Dataset Information

Analysis of the Constituents in Rat Serum after Oral Administration of Fufang Zhenzhu Tiaozhi Capsule by UPLC-Q-TOF-MS/MS.

ABSTRACT: A rapid and sensitive UPLC/Q-TOF-MS method has been established for analysis of the constituents in rat serum after oral administration of Fufang Zhenzhu Tiaozhi (FTZ) capsule, an effective compound prescription for treating hyperlipidemia in the clinic. The UPLC/MS information of samples was obtained first in FTZ preparation and FTZ-treated rat serum. Mass spectra were acquired in both negative and positive ion modes. Thirty-six constituents in rat serum after oral administration of FTZ were detected, including the alkaloids, ginsenosides, pentacyclic triterpenes, and their metabolites. These chemicals were identified based on the retention time and mass spectrometry data with those of authentic standards or comparison of the literatures reports. Twenty-seven prototype components originated from FTZ and nine were the metabolites of the FTZ constituents. These results shed light on the potential active constituents of the complex traditional Chinese medicinal formulas.

SUBMITTER: Zhong X

PROVIDER: S-EPMC3264872 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

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Analysis of the Constituents in Rat Serum after Oral Administration of Fufang Zhenzhu Tiaozhi Capsule by UPLC-Q-TOF-MS/MS.

Zhong Xunlong X Guo Jiao J Wang Laiyou L Luo Duosheng D Bei Weijian W Chen Yuanyuan Y Yan Kangqi K Peng Junhui J

Chromatographia 20111221 3-4

A rapid and sensitive UPLC/Q-TOF-MS method has been established for analysis of the constituents in rat serum after oral administration of Fufang Zhenzhu Tiaozhi (FTZ) capsule, an effective compound prescription for treating hyperlipidemia in the clinic. The UPLC/MS information of samples was obtained first in FTZ preparation and FTZ-treated rat serum. Mass spectra were acquired in both negative and positive ion modes. Thirty-six constituents in rat serum after oral administration of FTZ were de ...[more]

PMID: 22307991

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Project description:The aim of this study was to investigate the metabolic trajectory of liver aging, the effect of FTZ against liver aging in aging mice, and its mechanism using ultraperformance liquid chromatography/quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF/MS). Methods: A total of 80 C57BL/6J Narl mice were randomly divided into five groups: 3-month-old group, 9-month-old group, 14-month-old group, 20-month-old group, and FTZ treatment group (20 months old). The mice in the treatment group received a therapeutic dose of oral FTZ extract (1.0 g/kg, on raw material weight basis) once daily during the experiment. The other groups received the corresponding volume of oral normal saline solution. Liver samples of all five groups were collected after 12 weeks, and UPLC-Q-TOF/MS was used to analyze metabolic changes. Orthogonal partial least squares-discriminant analysis (OPLS-DA) was used to analyze the resulting data. Additionally, cholesterol (TC), triglyceride (TG), aspartate aminotransferase (AST), alanine aminotransferase (ALT), secretion levels of TNF-α, IL-6, 5-LOX, and COX-2, as well as their relative mRNA expression in the liver were determined. Results: The levels of TC, TG, AST, and ALT were increased, and liver tissue structure was damaged. The secretion levels of TNF-α, IL-6, 5-LOX, and COX-2, as well as their relative mRNA expression in the liver also increased with aging. FTZ administration reduced the symptoms of liver aging. The OPLS-DA score plot illustrated the effect of FTZ against liver aging, with N-acetyl-leukotriene E4, 20-hydroxy-leukotriene E4, leukotriene E4, and arachidonic acid among the key biomarkers. The pivotal pathways revealed by pathway analysis included arachidonic acid metabolism and biosynthesis of unsaturated fatty acids. The mechanism by which FTZ reduces the symptoms of liver aging in mice might be related to disorders of the abovementioned pathways. Conclusion: A metabolomic approach based on UPLC-Q-TOF/MS and multivariate statistical analysis was successfully applied to investigate the metabolic trajectory of liver aging. FTZ has a protective effect against liver aging, which may be mediated via interference with the metabolism of arachidonic acid, biosynthesis of unsaturated fatty acids, and downregulation of pro-inflammatory factors in the liver in mice in vivo.

Project description:Cinobufacini capsule and injection are two different formulations from the same source, obtained from the extraction of the skin of Bufo bufo gargarizans Cantor, which have been approved by the Chinese State Food and Drug Administration (CFDA) for the treatment of various cancers. Our previous study has found that the cinobufacini capsule and injection exhibited different anticancer effects, but their different pharmacokinetic behaviors, which could give a cause of that, have never been reported. So a sensitive and selective method for the simultaneous quantitation of 13 compounds in the rat plasma, including bufothionine, hellebrigenin, bufalin, gamabufotalin, telocinobufagin, cinobufagin, arenobufagin, cinobufotalin, desacetylcinobufotalin, bufotalin, pseudobufarenogin, resibufogenin, and desacetylcinobufagin, was established by using the Agilent 6460 mass spectrometer equipped with an ESI ion source in a multiple-reaction monitoring (MRM) mode. Chromatographic analysis was accomplished in 6 min by using an Agilent SB-C18 column and a mobile phase consisting of 0.1% formic acid in water and acetonitrile in an optimized gradient program at a flow rate of 0.3 ml/min. The correlation coefficients (r) of all analytes ranged from 0.9967 to 0.9996, while their lower limits of quantification ranged from 0.20 to 4.84 ng/ml. The method has been fully verified and applied for the pharmacokinetic difference study of the Cinobufacini capsule and injection in rats. The results showed that nine components could be quantitated in rat plasma samples after the administration of the cinobufacini capsule, while only bufothionine, bufalin, arenobufagin, and pseudobufarenogin could be detected in the cinobufacini injection group. Their pharmacokinetic studies indicated telocinobufagin, bufalin, desacetylcinobufagin, and arenobufagin were predicted as the potential active substances of the Cinobufacini capsule, while bufothionine was considered as a major ingredient in the cinobufacini injection due to its relatively high blood drug exposure. Also, the AUC of the nine components in cinobufacini capsule groups with three different doses showed a similar trend with significant differences, and the exposure increased with the increase of the dose. The pharmacokinetic characteristics of all major ingredients in cinobufacini capsules and injection were of wide variation, which could be used to explain differences in the efficacy of the cinobufacini capsule and injection and infer the pharmacodynamic ingredients of various cinobufacini preparations.

Dataset Information

Analysis of the Constituents in Rat Serum after Oral Administration of Fufang Zhenzhu Tiaozhi Capsule by UPLC-Q-TOF-MS/MS.

Publications

Analysis of the Constituents in Rat Serum after Oral Administration of Fufang Zhenzhu Tiaozhi Capsule by UPLC-Q-TOF-MS/MS.

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