Retrograded starch as colonic delivery carrier of taxifolin for treatment of DSS-induced ulcerative colitis in mice

Taxifolin, a natural dihydroflavonol compound, possesses notable anti-inflammatory properties and regulatory effects on intestinal microbiota. In this study, gelatinized-retrograded corn starch (GCS) was utilized as a carrier for colonic delivery of taxifolin, and its therapeutic efficacy against dextran sulfate sodium (DSS)-induced colitis in mice were systematically investigated. Taxifolin can integrate into the helical structure of starch, and the formation of GCS-Taxifolin complexes (GCS-Tax) significantly delayed the release of taxifolin in vitro. After oral administration of GCS-Tax, fecal excretion of taxifolin increased from 0.42 % to 10.89 % within 24 h compared to free taxifolin. Moreover, GCS-Tax facilitated the production of short-chain fatty acid in mice and effectively alleviated DSS-induced colitis symptoms, including weight loss, bloody stools, and colonic tissue damage. Additionally, GCS-Tax significantly suppressed proinflammatory factors such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and lipopolysaccharide (LPS), while elevating anti-inflammatory interleukin-10 (IL-10) level in mice serum. Furthermore, it restored intestinal mucosal barrier function by upregulating the expression of Mucin 2, Occludin, and zonula occludens-1 (ZO-1), reducing Beclin 1 expression, and exhibited hepatoprotective effects by enhancing total antioxidant capacity (T-AOC), catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) activities. High-throughput sequencing analysis revealed that GCS-Tax improved intestinal flora diversity, reducing inflammation-related Bacterium 1 and Staphylococcus, while promoting the abundance of beneficial bacteria like Lachnospiraceae.