Application of tremella polysaccharide in preparation of medicine for treating and / or preventing colorectal cancer
By regulating the intestinal flora through tremella polysaccharide, increasing the abundance of probiotics and upregulating taurine levels, the problem of unsatisfactory effects of existing plant polysaccharides in improving intestinal microecology and fighting colorectal cancer is solved, providing an effective drug option and significantly alleviating colorectal cancer symptoms.
Patent Information
- Application Number
- CN202511363294.9
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-09-23
- Publication Date
- 2025-11-25
AI Technical Summary
Existing plant polysaccharides have not been effective in improving gut microbiota and fighting colorectal cancer. There is a lack of effective basic research, and new drug options need to be found to improve the gut microenvironment and prevent or treat colorectal cancer.
By using Tremella polysaccharide to regulate intestinal flora, the abundance of the probiotic Akkermansia muciniphila is increased, the intestinal microenvironment is improved, the polarization of tumor-promoting M2 macrophages is inhibited, and the host metabolic state is improved by upregulating taurine levels, drugs with multiple administration routes are prepared.
Tremella polysaccharides significantly alleviated weight loss in mice with colorectal cancer, reduced tumor burden, improved gut microbiota, increased probiotic abundance, and inhibited pro-cancer polarization, providing an effective drug option for the prevention and treatment of colorectal cancer.
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Figure CN121003631A_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of biomedical technology, specifically relating to the application of Tremella fuciformis polysaccharide in the preparation of drugs for the treatment and / or prevention of colorectal cancer. Background Technology
[0002] In recent years, with population aging and changes in lifestyle and dietary structure, the incidence and mortality rates of colorectal cancer (CRC) have been gradually increasing, and the age of onset is becoming younger. With the continuous development of science and technology, CRC treatment methods have evolved from surgery, radiotherapy, and chemotherapy to targeted therapy and immunotherapy. Although these treatments have achieved certain results in CRC, patients still face serious problems such as high recurrence rates, short survival times, and significant drug side effects. Therefore, finding more efficient and safer prevention and treatment methods is of great significance for the control of colorectal cancer.
[0003] The gut microbiota (GM) is a community of microorganisms residing in the human gut. It not only participates in nutrient absorption but also influences digestion, immunity, and drug response. In recent years, the role of the gut microbiota in colorectal cancer has attracted widespread attention. Increasing evidence suggests that host-microbiota interactions play a crucial role in the development and progression of colorectal cancer, and that the gut microbiota is closely related to its occurrence, development, and treatment outcomes. Some gut microbes can enhance cancer treatment efficacy, while others have the opposite effect. Altering the composition of the gut microbiota and promoting the abundance of beneficial bacteria and metabolites may be a potentially effective anti-tumor strategy. Plant polysaccharides, as prebiotics, can directly regulate the gut microbiota and improve the gut microenvironment. Increasing intake of plant polysaccharides can regulate the structure of the gut microbiota and enrich beneficial gut bacteria, thereby improving the unfavorable gut microenvironment in cancer patients. A growing body of research focuses on the interaction between plant polysaccharides and the gut microbiota and their anti-tumor effects. However, in practical applications, the reported effects of plant polysaccharides on improving gut microbiota and fighting colorectal cancer are not yet ideal, and there is a lack of relevant basic research. Therefore, it is still necessary to seek a plant polysaccharide that can effectively improve gut microbiota and fight colorectal cancer, providing new ideas for the treatment of colorectal cancer.
[0004] Tremella fuciformis, the fruiting body of a fungus belonging to the Basidiomycetes phylum, is both an economically valuable edible fungus and a renowned medicinal herb in Traditional Chinese Medicine. The main active ingredient in the fruiting body of Tremella fuciformis is Tremella polysaccharide (TFPS). Related studies have shown that TFPS possesses anti-tumor, antioxidant, moisturizing, lipid-lowering, anti-inflammatory, and antibacterial functions, and can be applied in various fields such as pharmaceuticals, cosmetics, and food. However, the efficacy of TFPS against colorectal cancer has not yet been reported. Summary of the Invention
[0005] To address the problems existing in the prior art, the present invention aims to design and provide the application of Tremella fuciformis polysaccharide in the preparation of drugs for the treatment and / or prevention of colorectal cancer. Tremella fuciformis polysaccharide, by regulating the intestinal flora for the treatment or prevention of colorectal cancer, provides a potential new drug option for the treatment of colorectal cancer and also offers a novel application for Tremella fuciformis polysaccharide.
[0006] To achieve the above objectives, the present invention adopts the following technical solution:
[0007] On the one hand, the present invention provides the application of Tremella polysaccharide in the preparation of medicaments for treating and / or preventing intestinal diseases.
