Application of ellagic acid and metabolites thereof as natural inhibitors to preparation of anti-pyroptosis medicine

A technology of ellagic acid and inhibitors, which is applied in the application field of preparing anti-pyroptotic drugs, and can solve problems such as the lack of natural drugs

Pending Publication Date: 2021-04-20
XINJIANG MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, so far no natural medicines have been reported as GSDMD, GSDME inhibitors

Method used

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  • Application of ellagic acid and metabolites thereof as natural inhibitors to preparation of anti-pyroptosis medicine
  • Application of ellagic acid and metabolites thereof as natural inhibitors to preparation of anti-pyroptosis medicine
  • Application of ellagic acid and metabolites thereof as natural inhibitors to preparation of anti-pyroptosis medicine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] Example 1 Application of ellagic acid and its metabolites as natural inhibitors in the protection of pancreatic cell inflammation

[0044] 1.1 Experimental animals

[0045] 10-week-old c57BL / 6 male mice of SPF grade, weighing 24±2 g, were purchased from the Animal Center of Xinjiang Medical University (animal license number: SYXK (new) 2016-0002).

[0046] 1.2 Experimental materials

[0047] Ordinary feed was purchased from the Animal Experiment Center of Xinjiang Medical University; high-fat feed was purchased from Nantong Trofe Feed Co., Ltd.; STZ was purchased from Sigma Biological Co., Ltd.; EA was purchased from Shanghai Macklin Biochemical Technology Co., Ltd. (purity ≥ 98%); UroA Purchased from Shanghai Zhenzhun Biological Co., Ltd. (purity ≥ 98%); Glucagon (GC) ELISA detection kit, C-reactive protein (CRP) ELISA detection kit, both purchased from Shanghai Sibobestbio Biotechnology Co., Ltd.; NLRP3 , cleaved-caspase3 (cleaved-caspase3), IL-1β antibody, caspase1...

Embodiment 2

[0083] Example 2 Application of ellagic acid and its metabolites as natural inhibitors in the protection of liver cell inflammation

[0084] 1. Materials and methods

[0085] Experimental animals, experimental materials, animal model preparation, animal administration, hematoxylin-eosin staining to observe the pathological structure of mouse liver tissue refer to 1.1, 1.2, 1.3, 1.4, 1.6 of Example 1, respectively.

[0086] After the animal administration experiment, the mouse liver tissue was taken, and the appearance was photographed, see Figure 4 , Figure 4 a-d are Normal group, Model group, EA group and UroA group respectively. The results showed that the livers of the mice in the Normal group were fresh and pink; the mice in the Model group showed white ischemia and high fat content; the liver color of the mice in the EA group was significantly improved and turned pink; the liver appearance of the mice in the UroA group was significantly improved and turned pink. colo...

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Abstract

The invention belongs to the technical field of biological medicines, and particularly relates to an application of ellagic acid and metabolites thereof as natural inhibitors to preparation of an anti-pyroptosis medicine. The inventor finds that high glycolipid has a promotion effect on pyroptosis of pancreatic cells and liver cells, and expression levels of pyroptosis proteins GSDMD and GSDME in a pyroptosis signal path are increased, which indicates that pyroptosis plays a role in high-glucose and high-fat induced pancreatic and liver inflammatory reactions. GSDMD and GSDME mediated pyroptosis participates in diabetes pancreas and liver injury. It is found for the first time that the ellagic acid and intestinal tract metabolite uridine A thereof can inhibit GSDMD and GSDME mediated pyroptosis in an in-vivo experiment of a diabetic model mouse, and therefore, an anti-inflammatory protection effect on cells is achieved.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and specifically relates to the application of ellagic acid and its metabolites as natural inhibitors in the preparation of anti-pyroptotic drugs. Background technique [0002] Pyroptosis is a newly discovered mode of programmed cell death. After the inflammasome is activated, it cuts caspase-1 / 4 / 5 / 11, and the mature caspase acts on gasdermin D (GSDMD) to form GSDMD-N terminal will form holes in the cell membrane through oligomerization, resulting in water inflow, the ion gradient inside and outside the cell membrane disappears, cell swelling, osmotic dissolution, and finally rupture and death. [0003] More and more studies have found that after pyroptosis of cells, the cell membrane will form holes, and the cells will gradually expand until the cell membrane ruptures, which will eventually lead to the release of a large number of inflammatory mediators in the cells, accelerate the inflamma...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/366A61P3/10A61P1/16A61P1/18
Inventor 张之古丽海夏田林霭田亚丽
Owner XINJIANG MEDICAL UNIV
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