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Application of 5-aminolevulinic acid in preparation of product for preventing and treating inflammatory bowel disease

A technology of aminolevulinic acid and inflammatory bowel disease, which is applied in the field of application of 5-aminolevulinic acid in the preparation of products for the prevention and treatment of inflammatory bowel disease, and can solve the problems that have not yet been related to 5-aminolevulinic acid. To achieve the effect of alleviating inflammatory bowel disease

Pending Publication Date: 2022-03-22
THE THIRD XIANGYA HOSPITAL OF CENT SOUTH UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] There is no report on the relationship between 5-aminolevulinic acid and inflammatory bowel disease

Method used

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  • Application of 5-aminolevulinic acid in preparation of product for preventing and treating inflammatory bowel disease
  • Application of 5-aminolevulinic acid in preparation of product for preventing and treating inflammatory bowel disease

Examples

Experimental program
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Effect test

Embodiment 1

[0026] Six-week-old C57BL / 6 mice were used to establish an experimental colitis model with DSS. Intervention by intragastric administration of 5-ALA, once a day for 7 days, divided into three dose groups, among which the high dose group (HD) was 200mg / kg, the middle dose group (MD) was 100mg / kg, and the low dose group (LD) was 50mg / kg. The mice that were not treated with DSS were used as the blank control group (control group), and the colitis model mice that were not given 5-ALA intragastric intervention were used as the negative control group (DSS group). The colon length, body weight, disease, and intestinal mucosal changes of the five groups of mice were counted, and the results were as follows: figure 1 shown.

[0027] Depend on figure 1 It can be seen that after the intervention of 5-ALA intragastric administration in the middle dose group and the high dose group, the degree of shortening of the mouse colon was alleviated (pfigure 1 A-B), symptoms such as weight loss...

Embodiment 2

[0029] Intestinal tissues of mice in the control group, DSS group and 5-ALA high-dose intervention group in Example 1 were extracted for RNA-seq sequencing research. The results are shown in Table 1. Compared with mice with experimental colitis, the most significantly different Hub genes in the intestinal tissue of mice with experimental colitis administered 5-ALA include: Stat1, Irf7, Ifit3, Oasl2, Usp18, Rsad2, Isg15, Rtp4, Psmb8, Gbp2, these differential genes are important factors in the interferon-γ signaling pathway, which were all increased in intestinal tissue of mice with enteritis, but decreased after 5-ALA intervention.

[0030] Table 1 RNA-seq sequencing results

[0031] gene name LogFC value of 5-ALA intervention group v.s.DSS group Stat1 -1.891525777 Irf7 -3.122429087 Ifit3 -3.529132031 Oasl2 -3.650766538 Usp18 -2.411050953 Rsad2 -1.836606601 Isg15 -4.20883179 Rtp4 -2.46127824 Psmb8 -1.85042157 ...

Embodiment 3

[0033] Human normal intestinal epithelial cells NCM46024h were intervened with human recombinant IFN-γ at a final concentration of 20ng / mL to create a cell inflammation model, and at the same time intervened with 5-ALA, divided into 5 groups: Control, IFN-γ, IFN-γ+ALA (5mM ), IFN-γ+ALA (10mM), IFN-γ+ALA (20mM). The expression levels of Stat1, Irf7, Ifit3, Oasl2, Usp18, Rsad2, Isg15, Rtp4, Psmb8, and Gbp2 genes were detected in each group, and the results were as follows: figure 2 shown.

[0034] Depend on figure 2 It can be seen that after the intervention of 5-ALA with a final concentration of 20mM, Stat1, Irf7, Ifit3, Oasl2, Usp18, Rsad2, Isg15, Rtp4, Psmb8, Gbp2 and other genes were significantly decreased, proving that 5-ALA intervention can reduce the interferon pathway levels of related genes.

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Abstract

The invention provides application of 5-aminolevulinic acid in preparation of products for preventing and treating inflammatory bowel diseases, and belongs to the technical field of prevention and treatment of the inflammatory bowel diseases. Animal experiments and cell experiments show that 5-aminolevulinic acid can prevent and treat inflammatory bowel diseases by inhibiting interferon signal channels for the first time. Mouse experimental colitis model verification shows that after middle-dose group and high-dose group 5-aminolevulinic acid gavage intervention, the mouse colon shortening degree is reduced, the body weight is reduced, symptoms such as diarrhea and bloody stool are relieved, the disease activity index is reduced, HE staining shows that pathological characteristics such as intestinal mucosa structure damage and inflammatory cell infiltration degree are relieved, and the effect of treating colitis is achieved. The 5-ALA is prompted to be capable of relieving inflammation and intestinal mucosa injury of experimental colitis mice.

Description

technical field [0001] The invention belongs to the technical field of prevention and treatment of inflammatory bowel disease, and in particular relates to the application of 5-aminolevulinic acid in the preparation of products for the prevention and treatment of inflammatory bowel disease. Background technique [0002] Inflammatory bowel disease (IBD) is a group of chronic intestinal inflammatory diseases, including ulcerative colon (UC) and Crohn's disease (CD), with poor drug efficacy and high disability rate, which has a significant impact on the quality of life of patients. The etiology of IBD is unknown and is the result of a combination of genetics, environment, and gut microbes. For inflammatory bowel disease, there is currently no curative therapy, and most relapses and relapses occur repeatedly, so long-term medical management is required. [0003] The gut metabolome acts as a bridge connecting the host and gut microbes, exerts important and diverse effects on hos...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/197A23L33/10A61P1/00
CPCA61K31/197A61P1/00A23L33/10A23V2002/00A23V2200/32
Inventor 王晓艳马可嘉邓敏子张超廖洋洁杨燕
Owner THE THIRD XIANGYA HOSPITAL OF CENT SOUTH UNIV
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