Potential therapeutic effects of antagonizing adenosine A2A receptor, curcumin and niacin in rotenone-induced Parkinson’s disease mice model

Abstract

Parkinson’s disease (PD) is the second common age-related neurodegenerative disease. It is characterized by control loss of voluntary movements control, resting tremor, postural instability, bradykinesia, and rigidity. The aim of the present work is to evaluate curcumin, niacin, dopaminergic and non-dopaminergic drugs in mice model of Parkinson’s disease through behavioral, biochemical, genetic and histopathological observations. Mice treated with rotenone rerecorded significant increase in adenosine A2A receptor (A2AR) gene expression, α synuclein, acetylcholinesterase (AchE), malondialdehyde (MDA), angiotensin-II (Ang-II), c-reactive protein (CRP), interleukin-6 (IL-6), caspase-3 (Cas-3) and DNA fragmentation levels as compared with the control group. While, significant decrease in dopamine (DA), norepinephrine (NE), serotonin (5-HT), superoxide dismutase (SOD), reduced glutathione (GSH), ATP, succinate and lactate dehydrogenases (SDH &LDH) levels were detected. Treatment with curcumin, niacin, adenosine A2AR antagonist; ZM241385 and their combination enhanced the animals’ behavior and restored all the selected parameters with variable degrees of improvement. The brain histopathological features of hippocampal and substantia nigra regions confirmed our results. In conclusion, the combination of curcumin, niacin and ZM241385 recorded the most potent treatment effect in Parkinsonism mice followed by ZM241385, as a single treatment. ZM241385 succeeded to antagonize adenosine A2A receptor by diminishing its gene expression and ameliorating all biochemical parameters under investigation. The newly investigated agent; ZM241385 has almost the same pattern of improvement as the classical drug; Sinemet®. This could shed the light to the need of detailed studies on ZM241385 for its possible role as a promising treatment against PD. Additionally, food supplements such as curcumin and niacin were effective in Parkinson’s disease eradication.

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Contributions

TKM, NAHS and MAH: Participated in study design, revised the statistical analysis and revised the manuscript. SAA: Analyzed the histopathological pictures, drafted and revised this section. WKBH: Conducted the genetic and DNA analysis, drafted and revised this section. YRA: Conducted the biochemical parameters, analyzed the data and drafted the article. All authors revised the final form of the paper and agreed for publication.

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Correspondence to Manal A. Hamed.

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Ethical approval

Animals care during the experiments were carried out in keeping with agreement of the Medical Ethical Committee, National Research Centre, Egypt (Approval No. 16089) and Ethics Committee of Faculty of Pharmacy, Cairo University, Cairo, Egypt (BC 1839). Basic housing requirements and regular inspection of facilities that mandate the control of pain and suffering during the experiment were conducted. Euthanasia was done rapidly and painlessly to be sure that the animals do not suffer at any stage of the experiment. Getting-rid of the animals after termination was done rapidly by the aid of the Safety and Health Committee at National Research Centre, Dokki, Giza, Egypt.

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Motawi, T.K., Sadik, N.A.H., Hamed, M.A. et al. Potential therapeutic effects of antagonizing adenosine A2A receptor, curcumin and niacin in rotenone-induced Parkinson’s disease mice model. Mol Cell Biochem 465, 89–102 (2020). https://doi.org/10.1007/s11010-019-03670-0

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Keywords

  • Curcumin
  • Niacin
  • Rotenone
  • Parkinson’s disease
  • ZM241385