Ameliorating effect of swertisin in MK-801-induced prepulse inhibition deficits and cognitive impairment

Schizophrenia is a chronic neuropsychiatric disorder characterized by positive symptoms, negative symptoms and cognitive disturbance. Because of the narrow therapeutic effects and other adverse effects in schizophrenia patients, developing novel candidates for treating schizophrenia is required. Swertia japonica is a herbaceous plant within the family Gentianaceae. Extracts of S. japonica inhibited the dopamine D2 receptor signaling on gastrointestinal tracts, but its antipsychotic effects have not been studied until yet. In a pilot study, we found that ethanol extract of S. japonica ameliorated MK-801-induced sensorimotor gating impairments. Further studies were conducted for which ingredients would have the similar antipsychotic effect of S. japonica and isolated swertisin. We investigated the effects of swertisin on schizophrenia-like behaviors induced by MK-801 in mice. In the acoustic startle response test, the MK-801-induced prepulse inhibition deficit was significantly attenuated by the administration of swertisin (30 mg/kg, p.o.). Swertisin itself did not have any effects on the acoustic startle response or prepulse inhibition (PPI) level in normal naïve mice. In the novel objects recognition test, recognition memory impairments induced by MK-801 were reversed by the administration of swertisin (30 mg/kg, p.o). These results indicate that swertisin may be useful for the treatment of several symptoms of schizophrenia, including sensorimotor gating disruption, and cognitive impairment.