Metabolomics reveals how seasonal variation in essential oils of Ocotea odorifera (Vell.) Rohwer impacts its anti-inflammatory activity

Ocotea odorifera (sassafras or canela-sassafras) has a long history of traditional use in Brazil and documented bioactivities, including anti-inflammatory effects. Here, we applied untargeted metabolomics to investigate how seasonality shapes the chemical composition and anti-inflammatory potential of O. odorifera leaf essential oils. Leaves were collected monthly over one year, oils were obtained by hydrodistillation, and chemical profiles were determined by GC–MS, revealing marked seasonal shifts with safrole as the dominant constituent and camphor/bicyclogermacrene among the minor components. Anti-inflammatory activity was assessed ex vivo in LPS-stimulated human whole blood by quantifying prostaglandin E₂ (PGE₂) using UPLC–MS/MS. Untargeted metabolomics indicated higher PGE₂ inhibition for oils harvested in autumn and spring compared with summer, and OPLS-DA highlighted discriminant markers associated with activity (VIP > 1; p < 0.05). Although the high safrole content limits direct therapeutic use due to known hepatotoxicity, these results demonstrate that seasonal chemical dynamics modulate specialized metabolism and the anti-inflammatory profile of O. odorifera essential oils.