Protective Effects of <i>Pistacia atlantica</i> Oleoresin Nanoparticles Against Ethanol-Induced Gastric Ulcers in Rats

Background: Pistacia atlantica is known for its extensive therapeutic applications. Its oleoresin has demonstrated gastroprotective efficacy against peptic ulcers (PUs). Objectives: In this pioneering study, we developed nanoparticles from P. atlantica oleoresin and assessed their gastroprotective effects on ethanol-induced gastric ulcers in female rats. Methods: Nanoparticles were prepared using ethanol and acetone via the nanoprecipitation method and were characterized using dynamic light scattering, zeta potential analysis, transmission electron microscopy (TEM), and Fourier-transform infrared (FT-IR) spectroscopy. The size and nanoparticle Polydispersity Index (nPDI) were optimized using response surface methodology (RSM). Forty female Wistar rats were randomly divided into eight groups, including a normal control (NC), an ulcer control (UC), an omeprazole (OMP)-treated group (10 mg/kg), and six groups receiving oleoresin or nanoparticles at doses of 50, 100, and 200 mg/kg. Gastric ulcers were induced using 80% ethanol (1 mL/200 g), and ulcer severity was assessed macroscopically and microscopically one hour after induction. Results: Optimized nanoparticles exhibited a mean size of 173.6 nm and a PDI of 0.06, achieved at 3.18% (w/v) oleoresin concentration and a 1:14.85 aqueous/organic phase ratio. The TEM confirmed spherical morphology, and FT-IR analysis indicated the presence of terpenoids. The zeta potential demonstrated high colloidal stability. Macroscopic examination showed a dose-dependent reduction in Ulcer Index across all nanoparticle-treated groups, with the 200 mg/kg dose yielding the most significant protective effect. Histological analysis supported these findings, showing marked preservation of the gastric mucosa in nanoparticle-treated groups compared to both the UC and oleoresin-treated rats. Conclusions: Among the tested doses, the 200 mg/kg P. atlantica oleoresin nanoparticle group showed the most significant reduction in Ulcer Index and histopathological damage, surpassing both the plant oleoresin and OMP in protective efficacy against ethanol-induced gastric ulcers.