Application of matrine in preparing drug for preventing and treating alzheimer disease

A technology of Alzheimer's and matrine, applied in the field of drug research, can solve the problems such as difficulty in obtaining recognition of traditional Chinese medicine for AD treatment, few theoretical and experimental studies, lack of scientificity and persuasion, etc.

Inactive Publication Date: 2012-09-12
JILIN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

In recent years, researchers in my country have carried out research on the treatment of senile dementia with traditional Chinese medicine from various aspects. However, due to the complexity of the ingredients of traditional Chinese medicine, most of the research work is clinical reports, and there are few theoretical and experimental studies. Many clinical observations, diagnoses and curative effect evaluations are not rigorous and objective. The lack of targeted physical and chemical and imaging examinations makes the results unscientific and convincing
[0004] Some active ingredients in natural medicines, such as saponins, flavonoids, phenolic acids, terpenes, alkaloids, anthrone, etc., although their targets for AD are not the same, in vitro or clinical studies have shown different degrees of However, due to the characteristics of multi-target active ingredients, unclear mechanism of action, difficult to evaluate toxic and side effects, and unstable drug efficacy, it is difficult for traditional Chinese medicine to be recognized in the treatment of AD. Screening out monomeric compounds, studying their pharmacological effects, and analyzing their mechanism of action can give scientific connotations to traditional Chinese medicine for treating AD, and provide reference for further clinical application and new drug development

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  • Application of matrine in preparing drug for preventing and treating alzheimer disease
  • Application of matrine in preparing drug for preventing and treating alzheimer disease
  • Application of matrine in preparing drug for preventing and treating alzheimer disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0014] Example 1: Effect Analysis of Matrine Inhibiting or Neutralizing the Cytotoxicity of Aβ42 Monomers and Aβ42 Aggregates

[0015] (1) Preparation of Aβ42 monomer and Aβ42 oligomer

[0016] Aβ42 (purchased from Sigma-Aldrich, USA) was dissolved in ice-precooled hexafluoroisopropanol (HFIP) to a concentration of 1 mg / mL, sonicated in an ice-water bath for 10 min, dried in vacuum, and frozen at -20 °C. When using, first dissolve Aβ42 with dimethyl sulfoxide (DMSO) to a concentration of 1 mg / ml, and then dilute Aβ42 to a concentration of 10 μM in phosphate buffer (pH 7.4, 50 mM), with a final concentration of 20 μM. When the Aβ42 was regarded as Aβ42 monomer; the prepared Aβ42 was incubated at 37°C for 12h to form the aggregation state of Aβ42 oligomers, and the aggregation state was confirmed by transmission electron microscopy ( figure 1 ). Due to the irreversibility of Aβ42 to form aggregates, the use of Aβ42 oligomers is ready-to-use and can be stored at -80°C for short...

Embodiment 2

[0022] Example 2: Effects of Matrine on the Secondary Structure of Aβ42 Monomers and Aβ42 Oligomers

[0023] For the preparation method of Aβ42 monomer and Aβ42 oligomer, see Example 1 (1). 40 μM Aβ42 monomer or Aβ42 oligomer was mixed with 500 uM matrine, incubated at 37°C for 24 hours, and incubated at the same concentration and Time Aβ42 monomer or Aβ42 oligomer solution was used as control. The experiment was divided into four groups, namely 1: Aβ42 oligomer group, 2: (Aβ42 oligomer + matrine) group, 3: Aβ42 monomer group, 4: (Aβ42 monomer + matrine) group ; Inject the sample into a 0.1cm thick oval cuvette, and scan in the range of 190-260nm at 25°C under the condition of continuous nitrogen filling. JASCOJ-500 polarimeter was used to measure the changes of far-ultraviolet circular dichroism spectrum of Aβ42 under different aggregation states.

[0024] Molecular ellipticity [θ] calculation formula: [θ]=θ / (10CL); θ: ellipticity unit (mdeg) measured by JASCOJ-500 polarime...

Embodiment 3

[0026] Example 3: Transmission Electron Microscopy Observation of the Effect of Matrine on the Aggregation Form of Aβ42 Monomers and Aβ42 Oligomers

[0027] For the preparation method of Aβ42 monomer and Aβ42 oligomer, see Example 1 (1). Aβ42 monomer is prepared into a solution with a concentration of 20 μM in phosphate buffer (50 mM, pH 7.4), and mixed with 200 μM matrine Incubate at 37°C for 24h; in the same way, mix the prepared Aβ42 oligomer with a concentration of 20μM and 200μM matrine and incubate at 37°C for 12h. treatment as a control. The experiment was divided into four groups, namely 1: Aβ42 oligomer group, 2: (Aβ42 oligomer + matrine) group, 3: Aβ42 monomer group, 4: (Aβ42 monomer + matrine) group ;After the sample is processed, drop it on the carbon film of the copper grid, blot the excess liquid with filter paper, dry it in the air for 1min, and negatively stain it with 2% (w / v) phosphotungstic acid, TEM-1200EXⅡ type transmission electron The morphology of the...

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Abstract

The invention belongs to field of drug research and particularly relates to a new application of matrine in preparing a drug for preventing and treating an alzheimer disease. Found by long term study, the matrine has the effect of significantly inhibiting or neutralizing cytotoxicity of A beta 42 monomer or A beta 42 oligomer; found by further detection, the matrine can inhibit the cytotoxicity of A beta 42 through inhibiting the aggregation of the A beta 42 monomer or the A beta 42 oligomer; therefore, the new application of the matrine in preparing the drug for preventing and treating the alzheimer disease is confirmed and a new drug selection for clinic treatment of the alzheimer disease is provided.

Description

technical field [0001] The invention belongs to the field of drug research, and in particular relates to the new application of matrine in the preparation of drugs for preventing and treating Alzheimer's disease. Background technique [0002] Alzheimer's disease (AD) is a neurodegenerative disease with memory and cognitive dysfunction as the main symptoms, which occurs mainly in the elderly. The main pathological features of AD include the deposition of β-amyloid protein (Aβ42) (see the sequence SEQ ID NO: 1 in Chinese patent 201110094262.5 for its amino acid sequence) outside the brain neurons and the further formation of senile plaques (SP), intracellular Neurofibrillary tangles and trophic necrosis of neurons caused by hyperphosphorylated Tau protein. Many evidences indicate that the oligomerization and deposition of Aβ42 may be the key factor in the pathogenesis of AD. Aβ42 is formed by cleavage of amyloid precursor protein (APP) by β-secretase and γ-secretase successi...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/4375A61P25/28
Inventor 张应玖崔理立滕藤
Owner JILIN UNIV
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