Erectile dysfunction (ED) is associated with diabetes mellitus (DM). Pomegranate juice (PJ) is a potent antioxidant in diabetes induced oxidative stress. The aim of this study was to evaluate whether the administration of PJ ameliorates ED in streptozotocin (STZ)-diabetic rat model. Adult male Sprague-Dawley rats were divided into three groups (n=10–12, each): (1) Control, (2) STZ (25–35 mg kg−1, intravenously, 10 weeks) induced DM, and (3) PJ (100 mg kg−1 day−1, 10 weeks) treated DM rats. The in vivo erectile [a ratio of intracavernosal pressure (ICP)/mean arterial pressure (MAP)] and ex vivo corpus cavernosum (CC) responses were evaluated. Immunohistochemistry and Masson’s trichrome staining were performed. Malondialdehyde (MDA) levels were measured. The ICP/MAP value in diabetic rats was lower than controls, which was partially improved by PJ treatment. Electrical field stimulation (EFS)-induced relaxant responses in CC from the diabetic group were significantly decreased that were ameliorated by treatment. Phenylephrine- and EFS-induced contractions were not altered in diabetic rats. PJ treatment normalized raised MDA levels of diabetic CC samples. Although the intensities of endothelial nitric oxide synthase (NOS) and neuronal NOS enzymes were decreased, inducible NOS protein levels were stronger in diabetic slides than controls. This is the first study to show that PJ treatment ameliorates partially ED and completely oxidative stress and fibrosis in a diabetic rat model. Our results highlight the success of antioxidant mechanism of PJ in ED with diabetes and open the way for future understanding in alternative treatment combinations with PDE5 inhibitors.
Subscribe to Journal
Get full journal access for 1 year
only $55.50 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Jacobson AM, Braffett BH, Cleary PA, Dunn RL, Larkin ME, Wessells H et al. Relationship of urologic complications with health-related quality of life and perceived value of health in men and women with type 1 diabetes: the Diabetes Control and Complications Trial/Epidemiology of Interventions and Complications (DCCT/EDIC) cohort. Diabetes Care 2015; 38: 1904–1912.
Corona G, Mannucci E, Forti G, Maggi M . Following the common association between testosterone deficiency and diabetes mellitus, can testosterone be regarded as a new therapy for diabetes? Int J Androl 2009; 32: 431–441.
Shamloul R, Ghanem H . Erectile dysfunction. Lancet 2013; 381: 153–165.
Moore CR, Wang R . Pathophysiology and treatment of diabetic erectile dysfunction. Asian J Androl 2006; 8: 675–684.
Fonseca V, Seftel A, Denne J, Fredlund P . Impact of diabetes mellitus on the severity of erectile dysfunction and response to treatment: analysis of data from tadalafil clinical trials. Diabetologia 2004; 47: 1914–1923.
Sezen SF, Lagoda G, Musicki B, Burnett AL . Hydroxyl fasudil, an inhibitor of Rho signaling, improves erectile function in diabetic rats: a role for neuronal ROCK. J Sex Med 2014; 11: 2164–2171.
McMahon CN, Smith CJ, Shabsigh R . Treating erectile dysfunction when PDE5 inhibitors fail. BMJ 2006; 332: 589–592.
Martin-Morales A, Meijide F, Garcia N, Artes M, Munoz A . Efficacy of vardenafil and influence on self-esteem and self-confidence in patients with severe erectile dysfunction. J Sex Med 2007; 4: 440–447.
Huang TH, Peng G, Kota BP, Li GQ, Yamahara J, Roufogalis BD et al. Pomegranate flower improves cardiac lipid metabolism in a diabetic rat model: role of lowering circulating lipids. Br J Pharmacol 2005; 145: 767–774.
Lansky EP . Beware of pomegranates bearing 40% ellagic acid. J Med Food 2006; 9: 119–122.
Shirode AB, Bharali DJ, Nallanthighal S, Coon JK, Mousa SA, Reliene R . Nanoencapsulation of pomegranate bioactive compounds for breast cancer chemoprevention. Int J Nanomedicine 2015; 10: 475–484.
Dorsey PG, Greenspan P . Inhibition of nonenzymatic protein glycation by pomegranate and other fruit juices. J Med Food 2014; 17: 447–454.
