Astaxanthin–Turmeric–Honeysuckle Extract Combination Attenuates DSS-Induced Colitis with Preservation of the Epithelial Barrier and Reduced NLRP3/Caspase-1/GSDMD Signaling

Inflammatory bowel disease is characterized by recurrent mucosal inflammation, epithelial barrier disruption, and dysregulated cell death, highlighting the need for safe, multi-target interventions. Natural astaxanthin, renewably sourced from Haematococcus pluvialis or Phaffia rhodozyma, has shown greater tissue accumulation or antioxidant activity than synthetic astaxanthin in some preparations. Based on the complementary antioxidant, anti-inflammatory, and intestinal barrier-protective activities of its individual components, the astaxanthin–turmeric extract–honeysuckle extract combination (ATH) was investigated for its protective effects in a mouse model of dextran sulfate sodium (DSS)-induced colitis. Thirty-two male C57BL/6J mice were randomly allocated to four cohorts: Control, DSS, DSS + ATH, and ATH. ATH intervention mitigated the DSS-associated decline in body mass, lowered clinical disease scores, attenuated DSS-induced colon shortening, and ameliorated mucosal lesions. In DSS-treated mice, ATH attenuated goblet-cell loss, reduced intestinal permeability, and restored ZO-1 and occludin expression. ATH treatment also reduced DSS-induced increases in colonic IL-1β, IL-6, TNF-α, IL-18, and malondialdehyde levels while improving superoxide dismutase activity and glutathione content. At the signaling level, ATH reduced phosphorylated NF-κB and NLRP3 immunoreactivity and decreased N-GSDMD accumulation within E-cadherin-positive epithelial regions. Western blotting further showed reduced NLRP3 expression, caspase-1 cleavage, and N-GSDMD formation, although the p-NF-κB/NF-κB ratio was not significantly changed. Collectively, ATH alleviated DSS-induced colitis by improving mucosal barrier and redox–inflammatory homeostasis while attenuating the NLRP3/caspase-1/GSDMD pyroptotic cascade. These findings support the further development of ATH as a multi-component natural intervention for intestinal inflammatory injury.