QuYuShengXin formula reshapes bile-acid-mediated macrophage polarization in the treatment of ulcerative colitis.

BACKGROUND: QuYuShengXin Formula (QYSX), a multi-herbal preparation, has previously demonstrated robust clinical efficacy against ulcerative colitis (UC), with preliminary evidence suggesting that QYSX could reconfigure the fecal bile acid BA landscape and restore the M2/M1 macrophage balance, but their interaction remains unknown. We therefore dissected the therapeutic footprint of QYSX in a dextran sulfate sodium (DSS)-induced mice model of UC, focusing on its specific mechanism of regulating BA metabolism and macrophage polarization. METHODS: DSS-induced mice received QYSX or mesalazine for comparative efficacy. Disease activity index (DAI), body-weight trajectory and stool consistency were monitored daily. Colonic histopathology was graded after H&E staining. Liquid chromatography-mass spectrometry, enzyme-linked immunosorbent assay, flow cytometry, western blot and real-time quantitative PCR were conducted to evaluate the possible mechanism of QYSX. RESULTS: QYSX markedly attenuated he symptoms and colonic pathology of UC. It simultaneously downregulated IL-1β, IL-6, TNF-α, LPS and NF-κB p65, while elevating TGR5 expression. DSS-elicited disruption of the fecal BAs structure and concentration were largely reversed by QYSX. Flow-cytometric profiling revealed a decreased expression of M1 macrophages without alteration of M2 macrophages, yielding a rise in the M2/M1 ratio. CONCLUSION: By re-instating the physiologic fecal BA landscape, QYSX engages TGR5 to inhibit NF-κB signaling, thereby suppressing LPS- and TNF-α-driven M1 hyper-activation. This restoration of M2/M1 homeostasis curbs mucosal inflammation and maintains intestinal immune equilibrium, providing a mechanistic rationale for the clinical efficacy of QYSX in UC.