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Application of ouabain in preparation of anti-non-alcoholic fatty liver drug

A non-alcoholic, fatty liver technology applied in the field of sodium potassium ATPase inhibitors

Active Publication Date: 2019-05-28
NANJING UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, so far there is no research report on the effect of ouabain on NAFLD. In our work, we found that ouabain can reduce the hepatic fat content of mice fed with high-fat diet without affecting heart rate and blood pressure. damage, thus showing that ouabain has good application value and prospect in the treatment of fatty liver

Method used

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  • Application of ouabain in preparation of anti-non-alcoholic fatty liver drug
  • Application of ouabain in preparation of anti-non-alcoholic fatty liver drug
  • Application of ouabain in preparation of anti-non-alcoholic fatty liver drug

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0024] Example 1 Establishment of mouse non-alcoholic fatty liver model

[0025] 1.1 Experimental materials

[0026] 6-8 week-old male C57BL / 6 mice and 6-week-old male Ob / ob mice were from Nanjing University-Institute of Model Animals; 60% high-fat diet (D12492) and isocaloric control diet (D12450J) From the American ResearchDiets company.

[0027] 1.2 Experimental method

[0028] 1.2.1 Non-alcoholic fatty liver model in mice induced by high-fat diet feeding

[0029] Male C57BL / 6 mice aged 6-8 weeks were adaptively fed for several days and randomly divided into low-fat diet (NFD) and high-fat diet (HFD). Mice in NFD group were fed with D12450J feed every day for 12 consecutive weeks, while HFD mice were fed with D12492 high-fat feed every day for 12 consecutive weeks. All mice were given free access to drinking water, and the body weight of the mice was monitored weekly.

[0030] 1.2.2 Non-alcoholic fatty liver model in Ob / ob transgenic mice

[0031] Ob / ob mice are homoz...

Embodiment 2

[0034] Example 2 Oouabain reduces the accumulation of fat in the liver of mice in the state of non-alcoholic fatty liver disease

[0035] 2.1 Experimental materials

[0036] Oabain was purchased from Sigma, USA; Triglyceride (TG) and Cholesterol (TC) assay kits were purchased from Nanjing Jiancheng Bioengineering Institute; HE staining kits were purchased from Wuhan Sewell Biotechnology Co., Ltd.; Oil Red O reagent Purchased from Sigma, USA.

[0037] 2.2 Experimental method

[0038] 2.2.1 Administration method and sample collection of ouabain

[0039] Male C57BL / 6 mice aged 6-8 weeks were randomly divided into 4 groups (8 mice in each group), and 2 groups of mice were fed with NFD and HFD diets, respectively. After 6 weeks, the two groups of mice fed with NFD diet were given intraperitoneal injection of 0.1 mg / kg ouabain (NFD+Ouabain group) or the same amount of normal saline (NFD group) respectively, and injected continuously for 6 weeks; The two groups of mice were also ...

Embodiment 3

[0053] Example 3 Oouabain reduces liver damage in mice in the state of non-alcoholic fatty liver disease

[0054] 3.1 Experimental materials

[0055] The experimental mice were the same as in Example 1; the source of ouabain was the same as in Example 2; Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) assay kits were purchased from Nanjing Jiancheng Institute of Bioengineering.

[0056] 3.2 Experimental method

[0057] 3.2.1 Mice modeling and administration methods

[0058] The mouse model and the administration method of ouabain are the same as those in Example 1 and Example 2.

[0059] 3.2.2 Detection of AST, ALT and ALP activity in mouse serum

[0060] The serum of the mice was separated, and the activities of AST, ALT and ALP in the serum of the two mouse models were determined according to the kit instructions.

[0061] 3.3 Experimental results

[0062] The activities of AST, ALT, and ALP in the serum of high-fat-induc...

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Abstract

The invention relates to application of ouabain in preparation of an anti-non-alcoholic fatty liver drug. The experiment shows that the plant-derived ouabain which is firstly adopted can reduce the body weight of a high-fat-fed mouse, and reduce the liver weights of a high-fat-fed mouse and an Ob / 0b mouse, and reduce the contents of triglyceride and cholesterol in mouse serum, reduce the fat content in the liver and improve the liver histological change. In addition, the ouabain also can reverse the induction of high fat and the elevation of transaminase in the serum of Ob / ob mouse, and alleviate the liver damage. While exhibiting the above effects, the ouabain having the concentration does not significantly affect the heart rate, systolic pressure, mean arterial pressure, and diastolic pressure in the mouse, and also does not have significant toxic effects on the heart and the histological structure of aorta of the mouse. Therefore, the low-dose ouabain shows a good protective effectin the non-alcoholic fatty liver disease, and has good development value and application prospects in the treatment of the disease.

Description

technical field [0001] The invention relates to a new use of sodium potassium ATPase inhibitor ouabain in treating fat accumulation in the liver and liver cell damage in the state of non-alcoholic fatty liver disease. Background technique [0002] Nonalcoholic fatty liver disease (NAFLD) is a clinical disease state, first described in 1980, manifested by the presence of 5% or More hepatocellular bullous steatosis. NAFLD is the liver disease with the highest incidence rate in the world. In developed and developing countries, NAFLD is the most common cause of elevated serum transaminases. In most studies, the incidence rate is between 25% and 45%, and the rate is increasing year by year with the increase of inactive lifestyle and the globalization of Western diet. At present, it is estimated that the number of NAFLD patients in the world is as high as 1 billion, and it affects about 80 million to 100 million people in the United States. The incidence of NAFLD in China has gr...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/7048A61P1/16
Inventor 殷武季晓君程小迎
Owner NANJING UNIV
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