Eucommia ulmoides flavonoids alleviate intestinal oxidative stress damage in weaned piglets by regulating the Nrf2/Keap1 signaling pathway

This study examined how Eucommia ulmoides flavonoids (EUF) protect against intestinal oxidative stress induced by deoxynivalenol (DON) in weaned piglets. Forty weaned piglets were randomly assigned to four dietary groups for a period of 14 days. The piglets were fed a control diet (Control) or the Control diet supplemented with 100 mg EUF/kg (EUF group), 4 mg DON/kg diet (DON group) or both (EUF+DON group) in a 2×2 factorial design. DON-challenged piglets on the EUF-supplemented diet showed significant improvements in growth performance. They also had notably lower serum levels of alkaline phosphatase (ALP), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) compared to those not receiving supplementation (P<0.05). In the EUF group, the relative weights of the liver, spleen, and kidneys were significantly lower than those in the control group (P<0.05). However, there were no significant differences in the relative heart weights among the four groups (P>0.05). Piglets challenged with DON and fed a diet supplemented with EUF showed significantly lower levels of interleukin-8 (IL-8) and interferon-γ (IFN-γ) mRNA and protein expression in serum and intestinal tissues compared to those in the DON group (P < 0.05). The EUF+DON group significantly increased the serum levels of glutathione peroxidase (GSH-Px), reactive oxygen species (ROS), and total antioxidative capability enzymes compared to the DON group (P<0.05). The EUF and DON group had significantly higher villus height, crypt depth, and villus height to crypt depth ratio in the small intestine compared to the supplemented DON-challenged piglets (P<0.05). Moreover, compared to the DON group, EUF can significantly enhance the expression of nuclear factor erythroid 2-related factor 2(Nfr2)/Kelch-like ECH-associating protein 1(Keap1) and antioxidant genes (i.e., HO-1, GCLC, GCLM), as well as their proteins in the DON-induced small intestines of piglets (P<0.05). In conclusion, EUF helps protect piglets from intestinal oxidative stress caused by DON by influencing the Nrf2/Keap1 signaling pathway, thereby supporting their intestinal health.