Integrating network pharmacology, molecular docking and non-targeted serum metabolomics to illustrate pharmacodynamic ingredients and pharmacologic mechanism of Haizao Yuhu Decoction in treating hyperthyroidism

ObjectiveTo explore the pharmacodynamic ingredients and pharmacologic mechanism of Haizao Yuhu Decoction (HYD) in treating hyperthyroidism via an analysis integrating network pharmacology, molecular docking, and non-targeted serum metabolomics.MethodsTherapeutic targets of hyperthyroidism were searc...

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Main Authors: Wenbin Huang, Xiaoju Liu, Xingjia Li, Ruixiang Zhang, Guofang Chen, Xiaodong Mao, Shuhang Xu, Chao Liu
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-09-01
Series:Frontiers in Endocrinology
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Online Access:https://www.frontiersin.org/articles/10.3389/fendo.2024.1438821/full
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author Wenbin Huang
Xiaoju Liu
Xingjia Li
Ruixiang Zhang
Guofang Chen
Guofang Chen
Xiaodong Mao
Shuhang Xu
Chao Liu
Chao Liu
author_facet Wenbin Huang
Xiaoju Liu
Xingjia Li
Ruixiang Zhang
Guofang Chen
Guofang Chen
Xiaodong Mao
Shuhang Xu
Chao Liu
Chao Liu
author_sort Wenbin Huang
collection DOAJ
description ObjectiveTo explore the pharmacodynamic ingredients and pharmacologic mechanism of Haizao Yuhu Decoction (HYD) in treating hyperthyroidism via an analysis integrating network pharmacology, molecular docking, and non-targeted serum metabolomics.MethodsTherapeutic targets of hyperthyroidism were searched through multi-array analyses in the Gene Expression Omnibus (GEO) database. Hub genes were subjected to the construction of a protein-protein interaction (PPI) network, and GO and KEGG enrichment analyses. Targets of active pharmaceutical ingredients (APIs) in HYD and those of hyperthyroidism were intersected to yield hub genes, followed by validations via molecular docking and non-targeted serum metabolomics.Results112 hub genes were identified by intersecting APIs of HYD and therapeutic targets of hyperthyroidism. Using ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) in both negative and positive ion polarity modes, 279 compounds of HYD absorbed in the plasma were fingerprinted. Through summarizing data yielded from network pharmacology and non-targeted serum metabolomics, 214 common targets were identified from compounds of HYD absorbed in the plasma and therapeutic targets of hyperthyroidism, including PTPN11, PIK3CD, EGFR, HRAS, PIK3CA, AKT1, SRC, PIK3CB, and PIK3R1. They were mainly enriched in the biological processes of positive regulation of gene expression, positive regulation of MAPK cascade, signal transduction, protein phosphorylation, negative regulation of apoptotic process, positive regulation of protein kinase B signaling and positive regulation of MAP kinase activity; and molecular functions of identical protein binding, protein serine/threonine/tyrosine kinase activity, protein kinase activity, RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding and protein binding. A total of 185 signaling pathways enriched in the 214 common targets were associated with cell proliferation and angiogenesis.ConclusionHYD exerts a pharmacological effect on hyperthyroidism via inhibiting pathological angiogenesis in the thyroid and rebalancing immunity.
