Cargando…

An integrative analysis of Qingfei Paidu Decoction for its anti-HCoV-229E mechanism in cold and damp environment based on the pharmacokinetics, metabolomics and molecular docking technology

BACKGROUND: The novel coronavirus pneumonia (COVID-19) has spread rapidly around the world. As a member against the epidemic, Qingfei Paidu Decoction (QFPDD) has been approved for the treatment of COVID-19 in China. However, its antiviral mechanism was still largely unclear. PURPOSE: An integrated s...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhang, Yan, Gu, Xinru, Zhou, Yanyan, Si, Nan, Gao, Wenya, Sun, Bo, Sun, Jing, Li, Tao, Wang, Linna, Wei, Xiaolu, Guo, Shanshan, Cui, Xiaolan, Bian, Baolin, Wang, Hongjie, Wang, Liang, Zhao, Haiyu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier GmbH. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9605917/
https://www.ncbi.nlm.nih.gov/pubmed/36332393
http://dx.doi.org/10.1016/j.phymed.2022.154527
_version_ 1784818181857083392
author Zhang, Yan
Gu, Xinru
Zhou, Yanyan
Si, Nan
Gao, Wenya
Sun, Bo
Sun, Jing
Li, Tao
Wang, Linna
Wei, Xiaolu
Guo, Shanshan
Cui, Xiaolan
Bian, Baolin
Wang, Hongjie
Wang, Liang
Zhao, Haiyu
author_facet Zhang, Yan
Gu, Xinru
Zhou, Yanyan
Si, Nan
Gao, Wenya
Sun, Bo
Sun, Jing
Li, Tao
Wang, Linna
Wei, Xiaolu
Guo, Shanshan
Cui, Xiaolan
Bian, Baolin
Wang, Hongjie
Wang, Liang
Zhao, Haiyu
author_sort Zhang, Yan
collection PubMed
description BACKGROUND: The novel coronavirus pneumonia (COVID-19) has spread rapidly around the world. As a member against the epidemic, Qingfei Paidu Decoction (QFPDD) has been approved for the treatment of COVID-19 in China. However, its antiviral mechanism was still largely unclear. PURPOSE: An integrated strategy was used to explore the antiviral mechanisms of QFPDD in cold and damp environment, including pharmacokinetic (PK), network pharmacology, metabolomics and protein verification. METHODS: Firstly, the pharmacokinetic study of the prototype absorbed ingredients were analyzed by UHPLC-QqQ-MS. Secondly, the metabolomics analysis of the endogenous constituents was carried out. Based on the aforementioned results, an integrated network was constructed to identify the curative components, crucial endogenous differential metabolites and related pathways. Finally, the validation tests were implemented by molecular docking and western blotting (WB). RESULTS: According to the pharmacokinetic behaviors analysis of 31 components in vivo, the flavonoids presented more longer residence time and higher exposure compared with the other compounds. The efficacy and antiviral mechanism of QFPDD were verified by the poly-pharmacology, metabolomics, molecular docking and WB. For the occurrence of metabolic disorder, the change of amino acid transporters should not be neglected. Afterward, 8 curative compounds, 6 key genes and corresponding metabolic pathways were filtered by compound-reaction-enzyme-gene network. The molecular docking verified that the active ingredients bound to the relevant targets well. CONCLUSION: In the present study, an in vivo comprehensive pharmacokinetic behaviors of QFPDD was analyzed for the first time. The results illustrated that QFPDD could exhibit immune regulation, anti-infection, anti-inflammation and metabolic disorder to perform a corresponding therapeutic effect. Moreover, our findings highlighted the roles of amino acid transporters in the coronavirus infection situation.
format Online
Article
Text
id pubmed-9605917
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Elsevier GmbH.
