Abstract
Benign prostatic hyperplasia (BPH) is one of the most prevalent conditions among aged men. The use of 5α-reductase inhibitors (5-ARIs) to treat BPH was linked to erectile dysfunction (ED). Many medicinal plants and secondary metabolites are used in the management of ED. Onion (Allium cepa L.) is an economically affordable vegetable with vital phytochemicals and biological functions. The study aimed to identify the beneficial effects of onion juice on dutasteride (a 5-ARI)-induced ED. Rats were divided into two groups (n = 5 per group): control and dutasteride-treated rats (0.5 mg/kg/day). Dutasteride was administered in drinking water for 12 weeks. Experiments were performed at the end of the 12th week. In vivo erectile responses were measured before and after intracavernosal injection of onion. Relaxant responses to onion juice were examined in the corpus cavernosum (CC). Acetylcholine (ACh)-, electrical field stimulation (EFS)-, sodium nitroprusside (SNP)-induced relaxation responses in CC tissues were evaluated in the absence and presence of onion juice. Total intracavernosal pressure (ICP) and ICP/ mean arterial pressure were significantly reduced in dutasteride-treated rats (1881.14 ± 249.72 mmHg, P < 0.001;0.26 ± 0.03, P < 0.01) as compared to control rats (4542.60 ± 429.19 mmHg, 0.51 ± 0.05), which was normalized after the intracavernous administration of onion (3288.60 ± 185.45 mmHg, 0.58 ± 0.04). Onion markedly induced relaxant responses in control (72.5 ± 4.7) and dutasteride-treated (66.5 ± 2.7) groups after precontraction with phenylephrine. Relaxation responses to onion were partially inhibited after precontraction with KCl (32.5 ± 3.1, P < 0.001). The relaxant responses to ACh (14.9 ± 4.2, P < 0.01) were diminished in dutasteride-treated CC) compared to control CC (59.8 ± 3.4), which was enhanced after the incubation with onion (36.6 ± 4.8). There were no differences in relaxation response to SNP among all groups. However, relaxation response to SNP was reduced in dutasteride-treated CC at 1 μM (P < 0.05) and 10 μM dosages (P < 0.001), which was partially increased after the incubation with onion at 10 μM dosage (P < 0.01). The presence of onion did not change the reduction in EFS-caused relaxation in the dutasteride-treated group. The current data suggest that red onion juice has a restorative effect on erectile function and endothelium-dependent relaxation response following the treatment of dutasteride.
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References
Harbitz TB, Haugen OA. Histology of the prostate in elderly men. A study in an autopsy series. Acta Pathol Microbiol Scand A. 1972;80:756–68.
McVary KT. Clinical evaluation of benign prostatic hyperplasia. Rev Urol. 2003;5 Suppl 4:S3–11.
Alcaraz A, Carballido-Rodriguez J, Unda-Urzaiz M, Medina-Lopez R, Ruiz-Cerda JL, Rodriguez-Rubio F, et al. Quality of life in patients with lower urinary tract symptoms associated with BPH: change over time in real-life practice according to treatment-the QUALIPROST study. Int Urol Nephrol. 2016;48:645–56.
Oelke M, Bachmann A, Descazeaud A, Emberton M, Gravas S, Michel MC, et al. EAU guidelines on the treatment and follow-up of non-neurogenic male lower urinary tract symptoms including benign prostatic obstruction. Eur Urol. 2013;64:118–40.
McVary KT, Roehrborn CG, Avins AL, Barry MJ, Bruskewitz RC, Donnell RF, et al. Update on AUA guideline on the management of benign prostatic hyperplasia. J Urol. 2011;185:1793–803.
Clark RV, Hermann DJ, Cunningham GR, Wilson TH, Morrill BB, Hobbs S. Marked suppression of dihydrotestosterone in men with benign prostatic hyperplasia by dutasteride, a dual 5alpha-reductase inhibitor. J Clin Endocrinol Metab. 2004;89:2179–84.
Shigehara K, Miyagi T, Nakashima T, Izumi K, Kitagawa Y, Mizokami A, et al. Effects of dutasteride on lower urinary tract symptoms: a prospective analysis based on changes in testosterone/dihydrotestosterone levels and total prostatic volume reduction. Aging Male. 2016;19:128–33.
