Identification of BACE1 inhibitors from Panax ginseng saponins-An Insilco approach

Abstract

BACE1, a β secretase candidate enzyme, initiates the Alzheimer's disease (AD) pathogenesis via amyloid β (Aβ) peptide production serving as a potential therapeutic target. Previous experimental evidence suggested that ginsenosides, a key component of Panax ginseng, are effective against AD. In this study, we implemented a molecular modeling method to reveal the inhibitory action of ginsenosides on BACE1 activity. We selected 12 ginsenosides and performed molecular docking studies to evaluate its interaction with the BACE1 active site, which is essential for inhibition. Further ADMET filtration was applied to find drug-like molecules with a specific ability to cross blood brain barrier (BBB), and to determine toxicity. The BACE1-ginsenosides complex was further subjected to a molecular dynamics simulation to study the stability of the complex and its hydrogen bond interactions. In summary, our findings show ginsenosides CK, F1, Rh1 and Rh2 are potential BACE1 inhibitors from Panax ginseng.