Application of glycyrrhizic acid to prepare drugs for promoting medullary sheath regeneration to restrain neurogenic inflammation

A technology of remyelination and neuroinflammation, applied in the new application field of glycyrrhizic acid in pharmaceuticals, can solve important problems to be studied and other problems

Inactive Publication Date: 2019-03-29
SHAANXI NORMAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although these findings suggest that GA may also be beneficial in autoimmune diseases such as MS, important questions about its pharmacological activity, cellular basis and molecular mechanisms of GA's action remain to be investigated

Method used

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  • Application of glycyrrhizic acid to prepare drugs for promoting medullary sheath regeneration to restrain neurogenic inflammation
  • Application of glycyrrhizic acid to prepare drugs for promoting medullary sheath regeneration to restrain neurogenic inflammation
  • Application of glycyrrhizic acid to prepare drugs for promoting medullary sheath regeneration to restrain neurogenic inflammation

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] Example 1: Preventive effect of GA on MOG-induced acute EAE model

[0028] 1. EAE model preparation and drug treatment

[0029] Female C57BL / 6 mice (8 weeks old) were purchased from the Animal Center of Xi'an Jiaotong University School of Medicine. Myelin oligodendrocyte glycoprotein MOG35-55 polypeptide, purchased from Genescript Company, pertussis toxin, purchased from Sigma-Aldrich Company, complete Freund's adjuvant containing Mycobacterium tuberculosis, purchased from BD Difco Company, glycyrrhizic acid (GA) was purchased from Sigma-Aldrich Company.

[0030] Dissolve the MOG35-55 polypeptide with PBS, then mix it with an equal volume of complete Freund's adjuvant (containing 5 mg / ml Mycobacterium tuberculosis), and push it with a glass syringe until a water-in-oil white antigen emulsion is formed.

[0031] Mice were immunized at two sites on the back, and diluted pertussis solution (200 ng / mouse) was injected intraperitoneally on the day of immunization and 2 day...

Embodiment 2

[0045] Example 2: GA is effective in attenuating the disease process when treatment is initiated in the chronic phase of EAE

[0046] 1. EAE model preparation and drug treatment

[0047] The EAE model was prepared as in Example 1, and the EAE mice were randomly divided into the following treatment groups:

[0048] 1) PBS-treated control group: EAE mice were intraperitoneally injected with PBS.

[0049] 2) Glycyrrhizic acid (GA) treatment group: GA (50 mg / kg / d) was injected intraperitoneally every day from the 30th day of immunization.

[0050] 2. Post-experimental processing

[0051] On the 60th day after immunization, the mice were sacrificed and the heart was perfused with PBS, and the lumbar spinal cords of the mice in the control group and the GA administration group were removed for immunohistochemical analysis.

[0052] 3. Experimental results

[0053] (1) In the chronic stage of EAE, GA (50mg / kg / d) treatment significantly reduced the incidence of EAE compared with t...

Embodiment 3

[0058] Example 3: GA Promotes Remyelination in a Copper Hydrazone-Induced Demyelination Model

[0059] 1. Copper hydrazone model preparation and drug treatment 8-week-old male C57BL / 6 mice were fed cuprizone mouse food mixed with standard rodent mouse food and 0.2% copper chelating agent cuprizone, which inhibited mitochondrial function and caused CNS demyelination.

[0060] Demyelination experiments were divided into two groups:

[0061] 1) PBS control group: mice were fed copper hydrazone chow for 6 weeks, and PBS was injected intraperitoneally every day.

[0062] 2) GA treatment group: Rats were fed copper hydrazone chow for 6 weeks, and GA (50 mg / kg / d) was injected intraperitoneally every day.

[0063] Remyelination experiments were divided into two groups:

[0064] 1) PBS control group: mice were fed copper hydrazone chow for 4 weeks, and PBS was injected intraperitoneally every day during 4-6 weeks.

[0065] 2) GA treatment group: mice were fed copper hydrazone chow f...

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Abstract

The invention discloses an application of glycyrrhizic acid to prepare drugs for promoting medullary sheath regeneration to restrain neurogenic inflammation. Experiment proves that the glycyrrhizic acid can effectively relieve inflammatory reactions and restrain demyelinating lesion, and can relieve development of diseases courses of acute and chronic experimental autoimmuneencephalomyelitis. Theglycyrrhizic acid can promote medullary sheath regeneration in a cuprizone-induced cuprizone demyelination model, an in vitro mechanism study finds that the glycyrrhizic acid can directly regulate a GSK-3 beta signal channel to induce the polarization of oligodendroglia precursor cells, so that the mature polarization of the oligodendroglia cells can be notably promoted, and the synthesis of medullary sheath protein is stimulated. A mechanism for promoting medullary sheath regeneration by the lycyrrhizic acid proves that a new basis is provided for treating demyelinating diseases and multiplesclerosis, and clinical-usable new medicines are provided for central nervous system demyelinating diseases and the like.

Description

technical field [0001] The invention belongs to the technical field of pharmaceutical preparations containing active ingredients of natural medicines, and in particular relates to the new application of glycyrrhizic acid (Glycyrrhizic Acid) in pharmaceuticals. Background technique [0002] Multiple Sclerosis (MS) and its animal model, Experimental Autoimmune Encephalomyelitis (EAE), is a chronic autoimmune disease of the central nervous system (Central Nervous System, CNS), accompanied by significant Spinal cord injury and inflammation, axonal loss and demyelination. The disease process can be broadly defined as both acute neuroinflammatory responses and chronic demyelinating diseases. The incidence rate in our country is increasing year by year, mostly in women aged 20-40, and about 80% are in relapse-remitting course of disease. During the onset of MS, myelin-reactive CD4 + T cells are activated in the periphery and proliferate in large numbers, cross the blood-brain ba...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/704A61P25/00A61P25/02
CPCA61K31/704A61P25/00A61P25/02
Inventor 李星杨婷张媛张菲
Owner SHAANXI NORMAL UNIV
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