[0008] The aforementioned application states that the intestinal disease is related to the abundance of the probiotic Akkermansia myxotropicis or the metabolism of taurine.
[0009] The application in question refers to colorectal cancer.
[0010] Secondly, this invention provides the application of Tremella fuciformis polysaccharide in the preparation of products that regulate intestinal flora.
[0011] In the aforementioned application, the Tremella polysaccharide increases the abundance of the beneficial bacteria Akkermansia muciniphila in the intestine.
[0012] Thirdly, the present invention provides a medicament for treating and / or preventing intestinal diseases, comprising an active ingredient and pharmaceutically acceptable excipients;
[0013] The active ingredient is Tremella polysaccharide.
[0014] The drug is administered via injection, transdermal administration, oral administration, or rectal administration.
[0015] The drug is in the form of a solution, suspension, cream, ointment, gel, or solid dispersion.
[0016] Fourthly, the present invention provides a product for regulating intestinal flora, comprising an active ingredient and pharmaceutically acceptable excipients;
[0017] The active ingredient is Tremella polysaccharide.
[0018] Compared with existing technologies, the present invention has the following advantages:
[0019] This invention is the first to discover that Tremella fuciformis polysaccharide has a good therapeutic and alleviating effect on colorectal cancer. Tremella fuciformis polysaccharide can effectively alleviate weight loss and tumor burden in mice with colorectal cancer; improve the tumor immune microenvironment in mice with colorectal cancer, inhibit macrophage polarization towards the oncogenic M2 type; and effectively improve the intestinal microecology of mice with colorectal cancer, increasing the abundance of the probiotic Akkermansia muciniphila (Akk bacteria). All of the above indicate that Tremella fuciformis polysaccharide can effectively treat and / or prevent colorectal cancer. Therefore, Tremella fuciformis polysaccharide can be used to prepare drugs for the prevention and / or treatment of colorectal cancer, effectively improving the intestinal microecology and preventing the occurrence and development of colorectal cancer. Furthermore, this invention also explores the potential molecular mechanism of its action, providing a new approach for the application of Tremella fuciformis polysaccharide. Attached Figure Description
[0020] Figure 1 The statistical results of weight changes in different groups of mice;
[0021] Figure 2 Statistical results of the number and volume of colorectal tumors in different groups of mice;
[0022] Figure 3 The effects of Tremella fuciformis polysaccharide on the immune microenvironment of mice;
[0023] Figure 4 Metagenomic sequencing results of mouse feces;
[0024] Figure 5 The results are from a non-targeted metabolic analysis of mouse feces. Detailed Implementation
[0025] The present invention will be further described in detail below with reference to the accompanying drawings and specific embodiments. These embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Unless otherwise specified, the experimental methods used in the following embodiments are conventional methods; the materials and reagents used, unless otherwise specified, are commercially available.
[0026] Example 1: Construction and Experimental Setup of a Mouse Model of Colorectal Cancer
[0027] First, a colorectal cancer model was established using 20 six-week-old male C57BL / 6J mice. The mice were first given a single intraperitoneal injection of AOM (10 mg / kg), followed by one week of normal drinking water. Then, the mice were given drinking water containing 2% DSS for one week, and then returned to normal drinking water for two weeks, completing one cycle. This process was repeated three times. The AOM / DSS colorectal cancer mouse model was thus successfully established.
[0028] Subsequently, AOM / DSS colorectal cancer mice were randomly divided into two groups:
[0029] (1) Control group: Normal drinking water;
[0030] (2) Tremella polysaccharide group: A 1.25 mg / ml Tremella polysaccharide solution was prepared and used as drinking water for mice.
[0031] Among them, Tremella polysaccharide (TP) was purchased from Shanghai Macklin Biochemical Co., Ltd., item number T861210, CAS: 9075-53-0.
[0032] During the experiment, we continuously monitored the weight changes of mice in each group, and the results are as follows: Figure 1 As shown in the figure. Compared with the control group, the mice in the Tremella polysaccharide treatment group experienced a significantly reduced rate of weight loss, suggesting that Tremella polysaccharide helps alleviate tumor progression-related emaciation. Further direct assessment of tumor burden using tumor number and volume yielded the following results: Figure 2 As shown in the figure, compared with the control group, the number and volume of tumors in the mice treated with Tremella polysaccharide were significantly reduced.
