BIOLOGICAL RESPONSE OF TREATMENT WITH SAFFRON PETAL EXTRACT ON CYTOKYNE-INDUCED OXIDATIVE STRESS AND INFLAMMATION IN THE CACO-2/THP1 COCOLTURE MODEL

V. Panella¹, F. De Cecco², S. Franceschelli¹, M. A. Maggi³, S. Bisti⁴, A. Bravo Nuevo⁵, D. D’Ardes¹, F. Cipollone¹, L. Speranza¹ | ¹Department of Medicine and Aging Sciences, University «G. D’Annunzio», Chieti; ²Italian Institute of Technology, Genoa, Italy; ³Hortus Novus, L’Aquila, Italy; ⁴National Institute of Biostructure and Biosystem, Rome, Italy; ⁵Department of Biomedical Sciences, Philadelphia College of Osteopathic Medicine (PCOM), Philadelphia, USA

Inflammatory bowel disease (IBD) is a chronic disorder that affects the ileum, rectum and colon. It includes ulcerative colitis and Crohn’s disease. The global burden of IBD remains a persistent health problem due to the high costs of treatments that are not able to definitively cure the disease. The pathogenesis of IBD involves complex mechanisms, including immune dysregulation, gut microbiota imbalances, oxidative stress, and defects in the gastrointestinal mucosal barrier¹. Although the progression of IBD therapy is controlled with chemical drugs and biological therapies, healing results cannot yet be achieved, along with the inevitable side effects. As a result, a variety of research have focused on exploring novel therapies and found that natural products with anti-inflammatory and antioxidant could be used for IBD management^2,3. There is increasing interest in exploring food industry waste as a source of bioactive molecules with healthcare applications. In this study, a co-culture system of Caco-2 cells and PMA-differentiated THP-1 macrophages was used to simulate the human intestinal microenvironment. Inflammation was induced using TNF-α and IFN-γ, followed by treatment with Saffron Petal Extract (SPE). The results demonstrated that SPE significantly attenuated oxidative stress and inflammation by downregulating the expression of pro-inflammatory mediators such as iNOS, COX-2, IL-1β, and IL-6 via modulation of the Fbw7/NF-κB pathway, a key regulator of macrophage-driven inflammation. Furthermore, the results of our model suggest that SPE treatment restores the functionality of the intestinal barrier by reducing the destruction of tight junctions induced by the inflammatory stimulus. Our findings suggest that SPE could represent a complementary option to conventional drugs for those patients who develop resistance or intolerance to standard therapies.