Eucommia ulmoides Oliv. Leaf Extract Improves Erectile Dysfunction in Streptozotocin-Induced Diabetic Rats by Protecting Endothelial Function and Ameliorating Hypothalamic-Pituitary-Gonadal Axis Function.

Hui Fu,Dong Tian,Hai Gao,Xue Bai,Ke-ping Hu,Liang Le,Li-xin Qi

doi:10.1155/2019/1782953

Abstract

Erectile dysfunction (ED) is a major complication of diabetes mellitus. Eucommia ulmoides Oliv. is used as a traditional medicine for male impotence, but no systematic study has examined its effect on diabetes-associated ED. In this study, we investigated the effects of Eucommia ulmoides Oliv. leaf extract (EULE) on restoring erectile function in streptozotocin (STZ)-induced diabetic rats model. After 16 weeks of treatment, EULE administration had significantly increased intracavernosal pressure, nitric oxide (NO) levels, and cyclic guanosine monophosphate (cGMP) concentrations. Serum superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels were markedly higher and serum malondialdehyde (MDA) levels were lower in the EULE-treated groups than in the diabetic model group. EULE restored NO biosynthesis by significantly increasing protein kinase B (Akt) and endothelial NO synthase (eNOS) activation. Furthermore, EULE is likely to benefit the hypothalamic-pituitary-gonadal (HPG) axis, as it increased gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone (T) concentrations as well as hormone receptors Gnrhr, Fshr, and Lhr expression levels. Hence, EULE attenuates oxidative stress, increases NO production, and activates the Akt-eNOS pathway to restore endothelial function; moreover, EULE enhances the HPG axis to improve erectile function. These results suggest that EULE may represent a new therapeutic avenue for diabetes-associated ED.

Highlights

Erectile dysfunction (ED) is defined as an inability to attain or maintain penile erection sufficient for satisfactory sexual intercourse[1]
The pathogenesis of diabetic ED is the result of multiple factors, such as advanced glycation end products (AGEs), deficiency in the nitric oxide-cyclic guanosine monophosphate (NO-cGMP) signaling pathway, oxidative stress, nervous lesions, and hypogonadism[4, 5]
We found that Eucommia ulmoides Oliv. leaf extract (EULE) treatment markedly increased the intracavernous pressure (ICP)/mean arterial pressure (MAP) ratio in diabetic rats, suggesting that EULE is able to improve erectile dysfunction in diabetic rats

Summary

Introduction

Erectile dysfunction (ED) is defined as an inability to attain or maintain penile erection sufficient for satisfactory sexual intercourse[1]. In various investigations on antioxidative stress, treatments to restore NO biosynthesis and bioactivity helped to restore endothelial and erectile function in animal models of diabetic ED[8, 13, 14]. Transforming the superoxide dismutase (SOD) gene into cavernous tissue or treatment with antioxidants reduces free radical superoxide anion (O2 −) production, diminishes superoxide anion levels, increases NO levels, and restores erectile response in animal models of diabetic ED[8, 15, 16]. Reducing oxidative stress and restoring eNOS and NO bioactivity may be a potential strategy to recover erectile function in diabetic individuals. Leaf extract (EULE) exhibits antidiabetic activity in several animal models, and prior reports of its beneficial effects against hypertension and diabetes make this plant an appealing candidate treatment for diabetes-related ED. We detected the effects of EULE on erectile dysfunction in STZ-induced diabetic rats

Materials and Methods

Discussion

Conclusions

Findings

Conflicts of Interest