Amelioration of hippocampal CA1 neuronal dysfunction by Rhizoma Amorphophalli‑derived polysaccharide GM‑1 against Alzheimer’s disease

Disordered neural signaling in the hippocampal CA1 region represents the core pathological hallmark underlying cognitive impairment in Alzheimer’s disease (AD). This work aimed to investigate the restorative effects of GM-1, a purified polysaccharide isolated from Rhizoma Amorphophalli , on hippocampal neural circuits in APP/PS1 transgenic mice and to explore its underlying mechanisms in AD. A battery of behavioral tests combined with fiber photometry and in vivo multi-channel electrophysiology was performed to quantitatively evaluate cognitive performance, neuronal calcium signals, theta oscillation power and population firing patterns in the hippocampal CA1 region. The results revealed that GM-1 markedly rescued spatial memory deficits, elevating the residence time in the target quadrant by 108.8%. It also restored neuronal calcium signal amplitude and hippocampal theta oscillations, with therapeutic efficacy comparable to memantine. Mechanistically, GM-1 remodeled the neuronal microenvironment by suppressing excessive microglial activation and restoring cerebral cytokine homeostasis, thereby concurrently rescuing neuronal electrophysiological activity and synaptic function. Collectively, multi-level evidence demonstrates that GM-1 exerts dual protective effects against neuroinflammation and neuronal injury, with no observed hepatic or renal toxicity at therapeutically effective doses. This study addresses a critical research gap by elucidating the multi-dimensional in vivo neuromodulatory mechanisms of the polysaccharide GM-1, thereby providing essential experimental evidence to support the development of safe, functional food ingredients for AD intervention.