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Fitoterapia. 2010 Sep;81(6):644-8. doi: 10.1016/j.fitote.2010.03.010. Epub 2010 Mar 15.

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

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Department of Life and Nanopharmaceutical Science, Kyung Hee University, Hoeki-dong, Dongdaemoon-Ku, Seoul 130-701, Republic of Korea.


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 IC(50) of 63.7 microM. 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.

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