Antidepressant-like effect of hyperoside isolated from Apocynum venetum leaves: possible cellular mechanisms

In the present work, we studied the possible cellular mechanisms of hyperoside isolated from Apocynum venetum leaves in corticosterone-induced neurotoxicity, using PC12 cells as a suitable in vitro model of depression. Cell viability was quantitated by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. The release amount of lactic dehydrogenase (LDH) and intracellular Ca(2+) concentration were measured using kit and transcript abundances of brain-derived neurotrophic factor (BDNF) and cAMP response element binding protein (CREB) were determined by real-time RT-PCR. The results of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and lactic dehydrogenase (LDH) assays showed that 2.5, 5 and 10 μg/ml hyperoside or 10 μM fluoxetine (FLU) protected PC12 cells from the lesion induced by a 48 h treatment with 10 μM corticosterone. Fura-2/AM (acetoxymethyl ester) assays showed that 2.5, 5 and 10 μg/ml hyperoside or 10 μM FLU attenuated the intracellular Ca(2+) overloading in PC12 cells induced by corticosterone. The transcript abundance of BDNF and CREB in PC12 cells was elevated upon hyperoside treatment. These results suggest that the possible cellular mechanisms of hyperoside antidepressant-like effect is a cytoprotective action related to elevation the expression of BDNF and CREB through the signal pathway AC-cAMP-CREB.