Baicalin ameliorates dextran sulfate solidum-induced colitis by modulating Th17-macrophage immune network via JAK2/STAT3/IL-17/NF-κB pathway.

BACKGROUND

Ulcerative colitis (UC) arises from complex interactions among genetic predisposition, environmental factors, and immune dysregulation. Promotion of M1-polarized macrophages critically contribute to intestinal inflammation and subsequent tissue damage. Baicalin, a bioactive flavonoid isolated from the roots of Scutellaria baicalensis, exhibits potent anti-inflammatory effects, yet its therapeutic efficacy and regulatory mechanisms of macrophages in the development of UC remain poorly understood.

PURPOSE: This study aimed to investigate the protective effects of baicalin in a murine model of UC, examining the influence of baicalin on helper T cells 17 (Th17) differentiation, macrophage polarization, and associated signaling pathways.

METHODS

In a dextran sulfate sodium (DSS)-induced UC mice model (n = 10), the therapeutic effects of baicalin were evaluated based on weight monitoring, colon length measurement, histopathological examination, and inflammatory marker analysis. Transcriptomic analysis was conducted to predict the potential mechanism on baicalin-treated mice. Additionally, by integrating transcriptomic data from colon tissues of patients with UC in publicly available databases, dysregulated pathways were identified. Mechanistic studies focused on janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) and nuclear Factor kappa-B (NF-κB) signaling both in Th cells (n = 3) and Raw264.7 (n = 3).

RESULTS

Baicalin significantly alleviated DSS-induced colitis by attenuating weight loss, maintaining colon length, and restoring intestinal barrier function. Transcriptomic analysis revealed that baicalin suppressed Th17 cell differentiation and IL-17 signaling pathway which are found to be elevated in UC patients. Baicalin suppressed Th17 differentiation and IL-17 production by inhibiting JAK2/STAT3 phosphorylation in T cells. Baicalin suppressed IL-17RA expression in macrophages, thereby inhibiting NF-κB activation and M1 polarization. As a result, the intestinal inflammation was effectively alleviated in vivo.

CONCLUSION

Baicalin alleviates UC by modulating the Th17/M1 macrophage axis. Baicalin simultaneously suppresses JAK2/STAT3 signaling in Th cells and NF-κB activation in macrophages, thereby interrupting IL-17-mediated inflammatory crosstalk between these two immune pathways. These findings suggest a potential therapeutic target for UC intervention.