Corona G, Tirabassi G, Santi D, Maseroli E, Gacci M, Dicuio M, et al. Sexual dysfunction in subjects treated with inhibitors of 5alpha-reductase for benign prostatic hyperplasia: a comprehensive review and meta-analysis. Andrology. 2017;5:671–8.
Gupta AK, Carviel J, MacLeod MA, Shear N. Assessing finasteride-associated sexual dysfunction using the FAERS database. J Eur Acad Dermatol Venereol. 2017;31:1069–75.
Lee S, Lee YB, Choe SJ, Lee WS. Adverse sexual effects of treatment with finasteride or dutasteride for male androgenetic alopecia: a systematic review and meta-analysis. Acta Derm Venereol. 2019;99:12–17.
Sung HH, Yu J, Kang SJ, Chae MR, So I, Park JK, et al. Persistent erectile dysfunction after discontinuation of 5-alpha reductase inhibitor therapy in rats depending on the duration of treatment. World J Mens Health. 2019;37:240–8.
Oztekin CV, Gur S, Abdulkadir NA, Lokman U, Akdemir AO, Cetinkaya M, et al. Incomplete recovery of erectile function in rat after discontinuation of dual 5-alpha reductase inhibitor therapy. J Sex Med. 2012;9:1773–81.
Speakman MJ, Cornu JN, Gacci M, Gratzke C, Mamoulakis C, Herrmann TRW, et al. What is the required certainty of evidence for the implementation of novel techniques for the treatment of benign prostatic obstruction? Eur Urol Focus. 2019;5:351–6.
Song J, Lee SH, Kim H. Efficacy and safety of HT080 for lower urinary tract symptoms associated with benign prostatic hyperplasia: A study protocol for a randomized, double-blind, placebo-controlled trial. Med (Baltim). 2019;98:e17848.
Fourcade RO, Theret N, Taieb C, Group BUS. Profile and management of patients treated for the first time for lower urinary tract symptoms/benign prostatic hyperplasia in four European countries. Bju Int. 2008;101:1111–8.
Barnes PM, Bloom B, Nahin RL Complementary and alternative medicine use among adults and children: United States, 2007. Natl Health Stat Report 2008;1-23.
Rho J, Seo CS, Park HS, Jeong HY, Moon OS, Seo YW, et al. Asteris Radix et Rhizoma suppresses testosterone-induced benign prostatic hyperplasia in rats by regulating apoptosis and inflammation. J Ethnopharmacol. 2020;255:112779.
Choi HM, Jung Y, Park J, Kim HL, Youn DH, Kang J, et al. Cinnamomi cortex (cinnamomum verum) suppresses testosterone-induced benign prostatic hyperplasia by regulating 5alpha-reductase. Sci Rep. 2016;6:31906.
Liu J, Fang T, Li M, Song Y, Li J, Xue Z, et al. Pao pereira extract attenuates testosterone-induced benign prostatic hyperplasia in rats by inhibiting 5alpha-reductase. Sci Rep. 2019;9:19703.
Ooi SL, Pak SC. Serenoa repens for lower urinary tract symptoms/benign prostatic hyperplasia: current evidence and its clinical implications in naturopathic medicine. J Alter Complement Med. 2017;23:599–606.
Jena AK, Vasisht K, Sharma N, Kaur R, Dhingra MS, Karan M. Amelioration of testosterone induced benign prostatic hyperplasia by Prunus species. J Ethnopharmacol. 2016;190:33–45.
Guercio V, Galeone C, Turati F, La Vecchia C. Gastric cancer and allium vegetable intake: a critical review of the experimental and epidemiologic evidence. Nutr Cancer. 2014;66:757–73.
Nicastro HL, Ross SA, Milner JA. Garlic and onions: their cancer prevention properties. Cancer Prev Res (Philos). 2015;8:181–9.
Kim SH, Jo SH, Kwon YI, Hwang JK. Effects of onion (Allium cepa L.) extract administration on intestinal alpha-glucosidases activities and spikes in postprandial blood glucose levels in SD rats model. Int J Mol Sci. 2011;12:3757–69.
Lee B, Jung JH, Kim HS. Assessment of red onion on antioxidant activity in rat. Food Chem Toxicol. 2012;50:3912–9.
Gorinstein S, Leontowicz H, Leontowicz M, Jastrzebski Z, Najman K, Tashma Z, et al. The influence of raw and processed garlic and onions on plasma classical and non-classical atherosclerosis indices: investigations in vitro and in vivo. Phytother Res. 2010;24:706–14.
