American Society of Hirudotherapy

Hirudin-Based Treatment of Diabetes-Induced Erectile Dysfunction Through Inhibition of the HIF-1α to Regulate RhoA/ROCK Signaling Pathway: An In Vivo Animal Experiment

In vivo animal experiment published in American Journal of Men's Health (2025)

Last Updated: June 18, 2026Reviewed by: ASH Editorial Board
Research article — evidence reviewArticle reference
Evidence: Preclinical (animal)Drug DevelopmentSalivary PharmacologySun L et al. · American journal of men's health, 2025

Abstract

Diabetes-induced erectile dysfunction (DIED) is a type of refractory erectile dysfunction which can be clinically treated using the traditional Chinese medicine leech whose main ingredient is hirudin. Oxidative stress can damage vascular endothelial cells, affect blood circulation, and induce fibrosis of smooth muscle cells. This study assessed the efficacy of hirudin in treating DIED before exploring its potential mechanism of action. DIED was induced in rats using streptozotocin, while experimental apomorphine was used to screen for erectile dysfunction models. The rats were then divided into four groups: a blank control group (NC group), a model group (M group), a hirudin group (H group), and an inhibitor group (YC group). After 2 weeks, the serum levels of malondialdehyde (MDA), superoxide dismutase (SOD), and nitric oxide (NO) were determined. The histological features and HIF-1α/RhoA/ROCK signaling pathway-related proteins of the penile corpus cavernosum were detected. Erectile function improved in the H and YC groups without significantly affecting body weight and blood glucose levels, with histopathological analysis also showing improvement in penile structure in these groups. In addition, the expression of HIF-1α/RhoA/ROCK signaling pathway-related proteins was lower in the penile cavernous tissue of rats in the H and YC groups (p < .05), with the serum levels of NO and SOD also being higher in these groups (p < .05). The serum level of MDA decreased in the YC and H groups (p < .05). In this study, only animal experiments were conducted to investigate the regulation of Rho/ROCK pathway by HIF-1α. Cellular studies of the underlying mechanisms are lacking.

Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.

Publication typeJournal ArticleResearch Support, Non-U.S. Gov't
Indexed MeSH termsAnimalsMaleErectile DysfunctionRatsSignal TransductionHypoxia-Inducible Factor 1, alpha Subunitrho-Associated KinasesDiabetes Mellitus, ExperimentalHirudinsRats, Sprague-DawleyDisease Models, AnimalPenisOxidative StressrhoA GTP-Binding Protein

Summary

In streptozotocin-diabetic rats, hirudin improved erectile function and penile histology without significantly affecting body weight or blood glucose, while lowering HIF-1α/RhoA/ROCK pathway proteins and increasing serum NO and SOD.

Why This Matters for Hirudotherapy

This study examined hirudin's efficacy and mechanism in diabetes-induced erectile dysfunction (DIED) using a streptozotocin-induced rat model, finding improved erectile function, reduced oxidative stress markers (lower MDA, higher SOD and NO), improved penile histology, and downregulation of the HIF-1α/RhoA/ROCK signaling pathway after two weeks of treatment. The rationale connects to traditional Chinese medicinal use of leeches whose main ingredient is hirudin. The study is preclinical (rats only), with no cellular studies of the underlying mechanism and no human data.

Citation

Reference (Vancouver style)

Sun L, Huang N, Yang C, Feng J, Chen H, Feng W, et al. Hirudin-Based Treatment of Diabetes-Induced Erectile Dysfunction Through Inhibition of the HIF-1α to Regulate RhoA/ROCK Signaling Pathway: An In Vivo Animal Experiment. Am J Mens Health. 2025;19(1):15579883241310763. doi:10.1177/15579883241310763. PMID: 39936394

Bibliographic details (authors, volume, pages, DOI) are taken from the PubMed record.

Added to ASH library: May 27, 2026 · Site last updated: June 18, 2026

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