Network pharmacology approach and experimental verification of earthworm protein in the treatment of diabetes mellitus-induced erectile dysfunction

Abstract

Background

Diabetes mellitus-induced erectile dysfunction (DMED) is a common complication of diabetes mellitus. Earthworm protein (EWP) is an active protein extracted from the Chinese herbal medicine earthworm, which is used in clinical practice for treating DMED.

Objective

To investigate the mechanism of action of EWP in improving DMED in rats using network pharmacology and in vivo experimental validation.

Materials and methods

Network pharmacology predicts key targets. After identifying the DMED targets of EWP, a protein-protein interaction network was constructed using the STRING platform. The target genes were then enriched using Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes. A “drug-component-disease-target-pathway” network map with Cytoscape 3.9.1 software was constructed. The nuclear factor-kappa B (NF-κB) signaling pathway was selected for further in vivo experimental validation in rats.

Results

EWP was mainly involved in the inflammatory response and NF-κB signaling pathway to regulate DMED. In vivo experiments showed that EWP was able to reduce Interleukin-1β, Interleukin-6 and Tumour Necrosis Factor-α levels, significantly inhibit NF-κB, nuclear factor-κB inhibitor protein α and mRNA expression, increase serum testosterone (T), and improve the erectile function of DMED rats.

Conclusion

EWP improves erectile function in DMED rats. This mechanism may be related to the inhibition of the NF-κB signaling pathway, reduction of the inflammatory response in testicular tissue, promotion of testicular and penile tissue repair, and increase in serum T levels.