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The Effect of the Combination of Ginseng, Tribulus Terrestris, and L-arginine on the Sexual Performance of Men with Erectile Dysfunction: a randomized, double-blind, parallel, and placebo-controlled clinical trial

  • Reza Tahvilian (School of Pharmacy, Pharmaceutical Sciences Research Center, Research Institute for Health, Kermanshah University of Medical Sciences) ;
  • Mohammad Amin Golesorkhi (Kermanshah University of Medical Sciences) ;
  • Farajollah Parhoudeh (School of Medicine Imam Reza Hospital Kermanshah University of Medical Sciences) ;
  • Fatemeh Heydarpour (School of Health, Medical Biology Research Center, Research Institute for Health Technology, Kermanshah University of Medical Sciences) ;
  • Hossein Hosseini (Barij Essence Medicinal Plants Research Center) ;
  • Hojjat Baghshahi (Barij Essence Medicinal Plants Research Center) ;
  • Hossein Akbari (Social Determinants of Health (SDH) Research Center, Department of Biostatistics and Epidemiology, School of Public Health, Kashan University of Medical Sciences) ;
  • Mohammad Reza Memarzadeh (Barij Essence Medicinal Plants Research Center) ;
  • Mehdi Mehran (Barij Essence Medicinal Plants Research Center) ;
  • Hosna Bagheri (Kermanshah University of Medical Sciences)
  • Received : 2023.08.16
  • Accepted : 2024.04.22
  • Published : 2024.06.30

Abstract

Objectives: Nitric oxide is the most important mediator of penile erection after the onset of sexual excitement. It activates cyclic guanosine monophosphate (cGMP), increasing penile blood flow. Most pharmaceutical medications prevent enzyme phosphodiesterase type 5 (PDE-5) from breaking down cGMP, thus keeping its level high. However, due to the adverse effects of pharmacological therapies, herbal drugs that improve sexual function have gained attention recently. This study aimed to investigate the combined effects of ginseng, Tribulus terrestris, and L-arginine amino acid on the sexual performance of individuals with erectile dysfunction (ED) using the 5-item version of the International Index of Erectile Function (IIEF-5) questionnaire. Methods: Over three months, 98 men with erectile dysfunction were randomly assigned to receive either 500 mg of herbal supplements or placebo pills. Each herbal tablet contained 100 mg of protodioscin, 35 mg of ginsenosides, and 250 mg of L-arginine. Results: The results showed that the changes in the average scores of ILEF-5 within each group before and after the intervention indicated that all parameters related to the improvement of sexual function in patients with erectile dysfunction improved in the herbal treatment group (p < 0.001). The herbal group significantly improved IIEF-5 scores in nondiabetics (p < 0.05). However, there was no significant difference in the changes of IIEF-5 scores between the two intervention and control groups in diabetic patients. Conclusion: In conclusion, ginseng, Tribulus terrestris, and L-arginine have properties that increase energy and strengthen sexual function, making them suitable for patients with sexual disorders.

Keywords

Acknowledgement

This study was conducted using Highsense Barij® tablets manufactured by Barij Essence Company in Iran, and this company was supported all financial support.

