Dietary Dihydroartemisinin Supplementation Alleviates Intestinal Inflammatory Injury Through TLR4/NODs/NF-κB Signaling Pathway in Weaned Piglets with Intrauterine Growth Retardation

Abstract Background: Intrauterine growth retardation (IUGR) leads to impaired intestinal morphology and function. IUGR infants are at a risk for intestinal inflammatory diseases. Dihydroartemisinin (DHA) is a derivative of artemisinin, which possesses anti-inflammatory activity and immunomodulatory effect. However, little is known about the effects of DHA on IUGR piglets. Therefore, the present study was conducted to investigate whether dietary DHA supplementation could attenuate intestinal injury in IUGR weaned piglets. Methods: Piglets with normal birth weight or IUGR were fed the basal diet or basal diet supplemented with 80 mg/kg DHA from 21 d to 49 days of age. At 49 days of age, eight piglets from each group with nearly similar body weight were sacrificed. The jejunal and ileal samples were collected for further analysis.Results: IUGR impaired intestinal morphology, increased intestinal inflammatory response, raised enterocyte apoptosis and reduced enterocyte proliferation and activated TLR4/NODs/NF-κB signaling pathway. DHA supplementation improved intestinal morphology, indicated by higher villus height, villus height to crypt depth ratio, villus surface area and lower villus width of IUGR piglets (P < 0.05). DHA inclusion exhibited higher apoptosis index and the expression of caspase-3, and lower proliferation index and the expression of proliferating cell nuclear antigen in the intestine of IUGR piglets (P < 0.05). Diet supplemented with DHA could attenuate intesitnal inflammation, indicated by higher concentrations of intestinal inflammatory cytokines and lipopolysaccharides in IUGR piglets (P < 0.05). In addition, DHA down-regulated the related mRNA expressions of TLR4/NODs/NF-κB signaling pathway and up-regulated mRNA expressions of TLR4 and NODs signaling negative regulators in the intestine of IUGR piglets (P < 0.05). Dietary DHA supplementation decreased the protein expressions of toll-like receptors 4, phosphorylated NF-κB (pNF-κB) inhibitor α, nuclear pNF-κB, and increased the protein expression of cytoplasmic pNF-κB in the intestine of IUGR piglets (P < 0.05). Conclusions: Dietary DHA supplementation may have beneficial effects in improving intestinal morphology, regulating enterocyte proliferation and apoptosis, and alleviating intestinal inflammation through TLR4/NODs/NF-κB signaling pathway in IUGR weaned piglets.