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Psychopharmacology

, Volume 225, Issue 4, pp 839–851 | Cite as

The active alkaloids of Gelsemium elegans Benth. are potent anxiolytics

  • Ming Liu
  • Hui-Hui Huang
  • Jian Yang
  • Yan-Ping Su
  • Hong-Wei Lin
  • Li-Qing Lin
  • Wei-Jian Liao
  • Chang-Xi Yu
Original Investigation

Abstract

Rationale

An increasing number of herbal products has been introduced to treat anxiety and depression. Gelsemium elegans Benth (G. elegans) is a well-known herbal plant in Asia. Four major alkaloids (gelsemine, koumine, gelsevirine, and gelsenicine) have been isolated from G. elegans. Recently, interest has arisen to investigate the pharmaceutical potential of G. elegans alkaloids in the context of neuropsychopharmacology.

Objectives

We investigated whether G. elegans alkaloids are capable of producing anxiolytic and antidepressant effects in mouse models. In particular, we examined whether the anxiolytic action of G. elegans alkaloids is due to the agonist effects of glycine receptor in the brain.

Methods

Two mouse models (elevated plus-maze and light–dark transition model) were used to examine potential anxiolytic effects. Forced swim test and tail suspension test were used to test the antidepressive action of G. elegans alkaloids. Moreover, we also explored the anxiolytic mechanisms of G. elegans alkaloids by intracerebroventricular administration of strychnine, an antagonist of glycine receptor, in the elevated plus-maze.

Results

Gelsemine, koumine, and gelsevirine, but not gelsenicine, exhibited potent anxiolytic effects in the two anxiety models. None of the four G. elegans alkaloids exerted antidepressant effects in the two depression models. None of G. elegans alkaloids impaired spontaneous motor activities. The intracerebroventricular administration of strychnine significantly antagonized the anxiolytic effects of gelsemine, koumine, and gelsevirine administrated subcutaneously.

Conclusions

Gelsemine, koumine, and gelsevirine could be developed as the treatment of anxiety-related disorders in human patients. Their anxiolytic mechanism may be involved in the agonist action of glycine receptor in the brain.

Keywords

Gelsemium elegans alkaloids Anxiety Depression Mice Elevated plus-maze Light–dark transition model Forced swim test Tail suspension test Strychnine Glycine receptor 

Abbreviations

aCSF

Artificial cerebrospinal fluid

ANOVA

One-way analysis of variance

CCC

Counter-current chromatography

DZP

Diazepam

EPM

Elevated plus-maze

FLU

Fluoxetine

FST

Forced swim test

GABAA

Gamma aminobutyric acid A receptor

G. elegans

Gelsemium elegans Benth

Gly-R

Glycine receptor

GM

Gelsemine

G. sempervirens

Gelsemium sempervirens Ait

GS

Gelsenicine

GV

Gelsevirine

HSCCC

High-speed counter-current chromatography

i.c.v.

Intracerebroventricular

i.p.

Intraperitoneal

KM

Koumine

LDTM

Light–dark transition model

LD50

Median lethal dose

LSD

Least significant difference

s.c.

Subcutaneous

STR

Strychnine

TST

Tail suspension test

3α,5α-THP

Allopregnanolone

3α-HSD

3α-Hydroxysteroid dehydrogenase

5α-DHP

5α-Dihydroprogesterone

Notes

Acknowledgments

This work was supported by the National Natural Science Foundation of China (No. 81173046, No. 30973520), the Key Program of Scientific Research of Fujian Medical University (No. ZD009), and the Exploitation Program of Industrial Technology of Fujian Development and Reform Commission of China ([2009] No. 958).

Conflict of interest

All authors have no potential conflicts of interest to declare.

Supplementary material

213_2012_2867_MOESM1_ESM.pdf (742 kb)
ESM 1 Original data of elevated plus-maze, light–dark transition model, forced swim test, tail suspension test, spontaneous motor activity test, acute toxicity test, and strychnine antagonism test (PDF 742 kb)

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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Ming Liu
    • 1
  • Hui-Hui Huang
    • 1
  • Jian Yang
    • 1
  • Yan-Ping Su
    • 1
  • Hong-Wei Lin
    • 1
  • Li-Qing Lin
    • 1
  • Wei-Jian Liao
    • 1
  • Chang-Xi Yu
    • 1
  1. 1.Department of Pharmacology, College of PharmacyFujian Medical UniversityFuzhouPeople’s Republic of China

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