A new original nutraceutical formulation ameliorates the effect of Tadalafil on clinical score and cGMP accumulation

  • Vincenzo Mirone Department of Neurosciences, Sciences of Reproduction, and Odontostomatology, University of Naples Federico II, Naples, Italy.
  • Luigi Napolitano | dr.luiginapolitano@gmail.com Department of Neurosciences, Sciences of Reproduction, and Odontostomatology, University of Naples Federico II, Naples, Italy.
  • Roberta D’Emmanuele di Villa Bianca Department of Pharmacy, School of Medicine and Surgery, University of Naples, Federico II, Naples, Italy.
  • Emma Mitidieri Department of Pharmacy, School of Medicine and Surgery, University of Naples, Federico II, Naples, Italy.
  • Raffaella Sorrentino Department of Pharmacy, School of Medicine and Surgery, University of Naples, Federico II, Naples, Italy.
  • Arianna Vanelli Responsabile Ricerca e Sviluppo Nutrilinea SRL, Varese, Italy.
  • Domenico Vanacore Department of Pharmacy, School of Medicine and Surgery, University of Naples, Federico II, Naples, Italy.
  • Carlotta Turnaturi Department of Pharmacy, School of Medicine and Surgery, University of Naples, Federico II, Naples, Italy.
  • Roberto La Rocca Department of Neurosciences, Sciences of Reproduction, and Odontostomatology, University of Naples Federico II, Naples, Italy.
  • Giuseppe Celentano Department of Neurosciences, Sciences of Reproduction, and Odontostomatology, University of Naples Federico II, Naples, Italy.
  • Davide Arcaniolo Urology Unit, Department of Woman Child and of General and Specialist Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy.
  • Giuseppe Cirino Department of Pharmacy, School of Medicine and Surgery, University of Naples, Federico II, Naples, Italy.

Abstract

Objective: To assess the efficacy of the combination of Tadalafil 5 mg and nutritional supplements composed by Panax ginseng, Moringa Oleifera and Rutin on erectile function in men with mild and moderate vasculogenic ED.
Methods: we prospectively enrolled 86 patients divided into two groups A (45), B (33) in this multicenter randomized, doubleblind, placebo-controlled trial . Drop out was 8 patients (3 patients in group A and 5 in Group B). At screening visit patients underwent clinical examination, blood test (hormonal and metabolic profile) and filled out the IIEF-5 questionnaire and the SEP-2, SEP-3. Patients were randomized by a computergenerated list to receive either Tadalafil 5 mg once daily plus nutritional supplement once daily (group A) or Tadalafil 5 mg plus placebo with the same administration schedule (group B) for 3 months. Blood samples, IIEF-5, SEP-2 and SEP-3 have been collected again after 3 months. cGMP was measured in platelets of 38 patients at baseline and after one months.
Results: Mean age was 59.98 ± 6.90 (range 38-69), mean IIEF-5 score at baseline was 13.59 ± 3.90. After three months of treatment, IIEF-5 score significantly improved in both groups compared to baseline (13.18 ± 3.75 vs 20.48 ± 2.24, p < 0.0001; 14.15 ± 4.09 vs 19.06 ± 4.36, p < 0.0001, in group A and group B respectively). Patients treated with Tadalafil plus nutritional supplement showed a significantly higher increase in IIEF-5 score compared to those who received placebo (7.27 ± 2.20 and 4.9 ± 2.79, respectively; p < 0.0001;). No hormonal differences and metabolic effects were found. According cGMP result, nutritional supplements ameliorates and extends the activity of the chronic treatment.
Conclusions: IIEF-5 significant increase in group B, can be ascribed to the nutritional supplement properties and antioxidant effects of moringa oleifera, ginseng and rutin and this can enhance the endothelial NO and cGMP production.

Dimensions

Altmetric

PlumX Metrics

Downloads

Download data is not yet available.

