Asperuloside as a promising multi-target agent for Alzheimer’s disease: molecular mechanisms and therapeutic perspectives

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder marked by memory loss, cognitive decline, and neuronal dysfunction. Despite advancements in understanding AD pathology, including β-amyloid plaques and tau neurofibrillary tangles, effective disease-modifying treatments remain limited. Natural compounds are being explored for their therapeutic potential in AD. Asperuloside, a bioactive iridoid glycoside, has demonstrated multi-target activity, particularly through modulation of NF-κB, Nrf2/ARE, and Wnt/β-catenin pathways, implicated in neuronal survival and synaptic plasticity. These mechanisms are relevant to AD pathology involving neuroinflammation, oxidative stress, and synaptic dysfunction, although most evidence derives from peripheral or in vitro models. Emerging studies using AD-specific in vivo (e.g., C. elegans) and cellular models (e.g., Aβ-expressing SH-SY5Y cells) provide disease-relevant insights into ASP neuroprotective potential. This review focuses on disease-specific insights into Asperuloside therapeutic actions in AD, highlighting the need for further validation using transgenic mouse models and iPSC-derived neurons.