Preclinical and clinical investigation has shown that hippocampal neuronal atrophy and destruction can be observed in patients with depression, and this can be ameliorated with antidepressant medication. Neuroprotection has therefore been proposed as one of the mechanisms of action of antidepressants. Paeoniflorin, a monoterpene glycoside, has been reported to display antidepressant-like effects in animal models of behavioral despair. The present study aimed to examine the protective effect of paeoniflorin treatment on N-methyl-D-aspartate (NMDA)-induced neurotoxicity in cultured rat pheochromocytoma (PC12) cells. Paeoniflorin was shown to elevate cell viability, decrease lactate dehydrogenase (LDH) release in NMDA-treated PC12 cells. Paeoniflorin also reversed the increased intracellular calcium (Ca(2+)) concentration and the reduced Calbindin-D28K mRNA level caused by NMDA in PC12 cells. These results suggest that paeoniflorin exerts a neuroprotective effect on NMDA-induced neurotoxicity in PC12 cells, at least in part, via Ca(2+) antagonism.
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