In silico Exploration of Gmelina asiatica for Multitarget Neuroprotection in Alzheimer's Disease

Background: Gmelina asiatica, commonly known as Asian Bushbeach, has traditionally been used for neurological disorders. Objective: To identify the phytoconstituents activity in Alzheimer's disease through in silico approach. Materials and Methods: The following targets AChE, BACE1, GSK-3, and TACE1 were selected based on AD pathophysiology for in silico studies. The listed phytoconstituents were docked and MD simulations were carried out using Auto Dock and Desmond-maestro, respectively. Further, DFT studies were performed using Gaussview software. Results: Among all listed ligands, isorhoifolin was identified as the most effective compound based on binding scores of AChE (-10.9 kcal/mol), BACE1 (-10.2 kcal/mol), GSK-3 (-9.7 kcal/mol), and TACE1 (-9 kcal/mol). Further, molecular dynamics simulations of BACE1-isorhoifolin and AChE-isorhoifolin complexes demonstrated stability for up to 200 ns. Density Functional Theory (DFT) studies indicated isorhoifolin have energy gap of -0.162 eV along with that electrostatic potential surface map indicates its good reactivity and charge distribution. Additionally, ADMET analysis confirmed that isorhoifolin have drug-likeness properties and safe for human biological system. Conclusion: These study findings suggest that isorhoifolin from Gmelina asiatica may have potential anti-Alzheimer's activity meriting further biological evaluations.