References

Shamloul R, Ghanem H. Erectile dysfunction. Lancet. 2013; 381;153-165. DOI: https://doi.org/10.1016/S0140-6736(12)60520-0

Gareri P, Castagna A, Francomano D, et al. Erectile dysfunction in the elderly: an old widespread issue with novel treatment perspectives. Int J Endocrinol. 2014; 2014:878670. DOI: https://doi.org/10.1155/2014/878670

Yafi FA, Jenkins L, Albersen M, et al. Erectile dysfunction. Nat Rev Dis Primers. 2016; 2:16003. DOI: https://doi.org/10.1038/nrdp.2016.3

Baumann F, Hehli D, Makaloski V, et al. Erectile dysfunction— overview from a cardiovascular perspective. Vasa. 2017; 10:1-7. DOI: https://doi.org/10.1024/0301-1526/a000627

Eisenberg ML, Meldrum D. Effects of age on fertility and sexual function. Fertil Steril. 2017; 107:301-4. DOI: https://doi.org/10.1016/j.fertnstert.2016.12.018

Nguyen HMT, Gabrielson AT, Hellstrom WJG. Erectile dysfunction in young men-a review of the prevalence and risk factors. Sex Med Rev. 2017; 5:508-20. DOI: https://doi.org/10.1016/j.sxmr.2017.05.004

Hsu B, Hirani V, Naganathan V, et al. Sexual function and mortality in older men: the concord health and ageing in men project. J Gerontol A Biol Sci Med Sci. 2017; 72:520-7.

Dean RC, Lue TF. Physiology of penile erection and pathophysiology of erectile dysfunction. Urol Clin North Am. 2005; 32:379-95. DOI: https://doi.org/10.1016/j.ucl.2005.08.007

Andersson KE. Mechanisms of penile erection and basis for pharmacological treatment of erectile dysfunction. Pharmacol Rev. 2011; 63:811-59. DOI: https://doi.org/10.1124/pr.111.004515

Kass DA, Takimoto E, Nagayama T, Champion HC. Phosphodiesterase regulation of nitric oxide signaling. Cardiovasc Res. 2007; 75:303-14. DOI: https://doi.org/10.1016/j.cardiores.2007.02.031

Allen MS, Walter EE. Erectile dysfunction: an umbrella review of meta-analyses of risk-factors, treatment, and prevalence outcomes. J Sex Med. 2019; 16:531-541. DOI: https://doi.org/10.1016/j.jsxm.2019.01.314

Karatza AA, Bush A, Magee AG. Safety and efficacy of sildenafil therapy in children with pulmonary hypertension. Int J Cardiol. 2005; 100:267-273. DOI: https://doi.org/10.1016/j.ijcard.2004.09.002

Lewis RJ, Johnson RD, Blank CL. Quantitative determination of sildenafil (Viagra) and its metabolite (UK-103,320) in fluid and tissue specimens obtained from six aviation fatalities. J Anal Toxicol. 2006; 30:14-20. DOI: https://doi.org/10.1093/jat/30.1.14

Palmieri A, Arcaniolo D, Palumbo F, et al. Low intensity shockwave therapy in combination with phosphodiesterase-5 inhibitors is an effective and safe treatment option in patients with vasculogenic ED who are PDE5i non-responders: a multicenter single-arm clinical trial; SIA-Low intensity shock wave for Erectile Dysfunction (LED) Study Group. Int J Impot Res. 2020 Jul 18 doi: 10.1038/s41443-020-0332-7. DOI: https://doi.org/10.1038/s41443-020-0332-7

Corona G, Rastrelli G, Burri A, et al. First-generation phosphodiesterase type 5 inhibitors dropout: a comprehensive review and meta-analysis. Andrology. 2016; 4:1002-1009. DOI: https://doi.org/10.1111/andr.12255

Srivatsav A, Balasubramanian A, Pathak UI, et al. Efficacy and safety of common ingredients in aphrodisiacs used for erectile dysfunction: a review. Sex Med Rev. 2020; 8:431-442. DOI: https://doi.org/10.1016/j.sxmr.2020.01.001

Rosen RC, Riley A, Wagner G, et al. The International Index of Erectile Function (IIEF): a multidimensional scale for assessment of erectile dysfunction. Urology. 1997; 49:822-30. DOI: https://doi.org/10.1016/S0090-4295(97)00238-0

