Application of cyanidin-3,5-O-diglucoside in the preparation of drugs for treating colitis and colonic fibrosis

Abstract

The present invention discloses the application of cyanidin-3,5-O-diglucoside in the preparation of a drug for treating colitis and colonic fibrosis. The present invention has found that after treatment with cyanidin-3,5-O-diglucoside, the clinical symptoms of colitis and colonic pathological damage can be improved, the level of inflammatory factors in serum of chronic colitis induced by DSS can be reduced, the intestinal epithelial permeability can be reduced and the mucosal barrier damage can be repaired, the level of oxidative stress in the body of colitis can be improved, and the degree of colonic fibrosis can be reduced, and the normal function of the colon can be protected. Compared with the therapeutic effect of the positive drug 5-aminosalicylic acid, there is no significant difference in multiple indicators, and cyanidin-3,5-O-diglucoside has higher safety and lower side effects.

Description

Technical Field

[0001] The invention relates to the technical field of biopharmaceuticals, and in particular to application of cyanidin-3,5-O-diglucoside in preparing a drug for treating colitis and colon fibrosis. Background Art

[0002] Inflammatory bowel disease (IBD) is a chronic, nonspecific disease with a lifelong tendency to relapse. Ulcerative colitis (UC) is an important subtype of IBD. In recent decades, with the development of the economy and the continuous improvement of diagnostic capabilities, the incidence of IBD has gradually increased. Colonic fibrosis is one of the serious complications of colitis. Colonic fibrosis has symptoms such as narrowing of the lumen and stiffness of the intestinal wall after intestinal tissue remodeling, which in turn leads to colonic motility disorders and incontinence, which can easily cause physical and mental burdens on patients and seriously affect their quality of life. Summary of the invention

[0003] The purpose of the present invention is to provide an application of cyanidin-3,5-O-diglucoside in the preparation of a drug for treating colitis and colon fibrosis.

[0004] In order to achieve the above-mentioned object of the invention, the technical solution adopted by the present invention is:

[0005] Provided is the use of cyanidin-3,5-O-diglucoside in the preparation of a drug for treating colitis and colon fibrosis. The structural formula of cyanidin-3,5-O-diglucoside is as follows:

[0006]

[0007] The beneficial effects of the present invention are:

[0008] The present invention found that treatment with cyanidin-3,5-O-diglucoside can improve the clinical symptoms of colitis and colon pathological damage, reduce the level of inflammatory factors in the serum of DSS-induced chronic colitis, reduce intestinal epithelial permeability and repair mucosal barrier damage, improve the level of oxidative stress in colitis, reduce the degree of colon fibrosis, and protect the normal function of the colon. Compared with the therapeutic effect of the positive drug 5-aminosalicylic acid, there is no significant difference in many indicators, and cyanidin-3,5-O-diglucoside has higher safety and lower side effects. BRIEF DESCRIPTION OF THE DRAWINGS

[0009] Figure 1Effects of cyanidin-3,5-O-diglucoside on clinical symptoms and colon pathological damage in colitis mice; A. Body weight; B. DAI score; C. Colon length; D. Ratio of colon mass to length; E. Colon HE staining (different letters above the horizontal bar indicate significant differences between the two groups, P<0.05);

[0010] Figure 2 Effects of cyanidin-3,5-O-diglucoside on serum inflammatory factor levels in colitis mice; A. Interleukin-1β (IL-1β); B. Interleukin-6 (IL-6); C. Interleukin-17A (IL-17A); D. Interleukin-18 (IL-18); E. Tumor necrosis factor-α (TNF-α) level (different letters above the horizontal bar indicate significant differences between the two groups, P<0.05);

[0011] Figure 3 Effects of cyanidin-3,5-O-diglucoside on tight junction proteins in the colon of colitis mice; A. Immunohistochemistry (tight junction proteins Zo1, Claudinl and Occludin); B. mRNA levels of tight junction proteins (Zo1, Claudinl and Occludin) in the colon (different letters above the horizontal bar indicate significant differences between the two groups, P<0.05);

[0012] Figure 4 Effects of cyanidin-3,5-O-diglucoside on oxidative stress-related factors in serum and colon of colitis mice; AC. Oxidative stress indicators (SOD, MDA and CAT) in serum; DG. mRNA levels of antioxidant enzymes (Sod1, Sod2, Cat and Mgst1) in colon (different letters above the horizontal bar indicate significant differences between the two groups, P<0.05);

[0013] Figure 5 Effects of cyanidin-3,5-O-diglucoside on colon fibrosis in mice with colitis; A. Masson staining of colon tissue; B. Immunohistochemistry of colon tissue (α-SMA and Collagen I). DETAILED DESCRIPTION

[0014] The specific implementation modes of the present invention are described below so that those skilled in the art can understand the present invention. However, it should be clear that the present invention is not limited to the scope of the specific implementation modes. For those of ordinary skill in the art, as long as various changes are within the spirit and scope of the present invention as defined and determined by the attached claims, these changes are obvious, and all inventions and creations utilizing the concept of the present invention are protected.

