AUTHOR=Zhu De-Wei , Yu Qun , Sun Ji-Jia , Shen Yun-Hui 

TITLE=Evaluating the Therapeutic Mechanisms of Selected Active Compounds in Houttuynia cordata Thunb. in Pulmonary Fibrosis via Network Pharmacology Analysis

JOURNAL=Frontiers in Pharmacology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.733618

DOI=10.3389/fphar.2021.733618

ISSN=1663-9812

ABSTRACT=<p>Pulmonary fibrosis, a common outcome of pulmonary interstitial disease of various different etiologies, is one of the most important causes of respiratory failure. <italic>Houttuynia cordata</italic> Thunb. (family: Saururaceae) (<italic>H. cordata</italic>), as has been reported, is a Chinese herbal medicine commonly used to treat upper respiratory tract infection and bronchitis. Our previous study has proven that sodium houttuyfonate (an additional compound from sodium bisulfite and houttuynin) had beneficial effects in the prevention of pulmonary fibrosis (PF) induced by bleomycin (BLM) in mice. In the present study, network pharmacology was used to investigate the efficiency and potential mechanisms of <italic>H. cordata</italic> in PF treatment. Upon manual collection from the literature and databases such as TCMSP and TCM-ID, 10 known representative ingredients of <italic>H. cordata</italic> species were screened. Then, the prediction of the potential active ingredients, action targets, and signaling pathways were conducted through the Gene Ontology (GO), protein–protein interaction (PPI),and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. The results of network pharmacology prediction suggested that <italic>H. cordata</italic> may act through multiple signaling pathways to alleviate PF, including the phosphatidylinositol 3-kinase-protein kinase B (PI3K/AKT) pathways, mitogen-activated protein kinase (MAPK) pathways, the tumor necrosis factor (TNF) pathways, and interleukin-17 (IL-17) signaling pathways<italic>.</italic> Molecular docking experiments showed that the chemical constituents of <italic>H. cordata</italic> had good affinity with TNF, MAPK1, and AKT1, and using lipopolysaccharide (LPS)-induced A549 cells, a model was established to verify the anti-pulmonary fibrosis effects and related mechanisms of <italic>H. cordata</italic>–relevant constituents. Finally, these evidences collectively suggest <italic>H. cordata</italic> may alleviate PF progression <italic>via</italic> PI3K/Akt, MAPK, and TNF signaling pathways and provide novel insights to verify the mechanism of <italic>H. cordata</italic> in the treatment of PF.</p>