Calycosin improved long-term memory impairment in the very early of APP/PS1 mice.

Alzheimer's disease is a progressive syndrome characterized by cognitive dysfunction, with neuroinflammation and β-amyloid plaque deposition representing early pathological hallmarks. Activated microglia and astrocytes play pivotal roles in neuroinflammation, further exacerbating the progression of Alzheimer's disease. Calycosin, an active ingredient derived from radix astragali, binds to estrogen receptors to elicit estrogen-like effects and has demonstrated efficacy in alleviating cognitive impairment. However, the impact of calycosin on memory deficits and its underlying mechanisms in the very early stages of Alzheimer's disease remain unknown. In this study, we aimed to investigate whether calycosin can ameliorate early memory loss by inhibiting microglia and astrocyte activation in the initial stages of Alzheimer's disease. To this end, we selected 3-month-old APP/PS1 transgenic mice and administered 20 mg/kg of calycosin daily for 90 days. Our findings revealed that calycosin administration improved long-term memory impairment, but had no significant effect on short-term learning and memory. Furthermore, calycosin reduced the number of β-amyloid plaques and alleviated neuronal loss in the cortex, although no such effect was observed in the hippocampus. Notably, calycosin did not alter the number of activated astrocytes or microglia surrounding β-amyloid plaques. Collectively, these results suggest that the improvement in long-term memory function observed with calycosin is not mediated through the inhibition of glial cell activation. These findings contribute to our understanding of the potential mechanisms underlying the beneficial effects of calycosin in Alzheimer's disease and highlight the complexity of its actions in this disease.