Chemical characterization of anti-amyloidogenic phytochemicals from Aconogonon alpinum: Attenuation of cognitive impairment in scopolamine-induced mice

Neurodegenerative diseases are characterized by abnormal protein aggregation and oxidative stress, which contribute to neuronal damage and cognitive decline. Aconogonon alpinum, known as Shinga in Korea, is a perennial Polygonaceae plant traditionally used in folk medicine for its anti-inflammatory properties, yet its neurobiological potential remains poorly characterized. In this study, we investigated the amyloid-related processes and cognitive-enhancing effects of A. alpinum extract through bioactivity-guided isolation and pharmacological evaluation. In APPswe-transfected HeLa cells, A. alpinum extract significantly reduced amyloid-β (Aβ)42 secretion in a concentration-dependent manner. In addition, the extract attenuated glutamate-induced oxidative stress in HT-22 hippocampal cells, accompanied by upregulation of brain-derived neurotrophic factor (BDNF) and cAMP response element-binding protein (CREB), indicating enhanced neuronal resilience. In a scopolamine-induced cognitive impairment mouse model, oral administration of A. alpinum extract improved memory performance across behavioral paradigms, including passive avoidance, novel object recognition, and Y-maze tests. These effects were accompanied by modulation of cholinergic signaling, synaptic integrity, neuroplasticity, and amyloidogenic processing in the hippocampus and cortex. Bioactivity-guided isolation identified two flavonol-derived compounds that suppressed β-secretase activity, reduced Aβ40/42 secretion, and modulated amyloid-related processes in vitro. Collectively, these findings suggest that A. alpinum may modulate multiple pathways associated with cognitive dysfunction and may contribute to its cognitive supportive effects.