Zhou_2026_Chem.Biodivers_23_e03515

Owing to the complexity and diversity of chemical constituents in natural food ingredients, functional food research has long faced two major technical challenges: the rapid and accurate screening of bioactive compounds, and their targeted preparation. This study aimed to establish an efficient strategy for screening and preparing acetylcholinesterase inhibitors (AChEIs) from Cimicifuga foetida (C. foetida) to improve the efficiency of fungal food preparation. First, the extraction process of C. foetida was optimized using the Non-dominated Sorting Genetic Algorithm II (NSGA-II) regression model. Next, the potential anti-Alzheimer's effects of the extracted active compounds were evaluated by affinity-ultrafiltration mass spectrometry (AUF-MS), molecular docking, enzyme kinetics, and network pharmacology analyses. Five compounds, namely cimifugin, cimifugoside, caffeic acid, ferulic acid, and isoferulic acid, exhibited strong binding affinity to the active site of AChEIs. These findings highlight the potential of C. foetida as a valuable source for the discovery and development of novel therapeutic agents from natural food resources.