Predict potential pharmacological mechanisms of Ling-gui-Zhu-gan Decoction in treating unstable angina pectoris using liquid chromatography-mass spectrometry and network pharmacology

IntroductionLing-Gui-Zhu-Gan Decoction (LGZGD), one of the first batches of classical Chinese prescriptions formally recognized by the Chinese government, has a long-standing history of clinical application and significant potential for modern development. However, the chemical composition and conte...

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Main Authors: Xiaopeng Li, Tan Xue, Panpan Zhang, Fengyu Dong, Han Li, Jing Yao, Haiying Huang, Lizhuang Zhang, Ruixin Liu
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-08-01
Series:Frontiers in Chemistry
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Online Access:https://www.frontiersin.org/articles/10.3389/fchem.2025.1649538/full
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author Xiaopeng Li
Xiaopeng Li
Tan Xue
Tan Xue
Panpan Zhang
Panpan Zhang
Fengyu Dong
Fengyu Dong
Han Li
Han Li
Jing Yao
Haiying Huang
Lizhuang Zhang
Ruixin Liu
Ruixin Liu
Ruixin Liu
Ruixin Liu
Ruixin Liu
Ruixin Liu
Ruixin Liu
Ruixin Liu
author_facet Xiaopeng Li
Xiaopeng Li
Tan Xue
Tan Xue
Panpan Zhang
Panpan Zhang
Fengyu Dong
Fengyu Dong
Han Li
Han Li
Jing Yao
Haiying Huang
Lizhuang Zhang
Ruixin Liu
Ruixin Liu
Ruixin Liu
Ruixin Liu
Ruixin Liu
Ruixin Liu
Ruixin Liu
Ruixin Liu
author_sort Xiaopeng Li
collection DOAJ
description IntroductionLing-Gui-Zhu-Gan Decoction (LGZGD), one of the first batches of classical Chinese prescriptions formally recognized by the Chinese government, has a long-standing history of clinical application and significant potential for modern development. However, the chemical composition and content of different types of pharmaceutical preparations are not clear.MethodsThis study aimed to develop an analytical approach integrating HPLC and UHPLC-Q-Orbitrap/MS to comprehensively characterize the chemical constituents of LGZGD across different preparation stages and to investigate its pharmacodynamic basis in the treatment of unstable angina pectoris (UA) using network pharmacology. The content and transfer rate of six index components were quantified using HPLC.ResultsA total of 75 compounds were identified via UHPLC-Q-Orbitrap/MS, comprising 24 flavonoids, 25 organic acids, nine phenylpropanoids, eight terpenoids, five saponins, and four other compounds, based on precursor ion peaks and fragment ion spectra. Notably, five compounds—(-)-pterocarpin glucoside, γ-aminobutyric acid, calycosin, trimethyl citrate, and proline-phenylalanine—were absent following the drying of the concentrate. Using the LC-MS data as a foundation, network pharmacology and molecular docking analyses were conducted to elucidate the pharmacodynamic components responsible for LGZGD’s therapeutic effects on UA. This integrative analysis identified three key active compounds—naringenin, glycyrrhizin, and calycosin—and three core targets: TNF, EGFR, and PTGS2.DiscussionThe analytical method established in this study effectively delineates the chemical profile and index component transfer dynamics of LGZGD preparation intermediates, providing essential data for the development of both liquid and solid dosage forms. The constructed “medicine-component-target-pathway-disease” network preliminarily reveals the multi-component, multi-target, and multi-pathway mechanisms by which LGZGD may exert therapeutic effects on UA. This work provides a scientific foundation for its clinical application, supporting rational drug use and formulation development.
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spelling doaj-art-d64ac846f8a74c6e9f9f297d979dfdff2025-08-20T03:57:39ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462025-08-011310.3389/fchem.2025.16495381649538Predict potential pharmacological mechanisms of Ling-gui-Zhu-gan Decoction in treating unstable angina pectoris using liquid chromatography-mass spectrometry and network pharmacologyXiaopeng Li0Xiaopeng Li1Tan Xue2Tan Xue3Panpan Zhang4Panpan Zhang5Fengyu Dong6Fengyu Dong7Han Li8Han Li9Jing Yao10Haiying Huang11Lizhuang Zhang12Ruixin Liu13Ruixin Liu14Ruixin Liu15Ruixin Liu16Ruixin Liu17Ruixin Liu18Ruixin Liu19Ruixin Liu20Department of Pharmacy, First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, Henan, ChinaHenan University of Traditional Chinese Medicine College of Pharmacy, Zhengzhou, Henan, ChinaDepartment of Pharmacy, First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, Henan, ChinaHenan University of Traditional Chinese Medicine College of Pharmacy, Zhengzhou, Henan, ChinaDepartment of Pharmacy, First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, Henan, ChinaHenan University of Traditional Chinese Medicine College of Pharmacy, Zhengzhou, Henan, ChinaDepartment of Pharmacy, First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, Henan, ChinaHenan University of Traditional Chinese Medicine College of Pharmacy, Zhengzhou, Henan, ChinaDepartment of Pharmacy, First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, Henan, ChinaHenan University of Traditional Chinese Medicine College of Pharmacy, Zhengzhou, Henan, ChinaDepartment of Pharmacy, First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, Henan, ChinaHenan University of Traditional Chinese Medicine College of Pharmacy, Zhengzhou, Henan, ChinaTraditional Chinese Medicine Modernization School Enterprise