Astaxanthin mitigates dextran sulfate sodium-induced colitis by strengthening intestinal barrier function and suppressing oxidative stress and inflammasome activation

Astaxanthin (ASTX), a xanthophyll carotenoid derived from Haematococcus lacustris , exhibits potent antioxidant and anti-inflammatory activities; however, its immunopharmacological effects on intestinal barrier dysfunction and inflammasome-driven inflammation remain incompletely understood. This study investigated the protective effects and underlying mechanisms of ASTX using intestinal epithelial cell models and a dextran sulfate sodium (DSS)-induced colitis mouse model. In differentiated Caco-2 monolayers exposed to interleukin-6 (IL-6), ASTX significantly enhanced transepithelial electrical resistance and reduced paracellular permeability, accompanied by restoration of tight junction proteins ZO-1 and occludin. In DSS-induced colitis mice, oral administration of ASTX markedly alleviated body weight loss, disease activity, and colon shortening, and improved histopathological features, including mucosal inflammation, epithelial damage, crypt architecture, and goblet cell density. Mechanistically, ASTX activated the Nrf2/Keap1 signaling pathway, increased systemic superoxide dismutase and glutathione levels, and reduced myeloperoxidase activity, indicating attenuation of oxidative stress. Furthermore, ASTX suppressed NLRP3 inflammasome activation, as evidenced by decreased expression of NLRP3, ASC, caspase-1, and IL-1β, along with reduced systemic IL-6 and TNF-α levels. Collectively, these findings demonstrate that ASTX exerts immunopharmacological protection against experimental colitis by reinforcing epithelial barrier integrity, mitigating oxidative stress, and inhibiting inflammasome-mediated inflammatory signaling, highlighting its therapeutic potential for inflammatory bowel disease.