In Silico Studies on the Phytochemicals from Aframomum melegueta Leaves against Key Enzymes as Anti-Alzheimer’s Disease Target

Abstract

Traditional medicine has been practiced for ages across the world using plants as a memory booster and in the treatment of neurodegenerative diseases such as dementia and amnesia. The tau, amyloid hypothesis and neuroinflammation hypothesis are major partakers in a combinational approach in the development of therapy against Alzheimer’s disease (AD), Acetyl and butyryl cholinesterases inhibitors have been investigated in clinical trials of AD for a very long time. This research involved an in-silico approach to study the interactions of phytochemicals in Aframomum melegueta leaves with some enzymes that have been reported in the literature which contribute to neuronal death and memory loss associated in AD. In these studies, Curcumin and Lilacin are shown to have a higher glide score than the co-crystallized ligands of either Acetylcholinesterase, Butyrylcholinesterase or GSK-3β, they also have higher glide scores than AChE inhibitor Rivastigmine. The ADMET/tox properties of our lead compounds (curcumin and lilacin) ranked them as good candidates for AD drug development, as well as possess the highest docking scores against acetylcholinesterase, butyrylcholinesterase and GSK-3 beta suggesting potent compounds in Alzheimer’s disease therapy. The pharmacokinetics studies also showed that curcumin and lilacin would pass through the blood brain barrier into the brain. This work is in line with recent multi-dimensional approach in drug development in that a single compound might possess many active groups which can activate/inhibit more than one protein without any toxic effect.