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Application of trichothecin in preparing drug for preventing or treating hyperlipidemia

A trichothecenes, hyperlipidemia technology, applied in the field of biomedicine, can solve problems such as toxic and side effects

Inactive Publication Date: 2019-08-23
WEIFANG MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] More and more studies have shown that clinically used statins and other synthetic lipid-lowering drugs have certain toxic and side effects

Method used

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  • Application of trichothecin in preparing drug for preventing or treating hyperlipidemia
  • Application of trichothecin in preparing drug for preventing or treating hyperlipidemia
  • Application of trichothecin in preparing drug for preventing or treating hyperlipidemia

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0029] 1. Lipoprotein preparation

[0030] experimental method:

[0031] Lipoproteins were prepared by ultracentrifugation, the plasma density was adjusted to 1.006 g / mL, and ultracentrifuged at 400,000 × g for 24 hours at 10°C. The upper layer containing very low-density lipoprotein was removed, the density of the remaining plasma was adjusted to 1.063 g / mL, and low-density lipoprotein (LDL) was obtained by ultracentrifugation at 400,000 × g for 24 h at 10°C. Draw the upper layer containing low-density lipoprotein (LDL) and place it in the EP tube. The remaining liquid was then readjusted to a density of 1.21g / mL, and ultracentrifuged at 400,000×g for 48 h to obtain high-density lipoprotein (HDL).

[0032] HDL dialysis method: add chelated metal ions containing EDTA-2Na (0.1%, w / v) to PBS solution (pH7.2), so as to reduce oxidation during ultracentrifugation, and dialyze for 24 hours. Dialyze in EDTA-free PBS solution for 24 hours, during which the dialysate was changed 3-...

Embodiment 1

[0034] Example 1 Determination of Lipid Levels in Macrophages

[0035] experimental method:

[0036] (1) Raw 264.7 macrophages were mixed with 1×10 per well 4 The final density of cells was seeded into 6-well plates. After 12 hours, the medium was aspirated off and the cells were washed 3 times with PBS.

[0037] (2) Add 1.5 mL DMEM medium containing 1% FBS to the blank control group, add 1.5 mL DMEM medium containing 1% FBS and ox-LDL with a final concentration of 50 μg / mL to each well of the other groups, and continue to incubate for 48 Hour.

[0038] (3) After the incubation, the RAW264.7 cells were gently washed with PBS for 3 times, and the blank group (DMEM medium), model group (ox-LDL), and experimental group (ox-LDL+trichothecene , 5 μM), and then continue to treat RAW264.7 cells for 4 hours.

[0039] (4) Then, the cells were washed 3 times with PBS, and treated with 0.2 mL RIPA lysis buffer at 4°C for 30 minutes.

[0040] (5) The resulting mixture was heated in ...

Embodiment 2

[0044] Example 2 [ 3 H]-cholesterol efflux assay

[0045] experimental method:

[0046] (1) Raw 264.7 macrophages were mixed at 5.0×10 per well 3 The final density of cells was seeded into 12-well plates, and after 12 hours, the medium was aspirated and the cells were washed 3 times with PBS.

[0047] (2) Then, add 1.5 mL containing 1% FBS, ox-LDL (50 μg / ml) and 1 μCi / mL to each well [ 3 H]-cholesterol in DMEM medium, continue to incubate for 24 hours.

[0048] (3) After incubation, remove the3 H]-cholesterol medium, gently wash the cells 3 times with PBS. Subsequently, 500ul of DMEM medium containing 2% plasma was added to the blank group, and 500ul of DMEM medium containing trichothecene (5μM) and 2% plasma was added to the experimental group to treat the cells.

[0049] (4) After 4 hours, collect the culture medium in a 1.5ml microcentrifuge tube for later use.

[0050] (5) The cells in the culture plate were treated with 1 mL of n-hexane / isopropanol (3:2, v / v) at roo...

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Abstract

The invention discloses application of trichothecin in preparing a drug for preventing or treating hyperlipidemia, relates to the medical use of the trichothecin, and belongs to the field of biomedicine. The invention relates to the research of the detection and mechanism of the lipid-lowering activity of a trichothecin compound. Through related experiments, it is proved that the trichothecin compound can reduce the blood lipid, and the mechanism of the trichothecin compound is related to the expression of key genes and proteins which affect the reverse cholesterol transport process. Not onlyis the lipid-lowering activity of the trichothecin demonstrated, but also the underlying mechanism of lipid lowering of the trichothecin is revealed.

Description

technical field [0001] The invention relates to the medical application of trichothecenes, in particular to the application of trichothecenes in the preparation of drugs for preventing or treating hyperlipidemia, and belongs to the field of biomedicine. Background technique [0002] Hyperlipidemia is a major inducer of atherosclerosis, primarily by promoting the formation and accumulation of lipid plaques in arteries. Reverse cholesterol transport (RCT) refers to the process of transporting cholesterol in extrahepatic tissue cells to the liver through blood circulation, and undergoes metabolic transformation in liver cells. This pathway is of great significance for reducing the accumulation of cholesterol in blood vessel walls. [0003] In the early stage, some researchers obtained a fungus (Cordanam musae, AGR0073) with strong antagonistic effect on the banana wilt fungus (Cordanam musae, AGR0073) during the isolation of banana rhizosphere and endophytic fungi in the mounta...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/352A61P3/06
CPCA61K31/352A61P3/06
Inventor 郭守东林萍宋晓童周远明
Owner WEIFANG MEDICAL UNIV
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