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.

Objectives

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.