Molecular Mechanisms of Danhong Injection in Treatment of Pulmonary Fibrosis Based on Network Pharmacology and Experimental Validation

Backgroud: Danhong injection has been proven to be reliable and practical in the clinical treatment of Pulmonary Fibrosis (PF), whereas the mechanism of action is unclear. The aim of this study was to investigate the mechanism of action of Danhong injection in the treatment of PF through network pharmacology and experimental validation. Methods: In this paper, multiple databases were utilized to capture the targets of Danhong injection and PF disease-related targets. The interaction network such as active ingredient-target was constructed and protein interaction analysis was performed via Cytoscape software. Bioprocess and signaling pathway analysis of the targets was carried out through DIVID database. Based on the analytical results, pharmacodynamic validation and mechanistic investigation were conducted in mice. Results: In this study, 111 compounds and common targets for diseases were filtered, with key targets involving MDM2, IL-2, CCL5, AKT1, MMP9, CASP3, MMP2, etc. The KEGG and GO enrichment analysis identified 16 significantly different signaling pathways, encompassing bioprocesses such as cell proliferation, apoptosis, programmed death and immune response. Animal experiments demonstrated that Danhong injection could reduce bleomycin-induced PF in mice, and could decrease the mRNA of AKT1 and the protein expression of p-Pi3k and p-Akt, thereby reducing apoptosis in mouse lung tissues. Conclusions: This study initially revealed that Danhong injection may inhibit apoptosis through the Pi3k/Akt signaling pathway and thus reduce PF in mice.