Neuroprotective effect of naringin, a dietary flavonoid against 3-Nitropropionic acid-induced neuronal apoptosis

Abstract

The aim of this study was to investigate the protective effect of naringin, a flavonoid on 3-Nitropropionic acid (3-NP)-induced neurodegeneration through the modulation of intrinsic apoptotic cascade in Wistar rats. 3-NP is an irreversible inhibitor of complex II in the mitochondria. 3-NP-induced neurodegeneration has been widely used as an animal model of Huntington’s disease (HD). Increased oxidative stress is one of the major deleterious events in 3-NP-induced neuronal apoptosis. Rats administered with 3-NP showed increase in the levels of lipid peroxidation and protein carbonyl, which was significantly decreased upon naringin treatment (80 mg/kg body weight). 3-NP-induced rats showed decrease in the activities of enzymic antioxidants and reduced levels of non-enzymic antioxidants. Naringin treatment ameliorated the antioxidant status by increasing the activities of enzymic antioxidants and the levels of non-enzymatic antioxidants. 3-NP-induced rats showed decrease in the activities of ATPases in striatum, which was restored to normal level upon naringin treatment. Histopathological observation of the striatal tissue showed protective role of naringin in 3-NP-induced rats. Naringin also reduced the 3-NP-induced apoptosis via decrease in the cytochrome c release from mitochondria and caspase 3 activation as revealed by Western blot. Naringin treatment also decreased the expressions of pro-apoptotic markers like Bad and Bax. Further, naringin antagonized 3-NP-induced decrease in Bcl-2 mRNA expression. The results of this study show evidence on the neuroprotective effect of naringin against 3-NP-induced neuronal apoptosis through its antioxidant and anti-apoptotic effects.