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.
Department of Pharmacology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 1130033, Japan.
Yoshinori
Y
Mikami
Department of Molecular Physiology, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo 1058461, Japan. Electronic address: toshiko1998@jikei.ac.jp.
Toshiko
T
Yamazawa
D000818:Animals; D002118:Calcium / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002726:Chlorogenic Acid / Q000737:chemistry / Q000494:pharmacology*; D003069:Coffee / Q000737:chemistry*; D018698:Glutamic Acid / Q000633:toxicity*; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000633:toxicity
D003069:Coffee; D018696:Neuroprotective Agents; D002726:Chlorogenic Acid; D009569:Nitric Oxide; D018698:Glutamic Acid; D002118:Calcium
Chlorogenic acid; Chlorogenic acid (PubChem CID:1794427); Coffee polyphenol; Glutamate neurotoxicity; Glutamic acid (PubChem CID:611); MK-801 (PubChem CID:16219612); NOC12 (PubChem CID:1656); Neuroprotection; Nitric oxide (PubChem CID:145068)