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从蛋白质自组装的角度探析甘草附子配伍减毒机制(1)
http://www.100md.com 2015年2月15日 中国中药杂志 2015年第4期
     [摘要]甘草与附子配伍有减毒增效的作用。该研究从中药汤剂甘草和附子混煎过程中蛋白质自组装的现象入手,以甘草蛋白和附子主要毒性物质——乌头碱为研究对象,探析甘草附子配伍减毒机制。研究发现经分离纯化后的甘草蛋白在pH 5时可通过自组装形成粒径为(206.2±2.02) nm的稳定颗粒,且可与乌头碱形成平均粒径为(238.20±1.23) nm的甘草蛋白-乌头碱稳定颗粒。通过小鼠急性毒性实验发现注射乌头碱单体的小鼠全部死亡,而注射相同乌头碱含量的甘草蛋白-乌头碱颗粒的小鼠全部存活。对甘草蛋白-乌头碱胶体颗粒的稳定性的调查显示,该胶体颗粒在室温下较稳定,具有成为候选药物载体的可能性。综上所述,甘草蛋白可通过与乌头碱自组装而达到减毒效果。

    [关键词]甘草蛋白;乌头碱;自组装;减毒

    Investigating mechanism of toxicity reduction by combination of Glycyrrhizae
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    Radix et Rhizoma and Aconiti Lateralis Radix Preparata

    on terms of proteins self-assembly

    LI Bing-jie1, SHEN Yong1, LIAO Ri-tao1, GAO Guan-zhen2, KE Li-jing2, ZHOU Jian-wu2*, RAO Ping-fan2

    (1.Institute of Biotechnology, Fuzhou University, Fuzhou 350002, China;

    2.Shanghai Institutes for Biological Sciences of Chinese Academy of Sciences-Zhejiang Gongshang University Joint
, 百拇医药
    Centre for Food and Nutrition Research, Hangzhou 310035, China)

    [Abstract]The combination of Glycyrrhizae Radix et Rhizoma and Aconiti Lateralis Radix Preparata can increase efficacy and decrease toxicity. This study started from the phenomena of protein self-assembly in the mixed decoction of Glycyrrhizae Radix et Rhizoma with Aconiti Lateralis Radix Preparata. The attenuated mechanism was explored between the combination of Glycyrrhizae Radix et Rhizoma and Aconiti Lateralis Radix Preparata by using the protein of Glycyrrhizae Radix et Rhizoma and aconitine which was the major toxic component of Aconiti Lateralis Radix Preparata. Glycyrrhizae Radix et Rhizoma protein with aconitine could form stable particles which particle mean diameter was (206.2±2.02) nm and (238.20±1.23) nm at pH 5.0 in normal temperature. Through the mouse acute toxicity experiment found that injection of aconitine monomer all mice were killed, and injection of Glycyrrhizae Radix et Rhizoma protein- aconitine particles with the same content of aconitine all mice survived. Survey the stability of Glycyrrhizae Radix et Rhizoma protein-aconitine shows that the colloid particles is stable at room temperature, and it has the possibility to candidate drug carrier. Glycyrrhizae Radix et Rhizoma protein can reduce the toxicity of aconitine through self-assembly.
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    [Key words]Glycyrrhizae Radix et Rhizoma protein; aconitine; self-assembly; toxicity reduction

    doi:10.4268/cjcmm20150417

    附子是毛茛科植物乌头子根的加工品,味辛、甘,大热、有毒,附子的主要药效成分和毒性成分为乌头碱(aconitine,AC)[1-2]。在临床应用中,甘草与附子常配伍使用,其中的经典方剂当属四逆汤,近年来多项相关研究结果表明,甘草附子配伍能降低附子的毒性或附子有毒成分的含量,且随着甘草用量的增加,附子的毒性会相应减弱[3-8]。甘草能解附子之毒的观点己被大多数人所认识,亦有很多实验证明了此观点[9-11]。但对于甘草中何种成分解毒,具体的解毒机制、环节却众说纷纭。, 百拇医药(李冰洁 沈勇 廖日滔 高观祯 柯李晶 周建武 饶平凡)
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