Integrated GC-MS phytochemical profiling, network pharmacology, and molecular docking to elucidate the molecular mechanisms of Nymphoides hydrophyllum against Helminthiasis

Abstract

Helminthiasis continues to pose a significant worldwide health concern due to the rising resistance to traditional anthelmintic medications and the scarcity of viable treatments. This study sought to provide a scientific foundation for the anthelmintic efficacy of Nymphoides hydrophyllum using integrated GC–MS phytochemical profiling, network pharmacology, and molecular docking. GC–MS analysis identified numerous phytoconstituents, with phytol, squalene, and stigmasterol selected for additional computational analysis due to their pharmacological significance and drug-likeness. Network pharmacology research revealed several therapeutic targets linked to kinase-mediated signalling, oxidative stress management, immunological modulation, and cellular survival pathways. GO enrichment analysis revealed substantial participation in protein phosphorylation, membrane-associated signalling, and kinase activity. KEGG pathway enrichment demonstrated a substantial correlation with ErbB signalling, EGFR tyrosine kinase inhibitors resistance, the PD-L1/PD-1 checkpoint pathway, Th17 cell differentiation, PI3K–Akt signalling, and HIF-1 signalling pathways. Numerous hub genes, including EGFR, AKT1, MAPK1, MAPK8, JAK1, JAK2, MTOR, PIK3CA, SRC, and PRKCA, were recognised as pivotal regulators within the pathway-target network. Molecular docking studies revealed advantageous binding relationships between the chosen phytocompounds and target proteins, such as EGFR (5F19), AKT1 (2ITY), MAPK1 (2Y9Q), JAK kinase (5IKR), and acetylcholinesterase (4EJN). Among the evaluated compounds, stigmasterol demonstrated the highest binding affinity for EGFR and acetylcholinesterase, while phytol showed a favourable interaction with JAK kinase and Squalene demonstrated moderate binding affinity with acetylcholinesterase. The findings indicate that N. hydrophyllum exhibits significant anthelmintic potential by modulating many signalling pathways and parasite-related cellular mechanisms.