Application of metformin in preparations of drugs for treatment of Parkinson's disease

A technology for metformin and Parkinson's disease, applied in the field of preparation of drugs for the treatment of Parkinson's disease, can solve problems such as failure to prevent apoptosis of DA neurons in the substantia nigra, reduction of mitochondrial energy production, and axonal transmission dysfunction, etc., to achieve Improve the effect of lowering the level of dopamine in the brain, huge market value and social benefits, and inhibiting the production of ROS

Inactive Publication Date: 2012-10-24
NANJING MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, the pathogenesis of PD has not been fully elucidated, and many factors such as aging, inflammation, genetics, and environmental toxins are its common pathogenic factors; the pathological mechanism includes impaired neuron and glial cell function, axonal transmission dysfunction, glutamine Acid excitotoxicity, elevated reactive oxygen species (ROS) levels, impaired metabolic pathways, decreased mitochondrial energy production, increased formation or inadequate degradation of misfolded proteins
At present, there is still a lack of effective methods for clinical treatment, and levodopa (L-DOPA) replacement therapy is mainly used. Although it can relieve the early symptoms of most patients, it cannot prevent the pathological process of progressive apoptosis and necrosis of DA neurons in the substantia nigra. Mortality, long-term application can also produce severe complications such as movement disorders

Method used

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  • Application of metformin in preparations of drugs for treatment of Parkinson's disease
  • Application of metformin in preparations of drugs for treatment of Parkinson's disease
  • Application of metformin in preparations of drugs for treatment of Parkinson's disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] Example 1 Neuroprotective effect of metformin on chronic MPTP / p Parkinson's disease model mice

[0036] 1.1 Experimental materials

[0037] 3-4 months old, male C57BL / 6J mice. Feeding conditions included standard feed, tap water, room temperature maintained at (24 ± 2) °C, humidity 50-60%, and daily light and dark times of 12 hours each. Before the experiment, the animals were placed in the experimental environment for 3 days to adapt.

[0038] Metformin (Metformin, Met) was purchased from Sigma (St. Louis, MO, USA), and probenecid was purchased from Jinan Times Pharmaceutical Technology Co., Ltd. Met is prepared into drinking water with distilled water, the final concentration is 5mg / ml. MPTP was prepared with normal saline within 30 min before administration and kept on ice. Probenecid was prepared in DMSO within 30 minutes prior to dosing.

[0039] 1.2 Experimental method

[0040] Mice were randomly divided into 4 groups after weighing: A: Saline; B: MPTP / p; ...

Embodiment 2

[0053] Implementation example 2 metformin is to MPP + induce Protective effect of SH-SY5Y cell injury

[0054] 2.1 Experimental materials

[0055] SH-SY5Y cell line: dopaminergic neuron cell line, purchased from Union Cell Institute, Chinese Academy of Medical Sciences. MPP + and Compound C were purchased from Sigma Company (St. Louis, MO, USA); methazolium blue (MTT) was purchased from Guangzhou Chemical Reagent Factory; microplate reader was purchased from Thermo Company.

[0056] 2.2 Experimental method

[0057] Cells were seeded on 96-well plates and cultured for 24 hours, then the culture medium was replaced, and the cells were randomly divided into groups. After pretreatment with Met (1mM) for 30 min, give MPP + (500 μM, 48h), 20 μl of 5 mg / ml MTT solution was added to each well, and the incubation was continued for 4 hours before the culture was terminated. Carefully discard the culture supernatant in the wells, add 150 μl DMSO to each well, select a wavelengt...

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Abstract

The present invention provides an application of metformin in preparations of drugs for treatment of Parkinson's disease (PD). Experiment results show that: with the metformin, behavioral disorders of PD model mice are significantly improved; dopaminergic neuron loss of mice midbrain substantia nigra compact part (SNc) and ventral tegmental area (VTA) due to MPTP/p is reduced; levels of dopamine (DA) and metabolites thereof in corpus striatum are improved; excessive proliferation activation of astrocyte is inhibited; and reduction of dopaminergic neuron cell line SH-SY5Y cell viability, and increases of lactate dehydrogenase (LDH) generation and reactive oxygen species (ROS) generation are inhibited, wherein the reason of the reduction of dopaminergic neuron cell line SH-SY5Y cell viability, and the increases of lactate dehydrogenase (LDH) generation and reactive oxygen species (ROS) generation is MPP<+>. In addition, the results show that the metformin provides pharmacological effects for treatment of PD. According to the application of the present invention, the metformin is adopted as an active ingredient to prepare drugs for treatment of PD.

Description

technical field [0001] The invention belongs to the field of medicines and relates to the application of metformin in the preparation of medicines for treating Parkinson's disease. [0002] Background technique [0003] Metformin (Metformin, Met) is a biguanide oral hypoglycemic drug, clinically used for non-insulin-dependent diabetic patients who are not satisfied with simple diet control, especially obese patients. Metformin has multiple mechanisms of action, including delaying glucose uptake from the gastrointestinal tract, increasing peripheral glucose utilization by increasing insulin sensitivity, and inhibiting excessive gluconeogenesis in the liver and kidney. This product does not reduce the blood sugar level of non-diabetic patients. During the treatment period, the patients usually lose weight, the plasma cholesterol, triglyceride and pre-beta lipoprotein levels are reduced, and the peripheral glucose metabolism is improved. In recent years, studies have shown th...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/155A61P25/16
Inventor 胡刚苏存锦鲁明丁建花孙红彬乔晨
Owner NANJING MEDICAL UNIV
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