Jatrorrhizine reduces 5-HT and NE uptake via inhibition of uptake-2 transporters and produces antidepressant-like action in mice

1. Jatrorrhizine is an active ingredient found in various traditional Chinese medicinal plants. Based on our previous finding that jatrorrhizine was a potent inhibitor of OCT2 and OCT3, the aim of the present study was to explore whether jatrorrhizine has an antidepressant-like action action via inhibition of uptake-2 transporters.2. In vitro uptake tests showed that jatrorrhizine strongly inhibited PMAT-mediated MPP+ uptake with an IC50 value of 1.05 mu M and reduced 5-HT and NE uptake mediated by hOCT2, hOCT3 and hPMAT with IC50 values of 0.1-1 mu M (for OCT2 and OCT3) and 1-10 mu M (for PMAT).3. In mouse synaptosomes, jatrorrhizine suppressed 5-HT and NE uptake in a concentration dependently manner, where the role of uptake-2 inhibition is significant.4. The antidepressant-like action of jatrorrhizine was evaluated by mouse tail suspension test (TST). The TST showed that one week of jatrorrhizine (5, 10 and 20mg/kg, i.p.) or venlafaxine (20mg/kg, i.g.) can significantly reduce the duration of immobility when compared with vehicle control group.5. The concentration of jatrorrhizine shows a dose-dependent increase in brain tissues.6. Our study suggested that jatrorrhizine might be used as an antidepressant agent via inhibition of uptake-2 transporters.