RETRACTED: Hesperidin methylchalcone (HMC) hinders amyloid-β induced Alzheimer's disease by attenuating cholinesterase activity, macromolecular damages, oxidative stress and apoptosis via regulating NF-κB and Nrf2/HO-1 pathways

Abstract

Phytocompounds therapy has recently emerged as an effective strategy to treat Alzheimer's disease. Herein, the protective effect of hesperidin methylchalcone (HMC) was evaluated through Alzheimer's disease models of Neuro-2a cells and Wistar rats. The in vitro results showed that HMC possesses significant ability to inhibit the acetylcholinesterase enzyme and exhibiting anti-aggregation and disaggregation properties. Furthermore, HMC could protect the Neuro-2a cells against Aβ-induced neurotoxicity. Simultaneously, HMC treatment significantly improved the cognitive deficits caused by Aβ-peptide on spatial memory in Wistar rats. HMC significantly enhanced the cholinergic effects by inhibiting AChE, BuChE, β-secretase activity, caspase-3 activity, and attenuating macromolecular damages and apoptosis. Notably, HMC reduced the Aβ-induced oxidative stress by activating the antioxidative defence enzymes. In addition, the HMC treatment suppressed the expression of immunocytokines such as p-NF-κB p65, p-IκBα, induced by Aβ; whereas upregulating Nrf2, HO-1 in brain homogenate. These results suggest that HMC could attenuate Aβ-induced neuroinflammation in brain via suppressing NF-κB signalling pathway and activating the Nrf2/HO-1 pathway, thereby improving memory and cognitive impairments in Wistar rats. Overall, the present study reports that HMC can act as a potent candidate with multi-faceted neuroprotective potential against Aβ-induced memory dysfunction in Wistar rats for the treatment of Alzheimer's disease.