Synergistic Antidepressant Effects of Total Saikosaponins Combined with Volatile Oil of Cyperi Rhizoma in Mice Models Induced by Chronic Restraint plus Mild Stress

Abstract

This study aimed to evaluate the antidepressant effects of the combined administration of total saikosaponins (SSA) and volatile oil of Cyperi Rhizoma (VO) using a mouse depression model induced by chronic restraint plus mild stress (CRMS), and to compare the effects with the traditional antidepressant fluoxetine. Male Kunming mice were subjected to 14-day CRMS modeling and then randomly divided into four groups: the combined treatment group (intraperitoneal injection of SSA 3.5 mg/kg + VO 35 mg/kg), the fluoxetine treatment group (20 mg/kg), the normal saline treatment group, and the non-model group. Drugs were administered continuously for 14 days. Depressive-like behaviors were assessed using the Forced Swimming Test (FST), Tail Suspension Test (TST), and Open-Field Test (OFT). The results showed that the absolute immobility time of mice in the CRMS model group was significantly prolonged in FST and TST. Combined administration of SSA and VO significantly improved depressive-like behaviors, restoring the absolute immobility time in FST and TST to levels close to the control group, with efficacy comparable to fluoxetine. This study confirms that the combination of SSA and VO exhibits antidepressant effects equivalent to fluoxetine in the CRMS model, providing experimental evidence for the further clinical development of this traditional Chinese medicine (TCM) compatibility.