record_format MEDLINE/PubMed
spelling pubmed-96059172022-10-27 An integrative analysis of Qingfei Paidu Decoction for its anti-HCoV-229E mechanism in cold and damp environment based on the pharmacokinetics, metabolomics and molecular docking technology Zhang, Yan Gu, Xinru Zhou, Yanyan Si, Nan Gao, Wenya Sun, Bo Sun, Jing Li, Tao Wang, Linna Wei, Xiaolu Guo, Shanshan Cui, Xiaolan Bian, Baolin Wang, Hongjie Wang, Liang Zhao, Haiyu Phytomedicine Original Article BACKGROUND: The novel coronavirus pneumonia (COVID-19) has spread rapidly around the world. As a member against the epidemic, Qingfei Paidu Decoction (QFPDD) has been approved for the treatment of COVID-19 in China. However, its antiviral mechanism was still largely unclear. PURPOSE: An integrated strategy was used to explore the antiviral mechanisms of QFPDD in cold and damp environment, including pharmacokinetic (PK), network pharmacology, metabolomics and protein verification. METHODS: Firstly, the pharmacokinetic study of the prototype absorbed ingredients were analyzed by UHPLC-QqQ-MS. Secondly, the metabolomics analysis of the endogenous constituents was carried out. Based on the aforementioned results, an integrated network was constructed to identify the curative components, crucial endogenous differential metabolites and related pathways. Finally, the validation tests were implemented by molecular docking and western blotting (WB). RESULTS: According to the pharmacokinetic behaviors analysis of 31 components in vivo, the flavonoids presented more longer residence time and higher exposure compared with the other compounds. The efficacy and antiviral mechanism of QFPDD were verified by the poly-pharmacology, metabolomics, molecular docking and WB. For the occurrence of metabolic disorder, the change of amino acid transporters should not be neglected. Afterward, 8 curative compounds, 6 key genes and corresponding metabolic pathways were filtered by compound-reaction-enzyme-gene network. The molecular docking verified that the active ingredients bound to the relevant targets well. CONCLUSION: In the present study, an in vivo comprehensive pharmacokinetic behaviors of QFPDD was analyzed for the first time. The results illustrated that QFPDD could exhibit immune regulation, anti-infection, anti-inflammation and metabolic disorder to perform a corresponding therapeutic effect. Moreover, our findings highlighted the roles of amino acid transporters in the coronavirus infection situation. Elsevier GmbH. 2023-01 2022-10-27 /pmc/articles/PMC9605917/ /pubmed/36332393 http://dx.doi.org/10.1016/j.phymed.2022.154527 Text en © 2022 Elsevier GmbH. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Original Article
Zhang, Yan
Gu, Xinru
Zhou, Yanyan
Si, Nan
Gao, Wenya
Sun, Bo
Sun, Jing
Li, Tao
Wang, Linna
Wei, Xiaolu
Guo, Shanshan
Cui, Xiaolan
Bian, Baolin
Wang, Hongjie
Wang, Liang
Zhao, Haiyu
An integrative analysis of Qingfei Paidu Decoction for its anti-HCoV-229E mechanism in cold and damp environment based on the pharmacokinetics, metabolomics and molecular docking technology
title An integrative analysis of Qingfei Paidu Decoction for its anti-HCoV-229E mechanism in cold and damp environment based on the pharmacokinetics, metabolomics and molecular docking technology
title_full An integrative analysis of Qingfei Paidu Decoction for its anti-HCoV-229E mechanism in cold and damp environment based on the pharmacokinetics, metabolomics and molecular docking technology
title_fullStr An integrative analysis of Qingfei Paidu Decoction for its anti-HCoV-229E mechanism in cold and damp environment based on the pharmacokinetics, metabolomics and molecular docking technology
title_full_unstemmed An integrative analysis of Qingfei Paidu Decoction for its anti-HCoV-229E mechanism in cold and damp environment based on the pharmacokinetics, metabolomics and molecular docking technology
title_short An integrative analysis of Qingfei Paidu Decoction for its anti-HCoV-229E mechanism in cold and damp environment based on the pharmacokinetics, metabolomics and molecular docking technology
title_sort integrative analysis of qingfei paidu decoction for its anti-hcov-229e mechanism in cold and damp environment based on the pharmacokinetics, metabolomics and molecular docking technology
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9605917/
https://www.ncbi.nlm.nih.gov/pubmed/36332393
http://dx.doi.org/10.1016/j.phymed.2022.154527
work_keys_str_mv AT zhangyan anintegrativeanalysisofqingfeipaidudecoctionforitsantihcov229emechanismincoldanddampenvironmentbasedonthepharmacokineticsmetabolomicsandmoleculardockingtechnology
AT guxinru anintegrativeanalysisofqingfeipaidudecoctionforitsantihcov229emechanismincoldanddampenvironmentbasedonthepharmacokineticsmetabolomicsandmoleculardockingtechnology
AT zhouyanyan anintegrativeanalysisofqingfeipaidudecoctionforitsantihcov229emechanismincoldanddampenvironmentbasedonthepharmacokineticsmetabolomicsandmoleculardockingtechnology
