TheHMEadministered at doses of 25, 50 and 100 mg/kg caused a significant and dose dependent reduction in the total number of head dipping behaviours in the hole board tests. Moreover, the extract also induced a significant TG-101348 decrease in the total number of horizontal and vertical spontaneous locomotory activities of the animals in the activity cage tests. Locomotor activities result from brain activation, which is manifested as an excitation of central neurons involving different neurochemical mechanisms and an increase in cerebral metabolism. Therefore, the reduction in the spontaneous locomotory activities of the animals in the activity cage tests as well as the inhibition of exploratory behaviour in the hole board tests indicates a general inhibition of neuronal activity in the CNS.
To examine the possible sedative activity of HME, the Hxb induced sleeping test was performed. This test is considered to Marbofloxacin Marbocyl be a very sensitive means of assessing agents for CNS depressant action. Administration of HME significantly shortened the onset of sleeping and prolonged sleep duration, indicating that the tested extract possesses sedative activity. The prolongation of sleeping time with HME did not appear to be caused by inhibition of hepatic microsomal enzymes metabolizing Hxb, since previous studies have noted the microsomal enzymeinducing potential of Hypericum flavonoids. To investigate the possible mechanisms involved in the sedation induced by HME, mice were pre treated with different antagonists.
The possible contributions of muscarinic and opioidergic pathways were assessed by Atr and Nlx pre treatment, Telaprevir HCV protease inhibitor respectively. Neither Atr nor Nlx reversed the decrease in the total number of head dipping behaviours, the reduction in spontaneous locomotor activities, or the potentialization of Hxb induced sleeping parameters produced by 100mg/kg doses of HME, indicating that the muscarinic and opioidergic mechanisms were notinvolved in the observed sedative action. In contrast, pre treatment with Flu antagonized all of the alterations induced by administration of the extract in the holeboard, activity cage and sleeping tests, suggesting that the extract contains a compound or compounds that interact with the benzodiazepine site in the GABA/A benzodiazepine receptor complex.
Generally, drugs enhancing GABAergic neurotransmission in the CNS may CYP inhibitor also possess anticonvulsant effects. Based on the involvement of GABA/A benzodiazepine receptors in the pharmacological activity of the extract, the presence of a promising anticonvulsant effect was investigated by PTZ induced seizure tests. The HME administered at doses of 50 and 100mg/kg provided significant protection from PTZ induced seizures in a dose dependent manner. There was a significant delay in the onset of convulsions and a decrease in the incidence of convulsions. Mortality induced by PTZ administration was also decreased compared with the control values. This anticonvulsant activity was reversed by Flu pre treatment, confirming language our finding of the involvement of GABA/Abenzodiazepine receptors in the pharmacological activity of HME. Our research team has recently reported the phytochemical content of the HME used in the present study.