title: E-p-methoxycinnamic acid protects cultured neuronal cells against neurotoxicity induced by glutamate.
abstract: 1. 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. 2. The alpha,beta-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. 3. 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. 4. 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. 5. 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.
authors.affiliation: College of Pharmacy, Seoul National University, San 56-1, Shillim-Dong, Kwanak-Gu, Seoul 151-742, Korea.
authors.forename: So Ra
authors.initials: SR
authors.lastname: Kim
authors.forename: Sang Hyun
authors.initials: SH
authors.lastname: Sung
authors.forename: Young Pyo
authors.initials: YP
authors.lastname: Jang
authors.forename: George J
authors.initials: GJ
authors.lastname: Markelonis
authors.forename: Tae H
authors.initials: TH
authors.lastname: Oh
authors.forename: Young Choong
authors.initials: YC
authors.lastname: Kim
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002934:Cinnamates / Q000494:pharmacology*; D018698:Glutamic Acid / Q000633:toxicity*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007608:Kainic Acid / Q000633:toxicity; D016202:N-Methylaspartate / Q000633:toxicity; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D002934:Cinnamates; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D016202:N-Methylaspartate; C063318:4-methoxycinnamic acid; D007608:Kainic Acid