| Based on the theory of compatibility of Traditional Chinese Medicine. Polygala tenuifolia and Acorus tatarinowii were selected as the monarch drug and Acorus tatarinowii as the messenger drug in this study.3,4,5-trimethoxycinnamic acid-a-asarum alcohol ester (TMCA-a-AAE) was synthesized by applying the principle of drug split. Through the maximal electrical stimulation (MES) experiment and the rotating rod experiment, the anticonvulsive effect, neurotoxicity, the anticonvulsive effect and the neurotoxicity of TMCA-α-AAE were systematically studied. A RP-HPLC analysis method was established to study the pharmacokinetic of TMCA-a-AAE in rat vivo and the corresponding of bioavailability of TMCA-a-AAE was evaluated too. computed its bioavailability. Meanwhile, in order to furthermore evaluate the bioactive, the tissue distribution of TMCA-a-AAE was systemtically studied too. The main research content are as follows.1. In MES experiment, the seizures model was successfully builded by the pentylenetetrazol and 3-Mercaptopropionic acid, the anticonvulsants activity and neurotoxicity of TMCA-a-AAE were evaluated, to induce seizures model as well as rotating bar experiment to evaluate the anticonvulsants activity and neurotoxicity of TMCA-a-AAE. The result showed:ED50 value of TMCA-a-AAE was 90.3mg·kg-1with 95% confidence limit value in the range of 63.1～128.8 mg-kg-1; TD50 value of TMCA-a-AAE was 939.7 mg·kg-1 with 95% confidence limit value in the range of 706～1250.3 mg·kg-1. Based on this result, we could speculated that TMCA-a-AAE could decrease the clonicity attack rate of mice induced by pentylenetetrazol and 3-mercaptopropionic acid.2. In HPLC analysis, a method for analyzing TMCA-a-AAE in rat plasma were established to study the pharmacokinetics of TMCA-a-AAE in rats by intragastric administration and intravenous injection. The result showed that the pharmacokinet behavior of TMCA-a-AAE in rats was two compartment model.The T1/2α、T1/2β and V1/F was of no significant difference among rats with the dose of 20 mg·kg-1,50 mg·kg-1 and 100 mg·kg-1 groups; the ratio of AUC and Cmax. was consistent with the drug dose, which suggesting TMCA-α-AAEhad linear metabolism realtionship in the range of 20～100 mg·kg-1; the bioavailability of TMCA-α-AAE was 34.33% after intragastric administration.3. A HPLC analysis method in rats tissue samples was established to, determine the content of TMCA-α-AAE in heart, liver, spleen, lung, kidney, and brain tissue at different times, and studied the distribution characteristics of TMCA-α-AAE in each group. The result showed that at 10 min the content relationship at each tissue is heart> kidney> brain> lung> liver> spleen; for 30 min is heart> lung> kidney> brain> liver> spleen; for 60 min is heart > kidney> brain> liver> spleen> lung; for 120 min is heart> kidney> liver> brain> spleen> lung. |
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