Computational Analysis for Investigating the Efficacy of Rhodiola Rosea Phytoconstituents against Alzheimer’s disease

Abstract

Alzheimer's disease is a major neurodegenerative disease and the number one cause of dementia-related death, worldwide. While there are a number of therapeutic approaches, some of these options may have side effects, thereby limiting their clinical application and necessitating the development of safer options. Accordingly, there is a growing interest in plant bioactive compounds. Hence, the current study aimed to identify potential phytochemicals of Rhodiola rosea as a therapeutic agent against Alzheimer's disease by using computational approaches.

A total of ten (10) phytochemicals representing different classes of compounds from R. rosea were selected for analysis. The selection of tau protein as a molecular target for which molecular docking studies were conducted was based on its significance in neurofibrillary tangle formation. Drug-likeness was assessed using Lipinski’s Rule of Five and ADMET properties, as primary and secondary means of screening, respectively. Molecular docking was performed to evaluate binding affinity and interactions were analysed using PyMol (version 2.5) and LigPlot+(v.1.4.5) tools.

In this study, ferulic acid demonstrated comparatively favorable docking interactions and favorable pharmacokinetic properties than memantine. The latter is a drug which is used to treat Alzheimer’s disease and was used as a comparison in this study. Based on the results, ferulic acid showed a more favorable binding property than memantine and comparatively lower predicted toxicity. Hence, it can be considered as a promising lead compound. Although, further in vitro and in vivo research is needed to confirm these results.

Keywords: ADMET, Alzheimer’s disease, ferulic acid, Lipinski’s rule, memantine, molecular docking, Rhodiola rosea, tau protein