The herbal formula KH-204 is protective against erectile dysfunction by minimizing oxidative stress and improving lipid profiles in a rat model of erectile dysfunction induced by hypercholesterolaemia

Abstract

Background: Hypercholesterolaemia (HC) is a major risk factor for ischemic heart disease and is also known to be a risk factor for erectile dysfunction (ED). ED caused by HC is thought to be related to HC-induced oxidative stress damage in the vascular endothelium and erectile tissue. KH-204 is an herbal formula with a strong antioxidant effect. We evaluated the effects of KH-204 on erectile function in a rat model of HC-induced ED.

Methods: Male Sprague-Dawley rats (6 weeks old) were divided into normal control, high-fat and cholesterol diet (HFC), and HFC with KH-204 treatment (HFC + KH) groups (n = 12 each). Normal control group rats were fed normal chow diet. HFC and HFC + KH group rats were fed high-fat and cholesterol diets and treated with or without daily oral doses of KH-204 for 12 weeks. Subsequently, intracavernous pressure (ICP) and mean arterial pressure (MAP) were measured, and lipid profiles, expression of endothelial (eNOS) and neuronal (nNOS) nitric oxide synthase, oxidative stress (8-hydroxy-2-deoxyguanosine), and ratio of smooth muscle cells and collagen fibres were evaluated in the serum and corpora tissue.

Results: Compared to the HFC group, the HFC + KH group showed statistically significant increases in peak ICP and ICP/MAP ratio, expression of eNOS and nNOS, and ratio of smooth muscle cells and collagen fibres (p < 0.05). The HFC + KH group also showed statistically significant decreases in oxidative stress (p < 0.05). Further the lipid profiles of this group were ameliorated compared to those of the HFC group (p < 0.05).

Conclusions: The current study shows that the antioxidant and hypolipidemic effects of KH-204 are effective in ameliorating ED by restoring endothelial dysfunction and suggests that KH-204 may be a potential therapeutic agent for ED by correcting the fundamental cause of ED.

Keywords: Erectile dysfunction; Hypercholesterolaemia; Oxidative stress.

Fig. 1

HPLC chromatogram of each plant. a Loganin is the marker compound of Cornus officinalis Sieb. et Zucc. b Betain is the marker compound of Lycium chinense Miller. c Ellagic acid is the marker compound of Rubus coreanus Miquel. d Hyperoside is the marker compound of Cuscuta chinensis Lam. e Schizandrin is the marker compound of Schisandra chinensis Baillon

Fig. 2

Masson’s trichrome staining of corpora tissue. a, b, c Masson’s trichrome staining of corpora tissue: smooth muscle is shown in red (white arrow) and collagen is shown in green (Magnification: x200). d Ratio of smooth muscle and collagen fibres in corpora tissue. Data are expressed as mean ± standard deviation (SD). * = Significant difference between the control and high fat and cholesterol diet (HFC) groups. ** = Significant difference between the HFC and HFC + KH groups

Fig. 3

Phosphorylated-endothelial nitric oxide synthase (eNOS) protein expression in corpora tissue. a Western blot analysis of P-eNOS and eNOS in corporal tissue. b Densitometric analysis of P-eNOS relative to eNOS. Data are expressed as mean ± SD. * = Significant difference between the control and high fat and high cholesterol diet (HFC) groups. ** = Significant difference between the HFC and HFC + KH groups

Fig. 4

Immunostaining of neuronal nitric oxide synthase (nNOS) in the dorsal penile nerve. a, b, c Immunostaining for nNOS (red - white arrow) and β-III tubulin (green) in the dorsal penile nerve. Magnification: x400. d Mean intensity of nNOS expression for the dorsal penile nerve cross section. Data are expressed as mean ± SD. * Significant difference between the control and high fat and cholesterol diet (HFC) groups. ** Significant difference between the HFC and HFC + KH groups