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E‐p ‐Methoxycinnamic acid protects cultured neuronal cells against neurotoxicity induced by glutamate
Author(s) -
Kim So Ra,
Sung Sang Hyun,
Jang Young Pyo,
Markelonis George J,
Oh Tae H,
Kim Young Choong
Publication year - 2002
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0704576
Subject(s) - neurotoxicity , neuroprotection , glutamate receptor , biochemistry , kainic acid , chemistry , pharmacology , glycine , nmda receptor , glutamatergic , biology , amino acid , toxicity , receptor , organic chemistry
We previously reported that four new phenylpropanoid glycosides and six known cinnamate derivatives isolated from roots of Scrophularia buergeriana Miquel (Scrophulariaceae) protected cultured cortical neurons from neurotoxicity induced by glutamate. Here, we have investigated the structure‐activity relationships in the phenylpropanoids using our primary culture system. The α,β‐unsaturated ester moiety and the para ‐methoxy group in the phenylpropanoids appeared to play a vital role in neuroprotective activity. This suggested that E‐p ‐methoxycinnamic acid ( E‐p ‐MCA) might be a crucial component for their neuroprotective activity within the phenylpropanoid compounds. E‐p ‐MCA significantly attenuated glutamate‐induced neurotoxicity when added prior to an excitotoxic glutamate challenge. The neuroprotective activity of E‐p ‐MCA appeared to be more effective in protecting neurons against neurotoxicity induced by NMDA than from that induced by kainic acid. E‐p ‐MCA inhibited the binding of [propyl‐2,3‐ 3 H]‐CGP39653 and [2‐ 3 H]‐glycine to their respective binding sites on rat cortical membranes. However, even high concentrations of E‐p ‐MCA failed to inhibit completely [propyl‐2,3‐ 3 H]‐CGP39653 and [2‐ 3 H]‐glycine binding. Indeed, E‐p ‐MCA diminished the calcium influx that routinely accompanies glutamate‐induced neurotoxicity, and inhibited the subsequent overproduction of nitric oxide and cellular peroxide in glutamate‐injured neurons. Thus, our results suggest that E‐p ‐MCA exerts significant protective effects against neurodegeneration induced by glutamate in primary cultures of cortical neurons by an action suggestive of partial glutamatergic antagonism.British Journal of Pharmacology (2002) 135 , 1281–1291; doi: 10.1038/sj.bjp.0704576