Polypeptide for improving ulcerative colitis

Abstract

The invention discloses a polypeptide for improving ulcerative colitis. The amino acid sequence of the polypeptide is ATNIPFKVHFRCKAAFC, the polypeptide is named as Andersonin-W1, and the polypeptide Andersonin-W1 provided by the invention is a bioactive peptide derived from a specific amphibian odorrana yunnanensis in Yunnan. Experimental results show that the polypeptide Andersonin-W1 can significantly reduce the DAI score of a mouse with DSS colitis and relieve shortening of the colon length of the mouse with DSS colitis, has a good improvement effect on ulcerative colitis, has certain drug research and development and clinical application values, and opens up a new drug lead molecule for research and development of ulcerative colitis drugs.

Description

Technical Field

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

[0002] Ulcerative colitis (UC) is a chronic idiopathic intestinal disease of unknown etiology, mainly affecting the colon and distal rectum, often causing abdominal pain, diarrhea, and mucopurulent stools. Today, UC has become a global disease, with high incidence in developed countries and a significant increase in developing countries, posing a huge challenge to the global health system. UC is a complex disease that may be caused by a complex interaction of genetic susceptibility and environmental triggers (including intestinal flora and dietary components) leading to immune system dysregulation, which in turn leads to chronic intestinal inflammation. Although there is an increasing understanding of the contribution of environmental exposure, genetics, and the intestinal microbiome to the occurrence of the disease, the exact mechanism of the disease remains unclear. It is worth noting that if UC is not treated in time, it will lead to persistent intestinal damage, thereby increasing the risk of hospitalization, surgery, and colorectal cancer. At present, the treatment drugs for UC mainly include aminosalicylic acid preparations, hormones, immunosuppressants, biologics, and small molecule drugs. Among them, aminosalicylic acid preparations are used for induction remission and maintenance treatment of mild and moderate UC, but the efficacy varies greatly and relapse is easy during the maintenance period; hormones are only used for induction remission in moderate and severe patients and cannot be used for maintenance treatment. Many patients have hormone resistance or hormone dependence, and their adverse reactions cannot be ignored; immunosuppressants are used for conversion treatment and maintenance remission of hormone-resistant patients, but side effects such as bone marrow suppression, infection, tumors, and fertility effects are unavoidable problems; biological agents not only have risks such as opportunistic infection, nerve demyelination and malignant tumors, but also their extremely high prices limit their widespread use in my country. Today's drug treatments are difficult to completely treat UC and all have adverse reactions. In addition, drug treatments are very expensive, resulting in repeated recurrences and prolonged illness. Poverty, disability, and death due to illness occur from time to time, reducing the quality of life of patients and increasing the burden on families. It is an urgent disease to be conquered and a social problem to be solved. Therefore, finding new treatment approaches has become a top priority.

[0003] Amphibians are considered to be a treasure trove for the development of peptide drugs, with advantages such as high activity, high selectivity, and high stability. A variety of amphibian-derived peptide molecules with novel structures and unique functions have been discovered, including peptides with wound healing, hypoglycemic, antibacterial, analgesic and antioxidant properties and activities. However, there are few reports on active peptides derived from amphibians in the prevention and treatment of ulcerative colitis.

[0004] Yunnan stink frogs often live in relatively humid mountain streams in forest areas at an altitude of 200-2060 m. In order to adapt to the living environment, their skin secretions contain rich bioactive peptides. The present invention aims to provide a polypeptide Andersonin-W1 derived from Yunnan stink frogs that has the activity of improving ulcerative colitis. Summary of the invention

[0005] The object 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 polypeptide Andersonin-W1 provided by the present invention is a bioactive peptide derived from Yunnan stink frog, and has the common characteristics of bioactive peptides derived from amphibians: broad-spectrum action, strong activity, and not easy to produce drug resistance. The polypeptide Andersonin-W1 has excellent activity in improving ulcerative colitis. Experimental results show that the polypeptide Andersonin-W1 can significantly reduce the DAI score of DSS colitis mice, alleviate the shortening of the colon length of DSS colitis mice, and has a good improvement effect on ulcerative colitis. It 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. BRIEF DESCRIPTION OF THE DRAWINGS

[0008] Figure 1 is the structural formula of the polypeptide Andersonin-W1 of the present invention; Figure 2 The DAI score results of each group of DSS colitis mice are shown in the figure; Figure 3 This is a graph showing the effect of the polypeptide Andersonin-W1 of the present invention on the colon length of DSS colitis mice; 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

[0009] The present invention will be further described in detail below in conjunction with 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 protection scope of the present invention.

