Integrated UHPLC-Q-Orbitrap HRMS and Network Pharmacology Approach for Exploring Potential Active Ingredients and Pharmacological Mechanisms of Epimedii Folium Against Alzheimer's Disease.

Epimedii Folium has been widely used to treat Alzheimer's disease (AD) in China. However, the potential active components of Epimedii Folium and its mechanism against AD are still not clear. In this study, an ultra-high performance liquid chromatography coupled to quadrupole Orbitrap high-resolution mass spectrometry (UHPLC-Q-OrbitrapHRMS) method was applied to screen the ingredients of Epimedii Folium. Network pharmacology was utilized to explore the potential active components and pharmacological mechanisms of Epimedii Folium against AD. The binding affinity and conformation of key active ingredients and core targets were performed by molecular docking. Consequently, 72 chemical constituents were identified in Epimedii Folium, including four phenolic acids, two quinones, three 9,10-dihydrophenanthrenes, and 63 flavonoids. Network pharmacology analysis revealed that quercetin, apigenin, kaempferol, and luteolin exhibit favorable pharmacological activities. Molecular docking demonstrated that apigenin-TNF, kaempferol-TNF, kaempferol-TP53, and quercetin-TP53 represent compound-target pairs with strong binding affinities. These findings help elucidate the material basis and underlying mechanisms of Epimedii Folium against AD and offer valuable evidence supporting the further development and clinical application of Epimedii Folium.