Pre-clinical Evidence-based Neuroprotective Potential of Naringin againstAlzheimer’s Disease-like Pathology: A Comprehensive Review

Neurodegenerative disorders (NDs) are a group of progressive, chronic, and disabling disorders that are highly prevalent and the incidence is on a constant rise globally. Alzheimer's disease (AD), one of the most common neurodegenerative disorders is hallmarked by cognitive impairment, amyloid-β (Aβ) deposition, hyperphosphorylation of tau protein, cholinergic dysfunction, mitochondrial toxicity, and neurodegeneration. Available therapeutic agents only provide symptomatic relief and their use are limited due to serious side effects. Recent research has recognized flavonoids as potential multi-target biomolecules that can reduce the pathogenesis of AD. Naringin, a natural citrus flavonoid has been traditionally used to treat various NDs including AD, and has gained special attention because exhibits a neuroprotective effect by affecting numerous signaling pathways with minimum adverse effects. Naringin reduces deposition of Aβ, hyperphosphorylation of tau protein, cholinergic dysfunction, oxidative stress burden, mitochondrial toxicity, the activity of glutamate receptors, and apoptosis of the neuronal cells. Additionally, it reduces the expression of phosphorylated-P38/P38 and the NF-κB signaling pathway, showing that a wide range of molecular targets is involved in naringin's neuroprotective action. The present study describes the possible pharmacological targets, signaling pathways, and molecular mechanisms of naringin involved in neuroprotection against AD-like pathology. Based on the above pre-clinical reports it can be concluded that naringin could be an alternative therapeutic agent for the management of AD-like manifestation. Thus, there is a strong recommendation to perform more preclinical and clinical studies to develop naringin as a novel molecule that could be a multi-target drug to counteract AD.