Wang JY, Zhu C, Qian TW, Guo H, Wang DD, Zhang F et al. Extracts of black bean peel and pomegranate peel ameliorate oxidative stress-induced hyperglycemia in mice. Exp Ther Med 2015; 9: 43–48.
Azadzoi KM, Schulman RN, Aviram M, Siroky MB . Oxidative stress in arteriogenic erectile dysfunction: prophylactic role of antioxidants. J Urol 2005; 174: 386–393.
Zhang Q, Radisavljevic ZM, Siroky MB, Azadzoi KM . Dietary antioxidants improve arteriogenic erectile dysfunction. Int J Androl 2011; 34: 225–235.
Oztekin CV, Gur S, Abdulkadir NA, Kartal M, Karabakan M, Akdemir AO et al. Analysis of pomegranate juice components in rat corpora cavernosal relaxation. Int J Impot Res 2014; 26: 45–50.
Gur S, Sikka SC, Chandra S, Koka PS, Agrawal KC, Kadowitz PJ et al. Alfuzosin attenuates erectile dysfunction in rats with partial bladder outlet obstruction. BJU Int 2008; 102: 1651–1657.
Tomada I, Tomada N, Almeida H, Neves D . Androgen depletion in humans leads to cavernous tissue reorganization and upregulation of Sirt1-eNOS axis. Age 2013; 35: 35–47.
Pinsky MR, Gur S, Tracey AJ, Harbin A, Hellstrom WJ . The effects of chronic 5-alpha-reductase inhibitor (dutasteride) treatment on rat erectile function. J Sex Med 2011; 8: 3066–3074.
Un O, Yilmaz D, Bayatli N, Kaya E, Gur S . L-arginine and tetrahydrobiopterin, but not sodium nitrite partially restored erectile dysfunction in aged rats. Aging Male 2014; 17: 248–255.
Satoh K . Serum lipid peroxide in cerebrovascular disorders determined by a new colorimetric method. Clin Chim Acta 1978; 90: 37–43.
Kataoka T, Hotta Y, Maeda Y, Kimura K . Assessment of androgen replacement therapy for erectile function in rats with type 2 diabetes mellitus by examining nitric oxide-related and inflammatory factors. J Sex Med 2014; 11: 920–929.
Wu H, Sui C, Xia F, Zhai H, Zhang H, Xu H et al. Effects of exenatide therapy on insulin resistance in the skeletal muscles of high-fat diet and low-dose streptozotocin-induced diabetic rats. Endocr Res 2015; 41: 1–7.
Jafri MA, Aslam M, Javed K, Singh S . Effect of Punica granatum Linn. (flowers) on blood glucose level in normal and alloxan-induced diabetic rats. J Ethnopharmacol 2000; 70: 309–314.
Parsaeyan N, Mozaffari-Khosravi H, Mozayan MR . Effect of pomegranate juice on paraoxonase enzyme activity in patients with type 2 diabetes. J Diabetes Metab Disord 2012; 11: 11.
Banihani SA, Makahleh SM, El-Akawi Z, Al-Fashtaki RA, Khabour OF, Gharibeh MY et al. Fresh pomegranate juice ameliorates insulin resistance, enhances beta-cell function, and decreases fasting serum glucose in type 2 diabetic patients. Nutr Res 2014; 34: 862–867.
Nekooeian AA, Eftekhari MH, Adibi S, Rajaeifard A . Effects of pomegranate seed oil on insulin release in rats with type 2 diabetes. Iran J Med Sci 2014; 39: 130–135.
Liu T, Peng YF, Jia C, Yang BH, Tao X, Li J et al. Ginsenoside Rg3 improves erectile function in streptozotocin-induced diabetic rats. J Sex Med 2015; 12: 611–620.
Nunes KP, Teixeira CE, Priviero FB, Toque HA, Webb RC . Beneficial effect of the soluble guanylyl cyclase stimulator BAY 41-2272 on impaired penile erection in db/db-/- type II diabetic and obese mice. J Pharmacol Exp Ther 2015; 353: 330–339.
Kim SJ, Bae WJ, Han JH, Hong SH, Kim SW, Hwang TK et al. The influence of ethanol intake on RhoA/Rho kinase signaling pathway in corpus cavernosum of OLETF rats. Int Urol Nephrol 2013; 45: 429–438.
de Nigris F, Balestrieri ML, Williams-Ignarro S, D'Armiento FP, Fiorito C, Ignarro LJ et al. The influence of pomegranate fruit extract in comparison to regular pomegranate juice and seed oil on nitric oxide and arterial function in obese Zucker rats. Nitric Oxide 2007; 17: 50–54.
