Invivo and Invitro Metabolism Study of Timosapon

Authors: Yao Jia Zhiwen Fu Zhixiong Li Pei Hu Rui Xue Mingcang Chen Ting Xiang Chenggang Huang

Publish Date: 2015/07/08

Volume: 78, Issue: 17-18, Pages: 1175-1184

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Abstract

Timosaponin BII TBII 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 highperformance liquid chromatographyelectrospray ionization tandem mass spectrometry method was applied for the identification of TBII and its major metabolites in invivo and invitro samples Rat urine feces plasma and tissues were collected after oral administration of TBII at a single dose of 300 mg kg−1 Furthermore TBII 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 MS n 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 TBII 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 TBII mainly included dehydration deglycosylation hydroxylation oxidation and Ering cleavage This is the first comprehensive investigation of the invivo and invitro metabolism of TBII The result provided important information for further pharmacological research on TBIIWe 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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