Chlorogenic acid, a polyphenol in coffee, protects neurons against glutamate neurotoxicity.

OBJECTIVE

The present study has been designed to explore the molecular mechanism of chlorogenic acid (CGA) in the protective effect against glutamate-induced neuronal cell death.

METHODS

Cortical neurons in primary culture were exposed to 300 μM l-glutamic acid or vehicle, with or without 10 μM CGA or 10 μM MK-801. After 16 h, primary cultures were stained with propidium iodide (PI)/Hoechst or calcein. Double-staining with PI and Hoechst was performed to confirm whether cell death induced by glutamate was apoptotic. In addition, intracellular concentrations of Ca(2+) were observed using Ca(2+) indicator fura-2.

RESULTS

We investigated the protective effects of CGA on glutamate-induced neuronal cell death using primary cultures of mouse cerebral cortex because the release of glutamate during brain ischemia triggers death of neurons. Glutamate-induced neuronal cell death was inhibited by treatment with CGA. In addition, CGA prevented the increase in intracellular concentrations of Ca(2+) caused by the addition of glutamate to cultured neurons. On the other hand, there was little effect of CGA on cell death induced by nitric oxide, which is downstream of the ischemic neuronal cell death. Our results suggested that the polyphenol CGA in coffee protects neurons from glutamate neurotoxicity by regulating Ca(2+) entry into neurons.

CONCLUSIONS

CGA in coffee may have clinical benefits for neurodegenerative diseases such as ischemic stroke.