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


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.


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





Analysis of variance


Adenosine triphosphate


Bovine serum albumin


Carboxy methyl cellulose


Dopamine Transporter


3,4-dihydroxyphenylacetic acid


Reduced glutathione


Homovanillic acid




Interleukin 1 beta






Nitric oxide


Phosphate-buffered saline


Parkinson’s disease


Ribonucleic acid


Reverse transcriptase-polymerase chain reaction


Standard error of the mean


Substantia nigra


Superoxide dismutase




Tween phosphate-buffered saline


Tyrosine hydroxylase


Tumor necrosis factor alpha



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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