title: Comparative studies on the multi-component pharmacokinetics of Aristolochiae Fructus and honey-fried Aristolochiae Fructus extracts after oral administration in rats.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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 Cmaxand AUC values of AA I and AA II in the AF groups were much higher than those of the HAF groups.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, China. kings2008@163.com.|Tang Center for Herbal Medicine Research, and Department of Anesthesia & Critical Care, The University of Chicago, Chicago, IL, 60637, USA. kings2008@163.com.
authors.forename: Jinbin
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Research Center for the Resourcing of Traditional Chinese Medicine and Minority Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Ren
authors.affiliation: Research Center for the Resourcing of Traditional Chinese Medicine and Minority Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Liang
authors.affiliation: Tang Center for Herbal Medicine Research, and Department of Anesthesia & Critical Care, The University of Chicago, Chicago, IL, 60637, USA.
authors.forename: Chong-Zhi
authors.initials: CZ
authors.lastname: Wang
authors.affiliation: Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, China.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Yan
authors.affiliation: Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, China.
authors.forename: Jiankang
authors.initials: J
authors.lastname: Li
authors.affiliation: Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, China.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Liu
authors.affiliation: Tang Center for Herbal Medicine Research, and Department of Anesthesia & Critical Care, The University of Chicago, Chicago, IL, 60637, USA.
authors.forename: Chun-Su
authors.initials: CS
authors.lastname: Yuan
mesh_terms: D000284:Administration, Oral; D000818:Animals; D030022:Aristolochia / Q000737:chemistry*; D034341:Aristolochic Acids / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D005638:Fruit / Q000737:chemistry*; D006722:Honey; D057230:Limit of Detection; D016014:Linear Models; D008297:Male; D010936:Plant Extracts / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results
chemical_list: D034341:Aristolochic Acids; D010936:Plant Extracts
keywords: Aristolochiae Fructus; Aristolochic acids; HPLC-MS/MS; Honey-fried Aristolochiae Fructus; Pharmacokinetics