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Amaryllidaceae Alkaloids with Neuroprotective Effects

A technology of compounds and alkaloids, applied in the field of medicine, can solve the problems of unclear pathogenic mechanism of AD, treatment, failure to achieve therapeutic effect, etc.

Inactive Publication Date: 2015-10-28
HUAZHONG UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] At present, since the pathogenic mechanism of AD is not yet clear, the therapeutic drugs for AD can only improve the symptoms of AD patients, but cannot treat the cause of AD, so no good therapeutic effect has been achieved.

Method used

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  • Amaryllidaceae Alkaloids with Neuroprotective Effects
  • Amaryllidaceae Alkaloids with Neuroprotective Effects
  • Amaryllidaceae Alkaloids with Neuroprotective Effects

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] The preparation method of embodiment 1N-chloromethyl ricilamine

[0044] Mince 100kg of fresh bulbs of Lycoris aurea, heat extract 5 times with 95% ethanol (2 hours each time), combine the extracts, concentrate most of the ethanol under reduced pressure, and disperse the extract evenly in water (30 L in total). First extract with dichloromethane to remove non-alkaloid components. Then use saturated sodium hydroxide solution to adjust the pH value of the aqueous phase (9, 10, 11, 12), then extract with dichloromethane respectively, and combine the dichloromethane extracts to obtain 300 ml of total alkaloid extract.

[0045] Dissolve the total extract of alkaloids in methanol, carry out gel chromatography, thin-layer chromatography detection and combine the same fractions to obtain 4 parts (I-IV). Part III (7.9 g) crude silica gel mixed sample, 150 g silica gel column chromatography, dichloromethane:methanol 7:1, TLC detection The same fractions were combined to obtain 4...

Embodiment 2

[0046] The preparation method of embodiment 2O-desmethyl Riclavamine N-oxide

[0047] 5.6 kg of fresh bulbs of hybrid Lycoris (the hybrid of Lycoris L.aurea and L.radiata) were minced, 95% ethanol was hot-extracted and refluxed 5 times (2 hours each time), and the extracts were combined (about 15L) After concentrating under reduced pressure to remove most of the ethanol, the extract is evenly dispersed in water, adjusted to pH 2 with dilute hydrochloric acid, and extracted with dichloromethane to remove non-alkaloid components. Then adjust the pH value of the aqueous phase to 10 and 12 with sodium hydroxide solution, and extract with dichloromethane respectively to obtain 22.7 g of the total alkaloid extract of the pH 10 extraction site and 12.06 g of the total alkaloid extract of the pH 12 extraction site.

[0048] The total alkaloid extract of the pH 10 extraction site was dissolved in methanol, and subjected to gel column chromatography and thin-layer chromatography detecti...

Embodiment 3

[0049] Embodiment 3N-Chloromethyl licilamine and O-desmethyl licilamine N-oxide to H 2 o 2 Protective effect on induced neuronal injury

[0050] The results showed that N-chloromethyl ricilamine and O-desmethyl ricilamine N-oxides on H 2 o 2 Induced SH-SY5Y nerve cell injury has a protective effect. At concentrations of 12.5, 25, 50, and 100 μM, there were extremely significant differences (P2 o 2 Induced neuronal damage. Wherein the survival rate of the cells in the N-chloromethyl ricilamine administration group is higher than that in the O-desmethyl ricilamine N-oxide administration group.

[0051] 1. Experimental materials

[0052] 1.1 Test sample

[0053] N-chloromethyl liclamine and O-desmethyl ricilamine N-oxide were respectively dissolved in DMSO (sigma) and prepared as a 10000 μM stock solution, and then diluted to the required concentration with DMEM medium.

[0054] 1.2 Cell lines

[0055] SH-SY5Y (human neuroblastoma cells)

[0056] 1.3 Culture medium

[...

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Abstract

The invention belongs to the technical field of medicines, relates to Amaryllidaceae alkaloids, and particularly provides Lycoramine compound extracted from lycoris aurea, hybrid lycoris radiata (hybridization of lycoris aurea and lycoris radiata) or other lycoris plants. The compound has protective effect on neural cells, has preventive and curative effect on Alzheimer's disease, and is applicable to preparation of neuroprotective agents and medicines for preventing Alzheimer's disease.

Description

technical field [0001] The invention belongs to the technical field of medicine, and specifically relates to two novel Amaryllidaceae alkaloid compounds (N-chloromethyl lyclavamine and O-desmethyl lyclavamine N-oxide) in neuroprotection and prevention and treatment of Alzheimer's disease. applications in mutism. Background technique [0002] Alzheimer's disease (AD) is a primary degenerative disease of the central nervous system, with more than 36.5 million people suffering from it worldwide. The disease mainly manifests as a progressive decline in intelligence, memory and cognition, and patients gradually lose their ability to think, speak and move towards death. There are about 8 million AD patients in my country. Because advanced AD patients cannot take care of themselves and are often accompanied by severe mental and neurological symptoms, it not only seriously reduces the quality of life of the elderly, but also brings a heavy mental and economic burden to the family ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D491/107A61K31/55A61P25/28A61P25/00
Inventor 阮汉利李雪金岸
Owner HUAZHONG UNIV OF SCI & TECH
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