Quercetin-loaded nanophytosome ameliorates early life stress-induced hippocampal oxido-inflammatory damages

Phytosome-based nanocarriers have emerged as innovative drug delivery systems in recent years, demonstrating significant potential in the treatment of neurodegenerative disorders. This study aimed to evaluate the therapeutic efficacy of quercetin-loaded nanophytosome (QNP) in modulating the oxido-inflammatory response in a rat model of early life stress (ELS) induced by maternal isolation (MI). To establish the ELS model, male rat pups were isolated from their dam for 3 hours daily from postnatal days 1-9. Following the lactation period (postpartum days 1-21), treatments with quercetin (10 and 40 mg/kg) and QNP (10 and 40 mg/kg) were administered continuously for 21 days. Cognitive behaviors, oxidative stress markers, hippocampal dopamine levels, and mRNA expression of TNF-α and IL-6 were assessed after ELS induction. Treatment with QNP (40 mg/kg) significantly improved cognitive function (P < 0.01), increased hippocampal dopamine levels (P < 0.001), and reduced oxidative stress (P < 0.01) as well as the expression of TNF-α (P < 0.001) and IL-6 (P < 0.001). In conclusion, QNP demonstrates potent hippocampal anti-oxidoinflammatory effects, making it a promising therapeutic candidate for mitigating the adverse effects of maternal isolation-induced early life stress.