Chlorogenic acid attenuates oxidative stress-induced intestinal epithelium injury by co-regulating the pi3k/akt and iκbα/nf-κb signaling

Abstract

Chlorogenic acid (CGA) is a natural polyphenol compound abundant in green plants with antioxidant and anti-inflammatory activities. Here, we explore its protective effects and potential mechanisms of action on intestinal epithelium exposure to oxidative stress (OS). We show that CGA attenuated OS-induced intestinal inflammation and injury in weaned pigs, which is associated with elevated antioxidant capacity and decreases in inflammatory cytokine secretion and cell apoptosis. In vitro study showed that CGA elevated phosphorylation of two critical signaling proteins of the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) pathway, Akt and nuclear factor erythroid-derived-related factor 2, leading to the elevated expression of intracellular antioxidant enzymes and heme oxygenase-1 (HO-1). Specific inhibition of HO-1 partially abolished its anti-inflammatory effect in IPEC-J2 cells exposure to OS. Interestingly, CGA suppressed the tumor necrosis factor-α (TNF-α) induced inflammatory responses in IPEC-J2 cells by decreasing phosphorylation of two critical inflammatory signaling proteins, NF-kappa-B inhibitor alpha (IκBα) and nuclear factor-κB (NF-κB). Specific inhibition of HO-1 cannot fully abolish its anti-inflammatory effect on the TNF-α-challenged cells. These results strongly suggested that CGA is a natural anti-inflammatory agent that can attenuate OS-induced inflammation and injury of intestinal epithelium via co-regulating the PI3K/Akt and IκBα/NF-κB signaling pathway.