Literature DB >> 16949890

Characterization of metabolites and cytochrome P450 isoforms involved in the microsomal metabolism of aconitine.

Yuguang Wang1, Shengqi Wang, Yongxue Liu, Liangping Yan, Guifang Dou, Yue Gao.   

Abstract

Aconitine, a major Aconitum alkaloid, is well known for its high toxicity that induces severe arrhythmias leading to death. The current study investigated the metabolism of aconitine and the effects of selective cytochrome P450 (CYP) inhibitors on the metabolism of aconitine in rat liver microsomes. The metabolites were separated and assayed by liquid chromatography-ion trap mass spectrometry (LC/MS(n)) and further identified by comparison of their mass spectra and chromatographic behaviors with reference substances. Various selective inhibitors of CYP were used to identify the isoforms of CYP, that involved in the metabolism of aconitine. A total of at least six metabolites were found and characterized in rat liver microsomal incubations. Result showed that the inhibitor of CYP 3A had an inhibitory effect on aconitine metabolism in a concentration-dependant manner, the inhibitor of CYP1A1/2 had a modest inhibitory effect, whereas inhibitors of CYP2B1/2, 2D and 2E1 had no obvious inhibitory effects on aconitine metabolism. Aconitine might be metabolized by CYP 3A and CYP1A1/2 isoforms in rat liver microsome.

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Year:  2006        PMID: 16949890     DOI: 10.1016/j.jchromb.2006.07.059

Source DB:  PubMed          Journal:  J Chromatogr B Analyt Technol Biomed Life Sci        ISSN: 1570-0232            Impact factor:   3.205


  10 in total

1.  The Effects of Rheum palmatum L. on the Pharmacokinetic of Major Diterpene Alkaloids of Aconitum carmichaelii Debx. in Rats.

Authors:  Yan Li; Yun-Xia Li; Meng-Jie Zhao; An Yuan; Xiao-Hong Gong; Meng-Jun Zhao; Cheng Peng
Journal:  Eur J Drug Metab Pharmacokinet       Date:  2017-06       Impact factor: 2.441

2.  Identification of key transporters mediating uptake of aconitum alkaloids into the liver and kidneys and the potential mechanism of detoxification by active ingredients of liquorice.

Authors:  Yufei He; Ze Wang; Weidang Wu; Ying Xie; Zihong Wei; Xiulin Yi; Yong Zeng; Yazhuo Li; Changxiao Liu
Journal:  RSC Adv       Date:  2019-05-23       Impact factor: 4.036

Review 3.  In vivo and in vitro metabolites from the main diester and monoester diterpenoid alkaloids in a traditional chinese herb, the aconitum species.

Authors:  Min Zhang; Chong-Sheng Peng; Xiao-Bo Li
Journal:  Evid Based Complement Alternat Med       Date:  2015-02-03       Impact factor: 2.629

4.  Coadministration of Pinellia ternata Can Significantly Reduce Aconitum carmichaelii to Inhibit CYP3A Activity in Rats.

Authors:  Jinjun Wu; Zaixing Cheng; Lijun Zhu; Linlin Lu; Guiyu Zhang; Ying Wang; Ying Xu; Na Lin; Zhongqiu Liu
Journal:  Evid Based Complement Alternat Med       Date:  2014-10-14       Impact factor: 2.629

5.  Ester Hydrolysis Differentially Reduces Aconitine-Induced Anti-hypersensitivity and Acute Neurotoxicity: Involvement of Spinal Microglial Dynorphin Expression and Implications for Aconitum Processing.

Authors:  Teng-Fei Li; Nian Gong; Yong-Xiang Wang
Journal:  Front Pharmacol       Date:  2016-10-05       Impact factor: 5.810

6.  Using cell membrane chromatography and HPLC-TOF/MS method for in vivo study of active components from roots of Aconitum carmichaeli.

Authors:  Yan Cao; Xiao-Fei Chen; Di-Ya Lü; Xin Dong; Guo-Qing Zhang; Yi-Feng Chai
Journal:  J Pharm Anal       Date:  2012-01-30

Review 7.  Research progress of aconitine toxicity and forensic analysis of aconitine poisoning.

Authors:  Xiangting Gao; Jun Hu; Xincai Zhang; Yuanyi Zuo; Yun Wang; Shaohua Zhu
Journal:  Forensic Sci Res       Date:  2018-04-09

Review 8.  Relationships between the Toxicities of Radix Aconiti Lateralis Preparata (Fuzi) and the Toxicokinetics of Its Main Diester-Diterpenoid Alkaloids.

Authors:  Mengbi Yang; Xiaoyu Ji; Zhong Zuo
Journal:  Toxins (Basel)       Date:  2018-09-26       Impact factor: 4.546

9.  Towards polypharmacokinetics: pharmacokinetics of multicomponent drugs and herbal medicines using a metabolomics approach.

Authors:  Ke Lan; Guoxiang Xie; Wei Jia
Journal:  Evid Based Complement Alternat Med       Date:  2013-03-14       Impact factor: 2.629

10.  Analysis of the metabolites of mesaconitine in rat blood using ultrafast liquid chromatography and electrospray ionization mass spectrometry.

Authors:  Peng Tan; Xin Chen; Ruirui He; Yonggang Liu
Journal:  Pharmacogn Mag       Date:  2014-04       Impact factor: 1.085

  10 in total

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