LAUSR

Acetylcholinesterase (AchE) serves as an important target for Alzheimer's disease. Salvia miltiorrhiza has been used to treat cardiovascular disease for hundreds of years. However, the interaction between S. miltiorrhiza and AchE is still inadequate. Herein, an integrated method including molecular docking and experimental studies was employed to investigate the interaction. Consequently, some components were screened as potent AchE inhibitors by in silico and in vitro. Among them, miltirone (MT) and salvianolic acid A (SAA) reversibly inhibited AchE in a mixed-competitive manner. Fluorescence data revealed that SAA and salvianolic acid C (SAC) strongly quenched the intrinsic fluorescence of AchE through a static quenching mechanism, and the binding was spontaneous and dominated by hydrophobic interaction inferred by the thermodynamic parameters. The synchronous and ANS-binding fluorescence spectra suggested that SAA and SAC could bind to the enzyme and induce its conformation changes of secondary structures, which was further confirmed by Fourier transform infrared spectra. Meanwhile, molecular docking presented the probable binding modes of inhibitors to AchE and highlighted the key role of hydrophobic interaction and hydrogen bonds for the stability of docking complex. These findings put more insights into understanding the interaction of S. miltiorrhiza chemicals and AchE, as well as Alzheimer's disease.