Comparative molecular docking studies of lupeol and lupenone isolated from Pueraria lobata that inhibits BACE1: Probable remedies for Alzheimer's disease

ABSTRACT

Objective To discover lead lupane triterpenoid's potential isolated from Pueraria lobata roots against β-site amyloid precursor protein cleaving enzyme 1 (BACE1), which serve as a rate limiting step in amyloid beta (Aβ) production altering the course of Alzheimer's disease. In addition, enzyme kinetics study and molecular docking were conducted to establish the inhibition type and structure activity relationship. Methods A systematic study of 70% ethanolic P. lobata root extract was employed to identify its BACE1 inhibitory potential. Further, BACE1 inhibitory potential of two lupane terpenoids, yielded from ethanolic extract, was assessed. In order to determine their inhibition mode, Lineweaver–Burk plots and Michaelis–Menten model for BACE1 was performed. AutoDock 4.2 program in addition determined the molecular interaction of BACE1 with isolated terpenoids. Results Considering the inhibitory potential of 70% ethanolic extract of P. lobata against BACE1 (IC