Gut-brain axis modulation of Prosopis juliflora pods: Integrated in silico and in vivo approach for neuroprotective and gut restorative therapeutics

The invasive spread and ecological burden of Prosopis juliflora, especially its adverse effects on groundwater resources, underscore the urgent need for sustainable ways to utilize this species. This study aimed to valorize P. juliflora by exploring the gut health - promoting, metabolic, and therapeutic potential of its pod extracts. The phytochemical constituents of the aqueous pod extract were characterized using Gas Chromatography-Mass Spectrometry (GC-MS) and Fourier Transform Infrared (FTIR) spectroscopy. Network pharmacology software tools were used to identify the therapeutic significance and gene-level interactions of key bioactive compounds. The zebrafish (Danio rerio) model served as an in vivo system to evaluate toxicity and gut restoration effects. Analytical characterization using GC-MS and FTIR confirmed the presence of important phenolic compounds, alkaloids, flavonoids, and glycosides in the extract. Histopathological evaluation revealed a dose-dependent toxic response, mainly associated with phenolic and flavonoid constituents, with a calculated probit LC₅₀ of 15.20 ppm. Network pharmacology analysis revealed strong interactions between the extract’s bioactive compounds and several neuroprotective and gut-related targets, including GPR30, ESR1, and PPARG. These interactions suggest significant therapeutic potential for supporting neurological health and modulating inflammatory bowel conditions. The in vivo findings further underscore the importance of dose optimization to achieve the best therapeutic outcomes with minimal toxicity, indicating the biomedical potential of P. juliflora in treating gut-brain axis related disorders.