Large Volume Direct Injection Ultra-High Performance Liquid Chromatography–Tandem Mass Spectrometry-Based Comparative Pharmacokinetic Study between Single and Combinatory Uses of <i>Carthamus tinctorius</i> Extract and Notoginseng Total Saponins

The combination of <i>Carthamus tinctorius</i> extract (CTE) and notoginseng total saponins (NGTS), namely, CNP, presents a synergistic effect on myocardial ischemia protection. Herein, comparative pharmacokinetic studies between CNP and CTE/NGTS were conducted to clarify their synergist...

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Main Authors: Jinfeng Chen, Xiaoyu Guo, Yingyuan Lu, Mengling Shi, Haidong Mu, Yi Qian, Jinlong Wang, Mengqiu Lu, Mingbo Zhao, Pengfei Tu, Yuelin Song, Yong Jiang
Format: Article
Language:English
Published: MDPI AG 2020-02-01
Series:Pharmaceutics
Subjects:
Online Access:https://www.mdpi.com/1999-4923/12/2/180
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spelling doaj-e3b4793362cb4b24967a5cff760d1de22020-11-25T02:16:10ZengMDPI AGPharmaceutics1999-49232020-02-0112218010.3390/pharmaceutics12020180pharmaceutics12020180Large Volume Direct Injection Ultra-High Performance Liquid Chromatography–Tandem Mass Spectrometry-Based Comparative Pharmacokinetic Study between Single and Combinatory Uses of <i>Carthamus tinctorius</i> Extract and Notoginseng Total SaponinsJinfeng Chen0Xiaoyu Guo1Yingyuan Lu2Mengling Shi3Haidong Mu4Yi Qian5Jinlong Wang6Mengqiu Lu7Mingbo Zhao8Pengfei Tu9Yuelin Song10Yong Jiang11State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, ChinaState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, ChinaState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, ChinaState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, ChinaState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, ChinaState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, ChinaState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, ChinaState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, ChinaState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, ChinaState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, ChinaModern Research Center for Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, ChinaState Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, ChinaThe combination of <i>Carthamus tinctorius</i> extract (CTE) and notoginseng total saponins (NGTS), namely, CNP, presents a synergistic effect on myocardial ischemia protection. Herein, comparative pharmacokinetic studies between CNP and CTE/NGTS were conducted to clarify their synergistic mechanisms. A large volume direct injection ultra-high performance liquid chromatography&#8722;tandem mass spectrometry (LVDI-UHPLC-MS/MS) platform was developed for sensitively assaying the multi-component pharmacokinetic and in vitro cocktail assay of cytochrome p450 (CYP450) before and after compatibility of CTE and NGTS. The pharmacokinetic profiles of six predominantly efficacious components of CNP, including hydroxysafflor yellow A (HSYA); ginsenosides Rg<sub>1</sub> (GRg<sub>1</sub>), Re (GRe), Rb<sub>1</sub> (GRb<sub>1</sub>), and Rd (GRd); and notoginsenoside R<sub>1</sub> (NGR<sub>1</sub>), were obtained, and the results disclosed that CNP could increase the exposure levels of HSYA, GRg<sub>1</sub>, GRe, GRb<sub>1</sub>, and NGR<sub>1</sub> at varying degrees. The in vitro cocktail assay demonstrated that CNP exhibited more potent inhibition on CYP1A2 than CTE and NGTS, and GRg<sub>1</sub>, GRb<sub>1</sub>, GRd, quercetin, kaempferol, and 6-hydroxykaempferol were found to be the major inhibitory compounds. The developed pharmacokinetic interaction-based strategy provides a viable orientation for the compatibility investigation of herb medicines.https://www.mdpi.com/1999-4923/12/2/180<i>carthamus tinctorius</i> extractnotoginseng total saponinscomparative pharmacokinetic studylarge volume direct injectioncompatibility mechanism
collection DOAJ
language English
format Article
sources DOAJ
author Jinfeng Chen
Xiaoyu Guo
Yingyuan Lu
Mengling Shi
Haidong Mu
Yi Qian
Jinlong Wang
Mengqiu Lu
Mingbo Zhao
