Mechanism of Houttuynia cordata in treating acute lung injury based on network pharmacology

To explore the mechanism of action of Houttuynia cordata(HC) in treating acute lung injury(ALI) by leveraging network pharmacology, uncover potential molecular targets and signaling pathways, and experimentally validate its efficacy, thereby providing novel ideas for clinical prevention and treatment.

Online databases such as TCMSP, PubChem, Swiss Target Prediction, GeneCards, DrugBank, OMIM, and DisGENET were employed to obtain information on the active components of HC, as well as their component targets and disease targets. The Cytoscape software was utilized to construct a network of active components of HC - action targets for ALI. The target proteins were subjected to protein-protein interaction (PPI) network analysis using the String database, and gene ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were carried out through the DAVID database to predict the mechanism of action. Finally, experimental methods including CCK8 assay, ROS detection, and ELISA for IL-6 detection were used to observe the effect of HC on LPS-induced A549 cells.

A total of 7 major active components were screened from HC, involving 342 targets, among which 64 were related to ALI. Through PPI network analysis, key targets such as AKT1, STAT3, IL-6, HIF-1α, and SIRT1 were identified. GO and KEGG pathway enrichment analyses revealed that the treatment of ALI with HC might be associated with 663 GO functions covering phosphorylation, signal transduction, protein phosphorylation, protein binding, ATP binding, and identical protein binding, etc. It involved 167 signaling pathways such as the PI3K-Akt signaling pathway, metabolic pathway, chemokine signaling pathway, and calcium signaling pathway. Experimental results demonstrated that HC could effectively protect cells under inflammatory conditions and alleviate cell damage.

HC exhibits multi-component, multi-target, and multi-mechanism therapeutic characteristics for ALI. It is speculated that it can achieve the defense and treatment of ALI by regulating anti-inflammatory and immunomodulatory-related biological pathways.