An Integrated Pharmacoinformatics analysis on Prosopis juliflora bioactives to divulge EGFR-Mediated Crosstalk in the Gut–Brain Axis

The gut–brain axis (GBA) plays a pivotal role in maintaining neuroimmune and gastrointestinal homeostasis. Disruption of this bidirectional communication is implicated in disorders such as inflammatory bowel disease (IBD), autism spectrum disorders, and neuroinflammation. This study explores the therapeutic potential of phytocompounds derived from the lignocellulose extracted from the pods of Prosopis juliflora for modulating the GBA through an integrated in-silico approach. Gas Chromatography–Mass Spectrometry (GC-MS) analysis was used to identify 22 bioactive compounds from nanocellulose extract. Network pharmacology and protein–protein interaction (PPI) analysis was employed to identify key targets, followed by pathway enrichment to evaluate biological relevance. Molecular docking studies were conducted against EGFR (PDB ID: 4WKQ), and ADMET profiling was performed using SwissADME to assess pharmacokinetic fitness. EGFR emerged as a central hub gene bridging neurotrophic signalling and gut epithelial repair. Among the screened compounds, C13 (2H-Pyran-2-one, 5,6-dihydro-6-pentyl-) and C16 (2(3H)-Furanone, dihydro-3-(phenylmethyl)-) demonstrated strong binding affinity with key EGFR residues (THR854 and ASP855), suggesting a modulatory role. ADMET analysis confirmed high gastrointestinal absorption, blood-brain barrier permeability, and favourable drug-likeness without cytochrome P450 inhibition. The findings suggest that P. juliflora -derived compounds, particularly C13 and C16, hold promise for dual-targeted GBA modulation. These results warrant further in vitro and in vivo validation and support the development of lignocellulose-based nanocarriers for targeted delivery in gut-neurotherapeutics.