Neuroprotective upshot of isorhoifolin flavonoid of Gmelina asiatica for multitargeted approach in Alzheimer's disease: Exploration through in-silico studies

Abstract

Abstract Alzheimer's is a progressive neurodegenerative disease with amyloid-beta peptide deposition that impairs memory and cognitive decline. In previous reports, the plant Gmelina asiatica was reported to have anti-Alzheimer’s disease (AD) activity. However, the responsible chemical constituents of G. asiatica for anti-Alzheimer’s activity have not been explored. Therefore, the present study aimed to investigate hit compounds through an in silico approach. The reported phytoconstituents were initially screened through auto dock software. Then, the lead compound was further evaluated through molecular dynamic studies. Further hit compound isorhoifolin physicochemical and ADMET properties were analyzed. In docking studies, isorhoifolin showed the least binding energy and well resided at the active sites of AchE (-10.9 kcal/mol), BACE1 (-10.2 kcal/mol), GSK-3 (-9.7 kcal/mol), TACE1 (-9 kcal/mol). Further molecular dynamic simulation revealed that isorhoifolin is stable up to 200 ns. Furthermore, density functional theory (DFT) was analyzed using Gaussian software, where the quantum mechanics objective was focused. Besides, the physicochemical properties of isorhoifolin were studied, such as absorption, distribution, metabolism, excretion, and toxicity, through the pkcsm software. The study suggests isorhoifolin from the Gmelina asiatica plant may be responsible for anti-Alzheimer's activity, which may be considered for further investigation.