and is prepared into a pharmaceutically acceptable dosage form using pharmaceutically acceptable excipients.

[0011] Furthermore, the drug is used to adjust the balance of intestinal flora and / or promote the production of short-chain fatty acids, which are metabolites of intestinal flora.

[0012] Furthermore, the drug alleviates chronic obstructive pulmonary disease by regulating mucosal immunity.

[0013] The third object of the present invention is to provide a drug for alleviating chronic obstructive pulmonary disease, comprising an active ingredient and pharmaceutically acceptable excipients; the active ingredient is Poria cocos polysaccharide.

[0014] The third object of the present invention is to provide a drug for regulating intestinal bacteria metabolism, comprising an active component and pharmaceutically acceptable excipients; the active component is pachymaran.

[0015] Furthermore, the drug for regulating intestinal bacteria metabolism provided by the present invention can be used in combination with other components having anti-inflammatory activity.

[0016] Furthermore, the drug for alleviating chronic obstructive pulmonary disease provided by the present invention can be used in combination with other components having anti-inflammatory activity.

[0017] It is well known to those skilled in the art that the pharmaceutically acceptable carriers are generally recognized for this purpose and as inactive ingredients of medicaments.

[0018] The auxiliary substances include solvents, propellants, solubilizers, cosolvents, emulsifiers, colorants, adhesives, disintegrants, fillers, lubricants, wetting agents, osmotic pressure regulators, stabilizers, glidants, flavoring agents, preservatives, suspending agents, coating materials, fragrances, anti-adhesive agents, integrators, penetration enhancers, pH regulators, buffers, plasticizers, surfactants, foaming agents, defoamers, thickeners, inclusion agents, humectants, absorbents, diluents, flocculants and deflocculating agents, filter aids, and release retardants.

[0019] The diluent may be one or more of mannitol, sucrose, lactose, sorbitol, xylitol, polyethylene glycol, propylene glycol, vegetable oil, and mineral oil; the disintegrant may be one or more of cross-linked sodium carboxymethyl cellulose, colloidal silicon dioxide, and citric acid; the binder may be one or more of starch slurry, ethanol, water, and povidone alcohol solution; the preservative may be one or more of ethyl paraben, propyl paraben, sorbic acid, potassium sorbate, calcium propionate, sodium dehydroacetate, sodium diacetate, and sodium lactate; the antioxidant may be one or more of ethylenediaminetetraacetic acid, disodium ethylenediaminetetraacetic acid, butylated hydroxytoluene, glycine, inositol, ascorbic acid, hydroxyethyl ester ... The invention can be one or more of hemic acid, sodium ascorbate, lecithin, malic acid, hydroquinone, citric acid, succinic acid, and sodium metabisulfite; the flavoring agent can be one or more of aspartame, sucrose, xylitol, steviol glycosides, sodium cyclamate, sorbitol, cocoa, pure vanilla, vanillin, ethyl vanillin, chocolate, malt, and mint; the suspending agent can be one or more of xanthan gum, polyvinyl pyrrolidone, sodium alginate, aluminum stearate, and hydrogenated vegetable oil; the emulsifier can be one or more of alkyl sulfate, soap, dodecylbenzene sulfonate, lactate, sulfosuccinate, monoglyceride sulfonate, phosphate, silicone, and taurate.

[0020] The drug is in the form of tablets, capsules, pills, powders, granules, syrups, solutions, emulsions, injections, sprays, aerosols, and patches.

[0021] Wherein, the drug is administered via gastrointestinal and parenteral routes.

[0022] Particularly, the non-gastrointestinal administration route is selected from injection, respiratory tract administration, skin administration, mucosal administration or cavity administration.

[0023] Among them, the parenteral preparation is selected from injections, sprays, aerosols, patches and the like.

[0024] Particularly, the gastrointestinal administration preparation is selected from tablets, capsules, powders, granules, pills, solutions, emulsions or syrups.

[0025] The pharmaceutical composition of the present invention contains 0.1-90% by weight of active ingredients.

[0026] The pharmaceutical composition can be prepared according to methods known in the art. When used for this purpose, if necessary, the active ingredient can be combined with one or more solid or liquid pharmaceutical excipients and / or adjuvants to prepare a suitable administration form or dosage form for human use.

[0027] In addition, if necessary, colorants, preservatives, perfumes, flavoring agents, sweeteners or other materials may be added to the pharmaceutical preparations.

