Alpha-asarone Improves Cognitive Function of APP/PS1 Mice and Reducing Aβ42, P-tau and Neuroinflammation, and Promoting Neuron Survival in the Hippocampus

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disease most often characterized by memory impairment and cognitive decline. Alpha-asarone has been reported to have the potential to treat AD. Our previous studies have found that alpha-asarone improves aged rats’ cognitive function by alleviating neuronal excitotoxicity via type A gamma-aminobutyric acid (GABA) receptors. GABA level’s change, neuroinflammation, and dysfunctional autophagy are found to be associated with AD. However, the effect of alpha-asarone on cognitive function of APP/PS1 transgenic mice and its underlying mechanism in terms of aggregation of amyloid-β42 (Aβ42) and phosphorylated tau (p-tau), glutamic acid decarboxylase (GAD) level, neuroinflammation, and autophagy are unclear. Accordingly, we attempted to explore whether alpha-asarone improves AD mice’s cognitive function and alleviates pathological symptoms by regulating GAD level, inhibiting neuroinflammation, or restore autophagy. We found that alpha-asarone enhanced spatial learning memory and decreased Aβ42 and p-tau levels without influencing the GAD level in APP/PS1 transgenic mice. Also, it decreased the GFAP expression and reduced pro-inflammatory cytokines levels, thus alleviating neuroinflammation. Furthermore, alpha-asarone decreased the excess number of autophagosomes and promoted hippocampal neurons’ survival. In conclusion, the results confirmed the therapeutic effect of alpha-asarone on AD-related astrogliosis, dysfunctional autophagy, and neuronal damage, which indicates its great potential to treat AD.