Targeting Ferroptosis and Oxidative Stress: Ipomoea Pes-Caprae-synthesized Selenium Nanoparticles Accelerate Healing in Infected Wounds Via Nrf2/HO-1 Activation

This study was designed to uncover the therapeutic potential of Ipomoea pes-caprae extract (IPE) and its green-synthesized selenium nanoparticles (Se NPs) in enhancing the healing of Pseudomonas aeruginosa-infected wounds in rats, with a focus on the modulation of ferroptosis and the Nrf2/HO-1 signaling pathway. The HPLC analysis of IPE revealed 14 phenolic acids and flavonoid compounds. The green-synthesized Se NPs were characterized using UV-Vis spectroscopy with peaks at 233 and 277 nm, confirming nanoparticle formation. The XRD indicated a nanocrystalline structure with an average crystallite size of 68.43 nm. The FTIR identified functional groups from the IPE involved in capping and stabilizing the Se NPs. The SEM and TEM images showed predominantly spherical particles, while EDX confirmed elemental selenium alongside carbon and oxygen, indicating phytochemical-mediated synthesis. The DLS measured a hydrodynamic size of 273.76 +/- 0.31 nm with a low polydispersity index (0.202 +/- 0.014). Also, the zeta potential analysis showed a value of -26.42 +/- 0.35 mV, suggesting strong colloidal stability. These results validate the successful green synthesis of stable and nanoscale Se NPs using IPE. An in vivo infected wound model was triggered in rats. Colorimetric, ELISA, and qRT-PCR methods to measure different biochemical markers. It was found that the Se NPs upregulated the expression of GPX4, ferritin, and HO-1, while downregulating PTGS2 and ACSL4, indicating effective suppression of ferroptosis. Immunohistochemical analysis demonstrated enhanced Nrf2 and Ki-67 expression in the Se NPs-treated group, suggesting improved antioxidant activity and cellular proliferation. A computational network pharmacology analysis was also performed, and it revealed that the phytochemicals in IPE considerably enhanced wound healing, lessened oxidative stress, and modulated ferroptosis-related markers. In conclusion, the biosynthesized Se NPs exhibited superior wound healing potential via its antioxidant, anti-inflammatory, antimicrobial, and anti-ferroptotic mechanisms.