Investig Clin Urol.  2019 Jul;60(4):285-294. 10.4111/icu.2019.60.4.285.

Synergistic effects of extracorporeal shockwave therapy and modified Ojayeonjonghwan on erectile dysfunction in an animal model of diabetes

• Jeong HC
• Bae WJ
• Zhu GQ
• Jeon SH
• Choi SW
• Kim SJ
• Cho HJ
• Hong SH
• Lee JY
• Hwang SY
• Kim SW

• KMID: 2450546
• DOI: http://doi.org/10.4111/icu.2019.60.4.285

Abstract

PURPOSE
We investigated the synergy effect of extracorporeal shock wave therapy (ESWT) with modified Ojayeonjonghwan (Korean herbal formula, KH-204) in an animal model of diabetes mellitus (DM)-induced erectile dysfunction (ED).
MATERIALS AND METHODS
Eight-week-old male Sprague-Dawley rats were used in this study. DM was induced by an intraperitoneal injection of streptozotocin. DM rats were divided into 5 groups (n=10 per group): group 1, control; group 2, DM; group 3, DM+ESWT; group 4, DM+KH-204; and group 5, DM+ESWT+KH-204. In ESWT groups, rats were treated with ESWT at the penis 3 times a week for 2 weeks under anesthesia. The KH-204 groups were treated with a daily oral dose of KH-204 for 12 weeks. After all treatments, intracavernosal pressure (ICP) was measured, and the cavernous tissues were evaluated by Masson's trichrome, immunohistochemistry and western blot analysis.
RESULTS
ICP was evaluated as a measurement of erectile function. The DM+ESWT, DM+KH-204, and DM+ESWT+KH-204 groups showed significantly restored erectile function compared with the DM group (p<0.05). Among these groups, the DM+ESWT+KH-204 group showed the highest ICP. Moreover, ESWT and KH-204 treatment restored smooth muscle contents and many parameters related to potency (vascular endothelial growth factor, neuronal nitric oxide synthase (NOS), endothelial [NOS] and platelet endothelial cell adhesion molecule-1) compared with the DM group (p<0.05).
CONCLUSIONS
We confirmed the potential efficacy of ESWT and KH-204 in the treatment of ED patients using an animal model. The combination treatment of KH-204 and ESWT is expected to have good potential clinical results in the future treatment of refractory ED.

Keyword

Animals; Erectile dysfunction; Extracorporeal shockwave therapy; Herbal medicine

MeSH Terms

Anesthesia
Animals*
Blood Platelets
Blotting, Western
Diabetes Mellitus
Endothelial Cells
Endothelial Growth Factors
Erectile Dysfunction*
Herbal Medicine
Humans
Immunohistochemistry
Injections, Intraperitoneal
Male
Models, Animal*
Muscle, Smooth
Nitric Oxide Synthase Type I
Penis
Rats
Rats, Sprague-Dawley
Shock
Streptozocin
Endothelial Growth Factors
Nitric Oxide Synthase Type I
Streptozocin

Figure

• 

  Fig. 1 Intracavernosal pressure (ICP), ICP/mean arterial pressure (MAP) of each groups. (A) Representative ICP recordings in response to cavernous nerve stimulation. (B) ICP/MAP ratios after nerve stimulation of the different groups. DM, diabetes mellitus; ESWT, extracorporeal shock wave therapy; KH, Korean herbal formula. ICP: red line, MAP: blue line. Data are expressed as means±standard deviations. *Statistical significance in comparison with the DM+ESWT+KH-204 group. **Statistical significance in comparison with the DM group.

• 

  Fig. 2 Results of smooth muscle content evaluation by Masson's trichrome staining. Mean of the smooth muscle and collagen fiber ratios of the different groups (graph) (×40; inset, ×100). DM, diabetes mellitus; ESWT, extracorporeal shock wave therapy; KH, Korean herbal formula. Data are expressed as means±standard deviations. *Statistical significance in comparison with the DM+ESWT+KH-204 group. **Statistical significance in comparison with the DM group.

• 

  Fig. 3 Results of smooth muscle content evaluation by α-smooth muscle actin (α-SMA). Mean of the smooth muscle and collagen fiber ratios of the different groups (graph). DM, diabetes mellitus; ESWT, extracorporeal shock wave therapy; KH, Korean herbal formula. Data are expressed as means±standard deviations. *Statistical significance in comparison with the DM+ESWT+KH-204 group. **Statistical significance in comparison with the DM group.

• 

  Fig. 4 (A) Immunohistochemical (IHC) staining of vascular endothelial growth factor (VEGF) expression in the corpus cavernosum of each group. Mean intensities of VEGF expression in the different groups are represented in the graphs. (B) IHC staining of neuronal nitric oxide synthase (nNOS) expression in the dorsal penile nerve of each group. Mean intensities of nNOS expression levels of the different groups are represented in the graphs. DM, diabetes mellitus; ESWT, extracorporeal shock wave therapy; KH, Korean herbal formula. Data are expressed as means±standard deviations. *Statistical significance in comparison with the DM+ESWT+KH-204 group. **Statistical significance in comparison with the DM group.

• 

  Fig. 5 (A) Comparison of the relative platelet endothelial cell adhesion molecule-1 (PECAM-1)/β-actin band densities of the different groups by Western blot. (B) Phosphorylated endothelial nitric oxide synthase (P-eNOS) expression in the corporal tissue of each group assessed by Western blotting. The relative band densities of P-eNOS/eNOS (graph). DM, diabetes mellitus; ESWT, extracorporeal shock wave therapy; KH, Korean herbal formula. Data are expressed as means±standard deviations. *Statistical significance in comparison with the DM+ESWT+KH-204 group. **Statistical significance in comparison with the DM group.

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