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Application of beta hydroxybutyric acid in treatment of Parkinson disease

A technology for β-hydroxybutyric acid and Parkinson's disease, applied to nervous system diseases, anhydride/acid/halide active ingredients, drug combinations, etc.

Inactive Publication Date: 2014-06-18
XINXIANG MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The current clinical treatment of PD cannot prevent or slow down the progressive development of PD dopamine neuron damage, and the patient's condition gradually worsens with the prolongation of the disease time

Method used

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  • Application of beta hydroxybutyric acid in treatment of Parkinson disease
  • Application of beta hydroxybutyric acid in treatment of Parkinson disease
  • Application of beta hydroxybutyric acid in treatment of Parkinson disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0024] Example 1: β-Hydroxybutyrate reduces ROS in dopamine neurons in a rotenone PD cell model.

[0025] Day1: will be cultured at 25cm 2 The SH-SY5Y cells in the culture flask were made into a cell suspension, spread in a 6-well plate, about 1×10 cells per well 6 .

[0026] Day2: The cells were about 30-40% confluent, and β-hydroxybutyric acid was administered at a final concentration of 1, 2.5, and 5 mM.

[0027] Day3: Add rotenone after 24 hours, the final concentration is 0.5 μM.

[0028] Day4: After 24 hours, aspirate the medium, wash with PBS, add 1 ml of DCFH-DA fluorescent probe diluted 1:1000 with serum-free medium, incubate at 37°C for 30 min, wash the cells 3 times with serum-free medium, trypsin After digestion, centrifuge, resuspend in 1 ml PBS, and detect the fluorescence of DCF by flow cytometry. The results are shown in Table 1.

[0029] Table 1. Effect of β-hydroxybutyric acid on ROS production of dopamine neurons in rotenone PD cell model (n=6)

[003...

Embodiment 2

[0032] Example 2: Beta hydroxybutyrate reduces MPP + PD cell model dopamine neuron ROS.

[0033] Day1: will be cultured at 25cm 2 The SH-SY5Y cells in the culture flask were made into a cell suspension, spread in a 6-well plate, about 1×10 cells per well 6 .

[0034] Day2: The cells were about 30-40% confluent, and β-hydroxybutyric acid was administered at a final concentration of 1, 2.5, and 5 mM.

[0035] Day3: Join MPP after 24 hours + , with a final concentration of 1 mM.

[0036] Day4: After 24 hours, aspirate the medium, wash with PBS, add 1 ml of DCFH-DA fluorescent probe diluted 1:1000 with serum-free medium, incubate at 37°C for 30 min, wash the cells 3 times with serum-free medium, trypsin After digestion, centrifuge, resuspend in 1 ml PBS, and detect the fluorescence of DCF by flow cytometry. The results are shown in Table 2.

[0037] Table 2. Effect of β-hydroxybutyrate on MPP + PD cell model dopamine neurons produce ROS effects (n=6)

[0038] ...

Embodiment 3

[0040] Example 3: Effects of β-hydroxybutyrate on apoptosis of dopamine neurons in a rotenone PD cell model.

[0041] Apoptosis——Hoechst 33342 staining detection

[0042] Day1: Spread the dopamine neuron cell line SH-SY5Y on a 24-well plate.

[0043] Day2: The cells were about 30-40% confluent, and β-hydroxybutyric acid was administered at a final concentration of 1, 2.5, and 5 mM.

[0044] Day3: Add rotenone after 24 hours, the final concentration is 0.5 μM.

[0045] Day4: After 24 hours, Hoechst 33342 staining was performed, and cell apoptosis was detected by fluorescence microscopy.

[0046] The results showed that the rotenone PD cell model had obvious apoptosis, while pre-administration of β-hydroxybutyrate reduced the apoptosis induced by rotenone (see figure 1 ).

[0047] Apoptosis——PI Flow Cytometry

[0048] Day1: will be cultured at 25cm 2 The SH-SY5Y cells in the culture flask were made into a cell suspension, spread in a 6-well plate, about 1×10 cells per we...

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Abstract

The invention provides an application of beta hydroxybutyric acid in treatment of the Parkinson disease. The application provided by the invention has the advantages that proved by in-vitro and in-vivo pharmacological experiments, the beta hydroxybutyric acid has the effects of reducing oxidative stress of dopaminergic neurons of a Parkinson's disease model, reducing the apoptosis of the dopaminergic neurons and reducing the damage of the dopaminergic neurons of substantia nigra of a PD animal model so as to play a role in treating the Parkinson disease.

Description

technical field [0001] The invention relates to the application of β-hydroxybutyric acid, in particular to the application of β-hydroxybutyric acid in the treatment of Parkinson's disease. Background technique [0002] Parkinson's disease (PD) is the second most common neurodegenerative disease, with a prevalence of 0.3% in the population and 1-3% in people over 65 years old. The pathological features are the formation of Lewy bodies and the degeneration and damage of dopamine neurons in the substantia nigra compacta. [0003] At present, the treatment of PD is mainly to relieve motor symptoms, and there is no cure. The drugs used clinically to treat Parkinson's disease include compound levodopa preparations, anticholinergic drugs, amantadine, dopamine receptor agonists, and monoamine oxidase. B inhibitors, catechol? Oxygen? Methyltransferase inhibitors, and neuroprotective agents. Levodopa (L-dopa), as the precursor of dopamine, is the most important drug in the treatment...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/19A61P25/16
Inventor 赵营许重洁翟德胜张付美张瑞芳宋向凤杨玉新杜云红杨云雷李嵩箕谷争周度爽王平喜孙静李如利
Owner XINXIANG MEDICAL UNIV
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