Procyanidin-B1-Enriched Cyperus esculentus Extract Regulates Anti-Inflammatory Pathways in Chicken Macrophages Cells Through Transcription Factor STAT2 and HIF1A

Procyanidin B1 (PB1), a polyphenol abundant in <i>Cyperus esculentus</i> stems and leaves extract (CELE), exhibits antioxidant and anti-inflammatory activities, though its mechanisms are not fully understood. This study investigated CELE's effects in chickens and LPS-stimulated HD11 macrophages. Chickens fed CELE showed increased blood levels of SOD, GSH-Px, TNF-α, IL-1β, IL-6, and IL-10, while MDA decreased. RNA-seq of LPS + PB1 vs. LPS-treated cells identified 696 differentially expressed genes enriched in inflammation and antioxidant pathways. Analysis indicated 120 transcription factors (TFs) may regulate these changes, with FOSL1, HIF1A, and STAT2 significantly downregulated. In HD11 cells, PB1 reduced expression of HIF1A/STAT2-target genes (e.g., HMGA2, EPSTI1), lowered IL-1β, IL-6, and ROS, and shifted macrophage polarization from M1 to M2. PB1's effects were enhanced by an HIF1A inhibitor but reversed by a STAT2 activator. These findings support PB1 and CELE as potential feed additives for livestock.