Chlorogenic acid attenuates LPS-induced hepatic oxidative stress in broilers by regulating cyclooxygenase-2 expression.

Immune stress can impair growth performance and induce hepatic oxidative injury; however, the protective potential and underlying mechanisms of the dietary phenolic compound chlorogenic acid (CGA) remain unclear. In this study, we investigated whether CGA alleviates lipopolysaccharide (LPS)-induced hepatic oxidative damage in broilers and explored the involvement of cyclooxygenase-2 (COX-2). Since LPS challenge markedly upregulated PTGS2 (encoding COX-2) and COX-2 is closely associated with redox homeostasis, the selective COX-2 inhibitor celecoxib was included as a pharmacological comparator to determine whether the hepatoprotective effects of CGA are associated with COX-2 regulation. LPS challenge impaired growth performance, as indicated by decreased average daily gain and increased feed conversion ratio, elevated serum corticosterone levels, reduced hepatic antioxidant capacity and antioxidant enzyme activities (CAT and SOD), and increased lipid peroxidation (MDA). Dietary supplementation with CGA (1000 mg/kg) partially reversed these alterations. Transcriptome analysis suggested the involvement of FoxO signaling, and CGA downregulated PTGS2 and NOX1 while upregulating Nrf2, HO-1, FoxO1/3, GPX1, and GST expression. Celecoxib partially reproduced the effects of CGA by reducing PTGS2 and NOX1 expression and increasing FoxO3 expression. Collectively, CGA alleviates LPS-induced hepatic oxidative stress and partially improves growth performance, potentially by suppressing a COX-2-associated NOX1-mediated pro-oxidant response and enhancing Nrf2/FoxO3/GPX1-dependent antioxidant defenses.