Antidepressant-like effect of flavonoids extracted from Apocynum venetum leaves on brain monoamine levels and dopaminergic system

J Ethnopharmacol. 2013 May 2;147(1):108-13. doi: 10.1016/j.jep.2013.02.015. Epub 2013 Feb 27.


Ethnopharmacological relevance: Apocynum venetum L. (Apocynaceae), a traditional medicinal plant, has been used for the improvement of emotions in Asian countries.

Aim of the study: We explored the antidepressant-like effect and monoaminergic mechanism of a flavonoids extract from Apocynum venetum leaves (AV-extract).

Materials and methods: Effect of AV-extract (25, 50 and 100 mg/kg, i.g.) on mice's immobility time was assessed in forced swim test (FST) and tail suspension test (TST). The locomotor activity was evaluated in the open-field test (OFT). Additionally, the main monoamine neurotransmitters serotonin (5-HT), noradrenaline (NA) and dopamine (DA) and their metabolites 5-hydroxyindole-3-acetic acid (5-HIAA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the mouse hippocampus involved in the antidepressant-like effect of AV-extract was also determined by liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS-MS).

Results: AV-extract (50 and 100 mg/kg, i.g.) administration significantly reduced the immobility time in both the FST and TST without accompanying changes in locomotor activity in the OFT. It was also found that the AV-extract significantly increased the concentrations of the main neurotransmitters NE and DA along with their respective metabolites DOPAC, HVA in the hippocampus. The antidepressant-like effect of the AV-extract (50 mg/kg, i.g.) was prevented by the pretreatment of mice with SCH23390 (0.05 mg/kg, i.g., a dopamine D1 receptor antagonist) or sulpiride (50 mg/kg, i.g., a dopamine D2 receptor antagonist).

Conclusion: The AV-extract produced significant antidepressant-like effects, which likely attribute to increased NE and DA along with their respective metabolites DOPAC, HVA in the mouse hippocampus, and dependent on interaction with dopaminergic (D1 and D2 receptor) systems.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3,4-Dihydroxyphenylacetic Acid / metabolism
  • Animals
  • Antidepressive Agents / chemistry
  • Antidepressive Agents / isolation & purification
  • Antidepressive Agents / pharmacology*
  • Apocynum* / chemistry
  • Behavior, Animal / drug effects
  • Biogenic Monoamines / metabolism*
  • Chromatography, Liquid
  • Dopamine / metabolism
  • Dopamine Antagonists / pharmacology
  • Dose-Response Relationship, Drug
  • Flavonoids / chemistry
  • Flavonoids / isolation & purification
  • Flavonoids / pharmacology*
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Homovanillic Acid / metabolism
  • Hydroxyindoleacetic Acid / metabolism
  • Male
  • Mice
  • Mice, Inbred ICR
  • Motor Activity / drug effects
  • Norepinephrine / metabolism
  • Phytotherapy
  • Plant Extracts / chemistry
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Plant Leaves
  • Plants, Medicinal
  • Serotonin / metabolism
  • Spectrometry, Mass, Electrospray Ionization
  • Tandem Mass Spectrometry


  • Antidepressive Agents
  • Biogenic Monoamines
  • Dopamine Antagonists
  • Flavonoids
  • Plant Extracts
  • 3,4-Dihydroxyphenylacetic Acid
  • Serotonin
  • Hydroxyindoleacetic Acid
  • Dopamine
  • Norepinephrine
  • Homovanillic Acid