Studies on anti-depressant activity of four flavonoids isolated from Apocynum venetum linn (Apocynaceae) leaf in mice

Abstract

Purpose: To investigate the anti-depressant activity of kaempferol, quercetin, kaempferol-3-O-β-Dglucose and quercetin-3-O-β-D-glucose isolated from Apocynum venetum Linn. (Apocynaceae) leaf and their mechanisms of action. Methods: The four flavonoids were isolated from Apocynum venetum leaf by chromatography. Mice were divided into vehicle, fluoxetine, kaempferol, quercetin, kaempferol-3-O-β-D-glucose and quercetin-3-O-β-D-glucose groups (n = 10). Forced swimming (FST), tail suspension (TST) and locomotor activity (LAT) tests were used to evaluate the effects of the four flavonoids (0.35 mM/kg) on immobility time, monoamine neurotransmitters, viz, norepinephrine (NE), dopamine (DA) and 5-hydroxytryptamine (5- HT), as well as on the metabolite (5-HIAA) in mice brain and central nervous system (CNS) with the aid of video camera, HPLC-ECD and activity-monitoring system. Results: The four flavonoids significantly (p < 0.05) reduced mice immobility time (72.58 - 90.24; 52.58 - 70.24 s), 5-HIAA levels (940.8 - 1244.7; 880.8 - 1164.1 ng/g) and 5-HIAA/5-HT ratio (1.77 - 4.76; 1.83 - 4.16), but increased NE, DA and 5-HT levels (238.7 - 405.7, 308.4 - 528.1, 261.4 - 531.9; 243.9 - 423.6, 296.7 - 534.9, 279.8 - 481.4 ng/g) in FST and TST, compared with control group (146.18, 126.18 s; 1363.4, 1240.9 ng/g; 7.43, 6.16; 138.4, 235.4, 183.4 and 143.7, 218.6, 201.4 ng/g). The effects of the four flavonoids on the above indices were significant (p < 0.05) and positively related to their polarity. They had no CNS-stimulating effects in LAT. Conclusion: The anti-depressant activities of the four flavonoids are positively related to their polarity, and the mechanisms may be due to increased NE, DA and 5-HT and reduced 5-HT metabolism.