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Neurotoxicity Research

, Volume 33, Issue 3, pp 656–670 | Cite as

Naringenin Decreases α-Synuclein Expression and Neuroinflammation in MPTP-Induced Parkinson’s Disease Model in Mice

  • Sugumar Mani
  • Sathiya Sekar
  • Rajamani Barathidasan
  • Thamilarasan Manivasagam
  • Arokiasamy Justin Thenmozhi
  • Murugan Sevanan
  • Saravana Babu Chidambaram
  • Musthafa Mohamed Essa
  • Gilles J. Guillemin
  • Meena Kishore Sakharkar
ORIGINAL ARTICLE

Abstract

The present study was designed to ascertain the role of naringenin (NGN), a citrus fruit flavanone, against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced α-synuclein (SYN) pathology and neuroinflammation in a mouse model. NGN was administered to C57BL/6J mice once a day for 5 consecutive days prior to the MPTP intoxication. On day 5, 40–50 min after the NGN or vehicle administration, MPTP was injected in two divided doses (2× 40 mg/kg, i.p. at 16 h apart). The animals were observed for motor functions 48 h after the first MPTP injection. The animals were then euthanized, the brains collected to analyze SYN pathology, cytokines, and oxidative stress levels in the substantia nigra region. The NGN significantly downregulated SYN and upregulated dopamine transporter (DAT) and tyrosine hydroxylase (TH) protein expressions. It also downregulated tumor necrosis factor-α (TNFα) and interleukin 1β (IL1β) mRNA expressions and improved superoxide dismutase levels. It also reduced glutathione levels when compared to vehicle-treated PD animals. The upregulation of TH corroborates to an increase in dopamine, DOPAC, and homovanillic acid turnover and motor functions with NGN treatment. To summarize, NGN, a dietary flavone, has the potential to counteract MPTP-induced dopaminergic degeneration by regulating SYN pathology, neuroinflammation, and oxidative stress. This warrants the investigation of NGN’s potential effects in a genetic model of PD.

Keywords

Naringenin Parkinson’s disease MPTP α-Synuclein Neuroinflammation Oxidative stress Motor functions 

Abbreviations

AEC

3-amino-9-ethylcarbazole

ANOVA

Analysis of variance

ATP

Adenosine triphosphate

BSA

Bovine serum albumin

CMC

Carboxy methyl cellulose

DAT

Dopamine Transporter

DOPAC

3,4-dihydroxyphenylacetic acid

GSH

Reduced glutathione

HVA

Homovanillic acid

i.p.

Intraperitoneal

IL-1β

Interleukin 1 beta

MPTP

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

NGN

Naringenin

NO

Nitric oxide

PBS

Phosphate-buffered saline

PD

Parkinson’s disease

RNA

Ribonucleic acid

RT-PCR

Reverse transcriptase-polymerase chain reaction

SEM

Standard error of the mean

SNpc

Substantia nigra

SOD

Superoxide dismutase

SYN

α-Synuclein

TBS

Tween phosphate-buffered saline

TH

Tyrosine hydroxylase

TNF-α

Tumor necrosis factor alpha

Notes

Acknowledgements

SBC profusely thanks the Scientific and Engineering Research Board (SERB), Department of Science and Technology (DST), Govt of India, for awarding (NO:SB/FT/LS-293/2012) young scientist grant.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflicts of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Sugumar Mani
    • 1
  • Sathiya Sekar
    • 2
  • Rajamani Barathidasan
    • 3
  • Thamilarasan Manivasagam
    • 4
  • Arokiasamy Justin Thenmozhi
    • 4
  • Murugan Sevanan
    • 5
  • Saravana Babu Chidambaram
    • 6
  • Musthafa Mohamed Essa
    • 7
  • Gilles J. Guillemin
    • 8
  • Meena Kishore Sakharkar
    • 9
  1. 1.Research and Development CentreBharathiar UniversityCoimbatoreIndia
  2. 2.Department of BiotechnologyDr. M.G.R. Educational and Research Institute UniversityChennaiIndia
  3. 3.Centre for Animal Research, Training and Services, Central Inter-disciplinary Research FacilityPuducherryIndia
  4. 4.Department of Biochemistry and Biotechnology, Faculty of ScienceAnnamalai UniversityAnnamalainagarIndia
  5. 5.Department of Biotechnology, Karunya Institute of Technology and SciencesCoimbatoreIndia
  6. 6.Dept of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education and Research (JSSAHER)MysuruIndia
  7. 7.Department of Food Science and NutritionCAMS, Sultan Qaboos UniversityMuscatOman
  8. 8.Neuropharmacology group, Faculty of Medicine and Health Sciences, Deb Bailey MND Research LaboratoryMacquarie UniversitySydneyAustralia
  9. 9.College of Pharmacy and NutritionUniversity of SaskatchewanSaskatoonCanada

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