Costa, Eduardo M.Machado, ManuelaPintado, ManuelaSilva, Sara2025-10-142025-10-142025-10-09Costa, E. M., Machado, M., Pintado, M., & Silva, S. (in press). Evaluating pomegranate seed oil for potential topical applications: safety, anti-inflammatory activity and wound healing in skin cell models. Inflammopharmacology. https://doi.org/10.1007/s10787-025-02002-70925-469208295421-e1cb-4411-99b4-1f44e024f790http://hdl.handle.net/10400.14/55356Pomegranate seed oil (PSO), a by-product of pomegranate juice production, has a long-standing role in traditional medicine, yet is mechanistic and pharmaceutical potential for skin applications remains unexplored. This work explored the bioactivity of PSO in human keratinocytes (HaCaT) and dermal fibroblasts (HDFa) through evaluation of its impact upon cellular metabolism, anti-inflammatory properties and wound healing capacity. The data obtained showed that PSO exhibited no cytotoxic effects up to 500 µg/mL and significantly suppressed pro-inflammatory cytokines (IL-6, IL-8, TNF-?) under LPS-induced inflammatory conditions. Furthermore, wound closure in fibroblasts was accelerated by approximately 20% in a 24-h period. Although antioxidant activity was limited under induced oxidative stress, PSO exerted mild protective effects under basal conditions and fatty acid profiling revealed a PUFA-rich composition, including dihomolinolenic and punicic acids, potentially linked to the observed impact upon cellular metabolism. Overall, these findings offer novel insights into PSO’s dual functionality in skin regeneration and immune modulation, supporting its application as a bioactive ingredient for advanced topical therapies.engHaCaTHDFaImmune responsePomegranate seed oilWound healingresearch article10.1007/s10787-025-02002-710501831357041065959001589983800001