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

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.