The discovery of Yuanzhi-1, a triterpenoid saponin derived from the traditional Chinese medicine, has antidepressant-like activity.

Yuanzhi, the dried root of Polygala tenuifolia Willd., is a well-known traditional Chinese medicine used for its sedative, antipsychotic, cognitive improving, neuroprotective, and antidepressant effects. The present study was designed to screen and identify the antidepressant-like effect of six triterpenoid saponin components derived from Yuanzhi (Yuanzhi-1 to Yuanzhi-6) using in vitro radioligand receptor binding assays and in vivo behavioral tests. Yuanzhi-1, -3, -5 and -6 were shown to have antidepressant-like activity in the tail suspension test and forced swim test in mice, with no stimulant effect on locomotor activity. The minimal effective dose of Yuanzhi-1 (2.5 mg/kg) was lower than that of duloxetine (5mg/kg), a serotonin and norepinephrine reuptake inhibitor commonly used in the treatment of depression. Yuanzhi-1 (1 nM) had a high affinity for serotonin, norepinephrine and dopamine transporters. Acute toxicity tests indicated that the LD50 of Yuanzhi-1 (86.5mg/kg) was similar to that of duloxetine (73.2 mg/kg). These findings demonstrate that Yuanzhi-1 has a potential to be a novel triple monoamine reuptake inhibitor of antidepressant-like activity.