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Application of fumarate in preparing drugs for treating hepatopathy

A fumarate and drug technology, applied in the field of chemical medicine, can solve problems such as unreported liver diseases of DMF and MMF, and achieve good liver protection and damage prevention effects.

Inactive Publication Date: 2017-08-25
XIANGYA HOSPITAL CENT SOUTH UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Although DMF and MMF can activate the Nrf2 pathway to reduce cell inflammation and oxidative stress response, and Nrf2 plays an important role in fighting oxidative stress in the liver, DMF and MMF are important in the treatment of liver diseases related to oxidative stress damage. Whether there is an effect has not been reported, and no one in the world has conducted in-depth research

Method used

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  • Application of fumarate in preparing drugs for treating hepatopathy
  • Application of fumarate in preparing drugs for treating hepatopathy
  • Application of fumarate in preparing drugs for treating hepatopathy

Examples

Experimental program
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Effect test

Embodiment 1

[0020] Pathway experiment of DMF activating Nrf2 signaling in vitro

[0021] The selected cell lines include human liver cancer HepG2 cells, human liver cancer Huh7 cells, and mouse liver cells AML-12. Cells in the logarithmic growth phase were inoculated into 6-well plates, and the cells were cultured in DMF for 0, 2, 4, 6, 12, and 24 hours, then the culture plate was taken out, and the total protein and RNA of the cells were extracted, and Western blot and QPCR were used to extract the cells. Technology, detecting the expression of Nrf2 and its antioxidant target genes (GCLC, HO1) in cells.

[0022] The result is as Figure 1-3 As shown, DMF can enhance the expression of Nrf2 and its antioxidant target genes (GCLC, HO1) in hepatocytes.

Embodiment 2

[0024] Pathway experiment of MMF activating Nrf2 signaling in cells in vitro

[0025] The selected cell lines include human liver cancer HepG2 cells, human liver cancer Huh7 cells, and mouse liver cells AML-12. Cells in the logarithmic growth phase were inoculated in 6-well plates, and after the cells were cultured with drugs (MMF) for 0, 2, 4, 6, 12, and 24 hours, the culture plates were taken out, and the total protein and total RNA of cells were extracted, and Western Blot and QPCR techniques were used to detect the expression of Nrf2 and its antioxidant target genes (GCLC, HO1) in cells.

[0026] The result is as Figure 4-6 As shown, MMF can enhance the expression of Nrf2 and its antioxidant target genes (GCLC, HO1) in hepatocytes.

Embodiment 3

[0028] Study on the effect of DMF on the prevention and treatment of liver oxidative stress injury in mice with alcoholic liver disease

[0029] The mice selected for the experiment were C57BL / 6 mice (male, 8 weeks old, weighing 18-21 g) provided by Shanghai Slack Company. They were randomly divided into 4 groups, raised in a common barrier environment, and a mouse model of alcoholic liver disease was established by the NIAAA method. After the model was established successfully, two groups of mice were randomly selected and given different doses of DMF orally orally, once a day, for a total of 10 days. After 10 days, the mice in the four groups were euthanized, and the liver tissues were soaked in formalin. The liver tissues of each group were stained with HE, and observed under a 100-fold and 200-light microscope.

[0030] The result is as Figure 7-10 As shown, DMF can prevent and treat liver damage caused by oxidative stress in the mouse liver disease model, and has a goo...

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Abstract

The invention discloses application of fumarate in preparing drugs for treating hepatopathy. The application of fumarate in preparing the drugs for treating the hepatopathy includes application of dimethyl fumarate (DMF) and application of monomethyl fumarate (MMF) in treating various hepatic diseases. According to the application of fumarate in preparing the drugs for treating the hepatopathy, DMF and MMF are adopted to activate the express of nuclear factor-E2-related factor 2 (Nrf2) in various human hepatoma carcinoma cells and mice liver cells and the express of downstream antioxidant genes of the nuclear factor-E2-related factor 2 (Nrf2), a Keapl-Nrf2-ARE pathway which is the most important in a cellular anti-oxidation mechanism is started, in addition, the damage of oxidative stress in a mice hepatopathy model on the liver can be further prevented, and the liver protection effect is good. Fumarate has the potential of being developed into treatment drugs regarding the hepatopathy related to the oxidative stress damage, and has important development and application prospects in treating the various hepatic diseases such as fatty hepatopathy, drug induced hepatopathy, cholestatic hepatopathy, viral hepatitis, cirrhosis and liver cancer.

Description

technical field [0001] The invention relates to the field of chemical medicine. It specifically relates to the application of fumaric acid ester in the preparation of medicines for treating various liver diseases. Background technique [0002] Oxidative stress refers to the overproduction of highly reactive molecules such as reactive oxygen species (ROS) and reactive nitrogen radicals (RNS) in the body when the body is subjected to various harmful stimuli, and the degree of oxidation exceeds the removal of oxides, resulting in tissue damage . As an important metabolic organ, the liver is often exposed to high concentrations of xenobiotics and other chemicals. Although the liver has a series of mechanisms to defend against harmful chemicals and their metabolites, it is still vulnerable to oxidative damage caused by intermediate active substances. Oxidative stress is the common pathogenesis of many liver diseases. Oxidative damage is closely related to most liver diseases, ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/225A61P1/16A61P35/00A61P31/14A61P31/20
CPCA61K31/225
Inventor 陈永恒刘霆严璐陈娅琦张桂英陈主初
Owner XIANGYA HOSPITAL CENT SOUTH UNIV
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