The active alkaloids of Gelsemium elegans Benth. are potent anxiolytics

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.