Mirone V, d'Emmanuele di Villa Bianca R, Mitidieri E, et al. Platelet cyclic guanosine monophosphate as a biomarker of phosphodiesterase type 5 inhibitor efficacy in the treatment of erectile dysfunction: a randomized placebo-controlled study. Eur Urol. 2009; 56:1067-73. DOI: https://doi.org/10.1016/j.eururo.2009.09.031

d’Emmanuele di Villa Bianca R, Mitidieri E, Mirone V, et al. An ex vivo standardized assay to measure human platelet cGMP. J Pharmacol Toxicol Methods. 2011; 64:164-7. DOI: https://doi.org/10.1016/j.vascn.2011.07.001

Keefer LK, Nims RW, Davies KM, Wink DA. NONOates” (1-substituted diazen-1-ium-1, 2-diolates) as nitric oxide donors: convenient nitric oxide dosage forms. Methods Enzymol. 1996; 268:281-93. DOI: https://doi.org/10.1016/S0076-6879(96)68030-6

Malviya N, Malviya S, Jain S, Vyas S. A review of the potential of medicinal plants in the management and treatment of male sexual dysfunction. Andrologia. 2016; 48:880-93. DOI: https://doi.org/10.1111/and.12677

Jang DJ, Lee MS, Shin BC, et al. Red ginseng for treating erectile dysfunction: a systematic review. Br J Clin Pharmacol. 2008; 66:444-450. DOI: https://doi.org/10.1111/j.1365-2125.2008.03236.x

Kulaputana O, Thanakomsirichot S, Anomasiri W. Ginseng supplementation does not change lactate threshold and physical performances in physically active Thai men. J Med Assoc Thai. 2007; 90:1172-1179.

Helms S. Cancer prevention and therapeutics: Panax ginseng. Altern Med Rev. 2004; 9:259-274.

Kim S, Shin BC, Lee MS, et al. Red ginseng for type 2 diabetes mellitus: a systematic review of randomized controlled trials. Chin J Integr Med. 2011; 17:937-944. DOI: https://doi.org/10.1007/s11655-011-0937-2

Rhee MY, Kim YS, Bae JH, et al. Effect of Korean red ginseng on arterial stiffness in subjects with hypertension. J Altern Complement Med. 2011; 17:45-49. DOI: https://doi.org/10.1089/acm.2010.0065

de Andrade E, de Mesquita AA, Claro Jde A, et al. Study of the efficacy of Korean Red Ginseng in the treatment of erectile dysfunction. Asian J Androl. 2007; 9:241-4. DOI: https://doi.org/10.1111/j.1745-7262.2007.00210.x

Atawodi SE, Atawodi JC, Idakwo GA, et al. Evaluation of the polyphenol content and antioxidant properties of methanol extracts of the leaves, stem, and root barks of Moringa oleifera Lam. J Med Food. 2010; 13:710-716. DOI: https://doi.org/10.1089/jmf.2009.0057

Jaiswal D, Kumar RP, Kumar A, et al. Effect of Moringa oleifera Lam leaves aqueous extract therapy on hyperglycemic rats. J Ethnopharmacol. 2009; 123:392-396. DOI: https://doi.org/10.1016/j.jep.2009.03.036

Jung IL. Soluble extract of Moringa oleifera leaves with a new anticancer activity. PLOSOne 2014;9:e95492 DOI: https://doi.org/10.1371/journal.pone.0095492

Al-Roujeaie AS, Abuohashish HM, Ahmed MM, Alkhamees OA. Effect of rutin on diabetic-induced erectile dysfunction: Possible involvement of testicular biomarkers in male rats. Andrologia. 2017; 49. DOI: https://doi.org/10.1111/and.12737

Oboh G, Adebayo AA, Ademosun AO, Boligon AA. In vitro inhibition of phosphodiesterase-5 and arginase activities from rat penile tissue by two Nigerian herbs (Hunteria umbellata and Anogeissus leiocarpus). J Basic Clin Physiol Pharmacol. 2017; 28:393-401. DOI: https://doi.org/10.1515/jbcpp-2016-0143

Zhang Y, Huang C, Liu S, et al. Effects of quercetin on intracavernous pressure and expression of nitrogen synthase isoforms in arterial erectile dysfunction rat model. Int J Clin Exp Med. 2015; 8:7599-605.