References

  1. Adam DR, Alem MM. Erectile dysfunction: pharmacological pathways with understudied potentials. Biomedicines. 2022;11(1):46.
  2. Heruti R, Shochat T, Tekes-Manova D, Ashkenazi I, Justo D. Prevalence of erectile dysfunction among young adults: results of a large-scale survey. J Sex Med. 2004;1(3):284-91. https://doi.org/10.1111/j.1743-6109.04041.x
  3. Sin VJ, Anand GS, Koh HL. Botanical medicine and natural products used for erectile dysfunction. Sex Med Rev. 2021;9(4):568-92. https://doi.org/10.1016/j.sxmr.2020.10.005
  4. Wang H, Zhao M, Zhang J, Yan B, Liu S, Zhao F, et al. The efficacy of acupuncture on patients with erectile dysfunction: a review. Evid Based Complement Alternat Med. 2022;2022:4807271.
  5. Shankhwar SN, Mahdi AA, Sharma AV, Pv K. A prospective clinical study of a prosexual nutrient: Nano Leo for evaluation of libido, erection, and orgasm in Indian men with erectile dysfunction. Evid Based Complement Alternat Med. 2020;2020:4598217.
  6. Sangiorgi G, Cereda A, Benedetto D, Bonanni M, Chiricolo G, Cota L, et al. Anatomy, pathophysiology, molecular mechanisms, and clinical management of erectile dysfunction in patients affected by coronary artery disease: a review. Biomedicines. 2021;9(4):432.
  7. Irwin GM. Erectile dysfunction. Prim Care. 2019;46(2):249-55. https://doi.org/10.1016/j.pop.2019.02.006
  8. Castela A, Costa C. Molecular mechanisms associated with diabetic endothelial-erectile dysfunction. Nat Rev Urol. 2016;13(5):266-74. https://doi.org/10.1038/nrurol.2016.23
  9. Hatzimouratidis K, Salonia A, Adaikan G, Buvat J, Carrier S, El-Meliegy A, et al. Pharmacotherapy for erectile dysfunction: recommendations from the fourth International Consultation for Sexual Medicine (ICSM 2015). J Sex Med. 2016;13(4):465-88. https://doi.org/10.1016/j.jsxm.2016.01.016
  10. uckert S, Kuczyk MA, Oelke M. Phosphodiesterase inhibitors in clinical urology. Expert Rev Clin Pharmacol. 2013;6(3):323-32. https://doi.org/10.1586/ecp.13.16
  11. Panahi Y, Akhavan A, Sahebkar A, Hosseini SM, Taghizadeh M, Akbari H, et al. Investigation of the effectiveness of Syzygium aromaticum, Lavandula angustifolia and Geranium robertianum essential oils in the treatment of acute external otitis: a comparative trial with ciprofloxacin. J Microbiol Immunol Infect. 2014;47(3):211-6. https://doi.org/10.1016/j.jmii.2012.10.002
  12. Masuku NP, Unuofin JO, Lebelo SL. Promising role of medicinal plants in the regulation and management of male erectile dysfunction. Biomed Pharmacother. 2020;130:110555.
  13. Chauhan NS, Sharma V, Dixit VK, Thakur M. A review on plants used for improvement of sexual performance and virility. Biomed Res Int. 2014;2014:868062.
  14. Taghizadeh M, Ostad SN, Asemi Z, Mahboubi M, Hejazi S, Sharafati-Chaleshtori R, et al. Sub-chronic oral toxicity of Cuminum cyminum L.'s essential oil in female Wistar rats. Regul Toxicol Pharmacol. 2017;88:138-43.
  15. Taghizadeh M, Farzin N, Taheri S, Mahlouji M, Akbari H, Karamali F, et al. The effect of dietary supplements containing green tea, capsaicin and ginger extracts on weight loss and metabolic profiles in overweight women: a randomized double-blind placebo-controlled clinical trial. Ann Nutr Metab. 2017;70(4):277-85. https://doi.org/10.1159/000471889
  16. Zhang H, Abid S, Ahn JC, Mathiyalagan R, Kim YJ, Yang DC, et al. Characteristics of Panax ginseng cultivars in Korea and China. Molecules. 2020;25(11):2635.
  17. Kim JY, Lee HJ, Kim JS, Ryu JH. Induction of nitric oxide synthase by saponins of heat-processed ginseng. Biosci Biotechnol Biochem. 2005;69(5):891-5. https://doi.org/10.1271/bbb.69.891
  18. Hossein M, Hossein A, Mohsen T, Jamileh J, Mohadese M, Mahnaz M. Evaluation of the effects of capsules containing Tribulus terrestris extract and L-carnitine on treatment of oligospermia in males. J Evol Med Dent Sci. 2018;7(29):3266-70. https://doi.org/10.14260/jemds/2018/736
  19. Gunarathne R, Nadeeshani H, Lu A, Li J, Zhang B, Ying T, et al. Potential nutraceutical use of Tribulus terrestris L. in human health. Food Rev Int. 2022;39(8):5326-55. https://doi.org/10.1080/87559129.2022.2067172
  20. Santos CA, Reis LO, Destro-Saade R, Luiza-Reis A, Fregonesi A. Tribulus terrestris versus placebo in the treatment of erectile dysfunction: a prospective, randomized, double blind study. Actas Urol Esp. 2014;38(4):244-8. https://doi.org/10.1016/j.acuro.2013.09.014
  21. Gagnier JJ, Boon H, Rochon P, Moher D, Barnes J, Bombardier C. Reporting randomized, controlled trials of herbal interventions: an elaborated CONSORT statement. Ann Intern Med. 2006;144(5):364-7. https://doi.org/10.7326/0003-4819-144-5-200603070-00013
