Wei_2026_Bioorg.Chem_181_110451

Nelumbinis Plumula is a well-known traditional herb with medicinal and edible homology, which is commonly consumed as tea to clear heart-fire, calm the mind and improve sleep in daily life. A systematic phytochemical investigation on the extract of Nelumbinis Plumula was carried out, leading to the isolation of ten new benzylisoquinoline alkaloids (1-8, 17, and 18) and 14 known analogues (9-16, and 19-24). Their structures and absolute configurations were unambiguously established by comprehensive spectroscopic analysis and optical rotation measurements. Biological evaluation revealed that bisbenzylisoquinoline alkaloids 17, 18, 21, 22, and 23 possessed remarkable inhibitory effects against BChE, with IC(50) values ranging from 1.52 to 6.51 microM. Further mechanistic investigations revealed that the new compounds 17 and 18 inhibited BChE via a mixed-type inhibitory mechanism. Moreover, molecular dynamics simulation, MM/GBSA binding energy calculation, and surface plasmon resonance assay verified that compound 18 exhibited superior inhibitory activity against BChE compared with compound 17, which was in good agreement with the results of in vitro enzymatic activity assay. These bisbenzylisoquinoline alkaloids can serve as BChE inhibitors, providing a theoretical basis for the application of Nelumbinis Plumula in the prevention of neurodegenerative diseases.