Shen Hong, Wu Jie, Di Liu-Qing, Zhu Ling-Ying, Xu Jun, Yan Ru, Li Song-Lin
Department of Pharmaceutical Analysis and Metabolomics, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, People's Republic of China.
Biomed Chromatogr. 2013 May;27(5):556-62. doi: 10.1002/bmc.2825. Epub 2012 Oct 2.
Glycyrrhizae Radix (GR) is often prescribed together with Aconiti Laterlis Radix (ALR) (a so-called compatible drug pair) in traditional Chinese medicinal practice to reduce toxicity of ALR. However, the mechanisms involved remain to be addressed. In this study, the metabolic interactions between GR-ALR drug pair were investigated for the first time. First, an HPLC-TQ-MS/MS method was developed to analyze hypaconitine, a major bioactive and toxic component of ALR, in rat liver S9. Then the in vitro metabolic rates of hypaconitine by different rat liver S9 were compared using the established method. The experiments were designed in four groups: pure hypaconitine (group I) and ALR extract (group II) incubated with liver S9 of normal rats, and pure hypaconitine (group III) and ALR extract (group IV) incubated with liver S9 of GR-pretreated rats. When incubated for more than 4 h, the metabolic rates of hypaconitine in group III were significantly higher than those in group I, and when incubated for more than 2 h, the metabolic rates of hypaconitine in group IV were significantly higher than those in group II, suggesting that GR can enhance metabolic rate of hypaconitine, the mechanism of which might be related to hepatic metabolizing enzyme induction by GR.
甘草根（GR）在中国传统医学实践中常与附子（ALR）（一种所谓的配伍药对）一起使用，以降低ALR的毒性。然而，其中涉及的机制仍有待阐明。在本研究中，首次对GR-ALR药对之间的代谢相互作用进行了研究。首先，建立了一种HPLC-TQ-MS/MS方法，用于分析大鼠肝脏S9中ALR的主要生物活性和毒性成分次乌头碱。然后，使用所建立的方法比较不同大鼠肝脏S9对次乌头碱的体外代谢率。实验分为四组：纯次乌头碱（I组）和ALR提取物（II组）与正常大鼠的肝脏S9一起孵育，以及纯次乌头碱（III组）和ALR提取物（IV组）与经GR预处理的大鼠的肝脏S9一起孵育。孵育超过4小时时，III组中次乌头碱的代谢率显著高于I组，孵育超过2小时时，IV组中次乌头碱的代谢率显著高于II组，表明GR可提高次乌头碱的代谢率，其机制可能与GR诱导肝脏代谢酶有关。
