Roemerine, a Phytoconstituent of Annona senegalensis, Targets MAO-A in Alzheimer’s Disease: Network Pharmacology Integrated with Molecular Docking and Dynamics Studies

Abstract

Alzheimer’s disease (AD) is a common factor contributing to cognitive decline in aged people. The etiology of AD involves several mechanisms, including the breakdown of acetylcholine, the accumulation of amyloid beta, the formation of neurofibrillary tangles and inflammation. Several targets have been discovered in the study that are useful in reducing the cognitive decline associated with AD. By employing network pharmacology, molecular docking and MD simulations, we have ascertained that Roemerine can specifically interact with MAO-A. Network pharmacology identified a set of genes with a higher degree of interactions. MAO-A was identified as the gene with the highest interaction level with 37 other genes. MAO-A gene was interconnected with other top 10 genes with overall higher degrees of interactions. Roemerine molecule showed a binding energy of −5.27 kcal/mol, which was better than the reference ligand found to be −4.43 kcal/mol. MD simulations demonstrated that the average RMSD for Roemerine was 4.67 Å, whereas the average RMSF was 1.06 Å. Conversely, the unbound protein and the reference chemical exhibited average RMSD values of 5.57 Å and 5.74 Å, respectively. In addition, the average RMSF values for them were 1.30 Å and 1.00 Å, respectively. Based on these results, it may be inferred that Roemerine can inhibit MAO-A and potentially be used as a lead for AD.