Combining single-cell RNA sequencing data and network pharmacology to explore the mechanism of action of Dayuan Yin in the treatment of acute lung injury
Background: This study aimed to analyze the usefulness of combined single-cell RNA sequencing data and network pharmacology in understanding the molecular regulation mechanism of Dayuan Yin (DYY) in acute lung injury (ALI). Methods: The single-cell ALI dataset GSE224938 was acquired from the Gene Ex...
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KeAi Communications Co., Ltd.
2023-12-01
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| Series: | Journal of Holistic Integrative Pharmacy |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2707368824000025 |
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| author | Lei Zhang Wei Zhu Zepeng Zhang Yu Huang |
| author_facet | Lei Zhang Wei Zhu Zepeng Zhang Yu Huang |
| author_sort | Lei Zhang |
| collection | DOAJ |
| description | Background: This study aimed to analyze the usefulness of combined single-cell RNA sequencing data and network pharmacology in understanding the molecular regulation mechanism of Dayuan Yin (DYY) in acute lung injury (ALI). Methods: The single-cell ALI dataset GSE224938 was acquired from the Gene Expression Database and cellular heterogeneity was examined using the Seurat software package. Differential expression analysis was conducted using the R software to identify genes with significant expression differences. The active constituents and therapeutic targets of DYY were acquired from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Subsequently, the protein-protein interaction (PPI) networks, gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) were employed to analyze the key targets. A visual network depicting the interaction between compounds, targets, and pathways was constructed, and the CytoNCA plug-in was utilized to identify core targets. The active component-core target relationship was validated using MOE, AutoDockTools, AutoDockVina, and other software. Finally, a preliminary experiment was conducted using the lipopolysaccharide-induced acute lung injury (ALI) rat model. Results: In total, 5243 significantly differentially expressed genes were identified in ALI, and 260 genes were identified as DYY targets. Then, 81 target genes were identified at the intersection between drugs and diseases. The identified core target genes included PIK3R1, IL-1β, IL-6, ICAM1, and CCL2. GO analysis was mainly involved in cellular inflammatory response, dual regulation of cell apoptosis, and coordinated migration. KEGG analysis showed enrichment in inflammatory pathways. The major active components were well connected with IL-1β. DYY could significantly reduce the phosphorylation expression of PI3K, Akt, and NF-κBp65 in the lung tissue of ALI rats, and regulated the activation of related inflammatory cells. Conclusions: We successfully screened the potential active ingredients of DYY for the treatment of ALI. In addition, in vivo experiments preliminarily verified the predictions of network pharmacology, showing that DYY can inhibit the PI3K/Akt/NF−КВ signaling pathway, reduce cytokine release and regulate the number of inflammatory cells, providing an alternative for ALI treatment. |
| format | Article |
| id | doaj-art-c06b2ebf88a44f44ace6a8f6f714abc2 |
| institution | Kabale University |
| issn | 2707-3688 |
| language | English |
| publishDate | 2023-12-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Journal of Holistic Integrative Pharmacy |
| spelling | doaj-art-c06b2ebf88a44f44ace6a8f6f714abc22024-11-12T05:21:45ZengKeAi Communications Co., Ltd.Journal of Holistic Integrative Pharmacy2707-36882023-12-0144259271Combining single-cell RNA sequencing data and network pharmacology to explore the mechanism of action of Dayuan Yin in the treatment of acute lung injuryLei Zhang0Wei Zhu1Zepeng Zhang2Yu Huang3Corresponding author. Kunshan Hospital of Traditional Chinese Medicine, 60 Changyang Branch Road, 215300, China.; Kunshan Hospital of Traditional Chinese Medicine, Kunshan, 215300, ChinaKunshan Hospital of Traditional Chinese Medicine, Kunshan, 215300, ChinaKunshan Hospital of Traditional Chinese Medicine, Kunshan, 215300, ChinaKunshan Hospital of Traditional Chinese Medicine, Kunshan, 215300, ChinaBackground: This study aimed to analyze the usefulness of combined single-cell RNA sequencing data and network pharmacology in understanding the molecular regulation mechanism of Dayuan Yin (DYY) in acute lung injury (ALI). Methods: The single-cell ALI dataset GSE224938 was acquired from the Gene Expression Database and cellular heterogeneity was examined using the Seurat software package. Differential expression analysis was conducted using the R software to identify genes with significant expression differences. The active constituents and therapeutic targets of DYY were acquired from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Subsequently, the protein-protein interaction (PPI) networks, gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) were employed to analyze the key targets. A visual network depicting the interaction between compounds, targets, and pathways was constructed, and the CytoNCA plug-in was utilized to identify core targets. The active component-core target relationship was validated using MOE, AutoDockTools, AutoDockVina, and other software. Finally, a preliminary experiment was conducted using the lipopolysaccharide-induced acute lung injury (ALI) rat model. Results: In total, 5243 significantly differentially expressed genes were identified in ALI, and 260 genes were identified as DYY targets. Then, 81 target genes were identified at the intersection between drugs and diseases. The identified core target genes included PIK3R1, IL-1β, IL-6, ICAM1, and CCL2. GO analysis was mainly involved in cellular inflammatory response, dual regulation of cell apoptosis, and coordinated migration. KEGG analysis showed enrichment in inflammatory pathways. The major active components were well connected with IL-1β. DYY could significantly reduce the phosphorylation expression of PI3K, Akt, and NF-κBp65 in the lung tissue of ALI rats, and regulated the activation of related inflammatory cells. Conclusions: We successfully screened the potential active ingredients of DYY for the treatment of ALI. In addition, in vivo experiments preliminarily verified the predictions of network pharmacology, showing that DYY can inhibit the PI3K/Akt/NF−КВ signaling pathway, reduce cytokine release and regulate the number of inflammatory cells, providing an alternative for ALI treatment.http://www.sciencedirect.com/science/article/pii/S2707368824000025Single cell sequencingNetwork pharmacologyMolecular dockingDayuan yinAcute lung injury |
| spellingShingle | Lei Zhang Wei Zhu Zepeng Zhang Yu Huang Combining single-cell RNA sequencing data and network pharmacology to explore the mechanism of action of Dayuan Yin in the treatment of acute lung injury Journal of Holistic Integrative Pharmacy Single cell sequencing Network pharmacology Molecular docking Dayuan yin Acute lung injury |
| title | Combining single-cell RNA sequencing data and network pharmacology to explore the mechanism of action of Dayuan Yin in the treatment of acute lung injury |
| title_full | Combining single-cell RNA sequencing data and network pharmacology to explore the mechanism of action of Dayuan Yin in the treatment of acute lung injury |
| title_fullStr | Combining single-cell RNA sequencing data and network pharmacology to explore the mechanism of action of Dayuan Yin in the treatment of acute lung injury |
| title_full_unstemmed | Combining single-cell RNA sequencing data and network pharmacology to explore the mechanism of action of Dayuan Yin in the treatment of acute lung injury |
| title_short | Combining single-cell RNA sequencing data and network pharmacology to explore the mechanism of action of Dayuan Yin in the treatment of acute lung injury |
| title_sort | combining single cell rna sequencing data and network pharmacology to explore the mechanism of action of dayuan yin in the treatment of acute lung injury |
| topic | Single cell sequencing Network pharmacology Molecular docking Dayuan yin Acute lung injury |
| url | http://www.sciencedirect.com/science/article/pii/S2707368824000025 |
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