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

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.

Exploring the Anti-Pulmonary Fibrosis Mechanism of Jingyin Granule by Network Pharmacology Strategy

“…Our previous network pharmacology study of H. cordata Thunb. identified that it may act through multiple signaling pathways to alleviate PF (Zhu et al, 2021). Our in vivo experimental study also clarified that sodium houttuyfonate, an adduct compound of houttuynin and sodium bisulfite, may alleviate the degree of fibrosis in bleomycin-induced PF model mice through the transforming growth factor-β (TGF-β)/Smads pathway (Shen et al, 2021).…”

Therapeutic Effect of Astragali Radix Extract Injection Combined with Bone Marrow Mesenchymal Stem Cells in Bleomycin-Induced Pulmonary Fibrotic Rats

“…Pharmacological networks have predicted that Qimai feiluoping decoction exerts anti-PF effects via regulation of the epithelial-mesenchymal transition, extracellular matrix degradation, and TGF- β signaling pathway, and this has been verified in vitro [ 31 ]. Pharmacological networks have also found that Chinese herbs such as Curcuma Radix [ 32 ], Houttuynia cordata [ 33 ], Schisandra [ 34 ], and Astragalus can regulate PF via the TGF- β , PI3K/Akt, MAPK, and STAT3 signaling pathways. Astragalus is the most popular Chinese herb for supplementing Qi and is the main ingredient of the representative Buyang Huanwu decoction that also activates blood circulation.…”

The therapeutic potential of Houttuynia cordata: A current review

“…(2014) Anti-viral Pang et al. (2017) Anti-pulmonary fibrosis Zhu et al. (2021) Anti-fungal ( Candida albicans ) Shao et al.…”