Yilmaz D, Bayatli N, Un O, Kadowitz PJ, Sikka SC, Gur S . The effect of intracavernosal avanafil, a newer phosphodiesterase-5 inhibitor, on neonatal type 2 diabetic rats with erectile dysfunction. Urology 2014; 83: 508 e507–508 e512.
Vilahur G, Padro T, Casani L, Mendieta G, Lopez JA, Streitenberger S et al. Polyphenol-enriched diet prevents coronary endothelial dysfunction by activating the Akt/eNOS pathway. Rev Esp Cardiol (Engl Ed) 2015; 68: 216–225.
Claudino MA, Delbin MA, Franco-Penteado CF, Priviero FB, De Nucci G, Antunes E et al. Exercise training ameliorates the impairment of endothelial and nitrergic corpus cavernosum responses in diabetic rats. Life Sci 2011; 88: 272–277.
Nangle MR, Cotter MA, Cameron NE . The calpain inhibitor, A-705253, corrects penile nitrergic nerve dysfunction in diabetic mice. Eur J Pharmacol 2006; 538: 148–153.
Gurbuz N, Sagdic G, Sanli A, Ciftcioglu A, Bassorgun I, Baykal A et al. Therapeutic effect of combination of alagebrium (ALT-711) and sildenafil on erectile function in diabetic rats. Int J Impot Res 2012; 24: 114–121.
Yang J, Wang T, Yang J, Rao K, Zhan Y, Chen RB et al. S-allyl cysteine restores erectile function through inhibition of reactive oxygen species generation in diabetic rats. Andrology 2013; 1: 487–494.
Basu A, Newman ED, Bryant AL, Lyons TJ, Betts NM . Pomegranate polyphenols lower lipid peroxidation in adults with type 2 diabetes but have no effects in healthy volunteers: a pilot study. J Nutr Metab 2013; 2013: 708381.
Sohrab G, Angoorani P, Tohidi M, Tabibi H, Kimiagar M, Nasrollahzadeh J . Pomegranate (Punica granatum juice decreases lipid peroxidation, but has no effect on plasma advanced glycated end-products in adults with type 2 diabetes: a randomized double-blind clinical trial. Food Nutr Res 2015; 59: 28551.
Zhou F, Li GY, Gao ZZ, Liu J, Liu T, Li WR et al. The TGF-beta1/Smad/CTGF pathway and corpus cavernosum fibrous-muscular alterations in rats with streptozotocin-induced diabetes. J Androl 2012; 33: 651–659.
Abidu-Figueiredo M, Ribeiro IC, Chagas MA, Cardoso LE, Costa WS, Sampaio FJ . The penis in diabetes: structural analysis of connective tissue and smooth muscle alterations in a rabbit model. BJU Int 2011; 108: 400–404.
Huang TH, Yang Q, Harada M, Li GQ, Yamahara J, Roufogalis BD et al. Pomegranate flower extract diminishes cardiac fibrosis in Zucker diabetic fatty rats: modulation of cardiac endothelin-1 and nuclear factor-kappaB pathways. J Cardiovasc Pharmacol 2005; 46: 856–862.
The authors declare no conflict of interest.
About this article
Cite this article
Onal, E., Yilmaz, D., Kaya, E. et al. Pomegranate juice causes a partial improvement through lowering oxidative stress for erectile dysfunction in streptozotocin-diabetic rat. Int J Impot Res 28, 234–240 (2016). https://doi.org/10.1038/ijir.2016.34
Umbelliferone isolated from Zosima absinthifolia roots partially restored erectile dysfunction in streptozotocin-induced diabetic rats
Medicinal Chemistry Research (2019)
Evaluation of relaxant responses properties of cinnamon essential oil and its major component, cinnamaldehyde on human and rat corpus cavernosum
International braz j urol (2019)
MyD88 overexpression deteriorates Ang‐II‐induced ED via upregulating MPO and COX2 and downregulating eNOS in the corpus cavernosum of rats
Journal of Cellular Biochemistry (2019)
The Beneficial Effect of Fesoterodine, a Competitive Muscarinic Receptor Antagonist on Erectile Dysfunction in Streptozotocin-induced Diabetic Rats