Open Access Highly Accessed Research article

Hypericum perforatum treatment: effect on behaviour and neurogenesis in a chronic stress model in mice

Rosalia Crupi1, Emanuela Mazzon2, Angela Marino3, Giuseppina La Spada3, Placido Bramanti2, Fortunato Battaglia4, Salvatore Cuzzocrea12 and Edoardo Spina12*

Author Affiliations

1 Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, via Consolare Valeria, 98125 Messina, Italy

2 IRCCS Centro Neurolesi "Bonino-Pulejo", via Provinciale Palermo, C. da Casazza 98124 Messina, Italy

3 Department of Life Sciences "M.Malpighi", Section of General Physiology and Pharmacology, University of Messina, via F. Stagno D'Alcontres 31, 98166 Messina, Italy

4 Department of Psychiatry, Columbia University, New York College of Podiatric Medicine, 53 East 124thStreet, New York, 10035 NY, USA

For all author emails, please log on.

BMC Complementary and Alternative Medicine 2011, 11:7  doi:10.1186/1472-6882-11-7

Published: 27 January 2011



Extracts of Hypericum perforatum (St. John's wort) have been traditionally recommended for a wide range of medical conditions, in particular mild-to-moderate depression. The present study was designed to investigate the effect of Hypericum perforatum treatment in a mouse model of anxiety/depressive-like behavior, induced by chronic corticosterone administration.


CD1 mice were submitted to 7 weeks corticosterone administration and then behavioral tests as Open Field (OF), Novelty-Suppressed Feeding (NSF), Forced Swim Test (FST) were performed. Cell proliferation in hippocampal dentate gyrus (DG) was investigated by both 5-bromo-2'-deoxyuridine (BrdU) and doublecortin (DCX) immunohistochemistry techniques and stereological procedure was used to quantify labeled cells. Golgi-impregnation method was used to evaluate changes in dendritic spines in DG. Hypericum perforatum (30 mg/Kg) has been administered for 3 weeks and then neural development in the adult hippocampus and behavioral changes have been examined.


The anxiety/depressive-like state due to chronic corticosterone treatment was reversed by exogenous administration of Hypericum perforatum; the proliferation of progenitor cells in mice hippocampus was significantly reduced under chronic corticosterone treatment, whereas a long term treatment with Hypericum perforatum prevented the corticosterone-induced decrease in hippocampal cell proliferation. Corticosterone-treated mice exhibited a reduced spine density that was ameliorated by Hypericum perforatum administration.


These results provide evidence of morphological adaptations occurring in mature hippocampal neurons that might underlie resilient responses to chronic stress and contribute to the therapeutic effects of chronic Hypericum perforatum treatment.