Pengfei Tu
Yuelin Song
Yong Jiang
spellingShingle Jinfeng Chen
Xiaoyu Guo
Yingyuan Lu
Mengling Shi
Haidong Mu
Yi Qian
Jinlong Wang
Mengqiu Lu
Mingbo Zhao
Pengfei Tu
Yuelin Song
Yong Jiang
Large Volume Direct Injection Ultra-High Performance Liquid Chromatography–Tandem Mass Spectrometry-Based Comparative Pharmacokinetic Study between Single and Combinatory Uses of <i>Carthamus tinctorius</i> Extract and Notoginseng Total Saponins
Pharmaceutics
<i>carthamus tinctorius</i> extract
notoginseng total saponins
comparative pharmacokinetic study
large volume direct injection
compatibility mechanism
author_facet Jinfeng Chen
Xiaoyu Guo
Yingyuan Lu
Mengling Shi
Haidong Mu
Yi Qian
Jinlong Wang
Mengqiu Lu
Mingbo Zhao
Pengfei Tu
Yuelin Song
Yong Jiang
author_sort Jinfeng Chen
title Large Volume Direct Injection Ultra-High Performance Liquid Chromatography–Tandem Mass Spectrometry-Based Comparative Pharmacokinetic Study between Single and Combinatory Uses of <i>Carthamus tinctorius</i> Extract and Notoginseng Total Saponins
title_short Large Volume Direct Injection Ultra-High Performance Liquid Chromatography–Tandem Mass Spectrometry-Based Comparative Pharmacokinetic Study between Single and Combinatory Uses of <i>Carthamus tinctorius</i> Extract and Notoginseng Total Saponins
title_full Large Volume Direct Injection Ultra-High Performance Liquid Chromatography–Tandem Mass Spectrometry-Based Comparative Pharmacokinetic Study between Single and Combinatory Uses of <i>Carthamus tinctorius</i> Extract and Notoginseng Total Saponins
title_fullStr Large Volume Direct Injection Ultra-High Performance Liquid Chromatography–Tandem Mass Spectrometry-Based Comparative Pharmacokinetic Study between Single and Combinatory Uses of <i>Carthamus tinctorius</i> Extract and Notoginseng Total Saponins
title_full_unstemmed Large Volume Direct Injection Ultra-High Performance Liquid Chromatography–Tandem Mass Spectrometry-Based Comparative Pharmacokinetic Study between Single and Combinatory Uses of <i>Carthamus tinctorius</i> Extract and Notoginseng Total Saponins
title_sort large volume direct injection ultra-high performance liquid chromatography–tandem mass spectrometry-based comparative pharmacokinetic study between single and combinatory uses of <i>carthamus tinctorius</i> extract and notoginseng total saponins
publisher MDPI AG
series Pharmaceutics
issn 1999-4923
publishDate 2020-02-01
description The combination of <i>Carthamus tinctorius</i> extract (CTE) and notoginseng total saponins (NGTS), namely, CNP, presents a synergistic effect on myocardial ischemia protection. Herein, comparative pharmacokinetic studies between CNP and CTE/NGTS were conducted to clarify their synergistic mechanisms. A large volume direct injection ultra-high performance liquid chromatography&#8722;tandem mass spectrometry (LVDI-UHPLC-MS/MS) platform was developed for sensitively assaying the multi-component pharmacokinetic and in vitro cocktail assay of cytochrome p450 (CYP450) before and after compatibility of CTE and NGTS. The pharmacokinetic profiles of six predominantly efficacious components of CNP, including hydroxysafflor yellow A (HSYA); ginsenosides Rg<sub>1</sub> (GRg<sub>1</sub>), Re (GRe), Rb<sub>1</sub> (GRb<sub>1</sub>), and Rd (GRd); and notoginsenoside R<sub>1</sub> (NGR<sub>1</sub>), were obtained, and the results disclosed that CNP could increase the exposure levels of HSYA, GRg<sub>1</sub>, GRe, GRb<sub>1</sub>, and NGR<sub>1</sub> at varying degrees. The in vitro cocktail assay demonstrated that CNP exhibited more potent inhibition on CYP1A2 than CTE and NGTS, and GRg<sub>1</sub>, GRb<sub>1</sub>, GRd, quercetin, kaempferol, and 6-hydroxykaempferol were found to be the major inhibitory compounds. The developed pharmacokinetic interaction-based strategy provides a viable orientation for the compatibility investigation of herb medicines.
topic <i>carthamus tinctorius</i> extract
notoginseng total saponins
comparative pharmacokinetic study
large volume direct injection
compatibility mechanism
url https://www.mdpi.com/1999-4923/12/2/180
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