UHPLC-QTOF-ESI-/MS characterised methanolic leaves extract of Momordica foetida Schumach. (Cucurbitaceae: Cucurbitales) possesses anti-Salmonella properties: In vitro, in vivo, molecular docking and molecular dynamics simulations approach.

Ethnopharmacological practices have long utilized Momordica foetida Schumach. (Cucurbitaceae: Cucurbitales) in traditional medicine. Notwithstanding its extensive utilization, the scientific validation of its therapeutic effects, particularly in the context of typhoid diseases, remains scarce. This study aimed to evaluate the chemical composition, curative effect and in silico prediction of M. foetida extract against S. typhimurium-induced typhoid fever in rats. UHPLC-QTOF-ESI/MS analysis examined the chemical composition of M. foetida. Then, in vitro anti-Salmonella properties of the extract were evaluated on Salmonella strains and isolates. DPPH, ABTS and FRAP assays evaluated its antioxidant properties. S. typhimurium-induced typhoid fever in rats was used to evaluate the anti-Salmonella properties of the extract. Molecular dynamics simulations validated the binding interactions between the identified compounds against SseK3 and DNA gyrase B. UHPLC-QTOF-ESI/MS analysis revealed the presence of nine compounds. In vitro anti-Salmonella test of the extract showed inhibitory activity against bacteria used with MIC between 64 and 512 μg/mL. Crude extract of M. foetida leaves showed variable activities on DPPH (RSa50: 157.73 ± 0.02 μg/mL), ABTS (RSa50: 143.49 ± 0.02 μg/mL), and FRAP (RSa50: 125.35 ± 3.4 μg/mL). The extract restored haematological and biochemical parameters close to the normal control. Molecular docking and dynamics simulations further supported these findings, demonstrating strong and stable binding interactions between momordicoside E with SseK3 and quercetin with DNA gyrase B. Finally, toxicity prediction revealed an acceptable safety profile for quercetin and momordicoside E. These results indicate clear evidence supporting the anti-Salmonella activity of M. foetida, and may be good potential drugs in typhoid treatment.