Our results highlight the therapeutic potential of AST-LI as a SIRT-1 activator in reducing synaptic deficits and cognitive impairments linked to AD through the regulation of SIRT-1/BDNF/miRNA-134/GSK-3β axis that modulates the amyloidogenic, cholinergic, oxidative stress, neuroinflammatory, and apoptotic pathways. Here, BDNF is linked to Alzheimer disease.