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Application of ellagic acid and metabolic derivative urolithin compound thereof in preparation of immunoregulation medicine

A technology of immune regulation and urolithin, applied in the field of biomedicine, can solve the problems of toxic side effects, high cost, and scarce drug sources, etc., and achieve the effect of restoring the length of the colon, delaying the occurrence and development, and relieving the symptoms of blood in the stool

Inactive Publication Date: 2021-05-28
SHAANXI NORMAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although first-line drugs such as cyclosporine A (CsA), fingolimod (FTY-720), and cyclophosphamide (CTX) have been developed in recent years, these drugs such as fingolimod are scarce and expensive; Bacterin and cyclophosphamide have extensive immunosuppressive effects, which are easy to cause various toxic side effects and complications.

Method used

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  • Application of ellagic acid and metabolic derivative urolithin compound thereof in preparation of immunoregulation medicine
  • Application of ellagic acid and metabolic derivative urolithin compound thereof in preparation of immunoregulation medicine
  • Application of ellagic acid and metabolic derivative urolithin compound thereof in preparation of immunoregulation medicine

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0044] Effects of EA and its representative derivative URA on Th17 and Treg polarization in vitro.

[0045] 1. Experimental Treatment

[0046] The single cell suspension of the spleen of normal female C57BL / 6 mice (8-10 weeks) was mixed with anti-CD3 (0.5μg / mL), anti-CD28 (1μg / mL), TGF-β (2ng / mL), IL-6 (20ng / mL), IL-1β (10ng / mL), anti-IL-4 (10μg / mL) and anti-IFN-γ (10μg / mL) were co-cultured for 3 days to induce differentiation into Th17 cells ; co-culture with anti-CD3 (0.5 μg / mL), anti-CD28 (1 μg / mL), TGF-β (2ng / mL), IL-2 (10ng / mL) for 3 days to induce differentiation into Treg cells, Cytokines were detected by flow cytometry.

[0047] Total RNA was isolated using RNAprep Pure Cell / Tissue kit (TIANGEN) and reverse transcribed with HiScript QRT Supermix (Vazyme) according to the manufacturer's instructions. Using 2×ChamQTM qPCR Master Mix (Vazyme) measures mRNA expression by real-time PCR. Data were quantified on Roche Molecular Biochemicals Light Cycler Software Version...

Embodiment 2

[0055] Administration of ellagic acid and its metabolic derivative urolithin A at different stages relieves central inflammation in EAE mice.

[0056] 1. Experimental treatment

[0057] Female C57BL / 6 mice aged 8-12 weeks were purchased from Air Force Military Medical University (Xi'an, China). Mice were fed under standard light and temperature conditions, and all experimental procedures and protocols were approved by the Institutional Animal Care and Use Committee of Shaanxi Normal University and performed in accordance with approved institutional guidelines and regulations.

[0058] The EAE mice were randomly divided into EA group and URA group, wherein the EA group was blank control group, fingolimod positive control group (0.1mg / kg) and EA administration group (0.1 / mg / kg), URA group Divided into blank control group and URA administration group (25mg / kg). To induce EAE, 200 μL of myelin oligodendrocyte glycoprotein peptide (MOG 35-55 ), 50% volume complete Freund's adjuv...

Embodiment 3

[0071] Ellagic acid alleviates inflammatory response and restores colon length in colitis mice.

[0072] 1. Experimental treatment

[0073] The mice were randomly assigned to the control group and the EA treatment group, and 2.5% (w / v) DSS (dextran sodium sulfate) was added to the drinking water of the two groups of mice, and the treatment group was given EA 100mg / kg / d orally at the same time, and fed continuously Acute colitis was induced in mice by feeding for 7 days. During the modeling period, the body weight of the mice was weighed regularly every day and the percentage of change was calculated. In addition, the feces properties of the mice were observed daily, and they were divided into three grades according to the method of Berberat et al.: first, the feces of normal mice were shaped and granular; second, the feces were viscous and loose, but It is "loose" if it does not adhere to the anus; third, the stool is watery or shapeless and adheres to the anus, which is "lo...

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Abstract

The invention belongs to the technical field of biological medicines, and relates to an application of ellagic acid and a metabolic derivative urolithin compound thereof in preparation of medicines for treating autoimmune diseases and immunological rejection after organ / tissue transplantation. The invention takes classic animal models related to autoimmunity and immunoregulation, namely experimental autoimmune encephalomyelitis, ulcerative colitis and skin transplantation as examples. The multi-angle experiments in multiple aspects such as nerve function score, lesion tissue pathology change, inflammatory factor expression, pro-inflammatory cell number and the like prove that the ellagic acid and the metabolic derivative thereof remarkably relieve the degree of experimental autoimmune encephalomyelitis disease and inhibit infiltration of inflammatory cells to the center; the pathological state of ulcerative colitis is obviously improved, and the colon length is recovered; the inflammatory cell infiltration of the skin graft in a skin transplantation model can be inhibited, the regulatory T cell proportion can be up-regulated, the immune tolerance can be enhanced, and the clinical application value and the development prospect are relatively high.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and relates to the application of ellagic acid and its metabolic derivative urolithin compounds in the preparation of immunoregulatory drugs, especially in the preparation of drugs for the treatment of autoimmune diseases and immune rejection after organ / tissue transplantation in the application. Background technique [0002] Immunomodulator (Immunomodulator) is a class of drugs that can regulate the function of the immune system, by enhancing or inhibiting the function of cells (T lymphocytes, B lymphocytes, macrophages, etc.) Play a therapeutic role. Immunomodulators are mainly used for organ transplantation anti-rejection and autoimmune diseases such as rheumatoid arthritis (Rheumatoid arthritis, RA), systemic lupus erythematosus (Systemic Lupus Erythematosus, SLE), vitiligo (Vitiligo), psoriasis (Psoriasis) , inflammatory bowel disease (Inflammatory Bowel Disease, IBD), graft-versus-hos...

Claims

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Application Information

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IPC IPC(8): A61K31/366A61K31/37A61P37/06
CPCA61K31/366A61K31/37A61P37/06
Inventor 张媛邢琨李星申沛鑫赵莉
Owner SHAANXI NORMAL UNIV
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