[0028] The dosage of the pharmaceutical composition of the present invention depends on many factors, such as the sex, age, weight and individual response of the patient or animal, the route of administration and the number of times of administration, etc. The above dosage can be administered in a single dosage form or divided into several, such as two, three or four dosage forms. The dosage level must be selected based on the specific route of administration, the severity of the condition to be treated, and the condition and previous medical history of the patient to be treated. However, the practice in the art is to start the dosage from a level lower than that required to obtain the desired therapeutic effect and gradually increase the dosage until the desired effect is obtained.

[0029] However, it should be recognized that the total daily dosage of the pharmaceutical composition of the present invention must be determined by the attending physician within the scope of sound medical judgment. For any particular patient, the specific therapeutically effective dosage level must be determined based on a variety of factors, including the disorder being treated and the severity of the disorder; the specific composition used; the patient's age, weight, general health, sex and diet; administration time, route of administration and excretion rate; duration of treatment; drugs used in combination or concurrently; and similar factors known in the medical field. For example, it is practiced in the art to start the administration of a dose lower than the level required to obtain the desired therapeutic effect and gradually increase the dose until the desired effect is obtained.

[0030] Generally speaking, the dosage of the pharmaceutical composition of the present invention for mammals, especially humans, calculated as the active ingredient, can be between 1-1000 mg / kg body weight / day, for example, between 1-500 mg / kg body weight / day, for example, between 50-500 mg / kg body weight / day, or 100-500 mg / kg, or 150-500 mg / kg, or 200-500 mg / kg, or 250-500 mg / kg.

[0031] Through animal and molecular biology experiments, this study discussed the lung function improvement effect of Poria cocos polysaccharide on the COPD model induced by smoke combined with lipopolysaccharide from phenomenon to mechanism, and further explored the relationship between the lung function improvement effect of Poria cocos polysaccharide and its improvement of intestinal flora.

[0032] Compared with the prior art, the present invention discloses for the first time that Poria cocos polysaccharide has significant therapeutic effects on improving lung tissue lesions of chronic obstructive pulmonary disease, improving lung function and slowing down the progression of chronic obstructive pulmonary lesions, and reveals that it can improve intestinal mucosal immunity by improving intestinal flora, thereby improving lung mucosal immune function, preventing infection, and reducing the frequency of acute attacks of chronic obstructive pulmonary disease. This discovery will have a significant impact on the research and treatment of chronic obstructive pulmonary disease and has clinical practical value. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] Figure 1 The effect of PCP on the lung function of COPD mice;

[0034] Among them, 1A is the RV ratio change diagram; 1B is the TLC ratio change diagram; 1C is the FEV0.2 / FVC ratio change diagram; 1D is the MMEF ratio change diagram; 1E is the HE staining diagram of lung tissue; compared with the blank group####P<0.0001, P>0.05; compared with the model group***P<0.001, *P<0.05, P>0.05

[0035] Figure 2 The effect of PCP on immune factors in lung tissue of COPD mice;

[0036] Among them, 2A is the content change diagram of IL-1β; 2B is the content change diagram of IL-6; 2C is the content change diagram of TNF-a; D is the content change diagram of IL-8; E is IL-10. n=3; compared with the blank group####P<0.0001,###P<0.001,#P<0.05; compared with the model group****P<0.0001,***P<0.001,**P<0.01,*P<0.05

[0037] Figure 3 The effects of PCP on colonic inflammation and tight junction proteins in colonic tissue of COPD mice;

[0038] Among them, 3A-3C are the changes in the contents of sIgA, pIgR, and β-DF in lung tissue; 3D-3F are the changes in sIgA, pIgR, and a-DF in intestinal tissue, n=3; compared with the blank group ####P<0.0001, ###P<0.001, compared with the model group **P<0.01, *P<0.05, P>0.05;

[0039] Figure 4 The effect of PCP on SCFAs in the colon contents of COPD mice;

[0040] Among them, 4A is the HE staining image of intestinal tissue; 4B is the immunofluorescence detection of Claudin-1 expression in mouse colon tissue; 4C is the immunofluorescence detection of Occludin expression in mouse colon tissue; 4D is the immunofluorescence detection of ZO-1 expression in mouse colon tissue; 4E is the gray value of Claudin-1; 4F is the gray value of Occludin; 4G is the gray value of ZO-1. n=3; compared with the blank group ###P<0.001, compared with the model group ***P<0.001, **P<0.01, P>0.05. DETAILED DESCRIPTION

