Evaluation of the neuropharmacological effects of Gardenin A in mice

Drug Dev Res. 2020 Aug;81(5):600-608. doi: 10.1002/ddr.21659. Epub 2020 Mar 17.

Abstract

This work describes the neuropharmacological (sedative, anxiolytic, antidepressant, and anticonvulsant) actions of Gardenin A (GA) (0.1-25 mg/kg p.o.), a flavonoid found in medicinal plants. The sedative effects of GA were assessed with the pentobarbital-induced sleep test. The anxiolytic actions of GA were evaluated with the elevated plus-maze, the light-dark box test, the exploratory cylinder assay, and the open field test. Motor coordination was evaluated with the rotarod test and the open field test. The antidepressant-like actions of GA were evaluated with the tail suspension test and forced swimming test. The mechanisms of the anxiolytic-like and antidepressant-like effects of GA were assessed using inhibitors of neurotransmission pathways. The anticonvulsant activity of GA was evaluated with the strychnine-induced seizure test. The sedative effects of GA were evident only at a dose of 25 mg/kg, which increased the duration of sleep but did not alter sleep onset. GA showed anxiolytic-like actions with activity comparable to that of clonazepam in all experimental tests. The GABAA receptor antagonist bicuculline reversed the anxiolytic-like effects of GA. Furthermore, GA showed significant antidepressant-like actions in both models with activity comparable to that of fluoxetine. Yohimbine, an α2-adrenoceptor blocker, inhibited the antidepressant-like actions of GA. In addition, GA (1-10 mg/kg) did not affect locomotor coordination in mice and delayed the onset of convulsions. These findings suggest that GA induces anxiolytic-like effects and has anticonvulsant actions by the possible involvement of the GABAergic system. The antidepressant-like actions of GA may be mediated by noradrenergic neurotransmission.

Keywords: Gardenin a; anxiety; convulsion; depression; sedative.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Anxiety Agents / therapeutic use*
  • Anticonvulsants / therapeutic use*
  • Antidepressive Agents / therapeutic use*
  • Behavior, Animal / drug effects
  • Exploratory Behavior / drug effects
  • Flavones / therapeutic use*
  • Hypnotics and Sedatives / therapeutic use*
  • Male
  • Mice, Inbred BALB C
  • Rotarod Performance Test
  • Seizures / chemically induced
  • Seizures / drug therapy*
  • Strychnine
  • Swimming

Substances

  • Anti-Anxiety Agents
  • Anticonvulsants
  • Antidepressive Agents
  • Flavones
  • Hypnotics and Sedatives
  • gardenin A
  • Strychnine