Jiawei Taohe Chengqi decoction improves intestinal barrier damage in sepsis by modulating Notch-mediated macrophage...

During sepsis, multiple pathogenic factors - including hyperinflammatory responses, gut dysbiosis, and immune cell dysfunction - collectively compromise intestinal barrier integrity, thereby exacerbating disease progression. In this research, we have elucidated the in vivo therapeutic efficacy of Jiawei Taohe Chengqi Decoction (JTCD) in ameliorating sepsis-induced intestinal injury and elucidated its underlying molecular mechanisms.

The septic mice model was established to assess the pharmacological impact of JTCD and Taohe Chengqi Decoction (THCQD) in vivo. Network pharmacology analysis of the active components of JTCD was performed. Intestinal permeability was assessed by measuring FITC-Dextran flux, while tissue morphology and pathology were examined by H&E staining. The level of IL-6, IL-1β, TNF-α DAO, D-LA, I-FABP, IL-10 and IL-4 were evaluated by the corresponding ELISA kit. The expression of ZO-1, Claudin-1, Notch1, Jagged1 and HES1 was assessed by western blot. Immunofluorescence was applied to assess the expression of F4/80, iNOS, CD206 and Notch1. The cell counting kit-8 (CCK-8) was employed to evaluate the viability. Flow cytometry was applied to quantify the populations of F4/80 + CD86+ and F4/80 + CD163+. TEER assay was performed to assess the integrity of intestinal barrier.

JTCD ameliorated intestinal barrier dysfunction in septic mice by reducing permeability, mitigating histopathological damage, lowering serum injury biomarkers, and upregulating tight junction proteins. JTCD exerted therapeutic effects by modulating the Notch signaling pathway and intestinal macrophage polarization. JTCD attenuated Caco-2 cell barrier injury by regulating macrophage polarization through the Notch signaling pathway.

These results demonstrate that JTCD improves intestinal barrier damage in sepsis by modulating Notch-mediated macrophage polarization.