Molecular Docking
and Network-Based Analysis of Piper betle Linn Phytochemicals as Potential GABA_A
Receptor Modulators for Neuroprotection
Mohan Gaanappriya and Kesavan Amala
Res. J. Biotech.; Vol. 20(11); 214-224;
doi: https://doi.org/10.25303/2011rjbt2140224; (2025)
Abstract
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 GABA_A 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 GABA_A receptor. Future drug development endeavors
should focus on in vivo validation alongside structural modifications to improve
drugability and therapeutic efficacy.