[0041] In order to make those skilled in the art better understand the technical scheme of the present invention, the present invention is described in detail below in conjunction with specific embodiments. The experimental methods for which specific conditions are not indicated in the following examples are usually carried out under normal conditions or according to the conditions recommended by the manufacturer. The test materials used in the following examples, unless otherwise specified, are purchased from conventional biochemical reagent stores. Unless otherwise specified, percentages and parts are calculated by weight. Unless otherwise defined, all professional and scientific terms used in the text have the same meaning as those familiar to those skilled in the art. In addition, any method and material similar to or equal to the recorded content can all be applied to the present invention. The preferred implementation methods and materials described in the text are only for demonstration purposes.

[0042] The endpoints and any values ​​of the ranges disclosed in this article are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoint values ​​of each range, the endpoint values ​​of each range and the individual point values, and the individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed in this article.

[0043] The technical solution of the present invention is further described in detail below in conjunction with specific embodiments and drawings. It should be understood that the following embodiments are only used to explain the present invention and are not used to limit the present invention.

[0044] The experimental data were analyzed using Graphpad Prism 9.0 statistical software, and the statistical results were expressed as Mean ± SD. When the samples were in accordance with normal distribution and the variance was homogeneous, the measurement data among multiple groups were compared using variance analysis, with a = 0.05 as the test level, P < 0.05 indicated that the difference was statistically significant, and P < 0.01 indicated that the difference was significant.

[0045] Experimental animals: C57BL / 6J male mice, purchased from Sibeifu (Beijing) Biotechnology Co., Ltd.; Drug sources: Poria polysaccharide (product batch number CY221209) was purchased from Fufeng Ciyuan Biotechnology Co., Ltd., and the quality inspection report showed that its polysaccharide content was 90.13%; Fanfushu was purchased from Hangzhou Tiger Pharmaceutical Technology Co., Ltd.

[0046] Experimental groups: including blank control group (Control), model group (Model), low-dose Poria polysaccharide group (PCP-L), medium-dose Poria polysaccharide group (PCP-M), high-dose Poria polysaccharide group (PCP-H) and positive drug Fanfushu group (Y), with 10 mice in each group.

[0047] Experimental methods: The experimental animals were first adaptively fed for 1 week. Except for the blank control group, the other 5 groups were treated with airway instillation of lipopolysaccharide (LPS, SIGMA, USA) combined with fumigation (cigarettes were purchased from Hongta Tobacco Group Co., Ltd., with nicotine content in smoke: 1.0 mg, tar content: 10 mg, and carbon monoxide content in smoke: 11 mg) to prepare the COPD mouse model: on the first and 14th days of modeling, lipopolysaccharide (150 μg / ml, 7.5 μg per mouse) was instilled through the airway, and fumigation was performed on the remaining days (patent number of plexiglass fumigation box: ZL201921358122.2), for a total of 12 weeks. After the model was successfully replicated, the positive drug Fanfushu 0.91 mg / kg, Poria polysaccharide low dose 100 mg / kg, medium dose 200 mg / kg, and high dose 400 mg / kg were given by gavage, and the blank control group and the model group were given the same volume of 0.9% saline. The model group and each treatment group were fumigated every other day to maintain the lesions.

[0048] Example 1 Investigating the effect of PCP on lung tissue of COPD mice

[0049] After the end of the 16th week of drug administration, the mice were anesthetized, and the midline of the neck was incised to fully expose the trachea. A T-shaped incision was made on the trachea, and the trachea was connected to a small animal ventilator (EMMS, UK, CRFM100). The following indicators of lung function were tested by the Forced Maneuvers (FM) forced lung function system: the 50ms expiratory volume (Forced Expiratory Volume 50, FEV50) and the maximum mid-ventilation volume (Maximum midexpiratory flow, MMEF) reflecting the pulmonary ventilation function of COPD mice, as well as the residual volume (RV) and total lung capacity (TLC) of the lung volume function indicators. The experimental results are shown in the figure. Figure 1 As shown in AD.

