Toxicological and Gastro‐Protective Evaluation of Propolis‐Loaded Selenium‐BSA Nanoparticles Against Ethanol‐Induced Ulcer

ABSTRACT Stomach ulcers (SUs) are common gastrointestinal disorders associated with reactive oxygen species (ROS) and inflammation. In this study, we evaluated the gastroprotective effect of propolis‐loaded‐selenium‐encapsulated bovine serum albumin nanoparticles (Pro‐BSA‐Se NPs) following ethanol‐induced stomach ulceration in albino mouse model. The nano‐formulation was synthesized and characterized by UV, FTIR, zeta potential, and SEM. The Pro‐BSA‐Se NPs were characterized by particle size of 168 nm, and zeta potential of ‐29 mV, indicating uniform distribution and good stability. Mice were orally pre‐treated with Pro‐BSA‐Se NPs (50 mg/kg) or omeprazole (20 mg/kg) for seven days (prophylactic preventive protocol), after which SUs were induced by single oral administration of absolute ethanol. Pro‐BSA‐Se NPs treatment significantly reduced ulcer index (0.16 ± 0.09 mm 2 ) compared to 1.4 ± 0.18 mm 2 for omeprazole ( p = 0.001). Pro‐BSA‐Se NPs treatment significantly reduced TNF‐α and IL‐6, inhibited caspase‐3, and promoted antioxidant enzyme production, activating the Nrf2 pathway in the gastric mucosa. Histopathological analysis showed that both the Pro‐BSA‐Se nanoparticle‐treated group and the omeprazole‐treated group exhibited normal gastric mucosa compared to the SU‐induced group. In conclusion, treatment with Pro‐BSA‐Se nanoparticles demonstrated gastroprotective, antioxidant, and anti‐inflammatory effects in the gastric mucosa. Thus, Pro‐BSA‐Se NPs could be a promising therapeutic agent for SU.