Caffeic acid inhibits Staphylococcus aureus-induced endometritis through regulating AMPKα/mTOR/HIF-1α signalling pathway

Endometritis is mostly caused by childbirth or postpartum uterine infection. It is one of the important reasons leading to female infertility. Caffeic acid (CA) and its derivatives are widely found in some foods and traditional Chinese medicine, and have biological activities such as antioxidant, free radical scavenging, anti-inflammatory, and anti-infection. In this study, we aimed to explore the effect of CA on Staphylococcus aureus-induced endometritis. The contents of TNF-alpha and IL-1 beta were detected by ELISA in S. aureus-induced endometritis model. Western blot assay was used to detect the expression of AMPK alpha/mTOR/HIF-1 alpha pathway related proteins and GPX4 expression. In addition, the concentrations of MDA, GSH, and iron were tested by the assay kits. Compared with the model group, CA treatment significantly alleviated S. aureus-induced uterine injury, MPO activity, the contents of inflammatory factors TNF-alpha and IL-1 beta, and NF-kappa B activation. Meanwhile, CA significantly inhibited S. aureus-induced ferroptosis, as confirmed by decreased MDA and iron concentration and up-regulated GPX4 expression and GSH level. Furthermore, CA attenuated S. aureus-induced HIF-1 alpha and phosphorylated mTOR expression and increased phosphorylated AMPK expression. In conclusion, CA inhibits inflammation and ferroptosis by regulating AMPK alpha/mTOR/HIF-1 alpha signalling pathway to alleviate S. aureus-induced endometritis in mice.