Naringin Exhibits Mas Receptor–Mediated Neuroprotection Against Amyloid Beta–Induced Cognitive Deficits and Mitochondrial Toxicity in Rat Brain

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder with clinical manifestation of loss in cognitive functions in an individual. Though several drug candidates have been developed in the management of AD, an alternative option is still required due to serious adverse effects of the former. Recently, naringin exerts therapeutic benefits through rennin angiotensin system in experimental animals. However, its report on Mas receptor-mediated action against amyloid beta (Aβ)-induced mitochondrial dysfunction in AD-like animalsis lacking. The experimental dementia was induced in the male rats by intracerebroventricular administration of Aβ(1-42) on day 1 (D-1) of the experimental schedule of 14days. Naringin treatment for 14 days attenuated Aβ-induced cognitive impairments of the animals in Morris water maze (MWM) and Y-maze tests. Further, naringin ameliorated the Aβ-induced cholinergic dysfunction in terms of decrease in the activity of choline acetyl transferase (ChAT) and level of acetylcholine (ACh) and increase in the activity of acetylcholine esterase (AChE) in rat hippocampus, prefrontal cortex, and amygdala. Furthermore, naringin attenuated Aβ-induced decrease in mitochondrial function, integrity, and bioenergetics in all the brain regions. Naringin also attenuated Aβ-induced increase in mitochondrial and cytosolic calcium level in all the brain regions. Moreover, naringin reversed Aβ-induced increase in apoptosis and level of mitochondrial calcium uniporter and decrease in the level of hemeoxygenase-1 in all the brain regions. On the contrary, A779 significantly abolished the therapeutic potential of naringin on Aβ-induced alteration in behavioral, biochemical, and molecular observations in these experimental animals. Thus, these observations indicate that naringin could be potential alternative in the management of AD.