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Application for sulfated mannose glucuronic acid hexasaccharide in prevention and treatment of atherosclerosis

A technology for atherosclerosis and hexasaccharide of uronic acid, which is applied in the directions of medical preparations containing active ingredients, non-central analgesics, cardiovascular system diseases, etc. and other problems, to achieve the effect of inhibiting absorption effect and small toxic and side effects

Active Publication Date: 2020-03-27
ZHEJIANG HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

So far, there is no information on the application of sulfated mannoglucuronide oligosaccharides in the treatment of atherosclerosis

Method used

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  • Application for sulfated mannose glucuronic acid hexasaccharide in prevention and treatment of atherosclerosis
  • Application for sulfated mannose glucuronic acid hexasaccharide in prevention and treatment of atherosclerosis
  • Application for sulfated mannose glucuronic acid hexasaccharide in prevention and treatment of atherosclerosis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0056] The preparation of embodiment 1 sulfated mannoglucuronate hexasaccharide

[0057] 1. Preparation of mannoglucuronide oligosaccharides

[0058] Extract the dried kelp with 30 times the mass of distilled water at 100°C for 3 hours, filter the extract, concentrate, add ethanol to a final concentration of 75% to precipitate, let it stand for 12 hours, collect the precipitate, sink to the point of vacuum drying to obtain laminarin . Dissolve the laminarin sample in a sulfuric acid solution with a mass concentration of 4% (the ratio of solid to liquid is 60mg / mL), heat and reflux for 5 hours, neutralize with barium hydroxide to PH=6-7, centrifuge, and concentrate the supernatant to the original One-fifth of the volume, the concentrated solution is subjected to active carbon column chromatography, firstly equilibrated with distilled water, and then eluted with a gradient of 50%-90% ethanol, and the 50%-90% ethanol eluate is concentrated to one-fifth of the original volume 1....

Embodiment 2

[0065] Example 2 Regulation of Sulfated Mannoglucuronate Hexaose on Inflammatory Factors

[0066] THP-1 cells were seeded in 6-well plates (4 × 10 5 Cells / well, RPMI-1640 complete culture solution containing 10% FBS), phorbol ester (PMA) was added to a final concentration of 100ng / ml, and culture was continued for 48h to induce monocytes to differentiate into macrophages. The experimental group was added with 0.25mg / ml, 0.5mg / ml, 1mg / ml sulfated mannoglucuronide hexaose respectively. Cultivate for 48 hours, collect the culture solution, and remove the precipitate at 4000 rpm for 5 minutes. ELISA kits were used to detect the release levels of TNF-α and IL-1β.

[0067] The result is as figure 1 As shown, the sulfated mannoglucuronate hexaose with a concentration of 0.5 mg / ml can significantly reduce the inflammatory factor TNF-α ( figure 1 A) and IL-1β ( figure 1 The expression level of B) increased to 1mg / ml, and the effect of reducing the expression level of inflammatory ...

Embodiment 3

[0068] Example 3 Inhibitory regulation of sulfated mannoglucuronide hexaose on NF-κB signaling pathway

[0069] THP-1 cells were seeded in 60mm culture dishes (2×10 6Cells / well, RPMI-1640 complete culture solution containing 10% FBS), phorbol ester (PMA) was added to a final concentration of 100ng / ml, and culture was continued for 48h to induce monocytes to differentiate into macrophages. The experimental group was added with 0.5 mg / ml and 1 mg / ml sulfated mannoglucuronide hexaose respectively. Culture for 48 hours, remove the medium, wash with PBS, add 100 μL of RIPA lysate containing protease and phosphatase inhibitors, scrape off the cells with a cell scraper, pipette the cell lysate into a 1.5mL EP tube and lyse the cells on ice for 30min; 4 Centrifuge at 13000rpm for 15min, and pipette the supernatant into a new 1.5mL EP tube. Concentration determination was performed with BCA protein concentration determination kit, and stored in a -80°C refrigerator. Western blot was...

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Abstract

The invention discloses an application for sulfated mannose glucuronic acid hexasaccharide in prevention and treatment of atherosclerosis. The sulfated mannose glucuronic acid oligosaccharide disclosed by the invention can effectively inhibit inflammatory factors in macrophages related to the atherosclerosis and the absorption effect of the macrophages on oxidized low-density lipoprotein, so a novel means is provided for preventing and treating the atherosclerosis.

Description

technical field [0001] The invention belongs to the technical field of medicinal chemistry and medicine, and relates to the application of sulfated mannoglucuronide hexasaccharide in preventing and treating atherosclerosis. Background technique [0002] Atherosclerotic cardiovascular disease (ASCVD) has jumped to the top of the cause of human death (Smith S J.Adherence to Medical Therapy and the Global Burden of Cardiovascular Disease[J].J Am Coll Cardiol.2016,67 (13):1516-1518.). So far, no effective measures have been found to further reduce the residual cardiovascular risk of ASCVD patients (Colantonio L D, Bittner V. Managing Residual Risk After Myocardial Infarction Among Individuals with Low Cholesterol Levels[J]. Endocrinol Metab Clin NorthAm.2016,45(1) :171-184). The reason lies in the complexity of the mechanism of atherosclerosis (AS). Macrophages play a pivotal role in the development of AS. Macrophages take up oxidized low-density lipoprotein (Ox-LDL) through...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/737A61P9/10A61P29/00
CPCA61K31/737A61P9/10A61P29/00
Inventor 暴一众金维华毛根祥王继荣吴万里王三应刘小伟张文静
Owner ZHEJIANG HOSPITAL
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