[0050] from Figure 1 As can be seen from A-1B, the FEV50 and MMEF values ​​of the mice in the model group were significantly reduced, and the above data were significantly improved after drug administration; Figure 1 As shown in C-1D, compared with the blank group, the values ​​of RV and TLC in the model group mice increased significantly, and the above values ​​decreased after administration. The results showed that PCP can improve the lung function of COPD model mice.

[0051] The second lobe of the right lung and 1 cm of colon tissue above the anus were fixed in 4% paraformaldehyde solution, dehydrated with gradient ethanol, and then treated with xylene and embedded in paraffin. Tissue sections with a thickness of about 4 μm were taken, dewaxed to water, stained with hematoxylin and eosin, sealed with neutral gum, and pathological changes were observed under a microscope (see Figure 1 E).

[0052] from Figure 1 E As can be seen, HE staining of lung tissue sections showed that the alveolar walls of the mice in the model group became thinner and fused, a large number of inflammatory cells infiltrated and blocked the bronchi, and the lumen was significantly narrowed; inflammatory cells infiltrated around the blood vessels, and some arterial walls thickened; the arteries, veins, and bronchi were dilated and congested; a large number of inflammatory cells infiltrated in the lung interstitium, and the alveolar septa were narrowed and collapsed; after the administration of Poria polysaccharide and OM85-BV, these adverse changes were significantly improved, among which PCP-M and PCP-H had better improvement effects, and the improvement effect of OM85-BV was similar to that of PCP-M.

[0053] Example 2 Investigating the effect of PCP on lung inflammation in COPD mice

[0054] Total RNA from lung tissue was extracted using RNAiso Plus (AKA704) reagent. III 1 st Total RNA was reverse transcribed into cDNA using Strand cDNA Synthesis SuperMix for qPCR (gDNA digester plus) (YEASEN). Relative mRNA levels were detected using a real-time fluorescence quantitative PCR instrument (Applied Biosystems, Quant Studi). q-PCR SYBR Green Master Mix (Low Row Plus) (YEASEN), the cycle conditions are: 95℃ pre-denaturation for 5min, 95℃ denaturation for 10s, 60℃ annealing / extension for 30s, and 40 cycles. The mRNA expression of the target gene was normalized using ACTB and calculated using the 2-ΔΔCt method. The experimental results are shown in Figure 2 The specific primer sequences are shown in Table 1.

[0055] Table 1 Mouse RT-QPCR primer sequences

[0056]

[0057]

[0058] Figure 2 As shown in the results, the mRNA expression of proinflammatory cytokines IL-1β, IL-6, IL-8, and TNF-a in the lung tissue of COPD model mice increased significantly, and the mRNA expression of the anti-inflammatory factor IL-10 showed a downward trend. After administration, the mRNA expression of proinflammatory factors IL-1β, IL-6, IL-8, and TNF-a decreased significantly, and the mRNA expression of the anti-inflammatory factor IL-10 increased. These results indicate that PCP and OM85-BV help alleviate the lung inflammation response in COPD mice.

[0059] Example 3 Investigating the effect of Poria cocos polysaccharide (PCP) on the content of immune molecules in lung and colon tissues of COPD mice

[0060] 30 mg of mouse lung tissue and colon tissue were taken, added with 270 μl of 0.9% physiological saline, ground with a low-temperature tissue homogenizer (Ningbo Xinzhi, SCIENTZ-48L), placed on ice, and centrifuged in a desktop high-speed refrigerated centrifuge (Germany Eppendorf, 5427R) for 5 minutes, with the program set at 4°C, 2500 rpm, 20 min, and the supernatant was taken. Mouse ELISA kits (Jiangsu Enzyme Biotechnology Co., Ltd.) were used to detect the expression levels of β-defensin, pIgR, and sIgA in lung tissue and a-defensin, pIgR, and sIgA in colon tissue (see Figure 3 ).

[0061] like Figure 3 As shown in the figure, compared with the blank group, the secretion levels of sIgA, pIgR, β-DF in the lungs and sIgA, pIgR, and a-DF in the colon of the COPD group mice were significantly reduced. After administration, the above indicators showed an upward trend. These data indicate that PCP and OM85-BV can increase the secretion levels of sIgA, pIgR, β-DF, and a-DF in mucosal immunity.

