Subchronic administration of rosmarinic acid,a natural prolyl oligopeptidase inhibitor,enhances cognitive performances

It is well known that inhibition of prolyl oligopeptidase (POP) is involved in memory-related function. In this study, we observed that rosmarinic acid (RA) inhibits POP activity with an IC₅₀ of 63.7 μM. Subsequently, we investigated the cognitive-enhancing effects of RA employing the Morris water maze paradigm. The results demonstrated that RA is non-competitive POP inhibitor and that acute and subchronic RA treatments showed an inverted U-shaped dose–response curve in the platform crossings. Furthermore, chronic RA treatment significantly increased the platform crossings. These results suggest that RA has a cognitive-enhancing effect which may be mediated by inhibition of POP.