<i>Allium Macrostemon</i> Bge. Attenuates the Cognitive Decline of Aging Mice by Enhancing <scp>BDNF</scp>/<scp>TrkB</scp> Pathway

<i>Allium macrostemon</i> Bge. (AM) is a widely utilized culinary spice recognized for its numerous health-promoting properties. Aging-related cognitive impairment (ARCI) represents a significant global health concern during the aging process. However, the potential of AM to attenuate ARCI has not been investigated. This work aims to reveal the effects and potential mechanisms of the water extraction of AM (WEAM) in alleviating ARCI, with a particular emphasis on the BDNF/TrkB signaling pathway. The findings showed a significant enhancement in memory function and a reduction in hippocampal neuronal damage in aging mice following treatment with WEAM, manifested by an increased spontaneous alternation rate in the Y-maze, prolonged step-through latency, and decreased number of errors in the PAT test, a shortened escape latency and increased platform swimming time and platform crossing times in the MWM test. Additionally, WEAM reduced oxidative stress, elevated the expression of proteins related to synaptic plasticity (SYN and PSD95), and activated the BDNF/TrkB signaling pathway in D-galactose-induced aging mice. To elucidate the mechanism by which WEAM alleviates ARCI, both a TrkB activator (7,8-DHF) and an inhibitor (ANA-12) were employed. The results demonstrated that the effects of WEAM on synaptic plasticity were potentiated by 7,8-DHF and diminished by ANA-12. Finally, 11 chemical compositions of WEAM were analyzed and quantified using HPLC-MS/MS, including macrostemonoside, sarsasapogenin, diosgenin, timosaponin AIII, N-p-trans-coumaroyltyramine, guanosine, adenosine, phenylalanine, adenine, arginine, and valine. These results suggest that AM may serve as a promising culinary spice for mitigating ARCI by promoting the BDNF/TrkB signaling pathway, thereby enhancing synaptic plasticity.