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Application of ganoderic acid G to neurodegenerative diseases

A neurodegenerative, ganoderma lucidum acid technology, applied in the field of medicine, can solve problems such as end-of-drug phenomenon, switching phenomenon, neuronal cell apoptosis, etc.

Inactive Publication Date: 2018-12-11
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, this protective effect is short-lived, and the pathological accumulation of α-synuclein eventually leads to apoptosis or death of neuronal cells [Reference: Experimental models of Parkinson's disease, Nature Reviews Neuroscience, 2001]
[0005] Since the 1960s, Western medicine has been using levodopa replacement therapy in the treatment of PD, but the effect of the replacement therapy generally begins to decline after 3 to 5 years, and drug-induced movement disorders (dyskinesia) appear as manifestations Complications, early side effects include nausea, anorexia, dizziness; long-term use can cause end-of-dose phenomenon, on-off phenomenon and movement disorders
[0007] There is no report on the correlation between ganoderma acid G and neurodegenerative diseases

Method used

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  • Application of ganoderic acid G to neurodegenerative diseases
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  • Application of ganoderic acid G to neurodegenerative diseases

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0020] Example 1: Antagonistic effect of ganoderma acid G on 6-OHDA-induced dopamine neuron toxicity in Caenorhabditis elegans

[0021] 1. Escherichia coli OP50 cultivation and preservation

[0022] Cultivation of OP50 strain: Use an inoculation loop to dip a small amount of OP50 bacterial solution (purchased from Caenorhabditis Genetics Center, CGC), inoculate and streak on solid LB medium, and culture overnight at 37°C. Single clones on solid medium were picked, inoculated in liquid LB medium, and shaken overnight at 37°C and 200rpm. Bacteria can be stored at 4°C until use.

[0023] Pay attention to maintain aseptic operation in the above steps. The bacteria solution stored at 4°C was re-streaked every 7 days to obtain single clones to ensure the viability of the bacteria.

[0024] 2. Preparation of standard Caenorhabditis elegans growth culture plate (Nematode Growth Media, NGM)

[0025] Preparation of NGM culture plate: Weigh 3.0g sodium chloride, 2.5g peptone, and 17g...

Embodiment 2

[0042] Example 2: Inhibitory Effect of Ganoderma Acid G on α-Synuclein in Caenorhabditis elegans Muscle

[0043] 1. Inhibitory effect of ganoderma acid G on α-synuclein in nematode muscle

[0044] Transgenic Caenorhabditis elegans NL5901 ([unc-54p::aLphasynucLein::YFP+unc-119(+)]) (purchased from Caenorhabditis Genetics Center, CGC) expresses α-synuclein on muscle and is linked to YFP, The stronger the fluorescence intensity, the more α-synuclein.

[0045] See Example 1 for the cultivation and synchronization treatment methods of Caenorhabditis elegans. The medication board is divided into model group, positive medicine group, ganoderma acid A intervention group, ganoderma acid B intervention group, ganoderma acid D intervention group and ganoderma acid G intervention group. No drug was added to the model group, 10 μM levodopa was added to the positive drug group, and corresponding drugs were added to each ganoderma acid intervention group, with a final concentration of 30 μ...

Embodiment 3

[0050] Example 3: Inhibitory effect of ganoderma acid G on α-synuclein on Caenorhabd nerve

[0051] 1. Inhibitory effect of ganoderma acid G on α-synuclein in UA44 nematode neurons

[0052] Transgenic Caenorhabditis elegans UA44 (baInl1[Pdat-1::α-syn high, Pdat-1::gfp]) (purchased from Caenorhabditis Genetics Center, CGC) expresses α-synuclein on dopaminergic nerves and is linked with The more GFP and α-synuclein, the more damage the nematode neurons will cause, and the weaker the fluorescence intensity will be.

[0053] See Example 1 for the cultivation and synchronization treatment methods of Caenorhabditis elegans. The medication board is divided into model group, positive medicine group, ganoderma acid A intervention group, ganoderma acid B intervention group, ganoderma acid D intervention group and ganoderma acid G intervention group. No drug was added to the model group, 10 μM levodopa was added to the positive drug group, and corresponding drugs were added to each gan...

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Abstract

The invention relates to an application of ganoderic acid G to neurodegenerative diseases. 6-hydroxyl dopamine is a neurotoxin selectively acting on catecholaminergic neurons, can be generated in thebrain by metabolism of dopamine, has obvious neurotoxicity to the neurons, and can induce Parkinson disease or aggravate the illness state of Parkinson disease. Alpha-synuclein is a neuroprotein richin the brain, and not only participates in maintenance of normal synaptic functions, but also relates to various neurodegenerative diseases. Pathological accumulation of the alpha-synuclein finally leads to apoptosis or death of neuronal cells. The ganoderic acid G is discovered that can effectively antagonize the neurotoxicity of the 6-hydroxyl dopamine, effectively reduce the content of the alpha-synuclein, and can be made into drugs for preventing and treating neurodegenerative diseases such as Parkinson disease.

Description

technical field [0001] The invention belongs to the field of medicine, relates to the new application of known compounds, in particular to the application of ganoderma acid G in neurodegenerative diseases. Background technique [0002] Parkinsonism (PD) is a progressive neurodegenerative disease. According to statistics, there are about 4.5 million Parkinson's disease patients in the world, nearly half of whom are in China. The main clinical manifestations of PD include bradykinesia, resting tremor, rigidity, abnormal gait and decreased autonomy. The main pathological hallmark of this disease is a marked loss of dopamine producing neurons in the substantia nigra compacta, which leads to a dramatic depletion of dopamine (DA) in the striatum [Ref: Parkinson's disease, New England Journal of Medicine, 1998]. [0003] 6-hydroxydopa (6-hydroxydopamine, 6-OHDA) is a neurotoxin that selectively acts on catecholaminergic neurons, and can be produced by dopamine metabolism in the b...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/575A61P25/28A61P25/16
CPCA61K31/575A61P25/16A61P25/28
Inventor 徐晓军潘吾思钱程祁励丰荣钱飞
Owner CHINA PHARM UNIV
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