Rexiao Kuining decoction ameliorates ulcerative colitis by restoring immune homeostasis via the protein kinase C alpha-FMS-like tyrosine kinase 3 ligand axis: multi-omics evidence

  • J Ethnopharmacol. 2026 Nov 15:370:121985. doi: 10.1016/j.jep.2026.121985.
Si-Nan Xiao  1 ,  Tao Cai  2 ,  Jia-Yi Xia  3 ,  Ling Zhou  4 ,  Ruo-Xi Cao  5 ,  Bo Cao  6
Affiliations
  • 1. Guizhou University of Traditional Chinese Medicine, Guiyang, 550002, China. Electronic address: [email protected].
  • 2. Guizhou University of Traditional Chinese Medicine, Guiyang, 550002, China; The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, 550001, China. Electronic address: [email protected].
  • 3. Guizhou University of Traditional Chinese Medicine, Guiyang, 550002, China; The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, 550001, China. Electronic address: [email protected].
  • 4. Guizhou University of Traditional Chinese Medicine, Guiyang, 550002, China. Electronic address: [email protected].
  • 5. Guizhou University of Traditional Chinese Medicine, Guiyang, 550002, China. Electronic address: [email protected].
  • 6. Guizhou University of Traditional Chinese Medicine, Guiyang, 550002, China; The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, 550001, China. Electronic address: [email protected].
PMID: 42264446 DOI: 10.1016/j.jep.2026.121985
Abstract

Ethnopharmacological relevance: Ulcerative colitis (UC) is marked by epithelial barrier damage and immune dysregulation, and current therapies often fail to achieve both effective inflammation control and durable immune restoration. Rexiao Kuining decoction (RXKND), derived from San Huang Xie Xin decoction recorded in Synopsis of Prescriptions of the Golden Chamber, has been used clinically for UC, but its mechanisms remain unclear.

Aim of the study: To investigate the therapeutic effects and mechanisms of RXKND in UC using integrative multi-omics and experimental validation.

Materials and methods: RXKND constituents were identified by UHPLC-Q-Exactive Orbitrap MS. Network pharmacology, drug-target Mendelian randomization (MR), mediation MR, transcriptome-based machine learning, and single-cell RNA-seq were integrated to prioritize targets and pathways, followed by molecular docking and dynamics simulation. Validation was performed in DSS-induced colitis mice and LPS-stimulated dendritic cells with pathway-targeted pharmacological rescue assays.

Results: MR identified six genes significantly associated with UC, including PRKCA. Machine learning further highlighted five key genes (NOS3, FHIT, EDN3, SOCS1, and PRKCA) with strong diagnostic performance (AUC = 0.97 in training and 0.93 in validation). Mediation MR showed that PRKCA affected UC partly through FLT3L. Single-cell RNA-seq revealed increased PRKCA and decreased FLT3L in colonic dendritic cells from patients with UC. In vivo, RXKND alleviated DSS colitis, improved barrier integrity, reduced inflammatory cytokines, downregulated PKCα, upregulated FLT3L, and restored the Th17/Treg balance. Similar effects were observed in dendritic cells in vitro.

Conclusions: RXKND may alleviate UC by suppressing PKCα, relieving its negative regulation of FLT3L, restoring immune homeostasis, and promoting mucosal repair.

Keywords
Multi-omics; PKCα-FLT3L axis; Rexiao Kuining decoction; Th17/Treg; Ulcerative colitis.
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