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Application of polyketide compound pestalpolyol A as a drug for the treatment of Alzheimer's disease

A technology of Alzheimer's disease and polyketide compounds, which is applied in the application of drugs for the treatment of Alzheimer's disease. , the effect of simple structure

Inactive Publication Date: 2019-09-27
YUNNAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Despite understanding of the pathogenesis of Alzheimer's disease, current drugs to inhibit or reverse Alzheimer's disease are still very limited

Method used

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  • Application of polyketide compound pestalpolyol A as a drug for the treatment of Alzheimer's disease
  • Application of polyketide compound pestalpolyol A as a drug for the treatment of Alzheimer's disease
  • Application of polyketide compound pestalpolyol A as a drug for the treatment of Alzheimer's disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0013] Example 1 Screening of Compounds Effective on Alzheimer's Disease Model Nematode Strain CL4176

[0014] (1) Cultivate the Alzheimer's disease model nematode strain CL4176 on a medium covered with E. coli OP50, in a constant temperature incubator at 15°C for about 3-4 days, observe that most nematodes start to lay eggs and then synchronize change.

[0015] (2) After the worms in step (1) were synchronized, they were cultured in a constant temperature incubator at 15°C for 48 hours to hatch L1.

[0016] (3) Prepare a Petri dish containing NGM. Add 30 μM of pestalpolyol A and its structural analogues pestalpolyol B, pestalpolyol G, pestalpolyol E, and pestalpolyol F to 200 μL each and dry, then add 200 μl of E.coli OP50 to dry and place in a constant temperature incubator at 37°C for overnight culture. A blank control group was set up for each experiment, that is, only 200 μL of solvent acetone and 200 μL E.coli OP50 were added, and a positive control group was 200 μL of...

Embodiment 2

[0022] Example 2 Different concentrations of pestalpolyol A in the treatment of Alzheimer's disease

[0023] (1) Cultivate CL4176 nematodes on a medium covered with OP50 in a constant temperature incubator at 15°C for about 3-4 days, observe that most of the nematodes begin to lay eggs and then synchronize.

[0024] (2) After the worms in step (1) were synchronized, they were cultured in a constant temperature incubator at 15°C for 48 hours to hatch L1.

[0025] (3) Prepare a petri dish containing NGM, add 200 μL of compound pestalpolyol A with a concentration of 10, 30, 50, 100, 200, 300, and 500 μM respectively and dry it, then add 200 μL of E.coli OP50 to dry it and place it at 37 Cultivate overnight in a constant temperature incubator. A blank control group (only 200 μL of solvent acetone and 200 μL of E.coli OP50) and a positive control group (200 μL of 30 μM Galantamine and 200 μL of E.coli OP50) were set for each experiment, and each experiment was performed in triplic...

Embodiment 3

[0031] Example 3 Cytotoxicity detection of polyketide compound pestalpolyol A

[0032] MTT method:

[0033] (1) Collect the logarithmic phase cells, add 100 μL of cell suspension to each well of the 3-10 column of the 96-well cell plate, plate and adjust the cell density to 10 4 Add 100 μL of cell-free medium to the 2nd and 11th columns of the well plate, and fill the 1st and 12th columns of the well plate with 100 μL of sterile PBS.

[0034] (2) 5%CO 2 , and incubated at 37°C until the cell monolayer covered the bottom of the 96-well cell plate. Drugs can be added after the cells adhere to the wall. In this experiment, the plates were plated in the afternoon before the drug addition, and the drugs were added in the morning of the next day. Add 10 μM drug to column 3 and 4, add 30 μM drug to column 5 and 6, add 50 μM drug to column 7 and 8, 10 μL per well, and set 16 replicate wells.

[0035] (3) 5%CO 2 , incubated at 37°C for 48 hours, and observed under an inverted micr...

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Abstract

The invention discloses an application of polyketone compounds pestalpolyol A as a drug for treating the alzheimer disease. A caenorhabditis elegans model CL4176 of the alzheimer disease is taken as aresearch target, a commercial medicine galanthamine of the alzheimer disease is taken as positive control, and small molecule compounds capable of effectively inhibiting caenorhabditis elegans CL4176paralysis can be effectively screened from a large quantity of natural products or artificially synthesized compounds. A paralysis experiment result proves that compared with the positive control galanthamine, the added polyketone compounds pestalpolyol A with the same concentration have a better effect on inhibiting caenorhabditis elegans paralysis, the inhibition function has concentration dependence in the concentration range of 100 mu M, and the cytotoxicity is smaller.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and in particular relates to the application of polyketide compound pestalpolyol A as a drug for treating Alzheimer's disease. Background technique [0002] Alzheimer's disease (AD) is a common senile neurodegenerative disease. The clinical symptoms of the disease are progressive impairment of memory, cognition, and mental ability, which eventually leads to the loss of self-care ability and the need to rely on the help of others to carry out daily life. Therefore, Alzheimer's patients will bring a heavy economic burden to families and society. According to WHO statistics in 2014, there are more than 36 million Alzheimer's patients in the world, and by 2050, the number of Alzheimer's patients will reach 115 million. [0003] Amyloid beta peptide (Aβ) is a transmembrane protein that is a key causative factor in Alzheimer's pathogenesis. The precursor of β-amyloid produces Aβ through the prot...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/047A61P25/28C12P7/18C12R1/645
Inventor 黄晓玮赵沛基孙诺竹玛张东华李玉宏
Owner YUNNAN UNIV
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