Combination of Coptis chinensis polysaccharides and berberine ameliorates ulcerative colitis by regulating gut microbiota and activating AhR/IL-22 pathway

Coptis chinensis Franch. polysaccharide (CCP) and berberine (BBR) are the primary active components of Coptis chinensis Franch. BBR is clinically used for the treatment of intestinal infections and gastroenteritis. CCP was also reported to be effective for the treatment of ulcerative colitis (UC). However, whether CCP combined with BBR shows a synergistic effect on the treatment of UC has not been elucidated yet. This study aspired to investigate the therapeutic effect and the possible mechanisms of the combination of CCP with BBR on chronic UC. By periodic administration of dextran sulfate sodium (DSS) to C57BL/6J mice, chronic UC model mice were induced. CCP (15 mg/kg), BBR (50 mg/kg), and CCP.BBR (a combination of 15 mg/kg CCP and 50 mg/kg BBR) were orally administered to the model mice for 10 days. Changes of body weight, disease activity index, colon length, organ index, histopathological damage, expression of cytokines, and intestinal tight junction proteins were determined to evaluate the therapeutic effects. 16S rDNA sequencing, targeted short-chain fatty acid metabolomics, qPCR, and western blotting were performed to elucidate the potential mechanism. Both CCP and BBR alleviated UC via improving colon pathological damage, inhibiting the inflammatory response, and regulating the expression of intestinal tight junction proteins. The combination of CCP with BBR showed a more substantial therapeutic effect via increasing the relative abundance of short-chain fatty acids (SCFAs) producing bacteria, thereby increasing the contents of SCFAs in vivo and activating AhR/IL-22 pathway. The combination of CCP and BBR showed a synergistic effect on the therapy of chronic UC and the mechanism was associated with regulating gut microbiota and activating AhR/IL-22 pathway.