Roasted Astragalus membranaceus Inhibits Cognitive Decline in 5xFAD Mice by Activating the BDNF/CREB Pathway

Alzheimer's disease (AD) is a complex pathological process that incurs significant societal costs, yet effective treatments have not yet been developed. Novel compounds targeting β-amyloid, based on the amyloid cascade hypothesis, have failed to demonstrate clinical efficacy. Among natural products with diverse mechanisms, components contained in <i>Astragali radix</i> have shown anti-dementia effects in various preclinical studies, including improved cognitive function, reduced β-amyloid levels, and decreased insulin resistance. This study administered a water-extracted roasted <i>Astragali radix</i> (RA) to 3-month-old female 5xFAD mice for 3 months, observing changes in cognitive behavior, blood glucose, and neural signaling. RA lowered glucose levels, improved working memory, fear avoidance memory, and spatial memory, and reduced anxiety behavior in 5xFAD mice. In the hippocampus, the protein expression of BDNF and p-CREB/CREB was increased, while p-JNK/JNK was decreased. The effects of RA were similar to unroasted <i>Astragali radix</i> in 5xFAD mice, with some components being more abundant. Therefore, RA enhances its taste and aroma, making it suitable for long-term consumption in the form of tea, which could be effective in preventing neurodegenerative diseases such as dementia.