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In-vivo and In-vitro Metabolism Study of Timosaponin B-II Using HPLC-ESI-MSn

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Abstract

Timosaponin B-II (TB-II), a representative furostanol saponin in Rhizoma anemarrhenae, has been used as an emperor herb in many Chinese herbal formulas to treat diabetes and senile dementia. However, its metabolism and tissue distribution had not been investigated so far. In this work, a sensitive and specific high-performance liquid chromatography-electrospray ionization tandem mass spectrometry method was applied for the identification of TB-II and its major metabolites in in-vivo and in-vitro samples. Rat urine, feces, plasma and tissues were collected after oral administration of TB-II at a single dose of 300 mg kg−1. Furthermore, TB-II was incubated in artificial gastric juice (AGJ) and artificial intestinal juice (AIJ). As a result, 19 metabolites were detected and identified by comparing their HPLC behavior and MSn spectra profile with those of the parent drug. Moreover, the structures of its five metabolites were identified by using the standards prepared by the acid hydrolysis of TB-II. In addition to the parent drug, 14, 12, 6, 1, 1 and 7 metabolites were detected in rat urine, feces, plasma, heart, kidney and liver, respectively, while no metabolites or the parent drug were found in rat brain, spleen and lung. Seven metabolites appeared in AIJ incubation samples, but the parent drug was absent. Nine metabolites along with the parent drug were observed in AGJ incubation samples. The biotransformation pathways of TB-II mainly included dehydration, deglycosylation, hydroxylation, oxidation and E-ring cleavage. This is the first comprehensive investigation of the in-vivo and in-vitro metabolism of TB-II. The result provided important information for further pharmacological research on TB-II.

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Acknowledgments

Financial support for this research was provided by a grant from the Key Program and General Program of the National Natural Science Foundation of China (nos. 81030065 and 81274055).

Compliance with ethical standards

We confirm that the manuscript has been read and approved by all named authors and that there are no other persons who satisfied the criteria for authorship but are not listed. All authors involved have no commercial association or other arrangement that might pose or imply a conflict of interest in connection with the submitted article. All of the animal care and experimental procedures were approved by the Animal Ethical Committee of Shanghai Institute of Materia Medica (Shanghai, China).

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    Authors and Affiliations

    1. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Rd., ZhangJiang, Pudong, Shanghai, 201203, People’s Republic of China

      Yao Jia, Zhiwen Fu, Zhixiong Li, Pei Hu, Rui Xue, Mingcang Chen & Chenggang Huang

    2. Institute of Pharmaceutical Research, Yangtze River Pharmaceutical Group, 16 Shengming Yuan Road, Changpiing, Beijing, 102206, People’s Republic of China

      Yao Jia & Ting Xiang

    3. Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China

      Zhiwen Fu

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    1. Yao Jia
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    Correspondence to Ting Xiang or Chenggang Huang.

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    Y. Jia and Z. Fu contributed equally to the work.

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    Jia, Y., Fu, Z., Li, Z. et al. In-vivo and In-vitro Metabolism Study of Timosaponin B-II Using HPLC-ESI-MSn . Chromatographia 78, 1175–1184 (2015). https://doi.org/10.1007/s10337-015-2927-6

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    • DOI: https://doi.org/10.1007/s10337-015-2927-6

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