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Xiao-Chaihu-Tang preserves intestinal barrier and ameliorates irinotecan-evoked delayed diarrhea by anchoring endogenous tryptophol to modulate inflammation and oxidation dependent on AhR-UGT1A1-micro

a day ago
  • #Gut Microbiota
  • #Chemotherapy Side Effects
  • #Traditional Medicine
  • Xiao-Chaihu-Tang (XCHT) is a traditional formula used to treat diarrhea, including chemotherapy-induced delayed diarrhea (DD).
  • The study aimed to uncover the mechanisms behind XCHT's efficacy, focusing on endogenous metabolites, pathways, and gut bacteria.
  • XCHT and its key component, tryptophol, improved symptoms of DD, such as perianal status, body weight, and colon pathology.
  • Metabolomics and network pharmacology identified 33 potential biomarkers and highlighted the role of tryptophan metabolism and oxidative stress.
  • Tryptophol reduced inflammation and oxidative stress, enhancing intestinal barrier function via the AhR-UGT1A1 pathway.
  • Metagenomic sequencing revealed XCHT and tryptophol normalized gut bacteria like Lactobacillaceae bacterium and inhibited bacterial invasion.
  • Molecular studies confirmed strong binding between tryptophol and AhR-UGT1A1, supporting the therapeutic mechanism.
  • XCHT's protective effect is mediated through the tryptophol-AhR-UGT1A1-microbiota axis, offering insights for reducing chemotherapy toxicity.