Gennaro L, Leonardi C, Esposito F, Salucci M, Maiani G, Quaglia G, et al. Flavonoid and carbohydrate contents in Tropea red onions: effects of homelike peeling and storage. J Agric Food Chem. 2002;50:1904–10.
Gorinstein S, Leontowicz H, Leontowicz M, Namiesnik J, Najman K, Drzewiecki J, et al. Comparison of the main bioactive compounds and antioxidant activities in garlic and white and red onions after treatment protocols. J Agric Food Chem. 2008;56:4418–26.
Elberry AA, Mufti S, Al-Maghrabi J, Abdel Sattar E, Ghareib SA, Mosli HA, et al. Immunomodulatory effect of red onion (Allium cepa Linn) scale extract on experimentally induced atypical prostatic hyperplasia in Wistar rats. Mediators Inflamm. 2014;2014:640746.
Ma Z, Hung Nguyen T, Hoa Huynh T. Tien Do P, Huynh H. Reduction of rat prostate weight by combined quercetin-finasteride treatment is associated with cell cycle deregulation. J Endocrinol. 2004;181:493–507.
Khaleghi Ghadiri M, Gorji A. Natural remedies for impotence in medieval Persia. Int J Impot Res. 2004;16:80–83.
Malviya N, Jain S, Gupta VB, Vyas S. Management of drug induced sexual dysfunction in male rats by ethyl acetate fraction of onion. Acta Pol Pharm. 2013;70:317–22.
Allouh MZ, Daradka HM, Al Barbarawi MM, Mustafa AG. Fresh onion juice enhanced copulatory behavior in male rats with and without paroxetine-induced sexual dysfunction. Exp Biol Med (Maywood). 2014;239:177–82.
Lines TC, Ono M. FRS 1000, an extract of red onion peel, strongly inhibits phosphodiesterase 5A (PDE 5A). Phytomedicine. 2006;13:236–9.
Chen KK, Chan JY, Chang LS, Chen MT, Chan SH. Intracavernous pressure as an experimental index in a rat model for the evaluation of penile erection. J Urol. 1992;147:1124–8.
Italiano G, Calabro A, Pagano F. A simplified in vitro preparation of the corpus cavernosum as a tool for investigating erectile pharmacology in the rat. Pharm Res. 1994;30:325–34.
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;8:3066–74.
Valle G, Carmignani M, Stanislao M, Michelini S, Volpe AR. Traditional medicine, corpus cavernosum and hydrogen sulphide. J Sex Med. 2011;8:631–2.
Yilmaz-Oral D, Kaya-Sezginer E, Oztekin CV, Bayatli N, Lokman U, Gur S. Evaluation of combined therapeutic effects of hydrogen sulfide donor sodium hydrogen sulfide and phosphodiesterase type-5 inhibitor tadalafil on erectile dysfunction in a partially bladder outlet obstructed rat model. Neurourol Urodyn. 2020;39:1087–97.
Bucci M, Papapetropoulos A, Vellecco V, Zhou Z, Pyriochou A, Roussos C, et al. Hydrogen sulfide is an endogenous inhibitor of phosphodiesterase activity. Arterioscler Thromb Vasc Biol. 2010;30:1998–2004.
Coletta C, Papapetropoulos A, Erdelyi K, Olah G, Modis K, Panopoulos P, et al. Hydrogen sulfide and nitric oxide are mutually dependent in the regulation of angiogenesis and endothelium-dependent vasorelaxation. Proc Natl Acad Sci USA. 2012;109:9161–6.
Ebeigbe AB, Aloamaka CP. Role of endothelium in magnesium-induced relaxation of rat aorta. Res Exp Med (Berl). 1987;187:25–31.
Naseri MK, Arabian M, Badavi M, Ahangarpour A. Vasorelaxant and hypotensive effects of Allium cepa peel hydroalcoholic extract in rat. Pak J Biol Sci. 2008;11:1569–75.
Gasparotto Junior A, Dos Reis Piornedo R, Assreuy J, Da Silva-Santos JE. Nitric oxide and Kir6.1 potassium channel mediate isoquercitrin-induced endothelium-dependent and independent vasodilation in the mesenteric arterial bed of rats. Eur J Pharm. 2016;788:328–34.
