Integrated hepatic single-cell RNA sequencing and untargeted metabolomics reveals the immune and metabolic modulation of Qing-Fei-Pai-Du decoction in mice with coronavirus-induced pneumonia.
Phytomedicine
; 97: 153922, 2022 Mar.
Article
in English
| MEDLINE | ID: covidwho-1586870
ABSTRACT
BACKGROUND:
Although Qing-Fei-Pai-Du decoction (QFPDD) is extensively used clinically to treat COVID-19 patients, the mechanism by which it modulates the immunological and metabolic functions of liver tissue remains unknown.PURPOSE:
The purpose of this study is to investigate the mechanism of action of QFPDD in the treatment of mice with coronavirus-induced pneumonia by combining integrated hepatic single-cell RNA sequencing and untargeted metabolomics.METHODS:
We developed a human coronavirus pneumonia model in BALB/c mice by infecting them with human coronavirus HCoV-229E with stimulating them with cold-damp environment. We initially assessed the status of inflammation and immunity in model mice treated with or without QFPDD by detecting peripheral blood lymphocytes and inflammatory cytokines. Then, single-cell RNA sequencing and untargeted metabolomics were performed on mouse liver tissue.RESULTS:
HCoV-229E infection in combination with exposure to a cold-damp environment significantly decreased the percentage of peripheral blood lymphocytes (CD4+ and CD8+ T cells, B cells) in mice, which was enhanced by QFPDD therapy. Meanwhile, the levels of inflammatory cytokines such as IL-6, TNF-α, and IFN-γ were significantly increased in mouse models but significantly decreased by QFPDD treatment. Single-cell RNA sequencing analysis showed that QFPDD could attenuate disease-associated alterations in gene expression, core transcriptional regulatory networks, and cell-type composition. Computational predictions indicated that QFPDD rectified the observed aberrant patterns of cell-cell communication. Additionally, the metabolic profiles of liver tissue in the Model group were distinct from mice in the Control group, and QFPDD significantly regulated hepatic purine metabolism.CONCLUSION:
To the best of our knowledge, this study is the first to integrate hepatic single-cell RNA sequencing and untargeted metabolomics into a TCM formula and these valuable findings indicate that QFPDD can improve immune function and reduce liver injury and inflammation.Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Drugs, Chinese Herbal
/
Metabolomics
/
COVID-19 Drug Treatment
Type of study:
Experimental Studies
/
Prognostic study
Topics:
Traditional medicine
Limits:
Animals
/
Humans
Language:
English
Journal:
Phytomedicine
Journal subject:
Complementary Therapies
Year:
2022
Document Type:
Article
Affiliation country:
J.phymed.2021.153922
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