Proapoptotic and prepulse inhibition (PPI) disrupting effects of Hypericum perforatum in rats

Abstract

Ethnopharmacological relevance: St. John's wort extract is commonly used as a wound healing, anti-inflammatory, anxiolytic, diuretic, antibiotic, antiviral and cancer chemoprotective agent. It also has nootropic and/or antiamnestic effects. Aim of the study: Prepulse inhibition (PPI) of startle response is a valuable paradigm for sensorimotor gating processes. A previous study indicated that single administration of St. John's wort extract (500 mg/kg) caused PPI disruption in rats. The effect of antiamnestic doses of the extract on PPI has not been investigated despite the coexistence of impaired memory and PPI deficit in some neurological disorders. Materials and methods: The effects of acute (500 mg/kg) and chronic (200 mg/kg for 3 days) administration of St. John's wort extract were investigated for its antiamnestic activity. The effects of administration of the antiamnestic dose of the extract and hyperforin, its main active component, were tested on PPI of an acoustic startle response in rats. This study also investigated the proapoptotic effect of hyperforin in animals, demonstrating PPI deficit, by electrophoresis of DNA isolated from selected brain areas. Results: Disruption of PPI resulted after treatment of rats with an antiamnestic dose of the extract (200 mg/kg for 3 days) and with hyperforin. Gel electrophoresis showed DNA fragmentation of the cortices of hyperforin-treated animals exhibiting PPI deficit. Conclusions: The exacerbating effect of St. John's wort extract on PPI deficit may provide a limitation for using the extract to manage cognitive disturbance in psychotic and Huntington's disease patients manifesting PPI deficit. © 2009 Elsevier Ireland Ltd. All rights reserved.