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Integrating Pharmacokinetics Study, Network Analysis, and Experimental Validation to Uncover the Mechanism of Qiliqiangxin Capsule Against Chronic Heart Failure

Objectives: The purpose of this study was to propose an integrated strategy for investigating the mechanism of Qiliqiangxin capsule (QLQX) to treat chronic heart failure (CHF). Methods: Pharmacokinetics analysis was performed to screen the active components of QLQX using high-performance liquid chro...

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Autores principales: Zhang, Yu, Zhu, Mingdan, Zhang, Fugeng, Zhang, Shaoqiang, Du, Wuxun, Xiao, Xuefeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6759796/
https://www.ncbi.nlm.nih.gov/pubmed/31619994
http://dx.doi.org/10.3389/fphar.2019.01046
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author Zhang, Yu
Zhu, Mingdan
Zhang, Fugeng
Zhang, Shaoqiang
Du, Wuxun
Xiao, Xuefeng
author_facet Zhang, Yu
Zhu, Mingdan
Zhang, Fugeng
Zhang, Shaoqiang
Du, Wuxun
Xiao, Xuefeng
author_sort Zhang, Yu
collection PubMed
description Objectives: The purpose of this study was to propose an integrated strategy for investigating the mechanism of Qiliqiangxin capsule (QLQX) to treat chronic heart failure (CHF). Methods: Pharmacokinetics analysis was performed to screen the active components of QLQX using high-performance liquid chromatography–tandem mass spectrometry techniques. We then constructed the component–target network between the targets of active components in QLQX and CHF using Cytoscape. A network analysis, including topological parameters, clustering, and pathway enrichment, was established to identify the hub targets and pathways. Finally, some of the predicted hub targets were validated experimentally in human cardiac microvascular endothelial cell (HCMEC). Results: We identified 29 active components in QLQX, and 120 consensus potential targets were determined by the pharmacokinetics analysis and network pharmacology approach. Further network analysis indicated that 6 target genes, namely, VEGFA, CYP1A1, CYP2B6, ATP1A1, STAT3, and STAT4, and 10 predicted functional genes, namely, KDR, FLT1, NRP2, JAK2, EGFR, IL-6, AHR, ATP1B1, JAK1, and HIF1A, may be the primary targets regulated by QLQX for the treatment of CHF. Among these targets, VEGFA, IL-6, p-STAT3, and p-JAK2 were selected for validation in the HCMEC. The results indicated that QLQX may inhibit inflammatory processes and promote angiogenesis in CHF via the JAK/STAT signaling pathway. Conclusions: This study provides a strategy for understanding the mechanism of QLQX against CHF by combining pharmacokinetics study, network pharmacology, and experimental validation.
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spelling pubmed-67597962019-10-16 Integrating Pharmacokinetics Study, Network Analysis, and Experimental Validation to Uncover the Mechanism of Qiliqiangxin Capsule Against Chronic Heart Failure Zhang, Yu Zhu, Mingdan Zhang, Fugeng Zhang, Shaoqiang Du, Wuxun Xiao, Xuefeng Front Pharmacol Pharmacology Objectives: The purpose of this study was to propose an integrated strategy for investigating the mechanism of Qiliqiangxin capsule (QLQX) to treat chronic heart failure (CHF). Methods: Pharmacokinetics analysis was performed to screen the active components of QLQX using high-performance liquid chromatography–tandem mass spectrometry techniques. We then constructed the component–target network between the targets of active components in QLQX and CHF using Cytoscape. A network analysis, including topological parameters, clustering, and pathway enrichment, was established to identify the hub targets and pathways. Finally, some of the predicted hub targets were validated experimentally in human cardiac microvascular endothelial cell (HCMEC). Results: We identified 29 active components in QLQX, and 120 consensus potential targets were determined by the pharmacokinetics analysis and network pharmacology approach. Further network analysis indicated that 6 target genes, namely, VEGFA, CYP1A1, CYP2B6, ATP1A1, STAT3, and STAT4, and 10 predicted functional genes, namely, KDR, FLT1, NRP2, JAK2, EGFR, IL-6, AHR, ATP1B1, JAK1, and HIF1A, may be the primary targets regulated by QLQX for the treatment of CHF. Among these targets, VEGFA, IL-6, p-STAT3, and p-JAK2 were selected for validation in the HCMEC. The results indicated that QLQX may inhibit inflammatory processes and promote angiogenesis in CHF via the JAK/STAT signaling pathway. Conclusions: This study provides a strategy for understanding the mechanism of QLQX against CHF by combining pharmacokinetics study, network pharmacology, and experimental validation. Frontiers Media S.A. 2019-09-18 /pmc/articles/PMC6759796/ /pubmed/31619994 http://dx.doi.org/10.3389/fphar.2019.01046 Text en Copyright © 2019 Zhang, Zhu, Zhang, Zhang, Du and Xiao http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Zhang, Yu
Zhu, Mingdan
Zhang, Fugeng
Zhang, Shaoqiang
Du, Wuxun
Xiao, Xuefeng
Integrating Pharmacokinetics Study, Network Analysis, and Experimental Validation to Uncover the Mechanism of Qiliqiangxin Capsule Against Chronic Heart Failure
title Integrating Pharmacokinetics Study, Network Analysis, and Experimental Validation to Uncover the Mechanism of Qiliqiangxin Capsule Against Chronic Heart Failure
title_full Integrating Pharmacokinetics Study, Network Analysis, and Experimental Validation to Uncover the Mechanism of Qiliqiangxin Capsule Against Chronic Heart Failure
title_fullStr Integrating Pharmacokinetics Study, Network Analysis, and Experimental Validation to Uncover the Mechanism of Qiliqiangxin Capsule Against Chronic Heart Failure
title_full_unstemmed Integrating Pharmacokinetics Study, Network Analysis, and Experimental Validation to Uncover the Mechanism of Qiliqiangxin Capsule Against Chronic Heart Failure
title_short Integrating Pharmacokinetics Study, Network Analysis, and Experimental Validation to Uncover the Mechanism of Qiliqiangxin Capsule Against Chronic Heart Failure
title_sort integrating pharmacokinetics study, network analysis, and experimental validation to uncover the mechanism of qiliqiangxin capsule against chronic heart failure
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6759796/
https://www.ncbi.nlm.nih.gov/pubmed/31619994
http://dx.doi.org/10.3389/fphar.2019.01046
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