Application of Demethylzeylasteral (T-96) in preparation of drugs for preventing or treating hepatic fibrosis

A technology for norzelaminaldehyde and hepatic fibrosis, which is applied in the field of biomedicine and can solve the problems of undisclosed anti-hepatic fibrosis pharmacological activity and the like

Inactive Publication Date: 2021-08-13
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But so far, there is no technical disclosure that norzeramydal can be used to treat or prevent liver fibrosis, nor does it disclose that it can effectively inhibit AGAP2 to exert its pharmacological activity against liver fibrosis

Method used

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  • Application of Demethylzeylasteral (T-96) in preparation of drugs for preventing or treating hepatic fibrosis
  • Application of Demethylzeylasteral (T-96) in preparation of drugs for preventing or treating hepatic fibrosis
  • Application of Demethylzeylasteral (T-96) in preparation of drugs for preventing or treating hepatic fibrosis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] Example 1 Application of norzeratin in inhibiting the activation of LX-2 cells

[0027] 1. Drug treatment of LX-2 cells

[0028] LX-2 cells were purchased from the Cell Bank of Xiangya School of Medicine, Central South University. Norzeratal (T-96) was purchased from Med ChemExpress Company as a yellow powder with a purity of 99.90%. The LX-2 cells cultured at 37° C. under 5% CO2 conditions were stimulated with TGF-β1 (final concentration 5 ng / mL) to induce and stimulate the cell-forming model, and added different concentrations of norzeralin as the drug treatment group, In addition, cells cultured with DMEM not containing compounds and TGF-β1 were set as normal control group. Cell samples were collected after 24 h.

[0029] 2. Real-time fluorescent quantitative polymerase chain reaction detection (RT-qPCR)

[0030] Cells were lysed using TRIzol and total RNA was extracted. After reverse transcription, the RT-qPCR reaction was performed on a fluorescent quantitativ...

Embodiment 2

[0037] Embodiment 2 norzeratinyl in the treatment of CCl 4 Application of induced liver fibrosis in mice

[0038] 1. Experimental animals and reagents

[0039] 7-8 week old C57BL / 6J mice weighing about 18-22g were purchased from Jiangsu Jicui Yaokang Biotechnology Co., Ltd. Carbon tetrachloride (CCl 4 ) was purchased from Sigma.

[0040] 2. CCl 4 Construction of induced liver fibrosis mouse model and drug regimen

[0041] Inject CCl intraperitoneally at a dose of 10 mL / kg weekly 4 Solution (CCl 4 : corn oil=1:9 volume ratio configuration) or corn oil twice, two weeks after modeling, compound T-96 was administered, and drug treatment was started. The mice were set into the following 4 groups: Control group: Mice were fed 10 mL / kg of co-solvent every day, that is, a mixture of 10% DMSO, 40% PEG300, 5% Tween-80, and 45% saline. CCl4 model group: Mice were fed with 10 mL / kg of co-solvent every day. T-96 low-dose treatment group (15mg / kg): Mice were orally administered 15m...

Embodiment 3

[0058] Example 3 Application of norzeratin in inhibiting AGAP2 gene expression

[0059] According to literature reports, AGAP2 plays an important role in the development of liver fibrosis. It can promote the occurrence of liver fibrosis in response to TGF-β1 signaling factor. In addition, based on the comprehensive analysis of the transcriptome sequencing results in the previous stage, the AGAP2 gene was selected for further research to investigate its role in the process of norzeramydal in resisting liver fibrosis. RT-qPCR and Western Blot experiments were performed according to the same method as in Example 1, where the primer sequences used are shown in Table 3.

[0060] Table 3 Primer sequences

[0061]

[0062] First, verify the expression changes of AGAP2 in the liver of mice treated with norzeramylal, as shown in Figure 6 As shown in A, the mRNA expression of Agap2 in the liver of the mice in the drug treatment group was significantly down-regulated compared with...

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Abstract

The invention discloses application of Demethylzeylasteral (T-96) in preparation of drugs for preventing or treating hepatic fibrosis, and belongs to the technical field of biological medicines. In-vivo and in-vitro experiments prove that the Demethylzeylasteral (T-96) can inhibit activation of hepatic stellate cells, reduce collagen deposition in livers of hepatic fibrosis mice, inhibit fibroplasia, improve liver functions and down-regulate expression of hepatic fibrosis related proteins, which indicates that the Demethylzeylasteral (T-96) has an anti-hepatic fibrosis effect. In addition, transcriptome sequencing and experimental results show that the Demethylzeylasteral (T-96) can inhibit activation of the hepatic stellate cells by regulating expression of proteins such as AGAP2 and the like so as to improve hepatic fibrosis, and the Demethylzeylasteral (T-96) has the advantages of small toxic and side effects, wide raw material sources, low production cost and the like. Therefore, the Demethylzeylasteral (T-96) can be used for preparing drugs and pharmaceutical compositions for preventing / treating hepatic fibrosis, and has good development and application values.

Description

technical field [0001] The invention specifically relates to the application of norzeramydal in the preparation of drugs for preventing or treating liver fibrosis, and belongs to the technical field of biomedicine. Background technique [0002] Liver fibrosis is a chronic liver injury caused by a variety of etiologies including viral infection, autoimmunity, excessive alcohol intake, and bile duct obstruction. When hepatocytes are injured, accompanied by inflammatory response and compensatory repair response, persistent liver injury will lead to excessive deposition of extracellular matrix (ECM) and cause liver fibrosis. Liver fibrosis is a reversible process in the early stage. Without timely and effective intervention and treatment, it will develop into cirrhosis, accompanied by a series of fatal complications, such as liver failure, portal hypertension, ascites, hepatic encephalopathy, etc., and eventually lead to liver cancer. happened. However, no ideal anti-hepatic f...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/56A61P1/16A61P31/14A61P31/20A61P37/02
CPCA61K31/56A61P1/16A61P31/14A61P31/20A61P37/02
Inventor 王淑珍陈珂郭蔚然李荣欣
Owner CHINA PHARM UNIV
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