Alismatis Rhizoma prevents AβO-induced neuronal cell death and synaptic loss in Alzheimer's disease models

Alzheimer's disease (AD), the most prevalent form of dementia, is a neurodegenerative disease characterized by abnormal accumulation of amyloid-β (Aβ), which leads to memory impairment, synaptic dysfunction, and neuronal loss. This study investigated whether Alismatis Rhizoma (AR) could prevent Aβ oligomer (AβO)-induced synaptic dysfunction, neuronal cell death, and consequent memory decline.

For in vitro studies, HT22 cells and human embryonic stem cells (hESC)-derived hippocampal neurons exposed to AβO were treated with AR. For in vivo studies, we administrated AR orally at 50 and 200 mg/kg to mice intrahippocampally injected with AβO and memory function was assessed using behavioral tests. Cellular and hippocampal tissue samples were analyzed by Western blotting and immunostaining.

In AβO-injected mice, AR, particularly at 200 mg/kg, attenuated memory deficits, reduced hippocampal neuronal degeneration, preserved synaptic protein immunoreactivity and increased markers of hippocampal cell proliferation and immature neurons. These effects were accompanied by changes in PI3K/Akt/GSK-3β and ERK/CREB signaling, increased mature BDNF levels, and reduced cleaved caspase-3 levels. AR at 30 and 300 μg/mL protected HT22 cells and hESC-derived hippocampal neurons against AβO-induced loss of viability, while 300 μg/mL AR additionally reduced cleaved caspase-3 levels and increased inhibitory GSK-3β Ser9 phosphorylation in HT22 cells.

Collectively, AR attenuated AβO-induced neuronal and synaptic injury and the associated memory impairment in acute experimental models. These findings provide promising preclinical evidence for the neuroprotective potential of AR and support its further evaluation in chronic and progressive AD models.