Application of berberine dimer analog derivatives in the preparation of drugs for preventing and treating Parkinson's disease

A technology for catechin and Parkinson's disease, applied in the field of medicine, can solve the problem of not enough catechin, and achieve the effects of reducing apoptosis, preventing and treating Parkinson's disease, and protecting from oxidation

Active Publication Date: 2021-09-21
JINAN UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, there are not many studies on the structural modification of berberine to improve its activity

Method used

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  • Application of berberine dimer analog derivatives in the preparation of drugs for preventing and treating Parkinson's disease
  • Application of berberine dimer analog derivatives in the preparation of drugs for preventing and treating Parkinson's disease
  • Application of berberine dimer analog derivatives in the preparation of drugs for preventing and treating Parkinson's disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0056] The toxicity of embodiment 1 berberine and JJA-D0 to SH-SY5Y cells

[0057] SH-SY5Y cells were divided into 5×10 4 / mL inoculated in 96-well culture plate, 100 μL / well, put into 5% (v / v) CO 2 Cell culture incubator, cultured at 37 ℃ for 24h. Take out, except that the blank control group (Ctrl) is replaced with fresh culture medium, other each groups respectively replace culture medium with the culture medium that contains different concentrations of berberine (Apocynin) and JJA-D0; Wherein, the final concentration of berberine The final concentrations of JJA-D0 were 12.5, 25, 50, 100, 200, 400 μM respectively. Four replicate wells were set up for each group, and after continuing to culture for 24h, 36h, 48h, and 72h respectively, the 96-well culture plate was taken out, and MTT solution (15 μL / well) was added to each well to make the final concentration 0.5 mg / mL. After putting it into the incubator and incubating for 4 hours, suck out the solution in each well, then...

Embodiment 2

[0058] Example 2 MPP + Treatment of SH-SY5Y cells to establish in vitro Parkinson's disease cell model

[0059] SH-SY5Y cells were divided into 5×10 4 / mL inoculated in 96-well culture plate, 100 μL / well, put into 5% (v / v) CO 2 Cell culture incubator, cultured at 37 ℃ for 24h. Take it out, and replace the culture medium with different concentrations of 1-methyl-4-phenyl-pyridinium (MPP+ ) culture medium; wherein, MPP + The final concentrations were 0, 50, 125, 250, 500, 1000, 2000 μM, respectively. After continuing to culture for 24 hours, the 96-well culture plate was taken out, and MTT solution (15 μL / well) was added to each well with a final concentration of 0.5 mg / mL. After incubating for 4 hours in an incubator, suck out the solution in each well, then add DMSO (150 μL / well) to dissolve the crystals, shake for 10 minutes, and detect the OD value with a microplate reader at a detection wavelength of 570 nm. Calculate different MPP + The cell viability at the concentr...

Embodiment 3

[0060] Example 3 Protective effect of berberine on PD model cells

[0061] SH-SY5Y cells were divided into 5×10 4 / mL inoculated in 96-well culture plate, 100 μL / well, put into 5% (v / v) CO 2 In a cell culture incubator, culture at 37°C for 24h. Take out, replace the culture solution of the dosing group with the medium pre-protection 4h containing berberine of different concentrations, wherein, the final concentration of berberine is respectively 500, 1000, 1500 μ M; Blank control group (Ctrl) and model group ( Model) only fresh medium was added. After 4 hours, the medium of the model group and the drug-dosed group were added with MPP + The final concentration was 1 mM, and 4 replicate wells were set up for each group. After continuing to culture for 24 hours, the 96-well culture plate was taken out, and MTT solution (15 μL / well) was added to each well with a final concentration of 0.5 mg / mL. After putting it into the incubator and incubating for 4 hours, suck out the solu...

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Abstract

The invention discloses the application of berberine dimer analog derivatives in the preparation of medicines for preventing and treating Parkinson's disease. The structural formula of the berberine dimer analog derivative is shown in formula I. In the present invention, it is found that berberine dimer analogue derivatives or pharmaceutically acceptable salts thereof show better pharmacodynamic activity than the parent compound berberine on the in vitro cell model of Parkinson's disease, and it can obviously Improve the behavior of Parkinson's disease model mice, increase the number of dopaminergic neurons in the substantia nigra compacta, and increase the levels of dopamine and 3,4-dihydroxyphenylacetic acid in the striatum. Therefore, berberine dimer analog derivatives or pharmaceutically acceptable salts thereof can be made into related medicines for preventing and treating Parkinson's disease.

Description

technical field [0001] The invention belongs to the technical field of medicine, and relates to the application of a berberine dimer analog derivative in the preparation of drugs for preventing and treating Parkinson's disease, in particular to a berberine dimer analog derivative or its pharmaceutical Use of acceptable salts in the preparation of medicaments for preventing and treating Parkinson's disease. Background technique [0002] Parkinson's disease (Parkinson's disease, PD), also known as "parkinson's paralysis", is a common neurodegenerative disease, more common in the elderly, the average age of onset is about 60 years old, young people with onset Parkinson's disease under the age of 40 are more likely to It is rare, and the prevalence of PD in people over 65 years old in my country is about 1.7%. [0003] Parkinson's disease is a clinically incurable disease, which has a great impact on patients' physical and mental health and socioeconomic pressure. The main path...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/135A61K31/381A61K31/167A61P25/16A23L33/105
CPCA23V2002/00A61K31/135A61K31/167A61K31/381A23L33/105A61P25/16A61K2300/00A23V2200/322A23V2250/21A61P25/14C07C221/00C07C225/22C07C231/12C07C233/33C07C303/28C07C303/30C07C309/65C07C309/66C07C319/20C07C321/14C07D339/04
Inventor 蒋杰李沙王高芳冯国帅藕洋高瑞涛张志坚
Owner JINAN UNIVERSITY
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