DNA Barcoding, Phytochemical analysis, and Computational Insights into the Neuroprotective Potential of Benincasa hispida

Benincasa hispida is a traditionally employed medicinal plant recognized for its diverse therapeutic benefits, including neuroprotective effects. The present study evaluated the binding affinity of phytochemicals derived from this plant against selected molecular targets of Alzheimer’s disease (AD). Plant material was authenticated through morphological features and DNA barcoding. Phytochemical constituents were identified through literature survey and GC-MS analysis. Among 79 identified compounds, 74 satisfied Lipinski’s criteria for oral bioavailability. These compounds were virtually screened against selected AD targets: acetylcholinesterase (AChE), β-secretase 1 (BACE1), gamma-aminobutyric acid receptor (GABABR), and glycogen synthase kinase-3β (GSK3β). Molecular docking results revealed that several compounds exhibit strong binding affinities across multiple targets than the controls. Notably, ‘9-octadecenoic acid’ demonstrated the highest docking scores against AChE (133.87), BACE1 (159.36), and GABABR (154.74), whereas naringenin showed the strongest interaction with GSK3β (88.57). Network pharmacology analysis revealed that BACE1 had the highest number of interacting phytochemicals (35), followed by GABABR with 21 compounds. AChE displayed the fewest interactions, involving 14 phytochemicals. Among the top-scoring compounds, 11 were found to interact with all three targets. Overall, these findings highlight Benincasa hispida as a promising source of neuroprotective agents that merit further exploration for the development of AD therapeutics.