Synergistic effect of pinellia total alkaloids and uncaria total alkaloids on anticonvulsant action in mice and rats  

半夏生物总碱和钩藤生物总碱抗小鼠、大鼠惊厥的协同作用(英文)

作　　者：成银霞[1] 王明正[1] 陈靖京[1] 杨蓉[1] 何欣嘏[1] 马永刚[1] 杨李华[1] 张明升[1] 

机构地区：[1]山西医科大学药理教研室,山西太原030001

出　　处：《Journal of Chinese Pharmaceutical Sciences》2007年第2期139-145,共7页中国药学（英文版）

基　　金：Natural Science Foundation of Shanxi Province(No 20041109).

摘　　要：Aim To investigate the synergistic effect of the combination of pinellia total alkaloid （PTA） and uncaria total alkaloid （UTA）, and explore the mechanism of anticonvulsant action. Methods Anticonvulsant and toxic effect profiles of combinations of PTA with UTA, alone and at three fixed ratios of 1：4, 1 ：1, 4：1, were evaluated in maximal electroshock （MES）-induced seizures and acute toxicity test in mice. Respective ED50 and LD50 were calculated with Bliss＇s method. Their synergistic effect were evaluated by isobolographic analysis and allowed the determination of benefit indices （BI） for respective combinations. The model of convulsive rats kindled by penicillin topically injected into cortex was used to investigated the content of Glu, Asp, Gly and GABA in hippocampus using high performance liquid chromatography （HPLC）. Results Combinations of PTA and UTA at the ratio of 4：1 were synergistic in MES test and antagonistic in acute toxicity test, showing the best profile for combinations of PTA with UTA. In contrast, the ratios of 1 ：4 and 1 ： 1, despite synergistic in MES test, were additive in acute toxicity test. The 4：1 combination and two drugs alone significantly decreased Glu level and increased GABA level in the hippocampus, but the GABA level in the 4：1 combination group was higher than that in the two drugs alone groups. They did not have significant influence on the levels of ASp and Gly. Conclusion Combinations of PTA and UTA at 4：1 ratio demonstrated synergistic effect in anticonvulsant action and antagonistic effect in toxicity. The anticonvulsant mechanism might be related to decreasing the excitability of Glutamatergic neurons and increasing the inhibition of GABAergic neurons.目的研究半夏生物总碱(PTA)和钩藤生物总碱(UTA)抗惊厥的协同作用,并探讨其相互作用机制。方法采用小鼠最大电休克惊厥试验和急性毒性试验检测PTA和UTA单用和三种比例(1:1,1:4,4:1)配伍的抗惊厥作用及毒性效应,并采用bliss’s法分别计算它们的ED50和LD50。用等效线法评价其协同作用并计算各组配伍的受益指数(BI)。制备大鼠运动皮层定位注射青霉素惊厥模型,同时采用高效液相色谱法(HPLC)测定海马区癫痫相关递质Glu、Asp、Gly、GABA的含量。结果半夏、钩藤生物总碱4:1配伍的抗惊厥作用呈现协同,而毒性呈现相互拮抗,是PTA和UTA合用的最佳比例。而两药1:4和1:1比例配伍尽管在最大电休克惊厥试验中抗惊厥作用呈现协同,但是在毒性试验中毒性效应却呈现相加。PTA和UTA单用和4:1合用,均可明显减少海马Glu的水平,增加GABA的水平,且4:1合用组的GABA水平要比两单药组高。但对Asp、Gly无明显影响。结论PTA和UTA以4:1合用时抗癫痫效应协同、毒性拮抗。两药合用的抗惊厥作用机制可能与其同时降低Glu能神经的兴奋性,并协同提高GABA能神经功能有关。

关 键 词：Pinellia total alkaloids Uncaria total alkaloids Synergistic effect Anticonvulsant action Isobolographic analysis Maximal electroshock Penicillin kindling NEUROTRANSMITTERS 

分 类 号：R285[医药卫生—中药学]