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The Anti-Inflammatory Effect of a Combination of Five Compounds From Five Chinese Herbal Medicines Used in the Treatment of COPD
Effective compound combination (ECC; i.e, 20-S-ginsenoside Rh1, astragaloside, icariin, nobiletin, and paeonol), derived from Chinese herbal medicine, significantly ameliorates chronic obstructive pulmonary disease (COPD) in rats; however, the underlying mechanisms of ECC remain largely unclear. In...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8578279/ https://www.ncbi.nlm.nih.gov/pubmed/34776947 http://dx.doi.org/10.3389/fphar.2021.709702 |
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author | Li, Jiansheng Zhao, Peng Tian, Yange Li, Kangchen Zhang, Lanxi Guan, Qingzhou Mei, Xiaofeng Qin, Yanqin |
author_facet | Li, Jiansheng Zhao, Peng Tian, Yange Li, Kangchen Zhang, Lanxi Guan, Qingzhou Mei, Xiaofeng Qin, Yanqin |
author_sort | Li, Jiansheng |
collection | PubMed |
description | Effective compound combination (ECC; i.e, 20-S-ginsenoside Rh1, astragaloside, icariin, nobiletin, and paeonol), derived from Chinese herbal medicine, significantly ameliorates chronic obstructive pulmonary disease (COPD) in rats; however, the underlying mechanisms of ECC remain largely unclear. In this study, network pharmacology analysis integrated with experimental validation was used to explore the therapeutic mechanisms of ECC against COPD. ECC targets and COPD genes and targets were identified from multiple databases, and then used for an analysis of protein–protein interaction (PPI) networks, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and biological functioning. BisoGenet was used to comprehensively analyze the hub-network. We validated the therapeutic effect and mechanisms of ECC both in vivo and in vitro. We identified 45 ECC targets, which were mainly related to inflammatory processes, such as the NOD-like and NF-kappa B signaling pathways, hematopoietic cell lineage, Th17 cell differentiation, cellular response to lipopolysaccharide, and interleukin-8 secretion. In addition, 1180 COPD genes and 70 COPD targets were identified as being involved in the biological functions associated with COPD development, such as cytokine–cytokine receptor interaction, the TNF signaling pathway, the mitogen-activated protein kinase (MAPK) signaling pathway, regulation of lymphocyte proliferation, and positive regulation of leukocyte migration. Integrative analysis of COPD genes and targets and ECC target networks revealed that 54 genes were mainly involved in the inflammatory process, such as IL-17 signaling, NF-kappa B signaling, innate immune response–activating signal transduction, and macrophage cell differentiation. Six targets (AR, ESR1, HNRNPA1, PAPR1, TP53, and VCAM1) contained in the hub-network and their four related compounds were obtained and recognized as the key molecules associated with the effects of ECC. Molecular docking validation demonstrated that four compounds could bind to six targets that interact with COPD genes. Finally, in vivo and in vitro experiments verified that ECC treatment ameliorated the symptoms of COPD in rats by improving their lung function, reducing pathological changes, and suppressing oxidative responses and pro-inflammatory cytokine secretion, while inhibiting inflammation in LPS-induced macrophages, which may be associated with NF-kappa B and MAPK signaling regulation. This study demonstrates the therapeutic mechanisms and effects of ECC on COPD via regulation of the underlying inflammatory process. |
format | Online Article Text |
id | pubmed-8578279 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-85782792021-11-11 The Anti-Inflammatory Effect of a Combination of Five Compounds From Five Chinese Herbal Medicines Used in the Treatment of COPD Li, Jiansheng Zhao, Peng Tian, Yange Li, Kangchen Zhang, Lanxi Guan, Qingzhou Mei, Xiaofeng Qin, Yanqin Front Pharmacol Pharmacology Effective compound combination (ECC; i.e, 20-S-ginsenoside Rh1, astragaloside, icariin, nobiletin, and paeonol), derived from Chinese herbal medicine, significantly ameliorates chronic obstructive pulmonary disease (COPD) in rats; however, the underlying mechanisms of ECC remain largely unclear. In this study, network pharmacology analysis integrated with experimental validation was used to explore the therapeutic mechanisms of ECC against COPD. ECC targets and COPD genes and targets were identified from multiple databases, and then used for an analysis of protein–protein interaction (PPI) networks, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and biological functioning. BisoGenet was used to comprehensively analyze the hub-network. We validated the therapeutic effect and mechanisms of ECC both in vivo and in vitro. We identified 45 ECC targets, which were mainly related to inflammatory processes, such as the NOD-like and NF-kappa B signaling pathways, hematopoietic cell lineage, Th17 cell differentiation, cellular response to lipopolysaccharide, and interleukin-8 secretion. In addition, 1180 COPD genes and 70 COPD targets were identified as being involved in the biological functions associated with COPD development, such as cytokine–cytokine receptor interaction, the TNF signaling pathway, the mitogen-activated protein kinase (MAPK) signaling pathway, regulation of lymphocyte proliferation, and positive regulation of leukocyte migration. Integrative analysis of COPD genes and targets and ECC target networks revealed that 54 genes were mainly involved in the inflammatory process, such as IL-17 signaling, NF-kappa B signaling, innate immune response–activating signal transduction, and macrophage cell differentiation. Six targets (AR, ESR1, HNRNPA1, PAPR1, TP53, and VCAM1) contained in the hub-network and their four related compounds were obtained and recognized as the key molecules associated with the effects of ECC. Molecular docking validation demonstrated that four compounds could bind to six targets that interact with COPD genes. Finally, in vivo and in vitro experiments verified that ECC treatment ameliorated the symptoms of COPD in rats by improving their lung function, reducing pathological changes, and suppressing oxidative responses and pro-inflammatory cytokine secretion, while inhibiting inflammation in LPS-induced macrophages, which may be associated with NF-kappa B and MAPK signaling regulation. This study demonstrates the therapeutic mechanisms and effects of ECC on COPD via regulation of the underlying inflammatory process. Frontiers Media S.A. 2021-10-27 /pmc/articles/PMC8578279/ /pubmed/34776947 http://dx.doi.org/10.3389/fphar.2021.709702 Text en Copyright © 2021 Li, Zhao, Tian, Li, Zhang, Guan, Mei and Qin. https://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 Li, Jiansheng Zhao, Peng Tian, Yange Li, Kangchen Zhang, Lanxi Guan, Qingzhou Mei, Xiaofeng Qin, Yanqin The Anti-Inflammatory Effect of a Combination of Five Compounds From Five Chinese Herbal Medicines Used in the Treatment of COPD |
title | The Anti-Inflammatory Effect of a Combination of Five Compounds From Five Chinese Herbal Medicines Used in the Treatment of COPD |
title_full | The Anti-Inflammatory Effect of a Combination of Five Compounds From Five Chinese Herbal Medicines Used in the Treatment of COPD |
title_fullStr | The Anti-Inflammatory Effect of a Combination of Five Compounds From Five Chinese Herbal Medicines Used in the Treatment of COPD |
title_full_unstemmed | The Anti-Inflammatory Effect of a Combination of Five Compounds From Five Chinese Herbal Medicines Used in the Treatment of COPD |
title_short | The Anti-Inflammatory Effect of a Combination of Five Compounds From Five Chinese Herbal Medicines Used in the Treatment of COPD |
title_sort | anti-inflammatory effect of a combination of five compounds from five chinese herbal medicines used in the treatment of copd |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8578279/ https://www.ncbi.nlm.nih.gov/pubmed/34776947 http://dx.doi.org/10.3389/fphar.2021.709702 |
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