Dihydromyricetin attenuates lipopolysaccharide-induced intestinal injury in weaned piglets by regulating oxidative stress and inhibiting NLRP3 inflammasome

This study explored the effects of dihydromyricetin (DHM) on lipopolysaccharide (LPS)-induced intestinal injury in weaned piglets and also investigated its possible molecular mechanism. The results showed that dietary supplementation of DHM could improve the jejunum morphological structure of piglets induced by LPS, reduce jejunum mucosa inflammation and endoplasmic reticulum stress, increase jejunum mucosa antioxidant capacity and the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and improve jejunum mucosa permeability. In addition, DHM downregulated the expression of toll-like receptor 4 (TLR4), phosphor-nuclear factor kappa-B (NF-kappa B), hypoxia-inducible factor-1 alpha (HIF-1 alpha), and the activation of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome. Taken together, LPS could induce jejunum mucosa injury in weaned piglets, but dietary supplementation of DHM alleviated LPS-induced jejunum mucosa injury to a certain extent, and the mechanism may be related to the activation of Nrf2 to inhibit the oxidative stress and negatively regulate the activation of the TLR4/HIF-1 alpha/NLRP3 signaling axis. The present study provided the first evidence that dietary supplementation of DHM could inhibit LPS-induced jejunum mucosa injury in weaned piglets. Our findings provide new insights into the improvement of intestinal health in piglets by DHM. Intestinal injury can damage the health of weaned piglets. Oxidative stress and inflammatory response can induce intestinal injury in weaned piglets. Dihydromyricetin, a polyphenolic hydroxyl dihydroflavonol compound has multiple biological functions such as antioxidant and anti-inflammatory effects. Previous studies found that dihydromyricetin could inhibit reactive oxygen species generation and improve intestinal damage in mice and chicken ileum. However, the protective effect and possible molecular mechanisms of dihydromyricetin on intestinal damage in piglets remain to be further studied. Therefore, the aim of this study is to explore the protective effect and mechanism of dihydromyricetin on lipopolysaccharide-induced intestinal damage in weaned piglets. The results of this study indicate that dihydromyricetin alleviates jejunum mucosa damage by inhibiting the oxidative stress and the activation of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, providing reference materials for the development and utilization of dihydromyricetin in pig production.