E-p-Methoxycinnamic acid protects cultured neuronal cells against neurotoxicity induced by glutamate
Article first published online: 2 FEB 2009
2002 British Pharmacological Society
British Journal of Pharmacology
Volume 135, Issue 5, pages 1281–1291, March 2002
How to Cite
Kim, S. R., Sung, S. H., Jang, Y. P., Markelonis, G. J., Oh, T. H. and Kim, Y. C. (2002), E-p-Methoxycinnamic acid protects cultured neuronal cells against neurotoxicity induced by glutamate. British Journal of Pharmacology, 135: 1281–1291. doi: 10.1038/sj.bjp.0704576
- Issue published online: 2 FEB 2009
- Article first published online: 2 FEB 2009
- (Received July 6, 2001, Revised November 30, 2001, Accepted January 3, 2002)
- Scrophularia buergeriana;
- E-p-methoxycinnamic acid;
- primary neuronal culture;
- neuroprotective activity;
- glutamatergic antagonism;
- structure-activity relationship;
- neurodegenerative disorders
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-2,3-3H]-CGP39653 and [2-3H]-glycine to their respective binding sites on rat cortical membranes. However, even high concentrations of E-p-MCA failed to inhibit completely [propyl-2,3-3H]-CGP39653 and [2-3H]-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