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. 2015 Jun;4(1):132.
doi: 10.4172/2167-0250.1000132. Epub 2015 May 25.

Treatment With a Combination of Ginger, L-citrulline, Muira Puama and Paullinia Cupana Can Reverse the Progression of Corporal Smooth Muscle Loss, Fibrosis and Veno-Occlusive Dysfunction in the Aging Rat

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Free PMC article

Treatment With a Combination of Ginger, L-citrulline, Muira Puama and Paullinia Cupana Can Reverse the Progression of Corporal Smooth Muscle Loss, Fibrosis and Veno-Occlusive Dysfunction in the Aging Rat

Monica G Ferrini et al. Andrology (Los Angel). .
Free PMC article

Abstract

Aims: Aging associated erectile dysfunction is characterized within the corpora by a progressive apoptosis of the smooth muscle cells and their replacement by collagen. Nitric oxide from iNOS has been shown to inhibit these histological changes in the corpora while PDE5 inhibitors as well as certain nutraceuticals such as ginger, paullinia cupana, muira puama and L-citrulline are known to enhance the effects of NO. We evaluated whether the daily oral administration for 2 months with a combination of ginger, paullinia cupana, muira puama and L-citrulline (COMP-4) can effectively delay the ongoing corporal fibrosis, smooth muscle cell apoptosis and cavernosal veno-occlusive dysfunction (CVOD) seen in middle aged rats similar to that seen with tadalafil.

Methods: 10 Month old Fisher 344 rats were treated or not for two months with COMP-4, tadalafil or a combination of tadalafil plus COMP-4. CVOD was determined by dynamic infusion cavernosometry. Penile sections of the corpora cavernosa were subjected to Masson trichrome staining to evaluate fibrosis and immunohistochemistry for desmin as a marker of smooth muscle content and inducible nitric oxide synthase (iNOS) followed by image analysis. Oxidative stress levels were determined by GSH/GSSG ratio in whole blood.

Results: a decline in the non-treated rat's erectile function is evident by 10-12 months of age and is accompanied by a decrease in the corporal smooth muscle content determined by desmin expression and an increase in corporal fibrosis. The daily treatment for two months with COMP-4 reverses this process by reducing systemic oxidative stress and increasing desmin and iNOS expression, similar to that seen with tadalafil or the combination of COMP-4 plus tadalafil.

Conclusion: An oral combination of ginger, muira puama, Paullinia cupana and L-citrulline seems to be as effective as daily PDE5 inhibitor therapy in either delaying or reversing the onset of the histological and functional characteristics of aging related erectile dysfunction.

Keywords: Ginger; L-Citrulline corporal smooth muscle; Muira Puama; Paullinia cupana; corporal fibrosis; corporal veno-occlusive dysfunction.

Figures

Figure 1
Figure 1. Prevention of CVOD in middle aged Fischer 344 rat by oral treatment with tadalafil (TAD), COMP4 and combination of COMP4 + TAD, as determined by dynamic infusion cavernosometry
5MO: Five month-old animals at the time cavernosometry and euthanasia; 12 MO : Middle aged control, 12 month-old at the time of cavernosometry and euthanasia. COMP4: 10 mo old animals treated with composition 4 for two months and sacrificed at 12 months; -TAD: 10 month old animals treated with tadalafil for 2 months and sacrificed at 12 mo; COMP4+TAD: 10 mo old animals animals treated with a combination of composition 4 and tadalafil for 2 months and sacrificed at 12 months of age. **p<0.01; * p<0.05 respect to 12 MO. ### p<0.005 respect to 5-MO. (n=6)
Figure 2
Figure 2. Partial normalization by TAD and complete normalization by COMP4 and COMP4+TAD of the reduced smooth muscle/collagen ratio and increased collagen content in the middle aged rat corpora cavernosa
Top: representative pictures (40×, Bar=50 μm) of penile corpora cavernosa tissue sections from the rat groups presented on Figure 1, stained with Masson trichrome. Bottom: quantitative image analysis of the SMC/collagen ratio. *p<0.05, **p<0.01, ***p<0.005 respect to 12 MO. (n=6)
Figure 3
Figure 3. Effect of TAD, COMP4, and COMP4+TAD on the preservation of smooth muscle content in the middle aged rat corpora cavernosa
Top: representative pictures (200×, Bar=50 μm) of penile corpora cavernosa sections adjacent to those presented on Fig. 2, immunostained for desmin as a smooth muscle cell marker. Bottom: quantitative image analysis. *p<0.05, **p<0.01, respect to 12 MO (n=6)
Figure 4
Figure 4. iNOS expression in the middle aged rat corpora cavernosa is up regulated by COMP4 and by COMP 4 + TAD
Top: representative pictures (200×, Bar= 50μm) of penile corpora cavernosa sections adjacent to those presented in previous figures that were subjected to immunodetection for iNOS. Bottom right: quantitative image analysis * p<0.05. (n = 6).
Figure 5
Figure 5. COMP4 reduces oxidative stress in whole blood of middle aged rat
Oxidative stress was determined by measuring GSSG and GSH in whole blood after the addition or not of M2VP respectively. The GSH/GSSG ratio was calculated as (GSH-2*GSSG)/GSSG. *p<0.05 respect to 12 MO. (n=6)

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