A Synergistic Approach with Doxycycline and Spirulina Extracts in DNBS-Induced Colitis: Enhancing Remission and Controlling Relapse

<b>Background:</b> Chronic relapsing colitis involves immune dysregulation and oxidative stress, making monotherapies often insufficient. This study investigates a therapeutic strategy combining doxycycline (Dox), an immunomodulatory antibiotic, with <i>Arthrospira platensis</i> extracts to enhance anti-inflammatory and antioxidant effects, improving remission and controlling relapse. <b>Methods:</b> Ethanolic (ES) and aqueous (AS) extracts of <i>A. platensis</i> were chemically characterized by GC-MS after derivatization. Colitis was induced in mice using two intrarectal DNBS administrations spaced 7 days apart, with oral treatments (Dox, ES, AS, or combinations) given daily between doses. Disease progression was evaluated through clinical monitoring, histological scoring, and biochemical analysis, including MPO and CAT activities, as well as NO, MDA, and GSH levels. <b>Results:</b> GC-MS identified 16 bioactive compounds in each extract. ES contained mainly fatty acids and amino acids, whereas AS was rich in polysaccharides and phytol. Combined doxycycline and <i>A. platensis</i> extracts significantly enhanced recovery in reactivated DNBS colitis compared to monotherapies. Each treatment alone reduced disease severity, but their combination showed synergistic effects, significantly reducing disease activity index (<i>p</i> < 0.001), restoring mucosal integrity, and modulating inflammatory and oxidative markers (<i>p</i> < 0.001). <b>Conclusion:</b> Doxycycline potentiates the anti-colitic effects of <i>A. platensis</i> extracts via complementary mechanisms, offering a promising combination for managing relapsing colitis.