Bupleuri Radix can improve the clinical treatment effect of depressed patients.Saikosaponin A (SSA) is the main medicinal component of Bupleurum Radix.Here,we take SSA as the research object,systematically identifies the anti-depression target of SSA and studies the anti-depression mechanism of SSA.The experiment of CUMS model mouse tail suspension test (TST) and forced swimming test (FST) were used to identify the anti-depression effect of SSA.The molecular docking experiment was used to analyze and verify the target of SSA.The target of SSA was further verified by cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DARTS).In the mouse TST and FST,comparing the immobility time of the SSA experimental group and the model group,it was found that SSA can significantly shorten the immobility time of the mice,indicating that SSA has obviously antidepressant effects.Then using computer molecular docking,it was further found that the binding energy of SSA to the oxytocin receptor (OXTR) was low.The CETSA analysis showed that under a series of temperature gradient treatments,SSA can delay the thermal denaturation of OXTR.The DARTS analysis showed that under a series of enzyme concentration gradient treatments,SSA can reduce the sensitivity of OXTR to proteolysis.Western blotting analysis showed that SSA have no activating effect on the ERK pathway of OXTR.The study identified that the oxytocin receptor was the anti-depressant target of SSA,and preliminarily discussed the anti-depressant action mechanism of SSA,and provided the necessary theoretical basis in clinical treatment and new drug development.