Baicalin alleviates endometrial inflammatory injury through regulation of tight junction proteins

Endometritis is the foremost reason for reduced reproductive performance, which impedes the establishment of pregnancy in ruminants. Baicalin is extensively acknowledged as a tocolytic drug. However, the preventive effect of baicalin on endometrial inflammatory injury remains unclear. The present study aimed to determine the potential benefits of baicalin on endometrial inflammatory injury in animal and cellular models. The results showed that baicalin alleviated the impairment of tight junctions (TJs) and inflammation in the endometrium induced by LPS treatment. Baicalin increased claudin 3 (CLDN3) and tight junction protein 1 (TJP1) levels in a dose-dependent manner in endometrial epithelial cells (EECs) accompanied by autophagy activation with or without LPS treatment. Immunofluorescence staining revealed that baicalin pretreatment prompted MAP1LC3B-positive structures to surround TJ proteins in the cytoplasm and decreased the abnormal aggregation of CLDN3 and TJP1 in the cytosol of EECs. Activation or blockage of autophagy using pharmacologic methods affected the redistribution of TJ proteins by baicalin pretreatment with LPS treatment. The role of autophagy in the modulation of TJ proteins was also confirmed by ATG7 and TFEB overexpression, as evidenced by accelerated redistribution of CLDN3 and TJP1 from the EEC cytosol to the membrane and a loss of membranous CLDN2 in EECs. These data demonstrate that baicalin influences the redistribution of TJ proteins to maintain the barrier function during LPS-induced endometrial inflammatory injury by regulating autophagy and provides a new therapeutic to potentially prevent embryo loss and endometritis. Baicalin alleviates endometrial inflammatory injury in a mouse model. Baicalin activated autophagy in a mouse model and a cell model. Baicalin redistributed TJ proteins by regulating autophagy.