Molecular and Cellular Biochemistry

, Volume 409, Issue 1–2, pp 199–211 | Cite as

Neuroprotective efficacy of naringin on 3-nitropropionic acid-induced mitochondrial dysfunction through the modulation of Nrf2 signaling pathway in PC12 cells

  • Gopinath Kulasekaran
  • Sudhandiran Ganapasam


Oxidative stress and mitochondrial dysfunction are implicated in neuronal apoptosis associated with Huntington’s disease. Naringin is the flavanone present in grapefruit and related citrus species possess diverse pharmacological and therapeutic properties including antioxidant, anti-apoptotic, and neuroprotective properties. The aim of this study was to investigate the protective effect of naringin on 3-nitropropionic acid (3-NP)-induced neurotoxicity in pheochromocytoma cells (PC12) cells and to explore its mechanism of action. Naringin protects PC12 cells from 3-NP neurotoxicity, as evaluated the by cell viability assays. The lactate dehydrogenase release was decreased upon naringin treatment in 3-NP-induced PC12 cells. Naringin treatment enhances the antioxidant defense by increasing the activities of enzymatic antioxidants and the level of reduced glutathione. The increase in levels of reactive oxygen species and lipid peroxidation induced by 3-NP were significantly decreased by naringin. PC12 cells induced with 3-NP showed decrease in the mitochondrial membrane potential and mitochondrial respiratory complex enzymes, succinate dehydrogenase and cytochrome c oxidase activities, and it was significantly altered to near normal upon naringin treatment. Naringin reduced the 3-NP-induced apoptosis through the modulation in expressions of B-cell lymphoma 2 and Bcl-2-associated X protein. Further, naringin enhances the nuclear translocation of Nrf2 and induces the NAD(P)H:quinone oxidoreductase-1 and Heme oxygenase-1 expressions through the phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway. Taken together, the above findings suggest that naringin augments cellular antioxidant defense capacity and reduces the 3-NP-induced neurotoxicity in PC12 cells through the PI-3K/Akt-dependent Nrf2 activation in PC12 cells.


Naringin 3-Nitropropionic acid Oxidative stress Mitochondrial dysfunction Apoptosis Nrf2 PI-3K/Akt 



We thank Lady Tata Memorial Trust, Mumbai, India and Council of Scientific and Industrial Research, New Delhi, India for financial assistance awarded to KG.

Compliance with ethical standards

Conflict of interest

The authors declare that there are no conflicts of interest.


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© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Cell Biology Laboratory, Department of BiochemistryUniversity of MadrasChennaiIndia

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