[Mechanism investigation of Wumei Wan in treatment of ulcerative colitis in mice based on transcriptomics and...

In this study, a dextran sulfate sodium(DSS)-induced chronic ulcerative colitis(UC) model was established in C57BL/6 mice, and the therapeutic effects of Wumei Wan were systematically investigated through histopathological evaluation, transcriptomics, proteomics, and molecular experiments. Mice were subjected to four cycles of 2.5% DSS for the modeling of chronic UC and then treated with mesalazine or different doses of Wumei Wan from the third cycle. Transcriptomics and proteomics analyses were conducted for the high-dose Wumei Wan group. The results showed that Wumei Wan markedly ameliorated the DSS-induced body weight loss, elevation of disease activity index(DAI), and colon shortening. Histological examination revealed attenuation of mucosal destruction, crypt injury, and inflammatory cell infiltration by Wumei Wan. Immunostaining showed that Wumei Wan decreased positive signals of F4/80 antigen(F4/80) and myeloperoxidase(MPO), indicating a clear anti-inflammatory effect. Transcriptomics analysis showed that Wumei Wan reversed widespread DSS-induced transcriptional abnormalities and inhibited multiple mucosal immune activation pathways, including inflammatory response pathways, chemokine signaling pathways, the interleukin-17(IL-17) signaling pathway, the tumor necrosis factor(TNF) signaling pathway, and the NOD-like receptor(NLR) signaling pathway. The proteomics analysis indicated that Wumei Wan mainly regulated immune responses, immune cell infiltration, and the intestinal immunoglobulin A(IgA) immune network, and significantly downregulated the number and expression intensity of ITGA4 and ITGB7 positive cells, thereby inhibiting the expression of integrin alpha-4 beta-7(α4β7). The results of qPCR, Western blot, and immunofluorescence assay consistently demonstrated reduced α4β7 expression, suggesting that Wumei Wan inhibited the α4β7-mucosal vascular addressin cell-adhesion molecule-1(MAdCAM-1) homing axis, thereby decreasing inflammatory cell infiltration, restoring mucosal immune homeostasis, and alleviating barrier injury. In conclusion, Wumei Wan effectively alleviates UC-associated inflammation and mucosal injury through multi-pathway and multi-target regulation. Its core mechanisms involve suppressing inflammatory cascades, modulating the IgA immune network, and downregulating integrin α4β7. The findings provide comprehensive modern pharmacological evidence for deciphering the therapeutic potential of Wumei Wan for UC.