[Pharmacological characterization and mechanisms of the novel antidepressive- and/or anxiolytic-like substances identified from Perillae Herba].

The leaves of Perilla frutescens Britton var. acuta Kudo (Perillae Herba) are commonly found in traditional oriental herbal medicines, which are primarily used to treat depression and anxiety-related disorders. We have recently identified rosmarinic acid as well as its major metabolite caffeic acid as novel antidepressive and/or anxiolytic-like substances from components within Perillae Herba. The present article will review our previous findings and also provide a view of future studies. Behavioral as well as analytical studies have demonstrated that first, the extracts from Perillae Herba, which produced an antidepressive-like effect in the forced swimming test, contained abundant rosmarinic acid; second, the extracts from another species of Perillae Herba, which contains only low levels of rosmarinic acid, did not have an antidepressive-activity; third, rosmarinic acid and caffeic acid themselves also produced an antidepressive-like effect; finally, both compounds showed an anxiolytic-like activity in the conditioned fear stress test. Neurochemical studies have also revealed that neither rosmarinic acid nor caffeic acid affects the uptake of monoamines or monoamine oxidase activity, which may underlie the therapeutic value of existing clinically effective antidepressants. Furthermore, it has been found in the recent study that caffeic acid produces antidepressive- and/or anxiolytic-like effects through the modulation of the alpha1A-adrenoceptor-mediated signal transductions and also attenuates the down-regulation of BDNF transcription that results from the exposure to forced swimming stress. These results suggest that rosmarinic acid and caffeic acid may produce antidepressive- and/or anxiolytic-like effects via some mechanism(s) other than those of drugs that now clinically used. Therefore, further studies on the mechanisms involved in the antidepressive- and/or anxiolytic-like properties of both substances could help to explain the pathophysiology underlying depression and anxiety disorders, and pave the way for the development of new therapeutic drugs.