Unveiling the Therapeutic Potential of Piper chaba Hunter: Computational Approaches Shed Light on Targeting Proteins in Alzheimer's Disease.

Abstract

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder, while the existing treatments primarily focus on alleviating symptoms rather than addressing the underlying pathophysiology. Seeking a safer alternative, the study explores the potential of Piper chaba Hunter as a promising drug lead for AD by eliciting the major signaling pathway, key players, and their interaction with phytochemicals from the plant extract. Initially, the phytochemicals in the P. chaba crude extract were identified using GC-MS, and their physicochemical properties were verified using SwissADME. Protein-protein interaction (PPI) and signaling pathways-target proteins-compounds (STC) networks were analyzed to dig out target proteins and effective compounds for AD based on rigorous screening. Approximately 60 target proteins that interacted with GC-MS-identified compounds underwent PPI and STC networking which identified five compounds, a signaling pathway, and three target proteins with therapeutic potential. Three compounds, namely, bicyclo[7.2.0]undec-4-ene, 4,11,11-trimethyl-8-methylene-,[1R-(1R∗,4Z,9S∗)], 2-methoxybenzoic acid, 2,3-dichlorophenyl ester, and (E)-3-butylidene-4,5-dihydroisobenzofuran-1(3H)-one, have the potential to modulate PTGS2, PLA2G4A, and CYP2C19 within metabolic signaling pathway, thus serving as promising therapeutic agents. Moreover, the drug likeliness and efficacy of those phytochemicals were justified by molecular docking tests (MDTs), molecular dynamics simulations (MDSs), and quantum chemistry analyses, which confirmed their ability to inhibit key targets to mitigate AD-associated pathology.