Background. Pinellia ternata (PT), a medicinal plant, has had an extensive application in the treatment of asthma in China, whereas its underlying pharmacological mechanisms remain unclear. Methods. Firstly, a network pharmacology method was adopted to collect activated components of PT from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Targets of PT were assessed by exploiting the PharmMapper website; asthma-related targets were collected from the OMIM website, and target-target interaction networks were built. Secondly, critical nodes exhibiting high possibility were identified as the hub nodes in the network, which were employed to conduct Gene Ontology (GO) comment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis. Finally, the tissue expression profiles of key candidate genes were identified by the Gene Expression Omnibus (GEO) database, and the therapeutic effect of PT was verified by an animal experiment. Results. 57 achievable targets of PT on asthma were confirmed as hub nodes through using the network pharmacology method. As revealed from the KEGG enrichment analysis, the signaling pathways were notably enriched in pathways of the T-cell receptor signaling pathway, JAK-STAT signaling pathway, and cytokine-cytokine receptor interaction. The expression profiles of candidate genes including Mmp2, Nr3c1, il-10, il-4, il-13, il-17a, il-2, tlr4, tlr9, ccl2, csf2, and vefgα were identified. Moreover, according to transcriptome RNA sequencing data from lung tissues of allergic mice compared to normal mice, the mRNA level of Mmp2 and il-4 was upregulated ( P < 0.001 ). In animal experiments, PT could alleviate the allergic response of mice by inhibiting the activation of T-helper type 2 (TH2) cells and the expression of Mmp2 and il-4. Conclusions. Our study provides candidate genes that may be either used for future studies related to diagnosis/prognosis or as targets for asthma management. Besides, animal experiments showed that PT could treat asthma by regulating the expression of Mmp2 and il-4.
Background: Pinellia ternata (PT), a medicinal plant, has had an extensive application in the treatment of asthma in China, whereas its underlying pharmacological mechanisms remain unclear.Methods: Firstly, the therapeutic effect of PT was verified by an animal experiment. Secondly, a network pharmacology method was adopted to collect activated components of PT from Traditional Chinese Medicine Systems Pharmacology Database and Analysis (TCMSP); binding targets of PT were assessed by exploiting Pharmmapper website; asthma-related targets were collected, and Target-Target interaction networks were built. Subsequently, critical nodes exhibiting high-possibility were identified as the hub nodes in the network, which employed to conduct GeneOntology (GO) comment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis. Finally, the tissue expression profiles and single-cell RNA sequencing (scRNA-Seq) data of candidate genes were identified by Gene Expression Omnibus database (GEO) and PanglaoDB databases.Results: In animal experiments, PT could alleviate the allergic response of mice by inhibiting the activation of T-helper type 2 (TH2) cells and the secretion of IL-4 and IL-5. Subsequently, 57 achievable targets of PT on asthma were confirmed as hub nodes, included candidate genes matrix metalloproteinase-2 (MMP2) and nuclear receptor subfamily 3 group C member 1(NR3C1). Moreover, according to transcriptome RNA sequencing data from lung tissues of allergic mice compared to normal mice, mRNA level of MMP2 was up-regulated (P<0.001), and mRNA level of NR3C1 was no significant difference (P=0.0749). Finally, we compared their levels of expression and distributions to those present in the single-cell level. Conclusions: With network pharmacology, our study provides candidate genes that may be either used for future studies related to diagnosis/prognosis or as targets for asthma management. Besides, more attention should be paid to methods of identifying the origin of these genes and determining their expression at the single-cell level.
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