AT sinan anintegrativeanalysisofqingfeipaidudecoctionforitsantihcov229emechanismincoldanddampenvironmentbasedonthepharmacokineticsmetabolomicsandmoleculardockingtechnology
AT gaowenya anintegrativeanalysisofqingfeipaidudecoctionforitsantihcov229emechanismincoldanddampenvironmentbasedonthepharmacokineticsmetabolomicsandmoleculardockingtechnology
AT sunbo anintegrativeanalysisofqingfeipaidudecoctionforitsantihcov229emechanismincoldanddampenvironmentbasedonthepharmacokineticsmetabolomicsandmoleculardockingtechnology
AT sunjing anintegrativeanalysisofqingfeipaidudecoctionforitsantihcov229emechanismincoldanddampenvironmentbasedonthepharmacokineticsmetabolomicsandmoleculardockingtechnology
AT litao anintegrativeanalysisofqingfeipaidudecoctionforitsantihcov229emechanismincoldanddampenvironmentbasedonthepharmacokineticsmetabolomicsandmoleculardockingtechnology
AT wanglinna anintegrativeanalysisofqingfeipaidudecoctionforitsantihcov229emechanismincoldanddampenvironmentbasedonthepharmacokineticsmetabolomicsandmoleculardockingtechnology
AT weixiaolu anintegrativeanalysisofqingfeipaidudecoctionforitsantihcov229emechanismincoldanddampenvironmentbasedonthepharmacokineticsmetabolomicsandmoleculardockingtechnology
AT guoshanshan anintegrativeanalysisofqingfeipaidudecoctionforitsantihcov229emechanismincoldanddampenvironmentbasedonthepharmacokineticsmetabolomicsandmoleculardockingtechnology
AT cuixiaolan anintegrativeanalysisofqingfeipaidudecoctionforitsantihcov229emechanismincoldanddampenvironmentbasedonthepharmacokineticsmetabolomicsandmoleculardockingtechnology
AT bianbaolin anintegrativeanalysisofqingfeipaidudecoctionforitsantihcov229emechanismincoldanddampenvironmentbasedonthepharmacokineticsmetabolomicsandmoleculardockingtechnology
AT wanghongjie anintegrativeanalysisofqingfeipaidudecoctionforitsantihcov229emechanismincoldanddampenvironmentbasedonthepharmacokineticsmetabolomicsandmoleculardockingtechnology
AT wangliang anintegrativeanalysisofqingfeipaidudecoctionforitsantihcov229emechanismincoldanddampenvironmentbasedonthepharmacokineticsmetabolomicsandmoleculardockingtechnology
AT zhaohaiyu anintegrativeanalysisofqingfeipaidudecoctionforitsantihcov229emechanismincoldanddampenvironmentbasedonthepharmacokineticsmetabolomicsandmoleculardockingtechnology
AT zhangyan integrativeanalysisofqingfeipaidudecoctionforitsantihcov229emechanismincoldanddampenvironmentbasedonthepharmacokineticsmetabolomicsandmoleculardockingtechnology
AT guxinru integrativeanalysisofqingfeipaidudecoctionforitsantihcov229emechanismincoldanddampenvironmentbasedonthepharmacokineticsmetabolomicsandmoleculardockingtechnology
AT zhouyanyan integrativeanalysisofqingfeipaidudecoctionforitsantihcov229emechanismincoldanddampenvironmentbasedonthepharmacokineticsmetabolomicsandmoleculardockingtechnology
AT sinan integrativeanalysisofqingfeipaidudecoctionforitsantihcov229emechanismincoldanddampenvironmentbasedonthepharmacokineticsmetabolomicsandmoleculardockingtechnology
AT gaowenya integrativeanalysisofqingfeipaidudecoctionforitsantihcov229emechanismincoldanddampenvironmentbasedonthepharmacokineticsmetabolomicsandmoleculardockingtechnology
AT sunbo integrativeanalysisofqingfeipaidudecoctionforitsantihcov229emechanismincoldanddampenvironmentbasedonthepharmacokineticsmetabolomicsandmoleculardockingtechnology
AT sunjing integrativeanalysisofqingfeipaidudecoctionforitsantihcov229emechanismincoldanddampenvironmentbasedonthepharmacokineticsmetabolomicsandmoleculardockingtechnology
AT litao integrativeanalysisofqingfeipaidudecoctionforitsantihcov229emechanismincoldanddampenvironmentbasedonthepharmacokineticsmetabolomicsandmoleculardockingtechnology
AT wanglinna integrativeanalysisofqingfeipaidudecoctionforitsantihcov229emechanismincoldanddampenvironmentbasedonthepharmacokineticsmetabolomicsandmoleculardockingtechnology
AT weixiaolu integrativeanalysisofqingfeipaidudecoctionforitsantihcov229emechanismincoldanddampenvironmentbasedonthepharmacokineticsmetabolomicsandmoleculardockingtechnology
AT guoshanshan integrativeanalysisofqingfeipaidudecoctionforitsantihcov229emechanismincoldanddampenvironmentbasedonthepharmacokineticsmetabolomicsandmoleculardockingtechnology
AT cuixiaolan integrativeanalysisofqingfeipaidudecoctionforitsantihcov229emechanismincoldanddampenvironmentbasedonthepharmacokineticsmetabolomicsandmoleculardockingtechnology
AT bianbaolin integrativeanalysisofqingfeipaidudecoctionforitsantihcov229emechanismincoldanddampenvironmentbasedonthepharmacokineticsmetabolomicsandmoleculardockingtechnology
AT wanghongjie integrativeanalysisofqingfeipaidudecoctionforitsantihcov229emechanismincoldanddampenvironmentbasedonthepharmacokineticsmetabolomicsandmoleculardockingtechnology
AT wangliang integrativeanalysisofqingfeipaidudecoctionforitsantihcov229emechanismincoldanddampenvironmentbasedonthepharmacokineticsmetabolomicsandmoleculardockingtechnology
AT zhaohaiyu integrativeanalysisofqingfeipaidudecoctionforitsantihcov229emechanismincoldanddampenvironmentbasedonthepharmacokineticsmetabolomicsandmoleculardockingtechnology