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Despite advances in therapy, effective UC management remains challenging due to the limited efficacy and significant side effects of conventional treatments. Inspired by the synergistic mechanisms of bioactive compounds in traditional Chinese medicine, a colon\u2010targeted hydrogel integrating rhubarb\u2010derived polysaccharides and berberine\u2010loaded dendrimers is engineered. This hydrogel self\u2010assembles via intermolecular hydrogen bonding and electrostatic interactions, enabling localized accumulation in colonic tissues to suppress aberrant immune activation and remodel the dysbiotic microbiome. Mechanistic studies reveal that the hydrogel potently promotes the polarization of anti\u2010inflammatory M2 macrophages while suppressing pro\u2010inflammatory cytokine secretion, resulting in significant amelioration of colitis symptoms in murine models. Importantly, the therapeutic intervention not only restored gut microbiota composition but also corrected metabolic disturbances, collectively contributing to the re\u2010establishment of intestinal homeostasis. The findings underscore the potential of this polysaccharide\u2010based hydrogel as an effective oral therapeutic strategy for UC while demonstrating the translational value of combining natural bioactive constituents for targeted drug delivery.<\/jats:p>","DOI":"10.1002\/adhm.202404908","type":"journal-article","created":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T04:06:45Z","timestamp":1750824405000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Colon\u2010Targeted Natural Polysaccharide\u2010Berberine Armored Hydrogel for the Treatment of Colitis"],"prefix":"10.1002","volume":"14","author":[{"given":"Miao","family":"Guo","sequence":"first","affiliation":[{"name":"State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical Sciences University of Macau  Macao 999078 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