Application of Abemaciclib in preparation of medicine for treating NAFLD

A drug, liver technology, applied in the field of medicine

Pending Publication Date: 2020-11-24
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The clinical research of this drug for new indications of NASH has not been carried out in the European and American markets, and the setting of clinical trial endpoints may also have room for discussion. Whether it is a blockbuster drug or a temporary mistake is still to be determined by the market. further test

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  • Application of Abemaciclib in preparation of medicine for treating NAFLD
  • Application of Abemaciclib in preparation of medicine for treating NAFLD
  • Application of Abemaciclib in preparation of medicine for treating NAFLD

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0020] Example 1, Abemaciclib reduces hepatic steatosis and reduces triglyceride content in the liver

[0021] 50 C57BL / 6 mice, male, 6-8 weeks old, were randomly divided into five groups according to body weight after environmental adaptation, with 10 mice in each group, namely control group, Abemaciclib low dose (15mg / Kg), middle dose (30mg / Kg) Kg), high dose (60mg / Kg) group. The mice in each group were given MCD feed to construct the NASH model. Except the control group was given the corresponding volume of animal drinking water, the other groups were given the corresponding drug intervention for 3 consecutive weeks. At the end of the administration, the liver was dissected and removed, and part of the liver lobe was cut out and fixed in formalin solution for HE staining to detect the lipid degeneration of the liver tissue. The degree of fatty degeneration of liver tissue in both groups was significantly reduced ( figure 1 A). In addition, part of the liver lobe was cut ...

Embodiment 2

[0022] Example 2, Abemaciclib improves abnormal liver function caused by hepatic steatosis

[0023] NASH model construction and intervention measures are the same as figure 1 After the administration of animals in each group, the blood was collected from the orbit, and the serum was collected by centrifugation at 3000rpm for 10min at 4°C. The contents of ALT and AST in the serum were detected according to the kit instructions. The results showed that compared with the control group, 15mg / kg, 30mg / kg, 60mg / kg The serum AST in the kg dose group was significantly lower than that in the control group, suggesting that Abemaciclib can improve liver function abnormalities caused by hepatic steatosis ( figure 2 A-B).

Embodiment 3

[0024] Example 3, Abemaciclib upregulates SESN2 to induce autophagy and improves NAFLD

[0025] HepG2 cells were inoculated into two 6-well plates one day in advance, and Abemaciclib was prepared according to the concentration gradient of 2.5 μM, 1.25 μM, 0.625 μM, 0.3125 μM, and 0.15625 μM the next day. After administration, the cells were placed in a 37°C, 5% CO2 incubator to continue culturing for 24 hours. One of the 6-well plates was used to extract the total protein and perform Western blot to detect the expression of related proteins. The other 6-well plate was placed under a microscope for observation and Photograph. The results showed that compared with the control group, the expression of the antioxidant protein SESN2 was significantly up-regulated in a dose-dependent manner when different concentrations of Abemaciclib were administered to HepG2 cells for 48 hours, while SESN1 had no significant change. At the same time, our experimental results showed that the expr...

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Abstract

The invention discloses an application of Abemaciclib in preparation of a medicine for treating NAFLD. After the Abemaciclib is administered to a C57BL / 6 mouse by intragastric administration for 2 weeks, histopathology and serum biochemical results show that the Abemaciclib can improve the liver lipidemia of the mouse and reduce the contents of serum ALT, AST and liver triglyceride. In-vitro experiment results show that the Abemaciclib can resist oxidative stress damage of cells through SESN2 and other mediated anti-oxidative stress pathways. In addition, our studies found that Abemaciclib caninduce HepG2 cells to form intracytoplasmic vacuoles similar to autophagy, presuming that Abemaciclib may improve NASH by inducing autophagy and inhibiting liver fibrosis.

Description

technical field [0001] The invention belongs to the field of medicine and relates to the application of Abemaciclib in the preparation of medicines for treating NAFLD. Background technique [0002] Non-alcoholic fatty liver disease (NAFLD) is a clinicopathological syndrome characterized by excessive fat deposition in liver cells caused by alcohol and other definite liver-damaging factors. The disease spectrum includes simple steatosis, fatty liver Hepatitis (NASH), liver fibrosis, cirrhosis, and even liver cancer. In recent years, basic research on the pathogenesis of NAFLD / NASH has been very active, involving abnormal regulation of multiple metabolic pathways. At present, NASH drugs mainly play an anti-NASH role by inhibiting fatty acid synthesis, improving insulin resistance, inhibiting inflammatory signaling pathways, and resisting oxidative stress damage to reduce hepatic steatosis, activating hepatic stellate cells and inhibiting extracellular matrix synthesis. / NAFLD...

Claims

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Application Information

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IPC IPC(8): A61K31/506A61P1/16
CPCA61K31/506A61P1/16
Inventor 杨勇段静静段然王卓江经纬宋世东
Owner CHINA PHARM UNIV
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