Paeonol Prevents Excitotoxicity in Rat Pheochromocytoma PC12 Cells via Downregulation of ERK Activation and Inhibition of Apoptosis

Abstract

Paeonol, an active component of Moutan Cortex, has been recognized as a potential neuroprotective drug. In the present study, an injury model based on glutamate-induced cell death of rat pheochromocytoma cells was used to investigate the neuroprotective potential of paeonol and its mechanism of action. Our findings showed that paeonol dose-dependently prevented glutamate-induced cell death as evidenced by cell viability, lactate dehydrogenase release, and trypan blue exclusion. In addition, flow cytometry of propidium iodide-stained cells revealed that paeonol pretreatment reduced the level of glutamate-induced apoptosis in pheochromocytoma cells. Paeonol was also able to decrease the glutamate-induced injury of mitochondria by normalization of mitochondrial membrane potential and cytochrome c release. The glutamate-induced activity of caspase-3 and p-ERK were dose-dependently reduced by paeonol pretreatments. Taken together, our data suggest that paeonol develops its neuroprotective effect against glutamate neurotoxicity through inhibition of the apoptotic signaling pathway and upregulation of the p-ERK pathway.

Key words

paeonol - glutamate - apoptosis - ERK1/2 - Paeonia moutan - Paeoniaceae

References

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1 These authors contributed equally to this work.