Activity of micronized apigenin with supercritical CO2 on memory impairment and oxidative parameters

Apigenin (APG) is a natural flavone found in fruits, chamomile, parsley, and celery. Numerous studies have demonstrated its antioxidant, anti-inflammatory, and neuroprotective activities against oxidative stress in neurological disorders, such as cerebral ischemia and Alzheimer’s disease. Furthermore, its ability to mitigate cognitive impairment (such as memory loss) and its capacity to cross the blood-brain barrier are particularly noteworthy. Despite these therapeutic properties, the bioavailability of APG is limited by its poor aqueous solubility. Consequently, it is classified as a Class II compound under the Biopharmaceutical Classification System (BCS). Thus, we aim to evaluate the effect of micronized APG on memory impairment in zebrafish. The Gas Anti-Solvent (GAS) technique with CO₂ was used to micronize APG. The average particle size of the processed was reduced by a factor of approximately 8 while maintaining their functional integrity. Dissolution profile assays showed a significant increase in the dissolution rate in acidic (pH 1.2) and buffered (pH 6.8) solutions. The functional performance of both unprocessed and processed particles was assessed using a model of memory impairment induced by MK801in zebrafish (protocol 009/2025 CEUA/Unochapecó). Inhibitory avoidance, locomotor activity, and the analysis of oxidative parameters in the brain were evaluated. Raw and micronized APG at the dose used (30 mg.kg^-1) showed no effects on memory deficit in zebrafish. However, the micronized form increased exploratory behavior and antioxidant defenses (as indicated by increased NPSH levels). The data suggest that the antioxidant effect is enhanced in the micronized form. However, more research, including dose-response curves and additional assays, is needed to understand the effects of micronized APG.