[0015] Example

[0016] The colitis mouse model was established by circulating drinking water containing 2.5% DSS, and different doses of cyanidin-3,5-O-diglucoside were administered orally for intervention. The clinical disease index (DAI) of the mice was calculated during the intervention. After the intervention, the mice were weighed, and the superior vena cava blood was taken from the mice in each group after anesthesia to separate the serum to detect the levels of inflammatory factors and oxidative stress. The length and mass of the mouse colon were measured, and a small section of the colon was fixed for sectioning and HE staining, Masson staining and immunohistochemistry. The remaining colon tissue was used to detect the gene expression levels of proinflammatory cytokines, tight junction proteins and antioxidant enzymes by real-time fluorescence quantitative PCR.

[0017] The present invention provides cyanidin-3,5-O-diglucoside which can be used for the treatment of colitis and colonic fibrosis, which is suitable for oral administration and the course of treatment is 2 weeks. Cyanidin-3,5-O-diglucoside can improve the clinical symptoms of colitis, improve colon pathological damage, reduce the level of inflammatory factors in the serum of DSS-induced chronic colitis, reduce intestinal epithelial permeability and repair mucosal barrier damage, improve the level of oxidative stress in the body of colitis, reduce the degree of colonic fibrosis in colitis, and protect the normal function of the colon. The cyanidin-3,5-O-diglucoside used in this example is derived from Santa Cruz Biotechnology, Inc. (product introduction https: / / www.scbt.com / p / cyanin-chloride-2611-67-8?requestFrom=search).

[0018] In this embodiment, improving the clinical symptoms of colitis refers to improving the clinical symptoms of weight loss, colon shortening, decreased ratio of colon weight to length, and high DAI index score in colitis mice. Improving colon pathological damage means that cyanidin-3,5-O-diglucoside intervention can reduce the infiltration of inflammatory cells in colon tissue induced by DSS treatment, alleviate the occurrence of intestinal epithelial tissue damage caused by inflammation, reduce mucosal damage, crypt structure loss, and improve the symptoms of reduced goblet cells in colon mucosa induced by DSS ( Figure 1 ). Reducing the level of inflammatory factors in the serum of mice with chronic colitis induced by DSS refers to reducing the levels of inflammatory factors IL-1β, IL-6, IL-17A, IL-18 and TNF-α in the serum of mice with colitis ( Figure 2 ). Reducing intestinal epithelial permeability and repairing mucosal barrier damage refers to increasing the expression of tight junction proteins Zo1, Claudinl and Occludin in colon tissue, and the same results are also seen in mRNA expression ( Figure 3). The effect of cyanidin-3,5-O-diglucoside on improving the oxidative stress level in colitis mice is to increase the levels of SOD and CAT in the serum of colitis mice, and to reduce the levels of MDA in the serum and the mRNA expression levels of antioxidant enzymes (Sod1, Sod2, Cat and Mgst1) in the colon ( Figure 4 ). Cyanidin-3,5-O-diglucoside reduced the degree of colon fibrosis in colitis mice, which means that collagen deposition in the colon was reduced and the expression levels of α-SMA and CollagenI in the colon were reduced ( Figure 5 ).

[0019] The present study found that treatment with cyanidin-3,5-O-diglucoside can improve the clinical symptoms and colon pathological damage of colitis mice, reduce the level of inflammatory factors in the serum of DSS-induced chronic colitis mice, reduce intestinal epithelial permeability and repair mucosal barrier damage, improve the level of oxidative stress in colitis mice, reduce the degree of colon fibrosis, and protect the normal function of the colon. Compared with the therapeutic effect of the positive drug 5-aminosalicylic acid, there is no significant difference in many indicators.

[0020] It will be apparent to those skilled in the art that the present invention is not limited to the details of the exemplary embodiments described above, and that the present invention can be implemented in other specific forms without departing from the spirit or essential features of the present invention. Therefore, the embodiments should be considered exemplary and non-restrictive in all respects, and the scope of the present invention is defined by the appended claims rather than the above description, and it is intended that all changes falling within the meaning and scope of the equivalent elements of the claims be included in the present invention.

[0021] In addition, it should be understood that although the present specification is described according to implementation modes, not every implementation mode contains only one independent technical solution. This description of the specification is only for the sake of clarity. Those skilled in the art should regard the specification as a whole. The technical solutions in each embodiment may also be appropriately combined to form other implementation modes that can be understood by those skilled in the art.

Claims

1. Application of cyanidin-3,5-O-diglucoside as the sole active ingredient in the preparation of drugs for the treatment of colitis and colon fibrosis.

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