A polypeptide for improving ulcerative colitis

Abstract

The present invention discloses a polypeptide for improving ulcerative colitis. The polypeptide amino acid sequence is ATNIPFKVHFRCKAAFC, and is named Andersonin-W1. The polypeptide Andersonin-W1 provided by the present invention is a bioactive peptide derived from the Yunnan endemic amphibian, the Yunnan stinking frog. Experimental results show that the polypeptide Andersonin-W1 can significantly reduce the DAI score of mice with DSS colitis and alleviate the shortening of the colon length of mice with DSS colitis. It has a good improvement effect on ulcerative colitis, has certain drug research and development and clinical application value, and has opened up a new drug lead molecule for the research and development of ulcerative colitis drugs.

Description

Technical Field

[0001] The present invention belongs to the technical field of biomedicine, and particularly relates to a polypeptide for improving ulcerative colitis. Background Art

[0002] Ulcerative colitis (UC) is a chronic, idiopathic intestinal disease of unknown etiology that primarily affects the distal colon and rectum, often causing abdominal pain, diarrhea, and mucopurulent stools. UC has become a global disease, with high prevalence in developed countries and a significant increase in developing countries, posing a significant challenge to global health systems. UC is a complex disease that likely results from a complex interplay of genetic susceptibility and environmental triggers (including gut microbiota and dietary components), leading to immune system dysregulation and, in turn, chronic intestinal inflammation. While our understanding of the contributions of environmental exposures, genetics, and the gut microbiome to disease pathogenesis is increasing, the precise mechanisms of the disease remain unclear. Notably, if UC is not treated promptly, it can lead to persistent intestinal damage, increasing the risk of hospitalization, surgery, and colorectal cancer. Currently, treatments for UC primarily include aminosalicylic acid preparations, hormones, immunosuppressants, biologics, and small molecule drugs. Among them, aminosalicylic acid preparations are used for induction and maintenance of remission in mild to moderate UC, but their efficacy varies widely, and relapses are common during the maintenance period. Hormones are used only for induction of remission in moderate to severe patients and are not used for maintenance therapy. Many patients develop hormonal resistance or dependence, and their adverse effects are significant. Immunosuppressants are used for conversion therapy and maintenance of remission in steroid-resistant patients, but side effects such as bone marrow suppression, infection, tumors, and fertility impairment are unavoidable. Biologics not only carry risks of opportunistic infections, demyelination, and malignancy, but their extremely high price limits their widespread use in my country. Current drug therapies are inadequate to completely cure UC and are associated with adverse reactions. Furthermore, drug treatment is extremely expensive, leading to recurrent and prolonged disease, impoverishment, disability, and death, which can lead to reduced quality of life for patients and increased burden on families. This represents a critical medical and social issue that needs to be addressed. Therefore, the search for new treatment options has become a top priority.

[0003] Amphibians are considered a treasure trove for the development of peptide drugs, offering advantages such as high activity, selectivity, and stability. Numerous amphibian-derived peptide molecules with novel structures and unique functions have been discovered, including those with wound healing, hypoglycemic, antibacterial, analgesic, and antioxidant properties and activities. However, few studies have reported on active amphibian-derived peptides for the prevention and treatment of ulcerative colitis.

[0004] Yunnan stink frogs often inhabit moist mountain streams in forested areas at altitudes between 200 and 2060 meters. To adapt to this environment, their skin secretions contain a rich supply of bioactive peptides. This invention provides a peptide, Andersonin-W1, derived from Yunnan stink frogs, that has the potential to improve ulcerative colitis. Summary of the Invention

[0005] The purpose of the present invention is to provide a polypeptide Andersonin-W1 for improving ulcerative colitis.

[0006] The object of the present invention is achieved in that the polypeptide for improving ulcerative colitis has an amino acid sequence as shown in SEQ ID NO: 1: ATNIPFKVHFRCKAAFC.

[0007] The beneficial effects of the present invention are as follows: The peptide Andersonin-W1 provided herein is a bioactive peptide derived from the Yunnan stink frog and shares the common characteristics of amphibian-derived bioactive peptides: broad-spectrum action, strong activity, and a low resistance to drug resistance. The peptide Andersonin-W1 exhibits excellent activity in improving ulcerative colitis. Experimental results show that the peptide Andersonin-W1 can significantly reduce the DAI scores of mice with DSS colitis and alleviate the shortening of the colon length in these mice, demonstrating a significant improvement in ulcerative colitis. The peptide has considerable value in drug development and clinical application, opening up a new drug lead molecule for the development of ulcerative colitis drugs. BRIEF DESCRIPTION OF THE DRAWINGS

[0008] Figure 1 is the structural formula of the polypeptide Andersonin-W1 of the present invention;

[0009] Figure 2 Figure 2 is the DAI score result of DSS colitis mice in each group;

[0010] Figure 3 This figure shows the effect of the polypeptide Andersonin-W1 of the present invention on the colon length of DSS colitis mice;

[0011] Figure 4 This is a quantitative graph showing the effect of the polypeptide Andersonin-W1 of the present invention on the colon length of DSS colitis mice. DETAILED DESCRIPTION

[0012] The present invention will be further described in detail below with reference to the accompanying drawings and embodiments, but the present invention is not limited in any way. Any changes or improvements made based on the teachings of the present invention fall within the scope of protection of the present invention.

