Yuan Jinbin, Ren Gang, Liang Jian, Wang Chong-Zhi, Yan Zhihong, Huang Qun, Li Jiankang, Chen Yang, Tang Yi, Liu Xiaofei, Yuan Chun-Su
Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, China.
Tang Center for Herbal Medicine Research, and Department of Anesthesia & Critical Care, The University of Chicago, Chicago, IL, 60637, USA.
BMC Complement Altern Med. 2017 Feb 10;17(1):107. doi: 10.1186/s12906-017-1626-2.
Aristolochiae Fructus (AF) and honey-fried Aristolochiae Fructus (HAF) have been used in China for a long time as anti-tussive and expectorant drugs. Few clinical cases have been reported to be associated with the toxicity of AF and HAF, although relatively high amounts of aristolochic acids (AAs) have been found in them. Our previous experiments have verified from the chemical changes and from traditional toxicology that honey-processing can significantly reduce the toxicity of AF. To further elucidate the detoxification mechanism of honey-processing, comparative pharmacokinetics of AAs in AF and HAF are performed in this study.
An HPLC-MS/MS (high-performance liquid chromatography-tandem mass spectrometry) method was developed and validated for the determination of AA I, AA II, AA C, AA D and 7-OH AA I in rat plasma. The multi-component pharmacokinetics of AAs in AF and HAF extracts were investigated after the oral administration of three doses to rats. The relative pharmacokinetic parameters were compared systematically.
The five AAs shared a similar nonlinear PK (pharmacokinetic) process. They involve rapid absorption and elimination, and they were fit into a two-compartmental open model. Some significant pharmacokinetic differences were observed between the AF and HAF groups: the C and AUC values of AA I and AA II in the AF groups were much higher than those of the HAF groups.
Honey-frying technology can reduce the toxicity of AF by significantly decreasing the absorption of AA I and AA II. The PK parameters obtained in this work could provide valuable references for the toxicity research and clinical use of Aristolochiaceae herbs, including AF and HAF. Process diagram of comparative pharmacokinetics study.
马兜铃果实（AF）和蜜炙马兜铃果实（HAF）在中国长期用作止咳祛痰药。尽管已发现其中含有相对大量的马兜铃酸（AAs），但很少有临床病例报告与AF和HAF的毒性有关。我们之前的实验已从化学变化和传统毒理学方面证实，蜜炙可显著降低AF的毒性。为进一步阐明蜜炙的解毒机制，本研究进行了AF和HAF中AAs的比较药代动力学研究。
建立并验证了一种高效液相色谱 - 串联质谱（HPLC-MS/MS）法，用于测定大鼠血浆中AA I、AA II、AA C、AA D和7-OH AA I。给大鼠口服三种剂量的AF和HAF提取物后，研究AAs的多组分药代动力学。系统比较了相对药代动力学参数。
这五种AAs具有相似的非线性药代动力学过程。它们吸收和消除迅速，符合二室开放模型。在AF组和HAF组之间观察到一些显著的药代动力学差异：AF组中AA I和AA II的C 和AUC值远高于HAF组。
蜜炙技术可通过显著降低AA I和AA II的吸收来降低AF的毒性。本研究获得的药代动力学参数可为包括AF和HAF在内的马兜铃科草药的毒性研究和临床应用提供有价值的参考。比较药代动力学研究流程图。