[0062] Example 4 Investigating the effect of Poria cocos polysaccharide (PCP) on colonic tissue inflammation in COPD mice

[0063] Colon tissue 1 cm above the anus was fixed in 4% paraformaldehyde solution, dehydrated with gradient ethanol, treated with xylene, and then embedded in paraffin. Tissue sections with a thickness of about 4 μm were taken, dewaxed to water, stained with hematoxylin and eosin, sealed with neutral gum, and pathological changes were observed under a microscope (see Figure 4 A).

[0064] Take the mouse colon tissue and fix it in paraformaldehyde, embed the tissue, dehydrate it, then embed it in paraffin and slice it on a freezing embedding machine, and put the slices into environmentally friendly dewaxing solution I for 10 minutes-environmentally friendly dewaxing solution II for 10 minutes-environmentally friendly dewaxing solution III for 10 minutes-anhydrous ethanol I for 5 minutes-anhydrous ethanol II for 5 minutes-anhydrous ethanol III for 5 minutes-distilled water. Then perform antigen repair. After repair, cool it naturally, and place the slide in PBS (PH7.4) on a decolorizing shaker to wash it 3 times, each time for 5 minutes. After the slices are slightly dried, use a tissue pen to draw circles around the tissue, add 3% BSA, and block it for 30 minutes. Then add Claudin-1 (Servicebio, GB11032) diluted 1:200, Occludin (Servicebio, GB111401) diluted 1:500, and ZO-1 (Servicebio, GB111402) diluted 1:500, and incubate the slices flat in a humidified box at 4°C overnight. Add the corresponding secondary antibody Alexa Fluor 488 labeled goat anti-rabbit IgG (Servicebio, GB25303) diluted 1:400 and incubate at room temperature in the dark for 50 minutes. Then, counterstain the cell nucleus with DAPI. Place the slide in PBS (PH7.4) and wash it on a decolorizing shaker for 3 times, 5 minutes each time, add DAPI staining solution, and incubate it at room temperature in the dark for 10 minutes. Place the slide in PBS (PH7.4) and wash it on a decolorizing shaker for 3 times, 5 minutes each time, add autofluorescence quencher B solution for 5 minutes, rinse with running water for 10 minutes to quench tissue autofluorescence, and finally seal the slide with anti-fluorescence quenching sealing agent.

[0065] Figure 4 A: It can be seen that the intestinal mucosa of the mice in the blank group was intact, the number of goblet cells was normal, the intestinal crypt structure was clearly visible, and there was no obvious inflammatory cell infiltration; the integrity of the mucosal epithelial structure of the mice in the COPD group was severely damaged, the arrangement of cell glands was distorted, the crypts were severely atrophied, the goblet cells were reduced, and there was a large amount of inflammatory infiltration; compared with the mice in the model group, the integrity of the colon mucosa of the mice in the PCP treatment groups and the OM85-BV group was restored, the epithelium began to repair, the intestinal crypt structure was clearer, new goblet cells began to be produced, and the inflammatory cells were reduced. Figure 4 As shown in B-4G, compared with the Control group, the relative expression of tight junction proteins Claudin-1, Occludin, and ZO-1 in the colon tissue of mice in the Model group was significantly reduced. After PCP intervention, the above indicators increased significantly, indicating that PCP can upregulate the expression of tight junction proteins in the colon tissue of COPD mice. This indicates that PCP can repair the intestinal barrier damage of OVX mice and relieve intestinal inflammation.

[0066] Example 5 Investigating the effect of Poria cocos polysaccharide (PCP) on SCFA secretion levels in feces of COPD mice

[0067] The feces of experimental animals were collected, and the content of short-chain fatty acids in the fecal samples was detected by GC-Q-MS targeted metabolomics. The results are shown in Table 2.

[0068] Table 2 Effects of PCP on SCFA content in the colon of COPD mice (n=3, μg / ml)

[0069]

[0070]

[0071] Note: Compared with the blank group # P<0.01, P>0.05, compared with the model group **P<0.01, *P<0.05, P>0.05

[0072] As can be seen from Table 2, compared with the Control group, the content of Acetic acid, Propionic acid, Butyric acid, Valeric acid, and Hexanoic acid in the feces of the Model group mice showed a downward trend, while Isobutyric acid and Isovaleric acid showed an upward trend. Compared with the Model group, Acetic acid, Propionic acid, Butyric acid, Valeric acid, Hexanoic acid, Isobutyricacid, and Isovaleric acid in the feces of mice in each drug-treated group increased significantly, and the upward trend was more obvious in the PCP_M and PCP_H groups, and the overall content of Acetic acid, Propionic acid, and Butyric acid in the seven SCFAs was higher. It can be seen that the intervention of Poria polysaccharide and Panfushu can cause an increase in the content of SCFAs in the feces of COPD mice.

