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: Cold-damp environment; Coronavirus disease 2019; Qing-Fei-Pai-Du decoction; Single-cell RNA sequencing; Untargeted metabolomics.
【저자키워드】 Coronavirus disease 2019, Cold-damp environment, Qing-Fei-Pai-Du decoction, Single-cell RNA sequencing, Untargeted metabolomics., 【초록키워드】 Treatment, coronavirus disease, Inflammation, metabolomics, Coronavirus disease 2019, coronavirus, therapy, Cytokines, Gene Expression, Lymphocytes, Immunity, Coronavirus pneumonia, Pneumonia, T cells, IL-6, knowledge, Infection, B cells, CD4, CD8, metabolism, Single-cell RNA sequencing, RNA, Peripheral blood, Human coronavirus, Regulatory, mice, RNA sequencing, HCoV, Model, Control, Liver injury, HCoV-229E, immune function, Inflammatory cytokines, Mouse models, mouse model, mechanism of action, disease, mechanism, Inflammatory cytokine, COVID-19 patients, IFN-γ, TNF-α, Combination, TCM, Analysis, Cold, best, exposure to, control group, peripheral blood lymphocytes, profile, status, metabolic function, alteration, treat, BALB/c mice, damp environment, liver tissue, purine, infecting, immunological, transcriptional, significantly increased, IMPROVE, performed, significantly, indicated, clinically, treated, modulate, regulated, reduce, disease-associated, attenuate, peripheral blood lymphocyte, 【제목키워드】 metabolomics, immune, modulation, reveal,