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

Ethnopharmacological relevanceApocynum venetum L. (Apocynaceae), a traditional medicinal plant, has been used for the improvement of emotions in Asian countries.Aim of the studyWe explored the antidepressant-like effect and monoaminergic mechanism of a flavonoids extract from Apocynum venetum leaves (AV-extract).Materials and methodsEffect 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).ResultsAV-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).ConclusionThe 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.

Graphical abstractThe present study investigated a possible antidepressant-like activity of flavonoids extracted from Apocynum venetum leaves (AV-extract or Apocynum venetum leaf extract) using two predictive tests for antidepressant effect on rodents: the forced swimming test (FST) and the tail suspension test (TST). 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) levels in the mouse hippocampus involved in the antidepressant-like effect of AV-extract was also simultaneously determined by liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS-MS).The data demonstrated that AV-extract produced significant antidepressant-like effects, and their mechanism of action may be due to increased NE, DA and its metabolites DOPAC, HVA in the mouse hippocampus, and dependent on its interaction with dopaminergic (D1 and D2 receptor) systems Download high-res image (72KB)Download full-size image.