Chronic pancreatitis (CP) is characterized by progressive fibrosis and islet dysfunction, yet effective therapeutic strategies remain limited. This study elucidates the mechanism by which baicalin ameliorates CP progression through modulation of the interferon-α/β receptor (IFNAR)/janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway. In a caerulein-induced CP rat model, baicalin treatment (100 mg/kg/day, 6 weeks) markedly reduced pancreatic injury, collagen deposition, and α-smooth muscle actin (α-SMA) expression, alongside decreased serum levels of IL-6, TNF-α, TGF-β, amylase, and lipase. Flow cytometry revealed that baicalin suppressed pancreatic infiltration of CD8+ T cells, macrophages, and NK cells while elevating regulatory T (Treg) cell proportions. Transcriptomic analysis identified JAK/STAT signaling as a key pathway inhibited by baicalin, with molecular docking confirming its direct binding to IFNAR. In vitro, baicalin (10 μM) attenuated TGF-β1-activated pancreatic stellate cell (PSC) activation, evidenced by reduced lipid droplet loss and α-SMA/COL1A1 expression. Overexpression of IFNAR reversed baicalin's anti-fibrotic effects, whereas co-treatment with the JAK inhibitor ruxolitinib partially restored its efficacy. In vivo, IFNAR overexpression diminished baicalin's therapeutic benefits, but ruxolitinib co-administration mitigated pancreatic damage. These findings demonstrate that baicalin alleviates CP fibrosis and islet dysfunction by targeting IFNAR to suppress JAK/STAT signaling, modulating immune cell dynamics, and inhibiting PSC activation. This study highlights IFNAR as a novel therapeutic target and positions baicalin as a promising candidate for CP treatment.
Dou et al. (Mon,) studied this question.