  22. Zou H, Zhang X, Chen W, Tao Y, Li B, Liu H, et al. Vascular endothelium is the basic way for stem cells to treat erectile dysfunction: a bibliometric study. Cell Death Discov. 2023;9(1):143.
  23. Aversa A, Bruzziches R, Pili M, Spera G. Phosphodiesterase 5 inhibitors in the treatment of erectile dysfunction. Curr Pharm Des. 2006;12(27):3467-84. https://doi.org/10.2174/138161206778343046
  24. Papagiannopoulos D, Khare N, Nehra A. Evaluation of young men with organic erectile dysfunction. Asian J Androl. 2015;17(1):11-6. https://doi.org/10.4103/1008-682X.139253
  25. Jurys T, Burzynski B, Potyka A, Paradysz A. Post-radical prostatectomy erectile dysfunction assessed using the IIEF-5 questionnaire - a systematic literature review. Int J Sex Health. 2021;34(1):55-64. https://doi.org/10.1080/19317611.2021.1936333
  26. Su H, Lu Y, Ma C, Li H, Su X. Impact of atorvastatin on erectile dysfunction: a meta-analysis and systematic review. Andrologia. 2022;54(6):e14408.
  27. de Andrade E, de Mesquita AA, de Almeida Claro J, de Andrade PM, Ortiz V, Paranhos M, et al. Study of the efficacy of Korean Red Ginseng in the treatment of erectile dysfunction. Asian J Androl. 2007;9(2):241-4. https://doi.org/10.1111/j.1745-7262.2007.00210.x
  28. Choi YD, Park CW, Jang J, Kim SH, Jeon HY, Kim WG, et al. Effects of Korean ginseng berry extract on sexual function in men with erectile dysfunction: a multicenter, placebo-controlled, double-blind clinical study. Int J Impot Res. 2013;25(2):45-50. https://doi.org/10.1038/ijir.2012.45
  29. Qi LW, Wang CZ, Yuan CS. Isolation and analysis of ginseng: advances and challenges. Nat Prod Rep. 2011;28(3):467-95. https://doi.org/10.1039/c0np00057d
  30. Yu J, Eto M, Akishita M, Kaneko A, Ouchi Y, Okabe T. Signaling pathway of nitric oxide production induced by ginsenoside Rb1 in human aortic endothelial cells: a possible involvement of androgen receptor. Biochem Biophys Res Commun. 2007;353(3):764-9. https://doi.org/10.1016/j.bbrc.2006.12.119
  31. Leung KW, Cheng YK, Mak NK, Chan KK, Fan TP, Wong RN. Signaling pathway of ginsenoside-Rg1 leading to nitric oxide production in endothelial cells. FEBS Lett. 2006;580(13):3211-6. https://doi.org/10.1016/j.febslet.2006.04.080
  32. Wang X, Chu S, Qian T, Chen J, Zhang J. Ginsenoside Rg1 improves male copulatory behavior via nitric oxide/cyclic guanosine monophosphate pathway. J Sex Med. 2010;7(2 Pt 1):743-50. https://doi.org/10.1111/j.1743-6109.2009.01482.x
  33. Kang YJ, Sohn JT, Chang KC. Relaxation of canine corporal smooth muscle relaxation by ginsenoside saponin Rg3 is independent from eNOS activation. Life Sci. 2005;77(1):74-84. https://doi.org/10.1016/j.lfs.2004.12.016
  34. Najafabadi BT, Jafarinia M, Ghamari K, Shokraee K, Tadayyon F, Akhondzadeh S. Vitamin E and ginseng combined supplement for treatment of male erectile dysfunction: a double-blind, placebo-controlled, randomized, clinical trial. Adv Integr Med. 2021;8(1):44-9. https://doi.org/10.1016/j.aimed.2019.12.001
  35. Kamenov Z, Fileva S, Kalinov K. Evaluation of the efficacy and safety of Tribulus terrestris in male sexual dysfunction - a prospective, randomized, double blinded, placebo-controlled clinical trial. Maturitas. 2015;81(1):P208.
  36. Gauthaman K, Ganesan AP. The hormonal effects of Tribulus terrestris and its role in the management of male erectile dysfunction--an evaluation using primates, rabbit and rat. Phytomedicine. 2008;15(1-2):44-54. https://doi.org/10.1016/j.phymed.2007.11.011
  37. Kam SC, Do JM, Choi JH, Jeon BT, Roh GS, Hyun JS. In vivo and in vitro animal investigation of the effect of a mixture of herbal extracts from Tribulus terrestris and Cornus officinalis on penile erection. J Sex Med. 2012;9(10):2544-51. https://doi.org/10.1111/j.1743-6109.2012.02889.x
  38. Zhang H, Tong WT, Zhang CR, Li JL, Meng H, Yang HG, et al. Gross saponin of Tribulus terrestris improves erectile dysfunction in type 2 diabetic rats by repairing the endothelial function of the penile corpus cavernosum. Diabetes Metab Syndr Obes. 2019;12:1705-1716. https://doi.org/10.2147/DMSO.S205722
  39. Rhim HC, Kim MS, Park YJ, Choi WS, Park HK, Kim HG, et al. The potential role of arginine supplements on erectile dysfunction: a systemic review and meta-analysis. J Sex Med. 2019;16(2):223-34. https://doi.org/10.1016/j.jsxm.2018.12.002
  40. Klotz T, Mathers MJ, Braun M, Bloch W, Engelmann U. Effectiveness of oral L-arginine in first-line treatment of erectile dysfunction in a controlled crossover study. Urol Int. 1999;63(4):220-3. https://doi.org/10.1159/000030454