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Systems pharmacology dissection of pharmacological mechanisms of Xiaochaihu decoction against human coronavirus
BACKGROUND: Although coronavirus disease 2019 (COVID-19) pandemic is still rage worldwide, there are still very limited treatments for human coronaviruses (HCoVs) infections. Xiaochahu decoction (XCHD), which is one of the traditional Chinese medicine (TCM) prescriptions in Qingfeipaidu decoction (Q...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10357659/ https://www.ncbi.nlm.nih.gov/pubmed/37475019 http://dx.doi.org/10.1186/s12906-023-04024-6 |
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author | Xu, Lvjie Cai, Chuipu Fang, Jiansong Wu, Qihui Zhao, Jun Wang, Zhe Guo, Pengfei Zheng, Lishu Liu, Ailin |
author_facet | Xu, Lvjie Cai, Chuipu Fang, Jiansong Wu, Qihui Zhao, Jun Wang, Zhe Guo, Pengfei Zheng, Lishu Liu, Ailin |
author_sort | Xu, Lvjie |
collection | PubMed |
description | BACKGROUND: Although coronavirus disease 2019 (COVID-19) pandemic is still rage worldwide, there are still very limited treatments for human coronaviruses (HCoVs) infections. Xiaochahu decoction (XCHD), which is one of the traditional Chinese medicine (TCM) prescriptions in Qingfeipaidu decoction (QFPDD), is widely used for COVID-19 treatment in China and able to relieve the symptoms of fever, fatigue, anorexia, and sore throat. To explore the role and mechanisms of XCHD against HCoVs, we presented an integrated systems pharmacology framework in this study. METHODS: We constructed a global herb-compound-target (H-C-T) network of XCHD against HCoVs. Multi-level systems pharmacology analyses were conducted to highlight the key XCHD-regulated proteins, and reveal multiple HCoVs relevant biological functions affected by XCHD. We further utilized network-based prediction, drug-likeness analysis, combining with literature investigations to uncover the key ani-HCoV constituents in XCHD, whose effects on anit-HCoV-229E virus were validated using cytopathic effect (CPE) assay. Finally, we proposed potential molecular mechanisms of these compounds against HCoVs via subnetwork analysis. RESULTS: Based on the systems pharmacology framework, we identified 161 XCHD-derived compounds interacting with 37 HCoV-associated proteins. An integrated pathway analysis revealed that the mechanism of XCHD against HCoVs is related to TLR signaling pathway, RIG-I-like receptor signaling pathway, cytoplasmic DNA sensing pathway, and IL-6/STAT3 pro-inflammatory signaling pathway. Five compounds from XCHD, including betulinic acid, chrysin, isoliquiritigenin, schisandrin B, and (20R)-Ginsenoside Rh1 exerted inhibitory activity against HCoV-229E virus in Huh7 cells using in vitro CPE assay. CONCLUSION: Our work presented a comprehensive systems pharmacology approach to identify the effective molecules and explore the molecular mechanism of XCHD against HCoVs. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12906-023-04024-6. |
format | Online Article Text |
id | pubmed-10357659 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-103576592023-07-21 Systems pharmacology dissection of pharmacological mechanisms of Xiaochaihu decoction against human coronavirus Xu, Lvjie Cai, Chuipu Fang, Jiansong Wu, Qihui Zhao, Jun Wang, Zhe Guo, Pengfei Zheng, Lishu Liu, Ailin BMC Complement Med Ther Research BACKGROUND: Although coronavirus disease 2019 (COVID-19) pandemic is still rage worldwide, there are still very limited treatments for human coronaviruses (HCoVs) infections. Xiaochahu decoction (XCHD), which is one of the traditional Chinese medicine (TCM) prescriptions in Qingfeipaidu decoction (QFPDD), is widely used for COVID-19 treatment in China and able to relieve the symptoms of fever, fatigue, anorexia, and sore throat. To explore the role and mechanisms of XCHD against HCoVs, we presented an integrated systems pharmacology framework in this study. METHODS: We constructed a global herb-compound-target (H-C-T) network of XCHD against HCoVs. Multi-level systems pharmacology analyses were conducted to highlight the key XCHD-regulated proteins, and reveal multiple HCoVs relevant biological functions affected by XCHD. We further utilized network-based prediction, drug-likeness analysis, combining with literature investigations to uncover the key ani-HCoV constituents in XCHD, whose effects on anit-HCoV-229E virus were validated using cytopathic effect (CPE) assay. Finally, we proposed potential molecular mechanisms of these compounds against HCoVs via subnetwork analysis. RESULTS: Based on the systems pharmacology framework, we identified 161 XCHD-derived compounds interacting with 37 HCoV-associated proteins. An integrated pathway analysis revealed that the mechanism of XCHD against HCoVs is related to TLR signaling pathway, RIG-I-like receptor signaling pathway, cytoplasmic DNA sensing pathway, and IL-6/STAT3 pro-inflammatory signaling pathway. Five compounds from XCHD, including betulinic acid, chrysin, isoliquiritigenin, schisandrin B, and (20R)-Ginsenoside Rh1 exerted inhibitory activity against HCoV-229E virus in Huh7 cells using in vitro CPE assay. CONCLUSION: Our work presented a comprehensive systems pharmacology approach to identify the effective molecules and explore the molecular mechanism of XCHD against HCoVs. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12906-023-04024-6. BioMed Central 2023-07-20 /pmc/articles/PMC10357659/ /pubmed/37475019 http://dx.doi.org/10.1186/s12906-023-04024-6 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Xu, Lvjie Cai, Chuipu Fang, Jiansong Wu, Qihui Zhao, Jun Wang, Zhe Guo, Pengfei Zheng, Lishu Liu, Ailin Systems pharmacology dissection of pharmacological mechanisms of Xiaochaihu decoction against human coronavirus |
title | Systems pharmacology dissection of pharmacological mechanisms of Xiaochaihu decoction against human coronavirus |
title_full | Systems pharmacology dissection of pharmacological mechanisms of Xiaochaihu decoction against human coronavirus |
title_fullStr | Systems pharmacology dissection of pharmacological mechanisms of Xiaochaihu decoction against human coronavirus |
title_full_unstemmed | Systems pharmacology dissection of pharmacological mechanisms of Xiaochaihu decoction against human coronavirus |
title_short | Systems pharmacology dissection of pharmacological mechanisms of Xiaochaihu decoction against human coronavirus |
title_sort | systems pharmacology dissection of pharmacological mechanisms of xiaochaihu decoction against human coronavirus |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10357659/ https://www.ncbi.nlm.nih.gov/pubmed/37475019 http://dx.doi.org/10.1186/s12906-023-04024-6 |
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