Macleaya cordata Extract Ameliorates DSS-Induced Ulcerative Colitis via Inhibiting M1 Macrophages and Reshaping Gut Microbiota

Macleaya cordata, which is widely distributed in nature, exhibits pronounced anti-inflammatory, antioxidant, and anti-colitis potential. However, its therapeutic mechanism on DSS-induced ulcerative colitis (UC) remains unknown; therefore, we aimed to evaluate the protective effect of Macleaya cordata extract (MCE) on UC and investigate its active monomer component. In a mouse colitis model induced by DSS, MCE markedly alleviated pathological characteristics. 16S rRNA sequencing indicated a significant reduction in the relative abundance of pathogenic Streptococcus, while increasing that of beneficial genera Dubosiella and Akkermansia. Furthermore, flow cytometry analysis indicated the protective role of MCE on DSS-induced macrophage polarization in the colon (32.6% reduction in M1 macrophage compared to the DSS group; 5.3% increase in M2 macrophage compared to the DSS group) and spleen tissue (36.8% reduction in M1 macrophage compared to the DSS group; 22.3% increase in M2 macrophage compared to the DSS group). In addition, we found that sanguinarine (SAN) (27.9% reduction in body weight compared to the DSS group; p < 0.01) exhibited a superior anti-colitis effect compared to chelerythrine (CHE) (19.8% reduction in body weight compared to the DSS group) by inhibiting NF-κB activation and ROS production than CHE in LPS-induced RAW 264.7 macrophages. In conclusion, MCE ameliorates UC by reshaping gut microbiota and suppressing M1 polarization.