[0010] The present invention provides a polypeptide Andersonin-W1 for improving ulcerative colitis, and its amino acid sequence is: ATNIPFKVHFRCKAAFC, its structural formula is as follows Figure 1 shown.

[0011] 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.

[0012] The present invention further provides a pharmaceutical composition for preventing and treating ulcerative colitis, which comprises the active peptide Andersonin-W1 as a biologically active ingredient and a pharmaceutically relevant carrier thereof.

[0013] 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.

[0014] Example 1 Synthesis of Peptide Andersonin-W1 The inventors have identified a series of active peptides that promote tissue regeneration from secretions of Yunnan stink frogs, among which the amino acid sequence of the active peptide Andersonin-W1 is ATNIPFKVHFRCKAAFC, which can be prepared by conventional chemical synthesis or gene expression.

[0015] 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 ).

[0016] Example 2 Detection of the activity of peptide Andersonin-W1 in alleviating enteritis in DSS mice 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)), Andersonin-W1 low-dose group (10 nM), Andersonin-W1 medium-dose group (100 nM) and Andersonin-W1 high-dose group (1 uM).

[0017] Except for the blank group, the other groups were allowed to freely drink 2.5% DSS solution to establish colitis mouse models. The blank group drank distilled water every day.

[0018] From the second day of mouse modeling, mice in the blank group and modeling group were enemaed with 100uL PBS once a day. Mice in the treatment group were enemaed with 0.008mL / g Mesalazine once a day, and mice in other groups were enemaed with 100uL of the corresponding drugs once a day. From the first day of modeling, the weight and stool characteristics of mice were recorded at the same time every day, and fecal occult blood test was performed by o-benzidine method. From the eighth day of mouse modeling, mice were killed by cervical dislocation, fixed on foam boards, opened the abdominal cavity, and slowly freed the complete colon from the steel pipe, the lower end was cut off from the anal canal, and the upper edge was cut off from the ileocecal valve orifice. The length from the ileocecal valve to the anal canal was measured and photographed and recorded.

[0019] Results: Figure 2 As shown, with the increase of treatment time, different doses of Andersonin-W1 reduced the DAI score to varying degrees, and it was concentration-dependent. At the end of the modeling on the 7th day, the DAI score of the Andersonin-W1 high-dose group was significantly lower than that of the DSS group, and the DAI scores of the Andersonin-W1 different dose groups were all lower than those of the positive control group, indicating that the polypeptide Andersonin-W1 of the present invention can significantly alleviate the intestinal mucosal inflammation of ulcerative colitis.

[0020] like Figure 3 , 4 As shown, the colon length of the treatment group (Andersonin-W1) recovered compared with the DSS group, and was concentration-dependent. The high-dose group (P < 0.0001) and the medium-dose group (P < 0.05) were statistically significantly different from the modeling group, significantly longer than the modeling group and better than the positive control group, indicating that the polypeptide of the present invention can significantly prolong the colon length of mice with ulcerative colitis, and the effect is better than the positive drug Mesalazine.

[0021] 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. A polypeptide Andersonin-W1 for improving ulcerative colitis, whose amino acid sequence is ATNIPFKVHFRCKAAFC and whose structural formula is shown in Formula I:

2. Use of the polypeptide Andersonin-W1 according to claim 1 in the preparation of drugs for preventing and treating ulcerative colitis.

3. Use of the polypeptide Andersonin-W1 according to claim 1 in the preparation of a drug for alleviating intestinal mucosal inflammation.

4. A pharmaceutical composition for preventing and treating ulcerative colitis, comprising the polypeptide Andersonin-W1 according to claim 1 and a pharmaceutically relevant carrier thereof as a biologically active ingredient.

5. A pharmaceutical composition for relieving intestinal mucosal inflammation, comprising the polypeptide Andersonin-W1 according to claim 1 and a pharmaceutically relevant carrier thereof as a biologically active ingredient.

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