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spelling doaj-art-d9f97abd0dff4b288e1e545e2c9e7cb02025-08-20T01:55:12ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922024-09-011510.3389/fendo.2024.14388211438821Integrating network pharmacology, molecular docking and non-targeted serum metabolomics to illustrate pharmacodynamic ingredients and pharmacologic mechanism of Haizao Yuhu Decoction in treating hyperthyroidismWenbin Huang0Xiaoju Liu1Xingjia Li2Ruixiang Zhang3Guofang Chen4Guofang Chen5Xiaodong Mao6Shuhang Xu7Chao Liu8Chao Liu9Endocrine and Diabetes Center, The Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, ChinaEndocrine and Diabetes Center, The Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, ChinaKey Laboratory of Traditional Chinese Medicine (TCM) Syndrome and Treatment of Yingbing (Thyroid Disease) of State Administration of Traditional Chinese Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, ChinaEndocrine and Diabetes Center, The Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, ChinaEndocrine and Diabetes Center, The Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, ChinaKey Laboratory of Traditional Chinese Medicine (TCM) Syndrome and Treatment of Yingbing (Thyroid Disease) of State Administration of Traditional Chinese Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, ChinaKey Laboratory of Traditional Chinese Medicine (TCM) Syndrome and Treatment of Yingbing (Thyroid Disease) of State Administration of Traditional Chinese Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, ChinaEndocrine and Diabetes Center, The Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, ChinaEndocrine and Diabetes Center, The Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, ChinaKey Laboratory of Traditional Chinese Medicine (TCM) Syndrome and Treatment of Yingbing (Thyroid Disease) of State Administration of Traditional Chinese Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, ChinaObjectiveTo explore the pharmacodynamic ingredients and pharmacologic mechanism of Haizao Yuhu Decoction (HYD) in treating hyperthyroidism via an analysis integrating network pharmacology, molecular docking, and non-targeted serum metabolomics.MethodsTherapeutic targets of hyperthyroidism were searched through multi-array analyses in the Gene Expression Omnibus (GEO) database. Hub genes were subjected to the construction of a protein-protein interaction (PPI) network, and GO and KEGG enrichment analyses. Targets of active pharmaceutical ingredients (APIs) in HYD and those of hyperthyroidism were intersected to yield hub genes, followed by validations via molecular docking and non-targeted serum metabolomics.Results112 hub genes were identified by intersecting APIs of HYD and therapeutic targets of hyperthyroidism. Using ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) in both negative and positive ion polarity modes, 279 compounds of HYD absorbed in the plasma were fingerprinted. Through summarizing data yielded from network pharmacology and non-targeted serum metabolomics, 214 common targets were identified from compounds of HYD absorbed in the plasma and therapeutic targets of hyperthyroidism, including PTPN11, PIK3CD, EGFR, HRAS, PIK3CA, AKT1, SRC, PIK3CB, and PIK3R1. They were mainly enriched in the biological processes of positive regulation of gene expression, positive regulation of MAPK cascade, signal transduction, protein phosphorylation, negative regulation of apoptotic process, positive regulation of protein kinase B signaling and positive regulation of MAP kinase activity; and molecular functions of identical protein binding, protein serine/threonine/tyrosine kinase activity, protein kinase activity, RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding and protein binding. A total of 185 signaling pathways enriched in the 214 common targets were associated with cell proliferation and angiogenesis.ConclusionHYD exerts a pharmacological effect on hyperthyroidism via inhibiting pathological angiogenesis in the thyroid and rebalancing immunity.https://www.frontiersin.org/articles/10.3389/fendo.2024.1438821/fullHaizao Yuhu Decoctionhyperthyroidismnetwork pharmacologymolecular dockingnon-targeted serum metabolomics
spellingShingle Wenbin Huang
Xiaoju Liu
Xingjia Li
Ruixiang Zhang
Guofang Chen
Guofang Chen
Xiaodong Mao
Shuhang Xu
Chao Liu
Chao Liu
Integrating network pharmacology, molecular docking and non-targeted serum metabolomics to illustrate pharmacodynamic ingredients and pharmacologic mechanism of Haizao Yuhu Decoction in treating hyperthyroidism
Frontiers in Endocrinology
Haizao Yuhu Decoction
hyperthyroidism
network pharmacology
molecular docking
non-targeted serum metabolomics
title Integrating network pharmacology, molecular docking and non-targeted serum metabolomics to illustrate pharmacodynamic ingredients and pharmacologic mechanism of Haizao Yuhu Decoction in treating hyperthyroidism
title_full Integrating network pharmacology, molecular docking and non-targeted serum metabolomics to illustrate pharmacodynamic ingredients and pharmacologic mechanism of Haizao Yuhu Decoction in treating hyperthyroidism
title_fullStr Integrating network pharmacology, molecular docking and non-targeted serum metabolomics to illustrate pharmacodynamic ingredients and pharmacologic mechanism of Haizao Yuhu Decoction in treating hyperthyroidism
title_full_unstemmed Integrating network pharmacology, molecular docking and non-targeted serum metabolomics to illustrate pharmacodynamic ingredients and pharmacologic mechanism of Haizao Yuhu Decoction in treating hyperthyroidism
title_short Integrating network pharmacology, molecular docking and non-targeted serum metabolomics to illustrate pharmacodynamic ingredients and pharmacologic mechanism of Haizao Yuhu Decoction in treating hyperthyroidism
title_sort integrating network pharmacology molecular docking and non targeted serum metabolomics to illustrate pharmacodynamic ingredients and pharmacologic mechanism of haizao yuhu decoction in treating hyperthyroidism
topic Haizao Yuhu Decoction
hyperthyroidism
network pharmacology
molecular docking
non-targeted serum metabolomics
url https://www.frontiersin.org/articles/10.3389/fendo.2024.1438821/full
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