[0013] The present invention provides a polypeptide Andersonin-W1 for improving ulcerative colitis, the amino acid sequence of which is:

[0014] ATNIPFKVHFRCKAAFC, its structural formula is as follows Figure 1 shown.

[0015] The present invention also provides an application of the polypeptide Andersonin-W1, specifically an application in the preparation of a drug for preventing and treating ulcerative colitis or a drug for relieving intestinal mucosal inflammation.

[0016] The present invention further provides a pharmaceutical composition for preventing and treating ulcerative colitis, which comprises the active peptide Andersonin-W1 and a pharmaceutically relevant carrier thereof as a biologically active ingredient.

[0017] The present invention further provides a pharmaceutical composition for relieving intestinal mucosal inflammation, which comprises the active peptide Andersonin-W1 and a pharmaceutically relevant carrier thereof as a biologically active ingredient.

[0018] Example 1 Synthesis of polypeptide Andersonin-W1

[0019] The inventors have identified a series of tissue regeneration-promoting peptides from secretions of Yunnan stink frogs. Among them, the active peptide Andersonin-W1 has the amino acid sequence: ATNIPFKVHFRCKAAFC, and can be prepared by conventional chemical synthesis or gene expression.

[0020] The active peptide Andersonin-W1 of the present invention was synthesized by Wuhan Baiyixin Biotechnology Co., Ltd. according to the designed Andersonin-W1 structure ( Figure 1 ).

[0021] Example 2 Detection of the activity of the peptide Andersonin-W1 in alleviating enteritis in DSS mice

[0022] Experimental methods: Six C57BL / 6 male mice aged 6-8 weeks were randomly divided into a blank group (Control, PBS), a model group (DSS, PBS), a positive control group (Mesalazine (V Vifor AG ZweigniederlassungMedichemie Ettingen, H20150127, Switzerland)), a low-dose Andersonin-W1 group (10 nM), a medium-dose Andersonin-W1 group (100 nM), and a high-dose Andersonin-W1 group (1 uM).

[0023] Colitis mice were induced by freely drinking 2.5% DSS solution in all other groups except the blank group, which drank distilled water daily.

[0024] Starting from the second day of modeling, mice in the blank and modeling groups received a daily enema of 100 μL PBS. Mice in the treatment group received a daily enema of 0.008 mL / g mesalazine, while mice in the other groups received a daily enema of 100 μL of the corresponding drug. Starting from the first day of modeling, the body weight and stool characteristics of the mice were recorded at the same time every day, and fecal occult blood was tested using the o-benzidine method. Starting from the eighth day of modeling, mice were sacrificed by cervical dislocation, fixed on a foam board, and the abdominal cavity was opened. Starting from the steel tube, the entire colon was slowly freed, the lower end was severed from the anal canal, and the upper edge was severed from the ileocecal valve orifice. The length from the ileocecal valve to the anal canal was measured and photographed.

[0025] Results: As Figure 2 As shown, over time, different doses of Andersonin-W1 reduced the DAI score to varying degrees in a concentration-dependent manner. By the end of modeling on day 7, the DAI score in the high-dose Andersonin-W1 group was significantly lower than that in the DSS group. Furthermore, the DAI scores in all Andersonin-W1 dose groups were lower than those in the positive control group, demonstrating that the Andersonin-W1 polypeptide of the present invention can significantly alleviate intestinal mucosal inflammation in ulcerative colitis.

[0026] like Figure 3 、 4 As shown, the colon length of the treatment group (Andersonin-W1) recovered compared to the DSS group in a concentration-dependent manner. The high-dose group (P < 0.0001) and the medium-dose group (P < 0.05) showed statistically significant differences compared to the model group, and were significantly longer than the model group and better than the positive control group, indicating that the polypeptide of this invention can significantly prolong the colon length of mice with ulcerative colitis, and its effect is superior to that of the positive drug Mesalazine.

[0027] In summary, the polypeptide Andersonin-W1 provided by the present invention has a good improvement effect on ulcerative colitis and has certain value in drug development and clinical application.

Claims

1. Use of a polypeptide Andersonin-W1 in the preparation of a drug for preventing and treating ulcerative colitis, wherein the amino acid sequence of the polypeptide Andersonin-W1 is ATNIPFKVHFRCKAAFC and its structural formula is shown in Formula I: I。

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