Anti-stress effects of 3,4,5-trimethoxycinnamic acid, an active constituent of roots of Polygala tenuifolia (Onji)

3,4,5-trimethoxycinnamic acid (TMCA) is one of the constituents in Onji (roots of Polygala tenuifolia WILLD), an herbal medicine used for sedative in Japanese traditional Kampo medicine. Our previous study revealed that oral administration of this compound prolongs sleeping time induced by hexobarbital in mice to exhibit sedative action. In the present study, we investigate the effects of TMCA on the stress induced with repeated cold exposure or intracerebroventricular injection of corticotrophin-releasing hormone (CRH). Both types of stress significantly reduced the sleeping time induced with pentobarbital in rat, which was significantly prolonged by intraperitoneal injection of TMCA. The intracerebroventricular injection of CRH significantly augmented the content of norepinephrine (NE) in locus coeruleus (LC) of rats, which was significantly suppressed by the intracerebroventricular injection of TMCA. These findings suggest that TMCA would exhibit sedative effects by suppressing NE content in LC.