Exploring the neurofunctional potential of saffron bioactives: from mood-related behavioral modulation to brain access of safranal

quantification of dopamine and its metabolites by HPLC-ECD, combined with RT-qPCR analysis of related receptors and transporters, while kynurenine pathway activation was assessed through mRNA expression of its key enzymes in the prefrontal cortex and striatum. Both compounds reduced depressive-like behavior, albeit with distinct response patterns. Crocins primarily modulated the dopaminergic system, whereas safranal selectively downregulated neurotoxic components of the kynurenine pathway, shifting its neurotoxic/neuroprotective balance to promote neuroprotection. In parallel, serum and brain concentrations of safranal were measured at 15 and 30 min after oral administration of increasing doses, using a newly developed and validated UHPLC-DAD-MS/MS method. This allowed, for the first time, the detection of safranal in both serum and the brain following a single administration using a validated analytical method. Altogether, these findings provide novel and valuable insights into the disposition of safranal following oral administration and the distinct neurobiological mechanisms of saffron bioactives, highlighting their complementary roles and supporting their relevance as functional agents for mood-related disorders.