Total Flavonoids of Epimedium improve pulmonary vascular remodeling in pulmonary hypertension: network pharmacological analysis and experimental verification

Aims Total flavonoids of Epimedium (TFE), primarily composed of icariin, serve as Type 5 phosphodiesterase (PDE5) inhibitors. The multi-target mechanism of TFE on pulmonary hypertension (PH) is unclear. This study aims to explore the pharmacological outcomes of TFE in treating PH. Main methods: The structural information of the main components of TFE and their targets were obtained from the TCMSP, PubChem and SwissTargetPrediction databases. PH-related targets were obtained from the Gene Cards database. Cytoscape 3.8.2 was used to construct the target network, followed by PPI network analysis. KEGG and GO enrichment analyses were conducted using the R language. A PH rat model was established using monocrotaline (MCT). The effects of TFE on PH were studied in PH rats. Molecular docking was used to evaluate the docking effects of effective monomer drugs and molecules. Key findings: A total of 13 monomer components and 140 TFE and PH-related targets are identified. Core genes in the PPI network included p53, TNF, AKT1, EGFR, and RelA. In vitro experiments show that TFE reversed PDGF-BB-induced proliferation, migration and apoptosis of rat pulmonary artery smooth muscle cells (PASMCs). TFE attenuated the progression of MCT-induced PH in rats. The protective effects of TFE were mediated by promoting the expression of p53-p21. Molecular docking revealed a strong affinity between the bioactive compounds in TFE and its PH target p53.