Naringin modulates oxidative stress and inflammation in 3-nitropropionic acid-induced neurodegeneration through the activation of nuclear factor-erythroid 2-related factor-2 signalling pathway

Abstract

Nuclear factor-erythroid 2-related factor-2 (Nrf2) mediated regulation of cellular antioxidant production and the anti-inflammatory mechanism play an important role in neuroprotection against neurodegenerative diseases. Naringin a citrus flavonone, has been reported to possess neuroprotective effect against Huntington’s disease, and other neurodegenerative disorders, however the mechanisms underlying its beneficial effects on 3-nitropropionic acid (3-NP)-induced neurodegeneration are poorly defined. The objective of the present study was to investigate the neuroprotective role of naringin and delineate the mechanism of action on 3-NP-induced neurodegeneration. Rats were injected with 3-NP (10mg/kg body weight/day, i.p.) for 2weeks to develop neurodegeneration, while naringin (80mg/kg body weight/day, orally) was administered throughout the experimental period, 1h prior to 3-NP exposure. Thereafter rats were euthanized for biochemical, histological, and molecular studies. Treatment with naringin ameliorated the reduced glutathione/oxidized glutathione ratio with concomitant decrease in the levels of hydroxyl radical, hydroperoxide and nitrite in 3-NP-induced rats. Nissl staining and transmission electron microscopic studies showed that naringin modulated 3-NP-induced histological changes. Naringin induces NAD(P)H:quinone oxidoreductase-1, heme oxygenase-1, glutathione S-transferase P1 and gamma-glutamylcysteine ligase mRNA expressions through the activation of Nrf2 and decreased the expressions of pro-inflammatory mediators like tumour necrosis factor-alpha, cyclooxygenase-2 and inducible nitric oxide synthase. These results indicate that naringin might be beneficial in mitigating 3-NP-induced neurodegeneration through the enhancement of phase II and antioxidant gene expressions via Nrf2 activation; thereby modulating the oxidative stress and inflammatory responses.