Engineered prebiotic microcapsules Co-Encapsulating berberine and curcumin Elicit multi-synergistic therapy for ulcerative colitis

Ulcerative colitis (UC) is a common type of inflammatory bowel disease, where the vicious cycle of inflammation and oxidative stress poses a major challenge in its treatment, and existing therapies have limitations. Berberine (BBR) and curcumin (CUR) have the potential for synergistic treatment of UC, but this potential has not been verified in UC. Additionally, both BBR and CUR suffer from poor water solubility and low bioavailability. This study aims to construct prebiotic microcapsules (BBR/CUR@MC) for the co-delivery of BBR and CUR and explore their therapeutic mechanism in UC. Network pharmacology was used to predict the targets and pathways of BBR and CUR in UC. BBR/CUR@MC was prepared using microfluidic electrospray technology, and its colon targeting and biocompatibility were evaluated through in vivo experiments. In a Dextran sulfate sodium (DSS)-induced UC mouse model, the therapeutic effect was assessed using multiple indicators, and the mechanism of action was explored by transcriptome analysis. Network pharmacology showed that BBR and CUR can exert therapeutic effects on UC through synergistic regulation of TNF and AGE-RAGE signaling pathways. The successfully constructed BBR/CUR@MC had good colon targeting and biocompatibility. In the mouse colitis model, oral administration of BBR/CUR@MC inhibited ADAM17 in the TNF signaling pathway and MAPK11/13, COL4A1, and COL1A1 in the AGE-RAGE signaling pathway, thereby downregulating pro-inflammatory cytokines such as TNF-α and IL-1α, upregulating IL-10, scavenging ROS, significantly alleviating colonic inflammation and repairing the intestinal barrier in mice, with a therapeutic effect superior to that of single-drug microcapsules and 5-ASA. BBR/CUR@MC can exert synergistic anti-inflammatory and antioxidant effects in UC treatment by regulating TNF and AGE-RAGE signaling pathways, providing a new multi-mechanism therapeutic strategy for UC. Current UC therapies struggle with the inflammation-oxidative stress vicious cycle and low bioavailability of natural drugs. This study develops an innovative colon-targeted co-delivery system, BBR/CUR@MC, fabricated via microfluidic electrospray, synergistically regulating the TNF signaling pathway (anti-inflammatory), scavenging ROS while inhibiting AGE-RAGE signaling pathway targets (antioxidant), and repairing the intestinal mechanical barrier.