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

Abstract

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 μM and reduced 5-HT and NE uptake mediated by hOCT2, hOCT3 and hPMAT with IC₅₀ values of 0.1–1 μM (for OCT2 and OCT3) and 1–10 μM (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 20 mg/kg, i.p.) or venlafaxine (20 mg/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.

Keywords:

• Jatrorrhizine
• organic cation transporter
• plasma membrane monoamine transporter
• antidepressant
• uptake-2

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the Bureau of Zhejiang Traditional Chinese Medicine (Grant 2016ZZ014), by the National Natural Science Foundation of China (Grant No. 81673504) and by the Scientific Research Fund of Zhejiang Provincial Education Department (Grant Y201432325).