Application of Alpha-mangostin in preparing medicines for treating Alzheimer's disease

A technology of Alzheimer's disease and mangostin, applied in the field of pharmacology and chemical biology, to achieve the effect of improving pathological symptoms, enhancing normal physiological functions, and improving intervention

Inactive Publication Date: 2011-08-17
BOMAI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] At present, there is no relevant report on the use of α-mangostin to inhibit the aggregation and deposition of Aβ and to prepare drugs for Alzheimer's disease

Method used

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  • Application of Alpha-mangostin in preparing medicines for treating Alzheimer's disease
  • Application of Alpha-mangostin in preparing medicines for treating Alzheimer's disease
  • Application of Alpha-mangostin in preparing medicines for treating Alzheimer's disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] Example 1 Computer Simulation of the Binding Model of α-Mangostin and Aβ

[0030] Import Aβ from the protein structure database PDB 1-40The nuclear magnetic resonance NMR structure (PDB: 1BA4) of the molecular simulation software MOE. After removing water molecules and other heteromolecules added to obtain nuclear magnetic resonance experiments, and filling in the missing hydrogen atoms in nuclear magnetic resonance experiments, the Aβ is established by using the charge balance program and energy optimization program in the MOE software 1-40 3D simulation structure.

[0031] The two-dimensional simulation structure of α-mangostin was established in the molecular simulation software MOE, and the three-dimensional simulation structure of the molecule was established by using the charge balance program and energy optimization program in the MOE software.

[0032] remove Aβ 1-40 There is no specific conformational region (positions 1 to 13) in the three-dimensional simul...

Embodiment 2

[0034] Example 2 Determination of α-Mangostin Inhibition of Aβ Aggregation and Deposition by Fluorescence Kinetic Method

[0035] Dissolve 1 mg of Aβ in 500 microliters of hexafluoroisopropanol, place it at room temperature for 120 minutes, shake intermittently, dry the hexafluoroisopropanol gently with high-purity nitrogen, and then add 100 microliters of dimethyl Sulfoxide was prepared into a 2.3 mmol / L Aβ stock solution and stored at -20°C. After diluting the Aβ stock solution with dimethyl sulfoxide, take 2 microliters and add it to 16 microliters of 0.215 mol / liter sodium phosphate buffer solution with a pH value of 8.0, so that the concentration of Aβ in the final 100 microliters system is 25 μmol / L, add 2 μl of 25 μmol / L α-mangostin or other inhibitors or corresponding blank solvent, incubate for 30 minutes, add 80 μl of 50 mmol / L Thioflavin T Glycine-sodium hydroxide solution at pH 8.5 per liter was transferred to a fluorescence detection microwell plate, and placed o...

Embodiment 3

[0037] Example 3 ELISA Determination of α-Mangostin Depleting Aβ Oligomers

[0038] Dissolve 1 mg of Aβ in 500 μl of hexafluoroisopropanol and let stand at room temperature. Transfer 100 microliters of the solution to a clean 1.5 milliliter centrifuge tube, add 900 microliters of sterilized deionized water, and let stand at room temperature. After centrifugation, transfer the supernatant to another clean 1.5 ml centrifuge tube, and gently dry the hexafluoroisopropanol with high-purity nitrogen. Then add a micro-stirring bar to the solution, stir and incubate at 22 degrees Celsius and 500 rpm for 48 hours, and obtain a certain volume of Aβ oligomers diluted to 1 micromol / liter for the obtained product, wherein the final concentration of 5 micromol / liter is added. mol / L, 2 micromol / L, 1 micromol / L, 0.5 micromol / L and 0.2 micromol / L of α-mangostin, continue to shake and incubate at 22 degrees Celsius and 500 rpm for 12 hours. Or add α-mangostin at final concentrations of 5 micr...

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PUM

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Abstract

The invention discloses novel medical application of Alpha-mangostin, i.e. application of Alpha-mangostin in preparing medicines for treating Alzheimer's disease. Under a brand-new working concentration, the Alpha-mangostin shows the characteristic of restricting A Beta accumulation and deposition, simultaneously has a neuroprotection role, can effectively resist a neurotoxin role caused by A Beta oligomer, strengthen the normal physiological function of neuron cells of mammals and maintain the normal cell form of the neuron cells of the mammals, realizes the intervention to the pathological course of the Alzheimer's disease and the improvement to the pathological symptoms and provides a new path for treatment of the Alzheimer's disease.

Description

technical field [0001] The invention relates to the fields of pharmacology and chemical biology, in particular to the application of α-mangostin as an Aβ aggregation inhibitor in the preparation of Alzheimer's disease medicine. Background technique [0002] Alzheimer's disease (AD) is a progressive and fatal neurodegenerative disease, clinically manifested as deteriorating cognitive and memory functions, progressive decline in daily life ability, and various Neuropsychiatric symptoms and behavioral disturbances. [0003] Aβ aggregation deposition is an important pathological process in the development of Alzheimer's disease. With the accumulation and deposition of Aβ, Aβ oligomers with extremely strong neurotoxicity can be formed, as well as argentophilic senile plaques, an important pathological sign of Alzheimer's disease. Existing studies have shown that injection of aggregated Aβ can induce Alzheimer's disease-like symptoms in mice, and by inhibiting the aggregation an...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/352A61K9/20A61K9/14A61K9/48A61K9/19A61P25/28
CPCA61K31/352A61K9/0019A61P25/28
Inventor 夏铮
Owner BOMAI
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