[0073] Example 6 Investigating the effect of PCP on the intestinal flora of COPD mice

[0074] Fecal and cecal samples were collected from experimental animals, and genomic DNA of the samples was extracted using the CTAB / SDS method. Beta diversity analysis was used to evaluate the species complexity differences of the samples, and QIIME software (Version 1.9.1) was used to calculate the Beta diversity on weighted and unweighted unifrac. Systematic sequencing analysis of the 16S rRNA gene in mouse fecal samples was performed to evaluate the changes in intestinal flora, and the results are shown in Tables 3-4.

[0075] Table 3

[0076]

[0077]

[0078] As can be seen from Table 3, at the phylum level, the relative abundance of Bacteroidetes in the Model group decreased compared with the Control group, and increased significantly after drug administration. The relative abundance of Firmicutes in the Model group was higher than that in the Control group, and the relative abundance of each drug administration group decreased significantly compared with the Model group. Compared with the Control group, the Firmicutes / Bacteroidetes ratio in the Model group increased, and the Firmicutes / Bacteroidetes ratio in the medium-dose group of Poria polysaccharide was significantly reduced compared with the Model group.

[0079] Table 4

[0080]

[0081]

[0082] The results of the intestinal bacterial genus level detection of mice are shown in Table 4. It can be seen that at the genus level, the mice in each group were mainly composed of Prevotella, Allobaculum, Prevotellaceae_Prevotella, Akkermansia, etc. Compared with the Control group, the relative abundance of Akkermansia, Oscillospira, Ruminococcus, Ruminococcaceae_Ruminococcus, Helicobacter, and Desulfovibrio in the Model group decreased, and there was an upward trend after drug intervention; compared with the Control group, the relative abundance of Allobaculum, Coprococcus, and Paraprevotella in the Model group increased, and there was a downward trend after drug intervention. Among them, the abundance of Akkermansia and Ruminococcus decreased significantly in the model group and increased after drug administration, and Allobaculum increased significantly in the model group and decreased after drug administration. The medium-dose group of Poria polysaccharide can adjust the relative abundance of the intestinal flora genus level.

[0083] Finally, it should be noted that the above description is only a preferred embodiment of the present invention. Under the guidance of the present invention, those skilled in the art can make a variety of similar expressions without violating the purpose and claims of the present invention, and such changes all fall within the scope of protection of the present invention.

Claims

1. An application of Poria cocos polysaccharide in medicines, foods or health products for treating and / or alleviating chronic obstructive pulmonary disease.

2. Application of Poria cocos polysaccharide in drugs regulating intestinal bacteria metabolism.

3. The use according to claim 1 or 2, characterized in that: The drug action mechanism is manifested in reducing the expression levels of IL-1β, IL-6, IL-8, and TNF-a, and increasing the expression level of IL-10.

4. The use according to claim 1 or 2, characterized in that: The drug action mechanism is manifested in increasing the content of sIgA, pIgR, β-DF and a-DF.

5. The use according to claim 1 or 2, characterized in that: The medicine uses tuckahoe polysaccharide as an active ingredient and is prepared into a pharmaceutically acceptable dosage form using pharmaceutically acceptable auxiliary materials.

6. The use according to claim 1 or 2, characterized in that: The drug is used to adjust the balance of intestinal flora and / or promote the production of short-chain fatty acids, a metabolite of intestinal flora.

7. The use according to claim 1 or 2, characterized in that: The drug alleviates chronic obstructive pulmonary disease by regulating mucosal immunity.

8. The use according to claim 1 or 2, characterized in that: The application concentration of the polysaccharide is 1-500 mg / kg, for example 50-500 mg / kg, or 100-500 mg / kg, or 150-500 mg / kg, or 200-500 mg / kg, or 250-500 mg / kg.

9. A drug for alleviating chronic obstructive pulmonary disease, characterized in that: The invention comprises active components and pharmaceutically acceptable auxiliary materials; the active component is pachymaran.

10. A drug for regulating intestinal bacteria metabolism, characterized in that: The invention comprises active components and pharmaceutically acceptable auxiliary materials; the active component is pachymaran.

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