Antidepressant-like effects of Sanyuansan in the mouse forced swim test, tail suspension test, and chronic mild stress model

Abstract

Natural products have been widely reported as effective therapeutic alternatives for treatment of depression. Sanyuansan is a compound recipe composed of ginseng total saponins, fish oil, and valeriana. The aims of this study were to validate whether Sanyuansan has antidepressant-like effects through acute behavioral tests including the forced swimming test (FST), tail suspension test (TST), locomotor activity test, and chronic mild stress (CMS) mice model of depression. C57BL/6 mice were given oral administration of 30 mg/kg imipramine, Sanyuansan, and saline, respectively. The acute behavioral tests including the TST, FST, and locomotor activity test were done after the administration of drugs for consecutively three times (24 hours, 1 hour, and 0.5 hour prior to the tests). Furthermore, the sucrose preference and the serum corticosterone level of mice in the CMS model were examined. Sanyuansan only at 900 mg/kg markedly reduced immobility time in the TST compared with the saline-treated group of mice. Sanyuansan at doses of 225 mg/kg, 450 mg/kg, and 900 mg/kg significantly reduced immobility time of mice in the FST. Sanyuansan reversed the CMS-induced anhedonia and hyperactivation of the hypothalamus-pituitary-adrenal axis. In addition, our results showed that neither imipramine nor Sanyuansan at any dosage increased spontaneous motor activity. These results suggested that Sanyuansan induced significant antidepressant-like effects in mice in both acute and chronic animal models, which seemed unlikely to be attributed to an increase in locomotor activities of mice, and had no sedative-like effects.

Keywords: Antidepressant; Chronic mild stress (CMS); Forced swimming test (FST); Sanyuansan; Tail suspension test (TST).

Figure 1

Effects of drugs on immobility time in the tail suspension test (TST). The mice (7 for each group) were orally administered saline, low dose Sanyuansan (225 mg/kg), medium dose Sanyuansan (450 mg/kg), high dose Sanyuansan (900 mg/kg), and imipramine (30 mg/kg), respectively. The drugs were administered at 24 hours, 1 hour, and 0.5 hour prior to the TST. Results are expressed as mean (±SEM) of immobility time (in seconds). The differences were analyzed using one‐way ANOVA followed by a post hoc Dunnett's test. For statistical significance, *p < 0.05 and **p < 0.01 when compared to the saline group. ANOVA = analyses of variance; SEM = standard error of the mean.

Figure 2

Effects of drugs on immobility time in the forced swimming test (FST). The mice (7 for each group) were orally administered saline, low dose Sanyuansan (225 mg/kg), medium dose Sanyuansan (450 mg/kg), high dose Sanyuansan (900 mg/kg), and imipramine (30 mg/kg), respectively. The drugs were administered at 24 hours, 1 hour, and 0.5 hour prior to the FST. Results are expressed as mean (±SEM) of immobility time (in seconds). The differences were analyzed using one‐way ANOVA followed by a post hoc Dunnett's test. For statistical significance, *p < 0.05 and **p < 0.01 when compared to the saline group. ANOVA = analyses of variance; SEM = standard error of the mean.

Figure 3

Effects of drugs on locomotor activity. The mice (7 for each group) were orally administered saline, low dose Sanyuansan (225 mg/kg), medium dose Sanyuansan (450 mg/kg), high dose Sanyuansan (900 mg/kg), and imipramine (30 mg/kg), respectively. The drugs were administered at 24 hours, 1 hour, and 0.5 hour prior to the locomotor activity test. Results are expressed as mean (±SEM) of the times of (A) spontaneous activities and (B) spontaneous standings. The differences were analyzed using one‐way ANOVA followed by a post hoc Dunnett's test. For statistical significance, **p < 0.01 when compared to the saline group. ANOVA = analyses of variance; SEM = standard error of the mean.

Figure 4

Effects of drugs on sucrose preference in CMS mice (n = 8). Results are expressed as mean (±SEM) of sucrose preference index (%). The differences were analyzed using one‐way ANOVA followed by a post hoc Dunnett's test. For statistical significance, **p < 0.01 when compared to the CMS + Vehicle group. ANOVA = analyses of variance; CMS = chronic mild stress; SEM = standard error of the mean.

Figure 5

Effects of drugs on serum CORT level in CMS mice (n = 6). Results are expressed as mean (±SEM) of serum CORT level (ng/mL). The differences were analyzed using one‐way ANOVA followed by a post hoc Dunnett's test. For statistical significance, **p < 0.01 when compared to the CMS + Vehicle group. ANOVA = analyses of variance; CMS = chronic mild stress; CORT = corticosterone; SEM = standard error of the mean.