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Application of hydrogen sulfide donor to preparation of medicine for treating central nervous system disease

A technology for Alzheimer's disease and cysteine, which is applied in the field of hydrogen sulfide donors in the preparation of medicines for the treatment of central nervous system diseases and the preparation of medicines for the treatment of central nervous system diseases

Active Publication Date: 2014-01-08
FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The compound propargyl cysteine ​​and its analogs have anti-myocardial ischemic injury effects, but whether they are effective against central nervous system inflammatory diseases, including Alzheimer's disease and other degenerative diseases, such as Parkinson's disease There is no report on the therapeutic effect

Method used

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  • Application of hydrogen sulfide donor to preparation of medicine for treating central nervous system disease
  • Application of hydrogen sulfide donor to preparation of medicine for treating central nervous system disease
  • Application of hydrogen sulfide donor to preparation of medicine for treating central nervous system disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] Example 1 NaHS alleviates learning and memory impairment in rats

[0035] Sixty-eight ♂SD rats weighing 250-350g were randomly divided into 6 groups, namely Sham group (n=10), sham+NaHS group (n=10), LPS group (n=12), LPS+IBU group ( n=12), LPS+NaHS group (n=12), LPS+AOAA group (n=12). Administration began after grouping. The sham+NaHS group and LPS+NaHS group were intraperitoneally injected NaHS 5 mg / kg daily, the LPS+IBU group was intragastrically administered ibuprofen (IBU) 40 mg / kg daily, and the LPS+AOAA group was intraperitoneally injected daily Aminoacetic acid (beta cystathionine synthase inhibitor) 10mg / kg, Sham group and LPS group were intraperitoneally injected with equal volume of normal saline for 12 consecutive days.

[0036] Model making after administration 3 days, step: rat is anesthetized through 7% chloral hydrate 0.5ml / 100g, cut off head hair, disinfect, incise head skin and expose skull, bilateral drilling (coordinates: behind bregma 0.8mm, 1.4mm...

Embodiment 2

[0044] Example 2 NaHS increases the hydrogen sulfide content in rat hippocampus

[0045] After the water maze test, the rats were anesthetized and killed, and the hippocampus was separated on an ice tray, and one side was used for the determination of hydrogen sulfide content. The results are shown in Table 2, the hydrogen sulfide content in the hippocampus of the rats in the model group was significantly lower than that of the sham operation group (P<0.01), and the hydrogen sulfide content in the hippocampus of the positive drug ibuprofen group and the test drug NaHS group was higher than that of the model group ( P<0.05), while the content of hydrogen sulfide decreased after administration of endogenous hydrogen sulfide production blocker aminooxyacetic acid. This indicates that NaHS increases the hydrogen sulfide content in rat hippocampus.

[0046] Table 2 is the effect of NaHS on the hydrogen sulfide content of rat hippocampus

[0047] Table 2

[0048]

Embodiment 3

[0049] Example 3 NaHS inhibits the expression of rat hippocampal tumor necrosis factor-α mRNA

[0050] After the water maze test, the rats were anesthetized and killed, and the hippocampus was isolated on an ice tray. One side of the hippocampus was randomly selected from 4 rats in each group, and the expression of tumor necrosis factor-α mRNA was measured by real time PCR. The results were determined by the target gene / The internal reference gene (GAPDH) is indicated, and the sham operation group is indicated as 100. The result is as figure 1 As shown, it was found that the expression of tumor necrosis factor-α mRNA in the hippocampus of rats in the model group was significantly higher than that of the sham operation group (P<0.01), which was 3 times that of the sham operation group. The expression of TNF-α mRNA in the hippocampus of the positive drug ibuprofen group and the test drug NaHS group was significantly lower than that of the model group (P<0.05). This indicated ...

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Abstract

The invention belongs to the field of pharmacy, and relates to application of a hydrogen sulfide donor to the preparation of a medicine for treating central nervous system disease, in particular to application of the hydrogen sulfide donor, namely sodium hydrosulfide, or allyl cysteine and analogues thereof to the preparation of the medicine for treating the central nervous system disease. Integral animal model experiments prove that the sodium hydrosulfide and propargyl cysteine can reduce the learning and memory impairment of rats, increase the content of hydrogen sulfide in hippocampus tissues of the rats, inhibit the messenger ribonucleic acid (mRNA) expression of a tumor necrosis factor alpha and a receptor I thereof, inhibit an inflammatory mediator in the hippocampus tissues of rats with dementia and inhibit inflammation-related enzymes in the hippocampus tissues of the rats, and can be used as a medicine for treating Alzheimer disease and other inflammation-related central nervous system degenerative diseases such as Parkinson disease.

Description

technical field [0001] The invention belongs to the field of pharmacy, and relates to a new application of a hydrogen sulfide donor in pharmacy, in particular to the application of a hydrogen sulfide donor in the preparation of medicines for treating central nervous system diseases. In particular, it relates to the use of hydrogen sulfide donor sodium hydrosulfide, allyl cysteine ​​and their analogues in the preparation of drugs for treating central nervous system diseases. Background technique [0002] Central nervous system degenerative diseases are a group of chronic progressive neurological diseases based on primary neuronal degeneration. Such diseases mainly include Alzheimer's disease (Alzheimer, disease, AD), Parkinson's disease (Parkinson's disease, PD), Huntington's disease, amyotrophic lateral sclerosis and spinal muscular atrophy, etc. Studies have found that inflammation plays an important role in central nervous system degenerative diseases, and non-steroidal a...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/198A61K33/04A61P25/00A61P25/16A61P25/28A61P29/00
Inventor 朱依谆龚其海朱依纯王茜王先利
Owner FUDAN UNIV
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