[0033] Example 2:
[0034] This embodiment investigated the effects of Tremella fuciformis polysaccharide on the immune microenvironment of AOM / DSS model mice, as detailed below:
[0035] Tumor tissue separation in Example 1: Mouse tumors were dissected and immediately placed in a pre-cooled tissue preservation solution at 4°C; the tissues were then finely shredded into pieces <1 mm. 3 After fragmentation, the cells were mechanically disrupted using a tissue homogenizer and added to a preheated digestion solution containing type I / IV collagenase and DNase I at 37°C. The cells were then digested in a shaker at 37°C for 30-45 minutes (mixing by pipetting every 10 minutes during digestion). After digestion, the cells were passed through a 70μm filter to remove clumps and collected by centrifugation (400×g, 5 min, 4°C).
[0036] Flow cytometry analysis: (1) Fc receptor blocking: Incubate on ice for 15 minutes using anti-CD16 / 32 antibody (1:100 dilution); (2) Surface marker staining: Incubate at 4°C for 30 minutes with fluorescently labeled antibodies against target surface markers (such as CD11b, F4 / 80, MHCII, etc.) under light-protected conditions; (3) Intracellular staining: Fixation / permeabilization: Use BD Cytofix / Cytoperm TM Cells were treated with reagents for 20 minutes. Then CD206 fluorescently labeled antibody was added and incubated overnight at 4°C in the dark in cell permeabilization buffer. (4) Washing and loading: After staining, cells were washed with flow cytometry buffer, resuspended, and filtered through a 70 μm filter membrane before being analyzed. (5) Data analysis: After acquiring the data, the polarization ratio of macrophages was analyzed.
[0037] The results are as follows Figure 3 As shown, Tremella polysaccharide can significantly reduce the proportion of cancer-promoting M2 macrophages in the tumor microenvironment of mice.
[0038] Example 3: Effects of Tremella polysaccharides on intestinal microecology
[0039] Feces from the two groups of mice in Example 1 were collected and metagenomically sequenced. The results of the effect of Tremella fuciformis polysaccharide on the metagenomics of mouse gut microbiota are as follows: Figure 4 As shown in the figure. The results showed that, compared with the control group, the enrichment of probiotics such as Akkermansia muciniphila was significantly increased in the Tremella polysaccharide group. Akkermansia is a beneficial intestinal bacterium that gradually decreases as enteritis progresses. Supplementing with Akkermansia or its outer membrane protein Amuc_1100 can alleviate enteritis symptoms, regulate the immune response in the spleen, intestines, and mesenteric lymph nodes, and reduce the level of inflammation in the intestines.
[0040] Subsequently, we conducted further non-targeted metabolomics analysis. Specifically, fecal samples were collected from each group of mice, and metabolites were extracted using a pre-cooled methanol / water mixture. The metabolites were then detected using ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS / MS). The results of the effect of Tremella fuciformis polysaccharide on mouse fecal metabolites are as follows: Figure 5 As shown, the taurine level in the feces of mice treated with Tremella fuciformis polysaccharide was significantly increased. Previous studies have shown that taurine, as a sulfur-containing amino acid, plays an important role in regulating oxidative stress, maintaining bile acid metabolism balance, and improving the immune microenvironment. In particular, taurine can exert an inhibitory effect on tumor development and progression through mechanisms such as enhancing immune cell function.
[0041] Therefore, this invention provides that Tremella polysaccharide may improve the host's metabolic state and synergistically inhibit the occurrence and progression of colorectal tumors by upregulating taurine levels.
Claims
1. Application of Tremella polysaccharide in the preparation of drugs for the treatment and / or prevention of intestinal diseases.
2. The application as described in claim 1, characterized in that, The intestinal disease is related to the abundance of the probiotic Akkermansia muciniphila or the metabolism of taurine.
3. The application as described in claim 1, characterized in that, The intestinal disease mentioned is colorectal cancer.
4. Application of Tremella polysaccharide in the preparation of products that regulate intestinal flora.
5. The application as described in claim 4, characterized in that, The polysaccharide from Tremella fuciformis increases the abundance of the beneficial bacteria Akkermansia muciniphila in the gut.
6. A medicament for treating and / or preventing intestinal diseases, characterized in that, It consists of active ingredients and pharmaceutically acceptable excipients; The active ingredient is Tremella polysaccharide.
7. The drug as described in claim 6, characterized in that, The drug can be administered by injection, transdermal administration, oral administration, or rectal administration.
8. The drug as described in claim 6, characterized in that, The dosage form of the drug is solution, suspension, cream, ointment, gel, or solid dispersion.
9. A product for regulating intestinal flora, characterized in that, It consists of active ingredients and pharmaceutically acceptable excipients; The active ingredient is Tremella polysaccharide.