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

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.