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Application of menadione sodium bisulfite in prevention and treatment of Alzheimer's disease

A technology of sodium bisulfite menadione and pharmaceutical excipients, applied in the field of medicine, can solve problems such as inability to reach diseases

Inactive Publication Date: 2018-08-28
HUAZHONG UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The current drugs for the treatment of AD can only improve the symptoms to a certain extent, but cannot achieve a profound effect on the disease, so it is urgent to find drugs for the treatment and prevention of AD
[0003] At present, for the lead compound that inhibits the aggregation of β-amyloid 1-42, other types of compounds have not yet successfully entered the clinic due to druggability problems such as toxicity and solubility.
The effect of quinones on the aggregation of β-amyloid 1-42 has not been studied

Method used

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  • Application of menadione sodium bisulfite in prevention and treatment of Alzheimer's disease
  • Application of menadione sodium bisulfite in prevention and treatment of Alzheimer's disease
  • Application of menadione sodium bisulfite in prevention and treatment of Alzheimer's disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0020] Menadione sodium bisulfite can inhibit the amyloid aggregation of β-amyloid 1-42.

[0021] Specific operation: β-amyloid 1-42 (Aβ42) dry powder (purchased from Beijing Zexiyuan Biotechnology Co., Ltd.) was dissolved into a solution with a concentration of 20 micromoles per liter, and sodium bisulfite menadione ( MSB, purchased from Shanghai Aladdin Biochemical Technology Co., Ltd.) and 1,4-naphthoquinone (NQ, purchased from Shanghai Aladdin Biochemical Technology Co., Ltd.), prepared into a mixed solution, divided into Aβ42, Aβ42:NQ1:0.5 by molar ratio , Aβ42: MSB 1:0.5 / 1:1 / 1:2 (see Table 1), incubate statically in a water bath at 37°C for 12 hours, take the incubated solution at 0, 1, 3, 6, 9, and 12 hours for sulfur Primer T fluorescence detection (see figure 2 A), and in 4,12h sampling carries out transmission electron microscope detection (see figure 2 B).

[0022] Table 1. Grouping of Aβ42 solution and its mixed solution with NQ and MSB

[0023]

[0024] E...

Embodiment 2

[0026] Sodium bisulfite menadione can delay the secondary structure transition from random coil to β-sheet in the aggregation process of β-amyloid 1-42.

[0027] Specific operation: Place 20 micromoles per liter of Aβ42 samples in a 37°C water bath and incubate for 2 hours, take out the samples every 30 minutes and transfer them to a special circular dichroic cuvette with an optical path of 1 mm for wavelength scanning, and the parameters are set to The wavelength ranges from 260nm to 200nm, the bandwidth is 2nm, the data interval is 1nm, the response time is 1s, the scanning speed is 100nm / min, and nitrogen gas is passed through at a flow rate of 3ml / min throughout the whole process. As a control, subtract the control group when processing the data (see image 3 ).

[0028] Experimental results such as image 3 As shown, at the initial moment of incubation, Aβ42 in each group showed a negative peak at 200nm in the circular dichroism spectrum, showing a random coil structure...

Embodiment 3

[0030] Sodium bisulfite menadione can attenuate the cell membrane destruction ability and hemolysis of β-amyloid 1-42 toxic aggregates.

[0031]Specific operation: 1-palmitoyl-2-oleoylphosphatidylglycerol (POPG, purchased from Sigma-Aldrich, U.S.) was dissolved in chloroform, dried with nitrogen, and then treated with carboxyfluorescein (purchased from Sigma-Aldrich, U.S.) The solution dissolves to form a POPG liposome membrane wrapping carboxyfluorescein. Use PD-10 chromatography column (purchased from Sangon Bioengineering Co., Ltd.) to remove fluorescein not encapsulated into liposomes. Then the membrane was mixed with the incubated Aβ42 sample, and the fluorescence intensity of the sample was detected. The aggregation product of Aβ42 produces toxic effects by destroying the cell membrane in the human body. In this example, POPG is used to wrap carboxyfluorescein to form an artificial liposome membrane, which is used to simulate the structure of human cell membrane. The me...

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Abstract

The invention provides menadione sodium bisulfite (MSB), namely a drug with the functions of preventing and treating Alzheimer's disease. It is found in research that menadione sodium bisulfite has the functions of obviously inhibiting aggregation of beta-amyloid protein1-42 (Abeta42), namely pathogenic protein of Alzheimer's disease, retarding conversion of a secondary structure of beta-amyloid protein1-42 from random coils into beta lamellas during aggregation, weakening the cytomembrane destruction capability of beta-amyloid protein1-42 toxicity congeries, inhibiting aggregation of beta-amyloid protein1-42 in cells, obviously prolonging the life of nematode in a caenorhabditis elegans AD model, achieving high safety performance and the like. It is disclosed that menadione sodium bisulfite can be applied to preparation of drugs with the functions of preventing and / or treating Alzheimer's disease.

Description

technical field [0001] The invention belongs to the field of medicine, and relates to a medicine for treating Alzheimer's disease, in particular to the application of menadione sodium bisulfite in preventing and treating Alzheimer's disease. Background technique [0002] Alzheimer's disease (Alzheimer's disease, AD), also known as senile dementia, is a neurodegenerative disease with slow onset, the largest number of patients, age-related irreversible development, and clinical manifestations of short-term memory degradation , Comprehension and expression decline, cognitive impairment and personality changes. AD patients take an average of 9 years from diagnosis to death, which brings a heavy burden to the patients themselves, their families and the whole society. With the acceleration of the aging of the global population, the number of AD patients is increasing year by year. It is estimated that by 2050, the number of AD patients in the world will far exceed 100 million. T...

Claims

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Application Information

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IPC IPC(8): A61K31/122A61P25/28A61P43/00
CPCA61K31/122
Inventor 黄昆郑凌龚皓赵喻丹张煜黎阳
Owner HUAZHONG UNIV OF SCI & TECH
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