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Applications of 18beta-glycyrrhetinic acid in preparation drugs for diseases related to abnormal lipid metabolism

A technology for abnormal lipid metabolism and glycyrrhetic acid, which is applied in the application field of 18β-glycyrrhetic acid in the preparation of drugs for diseases related to lipid metabolism abnormality, and can solve the problem that the pharmacological action mechanism of 18β-glycyrrhetic acid lipid metabolism disorder diseases has not been found. , to reduce the degree of liver fat, improve liver function, reduce blood lipids

Pending Publication Date: 2020-04-07
SHENZHEN INST OF ADVANCED TECH CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although some studies have found that glycyrrhizic acid has lipid-lowering and hypoglycemic effects, there is no research report on the use of 18β-glycyrrhetinic acid in regulating lipid metabolism disorders and its pharmacological mechanism

Method used

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  • Applications of 18beta-glycyrrhetinic acid in preparation drugs for diseases related to abnormal lipid metabolism
  • Applications of 18beta-glycyrrhetinic acid in preparation drugs for diseases related to abnormal lipid metabolism
  • Applications of 18beta-glycyrrhetinic acid in preparation drugs for diseases related to abnormal lipid metabolism

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 118

[0054] Example 1.18 β-GA interferes with the experiment of HNF4a ligand-binding domain (LBD) interacting with co-activator PGC1a:

[0055] The experimental method is as follows:

[0056] Experimental group: Hela cells were treated with 1.5×10 4 The density per well was seeded on a 96 plate, with 3 replicate wells in each group; after the cells adhered to the wall, the internal reference plasmid pRL-TK, reporter plasmid pFR-Luc, DBD-HNF4a-LBD, and PGC1a were passed through using Lipofectamine3000 transfection reagent. The expression plasmid co-transfected cells were cultured for 24 hours, given as figure 1 The indicated 10μM, 20μM, 40μM different concentrations of 18β-GA were treated for 24 hours;

[0057] Control group: treated with reference to the experimental group, without adding 18β-GA;

[0058] Blank group: Hela cells.

[0059] After the experimental group, control group and blank group have been cultured, absorb the culture medium of each group, wash the cells with ...

Embodiment 218

[0061] Example 2.18 β-GA inhibits the activity of HNF4α / PGC-1a on the promoters of APOB, MTP and PLA2G12B genes:

[0062] The experimental method is as follows:

[0063] Experimental group: Hela cells were treated with 1.5×10 4 The density per well was inoculated on a 96 plate, and each group had 3 duplicate wells; the internal reference plasmid pRL-TK, the promoter reporter plasmid pGL3-PLA2G12B, MTP and APOB were respectively co-transfected with HNF4a and PGC1a expression vectors and cultured for 24 hours. Give different concentrations of 18β-GA treatment for 24 hours;

[0064] Control group: treated with reference to the experimental group, without adding 18β-GA;

[0065] Blank group: Hela cells.

[0066] After the experimental group, control group and blank group have been cultured, absorb the culture medium of each group, wash the cells with PBS, add 50 μl of cell lysate, shake and lyse the cells for 30 minutes; suck out 25 μl of lysate for each well, add 30 μl of luci...

Embodiment 318

[0068] Example 3.18 Experiment on the influence of β-glycyrrhetinic acid on key genes of lipid metabolism in liver cancer cells HepG2:

[0069] The experimental method is as follows:

[0070] HepG2 cells were divided into 6×10 4 The density of / mL was inoculated in a 6-well plate and cultured for 24 hours, the medium was replaced with DMEM containing 0.5% FBS, and the cells were treated according to the control group (DMSO) and the administration group (18β-GA 40μM). Discard the medium, wash with PBS, add Trizol to lyse the cells, extract the total RNA in the cells, and prepare cDNA by reverse transcription. The system is shown in Table 1 below:

[0071] Table 1. Reverse transcription system

[0072]

[0073] Reverse transcription PCR conditions:

[0074] Reaction: 42°C (60min), termination reaction: 70°C (5min). After the reverse transcription product was diluted 25 times, Realtime RCR detection was performed.

[0075] The Real time PCR reaction system is shown in Tab...

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Abstract

The invention discloses applications of 18beta-glycyrrhetinic acid taken as a conditioning agent for reduce lipid synthesis and / or the conditioning agent for reducing very low density lipoprotein formation and secretion in drugs. A drug containing the 18beta-glycyrrhetinic acid with effective doses is disclosed; the 18beta-glycyrrhetinic acid can be taken as a conditioning agent of HNF4alpha and can lower the expression of APOB, MTP and PLA2G12B; and a method for inhibiting the expression of FASN, SCD-1 and ACAC[alpha] is also disclosed. The 18beta-glycyrrhetinic acid can inhibit the expression of lipid metabolism related genes, so that lipid synthesis and the formation and secretion of very low density lipoprotein can be inhibited, lipid content in the liver can be lowered, the fatty degree of the liver can be reduced, liver functions can be obviously improved, blood fat can be reduced, and the effects of preventing and / or treating diseases related to abnormal lipid metabolism can befinally achieved. In addition, as the 18beta-glycyrrhetinic acid is a natural substance, the 18beta-glycyrrhetinic acid is good in curative effect and small in toxic and side effect.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and in particular relates to the application of 18β-glycyrrhetinic acid in the preparation of drugs for diseases related to abnormal lipid metabolism. Background technique [0002] Abnormal lipid metabolism refers to the abnormality of lipids and their metabolites in plasma and other tissues and organs, often accompanied by elevated cholesterol or triglyceride (TG) levels, which can be divided into two types: primary and secondary. Lipid metabolism disorder is a key factor affecting the pathogenesis of non-alcoholic fatty liver disease (NAFLD), atherosclerosis (AS), cardiovascular and cerebrovascular diseases, and diabetes. [0003] With the improvement of people's living standards and changes in lifestyle, the course of chronic diseases caused by abnormal lipid metabolism continues to grow rapidly. The prevalence of dyslipidemia among adults in my country is as high as 18.6%, of which hyper...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/56A61P3/00A61P3/06A61P1/16A61P9/10A61P9/00A61P3/10
CPCA61K31/56A61P3/00A61P3/06A61P1/16A61P9/10A61P9/00A61P3/10
Inventor 管敏刘庆礼
Owner SHENZHEN INST OF ADVANCED TECH CHINESE ACAD OF SCI
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