Exploring the mechanism of action of catalpol on the rat model of diabetic erectile dysfunction via transcriptome sequencing

Erectile dysfunction (ED) is common in diabetes mellitus (DM) patients. Catalpol can improve diabetic conditions, but its regulatory mechanisms for DM-induced ED (DMED) are unknown. This study analyzed transcriptomic data to identify catalpol-related genes and mechanisms, aiming to support new therapeutic targets. Differential expression analysis was performed between the Control and DMED groups, and between the DMED and catalpol groups. Common differentially expressed genes 3 (DEGs3) were obtained via Venn diagram analysis. Key genes (KGs) were identified via Protein-Protein Interaction (PPI) network analysis. Their regulatory mechanisms on DMED were explored through chromosomal localization, expression profiling, WebGestalt enrichment, miRNA-KGs network construction, and molecular docking simulations. Finally, a rat model was established (divided into control, DMED, and catalpol groups), and the expressions of key genes were verified by Immunohistochemistry (IHC) and Reverse transcription quantitative polymerase chain reaction (RT-qPCR) analyses. Altogether, 786 DEGs1 and 3,084 DEGs2 were detected between Control as opposed to DMED and DMED as opposed to catalpol group, respectively. A total of 378 DEGs3 were identified. Among them,found that Kdr, Vcam1, Sox18, and Emcn were jointly identified as KGs. Chromosomal localization indicated that Vcam1 and Emcn were located on chromosome 2, Sox18 on 3, and Kdr on 14.Compared with the controls, the KGs were upregulated in DMED, but relative to the DMED group, they were downregulated in the catalpol group. Functional enrichment analysis indicated that Vcam1 was involved in pathways such as cell adhesion molecules. The miRNAs-KGs regulatory network showed that 20 miRNAs could regulate Kdr,5 could regulate Vcam1,2 could regulate Sox18,and 9 could regulate Emcn.Molecular docking revealed robust binding energies of -7.3, -5.9, -6.4, and -5.1 kcal/mol for Kdr, Vcam1, Sox18, and Emcn with catalpol, respectively. Finally, the expression levels of both genes and proteins for Kdr, Vcam1, and Emcn were markedly higher in the DMED group than in the control group (P < 0.05). These results indicate that catalpol could have therapeutic potential for DMED by regulating the expression of these key factors. Kdr, Vcam1, Sox18, and Emcn offered crucial clues for DMED pathogenesis and targeted therapy.