Antidepressant-like effect of saponins extracted from Chaihu-jia-longgu-muli-tang and its possible mechanism

In this study, we investigated the antidepressant-like effect of saponins (SCLM) extracted from a traditional Chinese medicine, Chaihu-jia-longgu-muli-tang (CLM), in mice and rats using the tail suspension test (TST) and forced swimming test (FST). Subchronic administration of 100 and 200 mg/kg (p.o.) SCLM for 7 days reduced immobility time in the TST and FST in mice and also decreased immobility time at 70 and 140 mg/kg (p.o.) in the FST in rats. The results also showed that the anti-immobility activity of SCLM in these two tests is dose-dependent, without accompanying significant effects on locomotor activity. In addition, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and lactic dehydrogenase (LDH) assays showed that 25, 50 and 100 μg/ml SCLM or 10 μM fluoxetine (FLU), protected PC12 cells from the lesion induced by 10 μM corticosterone (Cort) treatment for 48 h. In the fura-2/AM (acetoxymethyl ester) labeling assay, 50 and 100 μg/ml SCLM, 10 μM FLU attenuated the intracellular Ca2+ overloading induced by 200 μM Cort treatment for 48 h in PC12 cells. Using RT-PCR, the mRNA level of nerve growth factor (NGF) was also detected. Treatment with SCLM (50, 100 μg/ml) for 48 h elevated the NGF mRNA expression in PC12 cells. In summary, these results suggest that SCLM possesses an antidepressant-like activity in behavioral models that might be mediated via the cytoprotective action shown in PC12 cells.