Engeletin Alleviates Lipopolysaccharide-Induced Endometritis in Mice by Inhibiting TLR4-mediated NF-κB Activation

Engeletin (dihydrokaempferol 3-rhamnoside) is a flavanonol glycoside. It can be found in the skin of white grapes and white wine and is widely distributed in southeast Asia, and the leaves are used in a tea. Here, we explored the impact of engeletin against the inflammatory reaction in a lipopolysaccharide (LPS)-induced endometritis mouse model. Engeletin treatment significantly attenuated uterus damage and decreased myeloperoxidase activity. ELISA and qPCR assays showed that engeletin dose-dependently suppressed the expression of TNF-α, IL-1β, and IL-6. Molecular studies also demonstrated that the levels of iNOS, COX-2, and TLR4, along with their downstream molecules MyD88, IRAK1, TRAF6, and TAK1, were also suppressed by engeletin. In addition, engeletin treatment inhibited NF-κB signaling-pathway activation. Moreover, immunofluorescence analysis demonstrated that engeletin suppressed NF-κB-p65 nuclear translocation. These data indicated the protective action of engeletin against LPS-stimulated endometritis in mice via negative regulation of pro-inflammatory mediators via the TLR4-regulated NF-κB pathway.