Abstract
Pulmonary fibrosis, a common outcome of pulmonary interstitial disease of various different etiologies, is one of the most important causes of respiratory failure. Houttuynia cordata Thunb. (family: Saururaceae) (H. cordata), 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 H. cordata in PF treatment. Upon manual collection from the literature and databases such as TCMSP and TCM-ID, 10 known representative ingredients of H. cordata 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 H. cordata 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. Molecular docking experiments showed that the chemical constituents of H. cordata 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 H. cordata–relevant constituents. Finally, these evidences collectively suggest H. cordata may alleviate PF progression via PI3K/Akt, MAPK, and TNF signaling pathways and provide novel insights to verify the mechanism of H. cordata in the treatment of PF.
Highlights
Pulmonary fibrosis (PF) is a chronic, progressive, and devastating interstitial lung disease mainly resulting from toxic insults, autoimmune injuries, drug-induced injuries, infectious injuries, or traumatic injuries
This study aims to utilize network pharmacology and molecular docking to seek the active compounds of H. cordata, construct the drug–compounds–genes–disease network, and to analyze the underlying mechanism of H. cordata in the treatment of pulmonary fibrosis (PF)
This study reveals the mechanism of the anti-pulmonary fibrosis pharmacological action of H. cordata by a TCM network pharmacology–based strategy and provides ideas for H. cordata for further drug development
Summary
Pulmonary fibrosis (PF) is a chronic, progressive, and devastating interstitial lung disease mainly resulting from toxic insults, autoimmune injuries, drug-induced injuries, infectious injuries, or traumatic injuries. As can be affected by age, genetic predisposing factors, and environmental exposures, PF produces many different pathological types, which are mainly classified as idiopathic pulmonary fibrosis (IPF) and fibrosing alveolitis. Alveolar epithelial cell (AEC) injury and excessive deposition of collagen in extracellular matrix (ECM) result in progressive scarring and loss of lung function (Wynn and Vannella, 2016). With approximately 3 million people being affected worldwide, as shown in the related literature, IPF has an increasing burden (George et al, 2020). There is no effective means or drugs that can ameliorate PF except lung transplantation in patients with a median survival of 3–5 years from the time of diagnosis (Meyer, 2017)
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