Key result
Cordycepin significantly reduced right ventricular systolic pressure and inhibited pulmonary vascular remodeling in MCT-induced PAH rats by targeting TP53, AKT1, CASP3, BAX, and BCL2L1.
Why the study?
Pulmonary arterial hypertension is a fatal disease with high morbidity and mortality, but the therapeutic role and mechanism of cordycepin in PAH remain unclear.
Does Cordycepin improve pulmonary vascular remodeling and hemodynamics in preclinical models of pulmonary arterial hypertension?
Does Cordycepin improve pulmonary vascular remodeling and hemodynamics in preclinical models of pulmonary arterial hypertension?
Cordycepin ameliorates pulmonary arterial hypertension in preclinical models by modulating TP53, AKT1, CASP3, BAX, and BCL2L1 pathways to inhibit PASMC proliferation and migration.
Supports further preclinical PAH research; leaves open any clinical translation or therapeutic role.
BACKGROUND: Pulmonary Arterial Hypertension (PAH) is a fatal disease with high morbidity and mortality. Cordycepin has anti-inflammatory, antioxidant and immune enhancing effects. However, the role of Cordycepin in the treatment of PAH and its mechanism is not clear. METHODS: The Cordycepin structure and PAH-related gene targets were obtained from public databases. The KEGG and GO enrichment analysis of common targets was performed in DAVID. PPI networks were also mapped using the STRING platform. AutoDock Vina, AutoDockTools, ChemBio3D and Pymol tools were selected for molecular docking of key targets. The therapeutic effects of Cordycepin on PAH were observed in Monocrotaline (MCT)-induced PAH rats and platelet-derived growth factor BB (PDGFBB)-induced rat pulmonary artery smooth muscle cells (PASMCs). The right ventricular systolic pressure (RVSP) was detected. HE staining, Western Blot, Scratch assay, EDU and TUNEL assays were used, respectively. RESULTS: Through Network Pharmacology and molecular docking, the Cordycepin-PAH core genes were found to be TP53, AKT1, CASP3, BAX and BCL2L1. In MCT-induced PAH rats, the administration of Cordycepin significantly reduced RVSP, and inhibited pulmonary vascular remodeling. In PDGFBB-induced PASMCs, Cordycepin reduced the migration and proliferation of PASMCs and promoted apoptosis. After the Cordycepin treatment, the protein expressions of TP53, Cleaved CASP3 and BAX were significantly increased, while the protein expressions of p-AKT1 and BCL2L1 were significantly decreased in MCT-PAH rats and PDGFBB-induced PASMCs. CONCLUSION: This study identified that TP53, AKT1, CASP3, BAX, and BCL2L1 were the potential targets of Cordycepin against PAH by ameliorating pulmonary vascular remodeling, inhibiting the abnormal proliferation and migration of PASMCs and increasing apoptosis of PASMCs. which provided a new understanding of the pharmacological mechanisms of Cordycepin in the treatment of PAH.
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Lin et al. (2024) studied Pulmonary Arterial Hypertension. Cordycepin was evaluated on Right ventricular systolic pressure (RVSP) and pulmonary vascular remodeling. Cordycepin significantly reduced right ventricular systolic pressure and inhibited pulmonary vascular remodeling in MCT-induced PAH rats by targeting TP53, AKT1, CASP3, BAX, and BCL2L1.
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