Nova E, Redondo-Useros N, Martínez-García RM, et al. Potential of Moringa oleifera to improve glucose control for the prevention of diabetes and related metabolic alterations: a systematic review of animal and human studies. Nutrients. 2020; 12:2050. DOI: https://doi.org/10.3390/nu12072050

Beavo JA. Cyclic nucleotide phosphodiesterases: functional implications of multiple isoforms. Physiol Rev. 1995; 75:725-48. DOI: https://doi.org/10.1152/physrev.1995.75.4.725

Wallis RM, Corbin JD, Francis SH, Ellis P. Tissue distribution of phosphodiesterase families and the effects of sildenafil on tissue cyclic nucleotides, platelet function, and the contractile responses of trabeculae carneae and aortic rings in vitro. Am J Cardiol. 1999; 83:3C-12C. DOI: https://doi.org/10.1016/S0002-9149(99)00042-9

Dunkern TR, Hatzelmann A. The effect of sildenafil on human platelet secretory function is controlled by a complex interplay between phosphodiesterases 2, 3 and 5. Cell Signal. 2005; 17:331-9. DOI: https://doi.org/10.1016/j.cellsig.2004.07.007

Francis SH, Morris GZ, Corbin JD. Molecular mechanisms that could contribute to prolonged effectiveness of PDE5 inhibitors to improve erectile function. Int J Impot Res. 2008; 20:333-42. DOI: https://doi.org/10.1038/ijir.2008.4

Moncada I, Jara J, Subirà D, et al. Efficacy of sildenafil citrate at 12 hours after dosing: re-exploring the therapeutic window. Eur Urol. 2004; 46:357-61. DOI: https://doi.org/10.1016/j.eururo.2004.04.025

Young JM, Feldman RA, Auerbach SM, et al. Tadalafil improved erectile function at twenty-four and thirty-six hours after dosing in men with erectile dysfunction: US trial. J Androl. 2005; 26:310-8. DOI: https://doi.org/10.2164/jandrol.04126

Shabsigh R, Seftel AD, Rosen RC, et al. Review of time of onset and duration of clinical efficacy of phosphodiesterase type 5 inhibitors in treatment of erectile dysfunction. Urology. 2006; 68:689-96. DOI: https://doi.org/10.1016/j.urology.2006.05.009

Direk Aekthammarat, Panot Tangsucharit, Patchareewan Pannangpetch, Thanaporn Sriwantana, Nathawut Sibmooh. Moringa oleifera leaf extract enhances endothelial nitric oxide production leading to relaxation of resistance artery and lowering of arterial blood pressure. Biomed Pharmacother. 2020; 130:110605. DOI: https://doi.org/10.1016/j.biopha.2020.110605

Nandave M, Ojha SK, Joshi S, et al. Moringa oleifera leaf extract prevents isoproterenol-induced myocardial damage in rats: Evidence for an antioxidant, antiperoxidative, and cardioprotective intervention. Journal of Medicinal Food. 2009; 12:47-55. DOI: https://doi.org/10.1089/jmf.2007.0563

Published
2021-06-28
Info
Issue
Section
Original Papers - Andrology
Keywords:
Erectile dysfunction, PDE5, Dietary supplement, Phosphodiesterase, Natural health product
Statistics
  • Abstract views: 409

  • PDF: 227
How to Cite
Mirone, V., Napolitano, L., D’Emmanuele di Villa Bianca, R., Mitidieri, E., Sorrentino, R., Vanelli, A., Vanacore, D., Turnaturi, C., La Rocca, R., Celentano, G., Arcaniolo, D., & Cirino, G. (2021). A new original nutraceutical formulation ameliorates the effect of Tadalafil on clinical score and cGMP accumulation. Archivio Italiano Di Urologia E Andrologia, 93(2), 221-226. https://doi.org/10.4081/aiua.2021.2.221