Integrating Network Pharmacology and Experimental Verification to Explore the Pharmacological Mechanisms of Cordycepin against Pulmonary Arterial Hypertension in Rats

Jiangpeng Lin; Yuzhuo Zhang; Shuangfeng Lin; Haiming Ding; Weihua Liu

doi:10.2174/0113862073267432230925112002

Integrating Network Pharmacology and Experimental Verification to Explore the Pharmacological Mechanisms of Cordycepin against Pulmonary Arterial Hypertension in Rats

Comb Chem High Throughput Screen. 2024 Jan 30. doi: 10.2174/0113862073267432230925112002. Online ahead of print.

Authors

Jiangpeng Lin¹, Yuzhuo Zhang¹, Shuangfeng Lin², Haiming Ding³, Weihua Liu¹

Affiliations

¹ Department of Cardiology, Guangzhou Institute of Cardiovascular Disease, Guangdong Key Laboratory of Vascular Diseases, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China，510260.
² The first Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China, 510405.
³ Department of Laboratory Medicine, Panyu Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China.

PMID: 38299286
DOI: 10.2174/0113862073267432230925112002

Abstract

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.

Keywords: Cordycepin; PAH; experimental verification; molecular docking.; network pharmacology.