Abstract
OBJECTIVES: To explore the therapeutic mechanism of Arctium lappa extract for treatment of Post-Viral Pneumonia Pulmonary Fibrosis (PPF). METHODS: The chemical constituents of Arctium lappa extracts were identified using UHPLC-Q-TOF-MS/MS. Mouse models of pulmonary fibrosis established by tracheal instillation of bleomycin were treated with Arctium lappa extract, and body weight changes were recorded and lung tissue pathology was examined using HE and Masson staining. Metabolomics analysis was used to identify the differential metabolites and the associated metabolic pathways in the treated mice. The common targets of viral pneumonia and pulmonary fibrosis were acquired from the publicly available databases, and the core targets and active constituents were screened using the protein-protein interaction (PPI) network, GO and KEGG enrichment analyses, and molecular docking, and a "gene-metabolite" regulatory network was constructed. The expressions of the core targets were detected in the lung tissues of the treated mice using Western blotting. RESULTS: Fifty-three chemical constituents were identified from Arctium lappa extract. In the mouse models of pulmonary fibrosis, treatment with Arctium lappa extract significantly improved weight loss and ameliorated lung inflammation and fibrosis. The differential metabolites in the treated mice were enriched in energy metabolism pathways involving citrate cycle, pentose phosphate pathway, glycolysis, tryptophan metabolism, glutamate metabolism and glutathione metabolism, which regulated the production of energy metabolism intermediates. Twenty-three key active compounds (mostly lignans and phenolic acids) and 82 core targets were screened, which were associated with the non-canonical Smad signaling pathways (including PI3K/AKT, HIF-1, MAPK, and Foxo) that participated in the regulation of energy metabolism. Arctium lappa extract also regulated the expressions of epithelial-mesenchymal transition (EMT)‑related proteins (fibronectin, vimentim, and Snail, etc.) and inhibited MAPK signaling pathway activation. CONCLUSIONS: Preliminary findings suggest that Arctium lappa treats fibrosis by regulating metabolism to inhibit EMT and involves the modulation of non-canonical Smad signaling pathways, such as MAPK providing theoretical support for its clinical application and further research in treating PPF.