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

Prog Neuropsychopharmacol Biol Psychiatry. 2014 Aug 4;53:9-14. doi: 10.1016/j.pnpbp.2014.02.013. Epub 2014 Mar 12.

Abstract

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.

Keywords: Antidepressant; Depression; Traditional Chinese medicine; Triple reuptake inhibitor; Yuanzhi.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antidepressive Agents / pharmacology
  • Antidepressive Agents / therapeutic use*
  • Citalopram / pharmacokinetics
  • Cocaine / analogs & derivatives
  • Cocaine / pharmacokinetics
  • Depression / drug therapy*
  • Disease Models, Animal
  • Female
  • Fluoxetine / analogs & derivatives
  • Fluoxetine / pharmacology
  • Male
  • Medicine, Chinese Traditional*
  • Membrane Transport Proteins / metabolism
  • Mice
  • Mice, Inbred ICR
  • Motor Activity / drug effects
  • Protein Binding / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Saponins / chemistry
  • Saponins / therapeutic use*
  • Swimming / psychology
  • Tritium / pharmacokinetics

Substances

  • Antidepressive Agents
  • Membrane Transport Proteins
  • Saponins
  • yuanzhi-1
  • Fluoxetine
  • Citalopram
  • Tritium
  • nisoxetine
  • (1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester
  • Cocaine