Anti-amnestic activity of E-p-methoxycinnamic acid from Scrophularia buergeriana

We previously reported that phenylpropanoids isolated from the roots of Scrophularia buergeriana Miquel (Scrophulariaceae) protected cultured cortical neurons against glutamate-induced neurotoxicity [Kim and Kim, Phytochemistry, 54 (2000) 503-509; Kim et al., Br. J. Pharmacol. 135 (2002) 1281-1291]. In the present study, we examined the anti-amnestic activities of phenylpropanoids in mice with amnesia induced in vivo by scopolamine. Among the phenylpropanoids tested through passive avoidance tasks, buergeriside A₁, buergeriside C₁, E-p-methoxycinnamic acid (E-p-MCA) and E-isoferulic acid significantly improved the deficit of memory induced by scopolamine. This suggested that the α,β-unsaturated carboxyl moiety and the para-methoxy group in phenylpropanoids (E-p-MCA) might be a crucial component in their cognition-enhancing activity. Indeed, E-p-MCA (0.01-2 mg/kg body weight, i.p.), given in pre- or post-treatment paradigms, significantly ameliorated scopolamine-induced amnesia as determined by passive avoidance tasks and prevented or aided in the recovery of memory to a level that was about 60% of control. In addition, E-p-MCA (0.1-1.0 mg/kg body weight, i.p.) significantly improved impairments of spatial learning and memory induced by scopolamine; the compound reduced deficits in both long- and short-term memories as measured by the Morris water maze test. We suggest, therefore, that E-p-MCA may ultimately hold significant therapeutic value in alleviating certain memory impairments observed in dementia.