Abstract
Polydatin (PD), a monocrystalline compound isolated from the root and rhizome of Polygonum cuspidatum, is widely used in inhibiting the inflammatory response and oxidative stress. PD has an anti-inflammatory effect on colitis mice; however, information regulating the mechanism by which maintains the intestinal epithelium barrier is currently scarce. Here, we assessed the anti-inflammatory and antioxidant of PD in lipopolysaccharide (LPS)-induced macrophages in vitro, and explored its effects on inhibiting intestinal inflammation and maintaining the intestinal epithelium barrier in dextran sodium sulfate (DSS)-induced colitis mice. Results showed that PD reduced the level of proinflammatory cytokines and enzymes, including tumor necrosis factor-α, interleukin-4 (IL-4), IL-6, cyclooxygenase-2, and inducible nitric oxide synthase, in LPS-induced macrophages, and improved the expression level of IL-10. PD maintained the expression of tight junction proteins in medium (LPS-induced macrophages medium)-induced MCEC cells. Additionally, PD inhibited the phosphorylation of nuclear factor-κB (NF-κB), p65, extracellular signal-regulated kinase-1/2, c-Jun N-terminal kinase, and p38 signaling pathways in LPS-induced macrophages and facilitated the phosphorylation of AKT and the nuclear translocation of Nrf2, improving the expression of HO-1 and NQO1. Furthermore, PD ameliorated the intestinal inflammatory response and improved the dysfunction of the colon epithelium barrier in DSS-induced colitis mice. Taken together, our results indicated that PD inhibited inflammation and oxidative stress, maintained the intestinal epithelium barrier, and the protective role of PD was associated with the NF-κB p65, itogen-activated protein kinases, and AKT/Nrf2/HO-1/NQO1 signaling pathway.