Liujunzi Decoction Ameliorates Ulcerative Colitis by Suppression of M1 Macrophage via the NF-κB/MAPK Pathway in DSS mice

Abstract Background Liujunzi Decoction is a traditional Chinese medicine prescription, which is made by decocting six herbs:Citrus reticulata Blanco (Family Rutaceae), Pinellia ternata (Thunb.) Makino (Family Araceae), Panax ginseng C. A. Meyer (Family Araliaceae), Atractylodes macrocephala Koidz. (Family Compositae), Poria cocos (Schw.) Wolf (Family Polyporaceae) and Glycyrrhiza glabra L. (Family Leguminosae). It is mainly used to treat Spleen-Stomach deficiency syndrome. Methods Network pharmacology and transcriptomics (RNA-seq) identified LJD’s potential targets and pathways. A DSS-induced mouse colitis model assessed LJD efficacy including symptom severity, colon length, histology. In vitro, RAW 264.7 macrophages stimulated with LPS + LJD-containing serum were analyzed via flow cytometry (CD86), RT-qPCR (cytokines), and Western blot (NF-κB P65, ERK, JNK, P38 phosphorylation). LC-MS/MS characterized LJD components. Results LJD significantly alleviated DSS-induced colitis, reducing disease activity, colon shortening, and histopathological damage. Network and transcriptomic analyses converged on NF-κB/MAPK pathway inhibition. LJD downregulated pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and suppressed M1 macrophage polarization in vivo (reduced CD86⁺) and in vitro (reduced CD86⁺ cells and iNOS). Mechanistically, LJD inhibited phosphorylation of NF-κB, ERK, JNK and P38 in colonic tissue and LPS-stimulated macrophages. Conclusion LJD ameliorates UC by inhibiting NF-κB/MAPK signaling, thereby suppressing pathogenic M1 macrophage polarization and inflammation. This supports LJD’s potential as a complementary UC therapy targeting macrophage plasticity.