Phytosomal Nanocarrier of <i>Tagetes erecta</i> for Anti‐Urolithiatic Therapy Through Network Systems Biology, in Vitro, and in Vivo Insights

Abstract Urolithiasis remains a persistent clinical challenge with limited preventive therapies and poor recurrence control. Despite the known antioxidant and hepatoprotective properties of Tagetes erecta (T. erecta) , its potential against urolithiasis and bioavailability enhancement through phytosomal formulation have not been explored. This study investigated the antiurolithiatic efficacy of T. erecta through an integrative in silico, in vitro, ex vivo , and in vivo approach. Network pharmacology and molecular docking identified 71 potential targets, with TP53, EGFR, SRC, and MAPK1 as major hubs. Rutin exhibited strong binding affinity with MAPK1 (–11.597 kcal/mol), confirmed by molecular dynamics (MD) simulations. A hydroalcoholic extract of T. erecta was formulated into phytosomes and evaluated for antioxidant and antiurolithiatic activities using DPPH, nitric oxide, turbidity, nucleation, aggregation, and egg membrane assays. The extract showed significant inhibition of nucleation (88.88%), aggregation (63.49%), and crystal formation (70.78%). In ethylene glycol‐induced urolithiatic rats, the phytosomal formulation (200 mg/kg) effectively restored GSH and SOD levels, reduced MDA, and improved renal histology. This is the first study to report the antiurolithiatic potential of T. erecta and its phytosomal formulation. The integrative computational to in vivo approach highlights its mechanism via oxidative stress modulation and renal protection, suggesting translational promise for phytosome‐based interventions in recurrent urolithiasis management.