In our study, the aim of this study was to explore the effect of XYP on the expression of BDNF, glucocorticoids receptor (GR), Cx43, and c-Src in the hippocampus of rats with depression, and further investigated the mechanism of XYP regulates GR/BDNF signaling pathway and gap junction in hippocampal neurons of rats with chronic stress. Here, GJA1 is linked to major depressive disorder.