In the present study, we evaluated the neuroprotective potential of
Hesperidin Methyl
Chalcone (HMC) against the neurotoxicity induced by Aβ(25-35)
peptide. HMC demonstrated higher
free-radical scavenging activity than
Hesperidin in initial cell-free studies. Investigations using the
fluorescent dye thioflavin T with Aβ(25-35)
peptide showed that HMC has the ability to combat extracellular
amyloid aggregation by possessing anti-aggregation property against oligomers and by disaggregating mature fibrils. Also, the results of the molecular simulation studies show that HMC ameliorated oligomer formation. Further, the anti-Alzheimer's property of HMC was investigated in in vitro cell conditions by pre-treating the neuro 2a (N2a) cells with HMC before inducing Aβ(25-35) toxicity. The findings demonstrate that HMC increased cell viability, reduced oxidative stress, prevented macromolecular damage, allayed
mitochondrial dysfunction, and exhibited
anticholinesterase activity. HMC also reduced Aβ induced neuronal cell death by modulating
caspase-3 activity, Bax expression and Bcl2 overexpression, demonstrating that HMC pre-treatment reduced mitochondrial damage and intrinsic apoptosis induced by Aβ(25-35).In silico evaluation against potential AD targets reveal that HMC could be a potent inhibitor of BACE-1, inhibiting the formation of toxic Aβ
peptides. Overall, the findings imply that the neuroprotective efficacy of HMC has high prospects for addressing a variety of pathogenic consequences caused by
amyloid beta in AD situations and alleviating
cognitive impairments.