R & D Center, Henan University of Traditional Chinese Medicine, Henan Tailong Pharmaceutical Co., Ltd., Zhengzhou, Henan, ChinaDepartment of Pharmacy, First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, Henan, ChinaHenan University of Traditional Chinese Medicine College of Pharmacy, Zhengzhou, Henan, ChinaTraditional Chinese Medicine Modernization School Enterprise R & D Center, Henan University of Traditional Chinese Medicine, Henan Tailong Pharmaceutical Co., Ltd., Zhengzhou, Henan, ChinaHenan Traditional Chinese Medicine Clinical Application, Evaluation and Transformation Engineering Research Center, Zhengzhou, Henan, ChinaHenan Provincial Key Laboratory of Clinical Pharmacy of Traditional Chinese Medicine, Zhengzhou, Henan, ChinaHenan University of Traditional Chinese Medicine Respiratory Disease Prevention and Treatment of Traditional Chinese Medicine to Build Collaborative Innovation Center, Zhengzhou, Henan, ChinaHenan Institute of Chinese Medicine, Henan University of Traditional Chinese Medicine, Zhengzhou, Henan, ChinaEngineering Research Center of Ministry of Education, Pharmaceutical and New Drug Development of Traditional Chinese Medicine, Beijing, ChinaIntroductionLing-Gui-Zhu-Gan Decoction (LGZGD), one of the first batches of classical Chinese prescriptions formally recognized by the Chinese government, has a long-standing history of clinical application and significant potential for modern development. However, the chemical composition and content of different types of pharmaceutical preparations are not clear.MethodsThis study aimed to develop an analytical approach integrating HPLC and UHPLC-Q-Orbitrap/MS to comprehensively characterize the chemical constituents of LGZGD across different preparation stages and to investigate its pharmacodynamic basis in the treatment of unstable angina pectoris (UA) using network pharmacology. The content and transfer rate of six index components were quantified using HPLC.ResultsA total of 75 compounds were identified via UHPLC-Q-Orbitrap/MS, comprising 24 flavonoids, 25 organic acids, nine phenylpropanoids, eight terpenoids, five saponins, and four other compounds, based on precursor ion peaks and fragment ion spectra. Notably, five compounds—(-)-pterocarpin glucoside, γ-aminobutyric acid, calycosin, trimethyl citrate, and proline-phenylalanine—were absent following the drying of the concentrate. Using the LC-MS data as a foundation, network pharmacology and molecular docking analyses were conducted to elucidate the pharmacodynamic components responsible for LGZGD’s therapeutic effects on UA. This integrative analysis identified three key active compounds—naringenin, glycyrrhizin, and calycosin—and three core targets: TNF, EGFR, and PTGS2.DiscussionThe analytical method established in this study effectively delineates the chemical profile and index component transfer dynamics of LGZGD preparation intermediates, providing essential data for the development of both liquid and solid dosage forms. The constructed “medicine-component-target-pathway-disease” network preliminarily reveals the multi-component, multi-target, and multi-pathway mechanisms by which LGZGD may exert therapeutic effects on UA. This work provides a scientific foundation for its clinical application, supporting rational drug use and formulation development.https://www.frontiersin.org/articles/10.3389/fchem.2025.1649538/fullLing-Gui-Zhu-Gan Decoctiontransfer rateUHPLC-Q-Orbitrap/MSunstable anginanetwork pharmacology
spellingShingle Xiaopeng Li
Xiaopeng Li
Tan Xue
Tan Xue
Panpan Zhang
Panpan Zhang
Fengyu Dong
Fengyu Dong
Han Li
Han Li
Jing Yao
Haiying Huang
Lizhuang Zhang
Ruixin Liu
Ruixin Liu
Ruixin Liu
Ruixin Liu
Ruixin Liu
Ruixin Liu
Ruixin Liu
Ruixin Liu
Predict potential pharmacological mechanisms of Ling-gui-Zhu-gan Decoction in treating unstable angina pectoris using liquid chromatography-mass spectrometry and network pharmacology
Frontiers in Chemistry
Ling-Gui-Zhu-Gan Decoction
transfer rate
UHPLC-Q-Orbitrap/MS
unstable angina
network pharmacology
title Predict potential pharmacological mechanisms of Ling-gui-Zhu-gan Decoction in treating unstable angina pectoris using liquid chromatography-mass spectrometry and network pharmacology
title_full Predict potential pharmacological mechanisms of Ling-gui-Zhu-gan Decoction in treating unstable angina pectoris using liquid chromatography-mass spectrometry and network pharmacology
title_fullStr Predict potential pharmacological mechanisms of Ling-gui-Zhu-gan Decoction in treating unstable angina pectoris using liquid chromatography-mass spectrometry and network pharmacology
title_full_unstemmed Predict potential pharmacological mechanisms of Ling-gui-Zhu-gan Decoction in treating unstable angina pectoris using liquid chromatography-mass spectrometry and network pharmacology
title_short Predict potential pharmacological mechanisms of Ling-gui-Zhu-gan Decoction in treating unstable angina pectoris using liquid chromatography-mass spectrometry and network pharmacology
title_sort predict potential pharmacological mechanisms of ling gui zhu gan decoction in treating unstable angina pectoris using liquid chromatography mass spectrometry and network pharmacology
topic Ling-Gui-Zhu-Gan Decoction
transfer rate
UHPLC-Q-Orbitrap/MS
unstable angina
network pharmacology
url https://www.frontiersin.org/articles/10.3389/fchem.2025.1649538/full
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