Maeda Y, Aoki Y, Sekiguchi F, Matsunami M, Takahashi T, Nishikawa H, et al. Hyperalgesia induced by spinal and peripheral hydrogen sulfide: evidence for involvement of Cav3.2 T-type calcium channels. Pain. 2009;142:127–32.
Marques-da-Silva D, Samhan-Arias AK, Tiago T, Gutierrez-Merino C. L-type calcium channels and cytochrome b5 reductase are components of protein complexes tightly associated with lipid rafts microdomains of the neuronal plasma membrane. J Proteom. 2010;73:1502–10.
Streng T, Axelsson HE, Hedlund P, Andersson DA, Jordt SE, Bevan S, et al. Distribution and function of the hydrogen sulfide-sensitive TRPA1 ion channel in rat urinary bladder. Eur Urol. 2008;53:391–9.
Gur S, Kadowitz PJ, Sikka SC, Peak TC, Hellstrom WJ. Overview of potential molecular targets for hydrogen sulfide: A new strategy for treating erectile dysfunction. Nitric Oxide. 2015;50:65–78.
Chen JH, Tsai SJ, Chen HI. Welsh onion (Allium fistulosum L.) extracts alter vascular responses in rat aortae. J Cardiovasc Pharm. 1999;33:515–20.
Gonzalez-Pena D, Angulo J, Vallejo S, Colina-Coca C, de Ancos B, Sanchez-Ferrer CF, et al. High-cholesterol diet enriched with onion affects endothelium-dependent relaxation and NADPH oxidase activity in mesenteric microvessels from Wistar rats. Nutr Metab (Lond). 2014;11:57.
Sanchez M, Galisteo M, Vera R, Villar IC, Zarzuelo A, Tamargo J, et al. Quercetin downregulates NADPH oxidase, increases eNOS activity and prevents endothelial dysfunction in spontaneously hypertensive rats. J Hypertens. 2006;24:75–84.
Adefegha SA, Oyeleye SI, Dada FA, Olasehinde TA, Oboh G. Modulatory effect of quercetin and its glycosylated form on key enzymes and antioxidant status in rats penile tissue of paroxetine-induced erectile dysfunction. Biomed Pharmacother. 2018;107:1473–9.
Boydens C, Pauwels B, Vanden Daele L, Van, de Voorde J. Protective effect of resveratrol and quercetin on in vitro-induced diabetic mouse corpus cavernosum. Cardiovasc Diabetol. 2016;15:46.
Boydens C, Pauwels B, Decaluwe K, Brouckaert P, Van, de Voorde J. Relaxant and antioxidant capacity of the red wine polyphenols, resveratrol and quercetin, on isolated mice corpora cavernosa. J Sex Med. 2015;12:303–12.
Slimestad R, Fossen T, Vagen IM. Onions: a source of unique dietary flavonoids. J Agric Food Chem. 2007;55:10067–80.
Nakayama Y, Tanaka K, Hiramoto S, Yahata N, Inagawa Y, Nukui K, et al. Alleviation of the aging males’ symptoms by the intake of onion-extracts containing concentrated cysteine sulfoxides for 4 weeks—Randomized, double-blind, placebo-controlled, parallel-group comparative study. Japn Pharmacol Ther. 2017;45:595–608.
Tsujimoto M, Agawa C, Ueda S, Yamane T, Kitayama H, Terao A, et al. Inhibitory effects of juices prepared from individual vegetables on CYP3A4 activity in recombinant CYP3A4 and LS180 cells. Biol Pharm Bull. 2017;40:1561–5.
Andriole GL, Kirby R. Safety and tolerability of the dual 5alpha-reductase inhibitor dutasteride in the treatment of benign prostatic hyperplasia. Eur Urol. 2003;44:82–88.
Tayeb MT, Clark C, Haites NE, Sharp L, Murray GI, McLeod HL. CYP3A4 and VDR gene polymorphisms and the risk of prostate cancer in men with benign prostate hyperplasia. Br J Cancer. 2003;88:928–32.
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Yilmaz-Oral, D., Onder, A., Kaya-Sezginer, E. et al. Restorative effects of red onion (Allium cepa L.) juice on erectile function after-treatment with 5α-reductase inhibitor in rats. Int J Impot Res 34, 269–276 (2022). https://doi.org/10.1038/s41443-021-00421-y
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DOI: https://doi.org/10.1038/s41443-021-00421-y
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