Neurodegenerative diseases are characterized by ongoing degeneration of neurons, frequently associated with neuroinflammation, oxidative stress and excitotoxicity. The GABAergic system is crucial for inhibitory neurotransmission and its dysregulation has been implicated in conditions such as Alzheimer's disease (AD), Parkinson's disease (PD) and Amyotrophic Lateral Sclerosis (ALS). The present study aims to isolate neuroprotective agents from the phytochemicals of Piper betle Linn. utilizing methodologies such as molecular docking, network-based interaction analyses and pharmacokinetic profiling. Molecular docking studies revealed strong interactions between the compounds Stigmasterol, Kurchessine and Aletamine with the GABAA receptor (PDB ID: 4COF). These interactions demonstrated high binding affinity and significant interactions with key amino acids including TYR97, LEU99 and GLU155. ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) profiling confirmed the permeability of these compounds across the blood-brain barrier. Furthermore, network analysis using tools such as GeneMANIA and STRING elucidated their role in modulating GABAergic pathways. This investigation proposes the phytochemicals of Piper betle Linn as potential therapeutic agents for targeting neurodegenerative disorders through modulation of the GABAA receptor. Future drug development endeavors should focus on in vivo validation alongside structural modifications to improve drugability and therapeutic efficacy.
Mohan et al. (Tue,) studied this question.