藜芦与人参配比毒性与生物碱类成分变化的相关性研究

目的 探索中药“十八反”中藜芦-人参药对的毒性与生物碱类成分的关系.方法 通过动物毒性实验比较藜芦与人参不同配比的毒性,采用超高效液相色谱-四级杆/飞行时间质谱联用(UPLC/Q-TOFMS)技术检测藜芦与人参1∶2.63配比的合煎液、单煎后合并液(简称合并液)、合并液再煎液中生物碱类成分;Mass Lynx 4.1软件分析生物碱类成分的变化.结果 动物毒性实验显示藜芦与人参1∶2.63配比时动物死亡较多,且此时合煎液与合并液毒性差别最为明显.将合并后再煎液可能引起物质变化的两个因素(即毒性生物碱的溶出增加和药物相互反应)单一化,即去除溶出影响因素时突显的药物本身化学反应的影响,可见藜芦胺和芥芬胺在合煎后溶出量增大,生物碱成分增加;计米亭碱、3-当归酰棋盘花胺在合煎液及合并液再煎液中的量均升高,提示可能是化学反应导致相关成分溶出增多.结论 藜芦与人参合用后毒性增大,可能与生物碱的溶出量增加及药物相互作用密切相关.

Correlation between toxicity and changes of alkaloids in combination of Yeratrum ni}grum and ginseng

Objective To explore the correlation between the toxicity of Veratrum nigrum-ginseng combination(VGC) and alkaloids in eighteen incompatible medications(Shibafan) in the theory of traditional Chinese medicines.Methods The toxicities of different ratios of VGC were investigated by animal toxicity experiment.Through ultra performance liquid chromatography coupled with time-of-flight mass spectrometry(UPLC/Q-TOFMS),alkaloids among co-decoction,mixed decoction,and re-decoction of VGC in the ratio of 1:2.63 were detected.The datasets were processed with Mass Lynx V14.1 software to analyze the changes of alkaloids.Results Animal toxicity experiment indicated that there was a high mortality and the difference of toxicity between the co-decoction and mixed decoction was the most significant,as the ratio of VGC was 1:2.63.The two factors in the VGC re-decoctions,i.e.the increased dissolution of toxic alkaloids and the drug interreaction,which could cause the material change,were unified.It could be observed that the dissolution of jervine and veratramine and the content of alkaloids were increased.The contents of germidine and 3-angeloylzygadenine in co-decoction and mixed decoction were increased,which might mean that the chemiccal interaction could lead to the stripping components of the related components increased.Conclusion The toxicity increases of VGC may be closely related to the increased dissolution of alkaloids and drug interaction.