The Pharmacodynamics Comparison Study Of Supercritical-CO₂ Fluid Extractions Of Chinese Herb On Anticonvulsant Action

Objective To compare the pharmacodynamics of supercritical-CO2 fluid extractions(SFE-CO2) of Radix Bupleuri, et al on anticonvulsion, and explore their mechanism of anticonvulsant action. Methods Maximal electroshock seizure(MES) were used to analyse the relative of dose and effect, relative of time and effect, maximum efficacy and potency of supercritical-CO2 fluid extractions in mice given by ig administration. Metrazol seizure test(MET) was adopted to compare seizure latency, anticonvulsant rate and mortality of mice with each of extractions. Using the model of seizure rats induced by penicillin localized injected in cortex investigated the effect of extractions on seizure latency, frequency of epileptiform discharge, highest wave of hippocampus and cortex EEG(Recoded by RM6240C multichannel physiological signal collection and analysis recorde), the changes of convulsant behaviors and the latency of seizure. The neurotransmitters content in brain related to epilepsy were determined by high performance liquid chromatography(HPLC) in order to compare the effect of extractions on Glu, Asp, Gly and GABA of hippocampus. Results and conclusions (1)Except for RBâ…¡and SBâ… , all the other seven extractions could dose-dependently antagonized MES in mice. Maximum efficacy of extractions ranged from maximum to minimum were PTâ…¡, RPâ…¡, UNâ…¡, RATâ…¡, SCLâ… , RBâ… , RATâ… , and the sequence of potency were SCLâ… , RBâ… , RATâ… , RPâ…¡, RATâ…¡, UNâ…¡, PTâ…¡. (2) All of the seven extractions could prolong latent period on MET in mice, and the sequence from maximum to minimum were RPâ…¡, UNâ…¡, RATâ… , PTâ…¡, SCLâ… , RBâ… , RATâ…¡. The effect of RPâ…¡was better than Topamax. (3) Produced effect time of extractions with SFE-CO2 SCLâ… , RBâ… , RATâ… was faster than that of supercritical-CO2 alcohol fluid extractions (SAFE-CO2) RPâ…¡, RATâ…¡, UNâ…¡, PTâ…¡and persist time was shorter than the latter. Persist time of RPâ…¡could last 8h, and it was the longest one in all of the extractions. (4) PTâ…¡ was the most effective extraction to antagonize the penicillin-induced seizure. Anticonvulsant properties of PTâ…¡resembled Topamax, but the effect of it was better than Topamax. RBâ… , RPâ…¡, UNâ…¡and RATâ… also had effect in penicillin-kindling model, but RATâ…¡hadn't. (5) The anticonvulsant mechanism of RBâ… , RATâ…  and RPâ…¡might have been due to increase the level of GABA, however, UNâ…¡ related to decrease Glu level. The anticonvulsant mechanism of PTâ…¡ might had relation with these two aspects.