Ameliorative effect of cranberry on erectile function in diabetic rats

Abstract

Background and Aims: Cranberry products are beneficial in erectile dysfunction (ED). Therefore, we assessed the impact of Cranberry fruit extract (Cranberry-E) on in vivo erectile response and in vitro relaxant responses in the corpus cavernosum (CC). Methods: Rats (n=10) were divided into control and diabetic groups. In vivo erectile function was measured following intracavernosal injection of Cranberry-E. The relaxation responses to Cranberry-E were obtained after pre-contraction with phenylephrine (Phe, 10 𝜇M) and KCl (60 mM). Cranberry-E caused relaxant responses in the incubation with nitric oxide synthase (NOS) blocker (L-NAME, 100 𝜇M) and soluble guanylate cyclase (sGC) blocker (ODQ, 30 𝜇M), and relaxation responses of cavernosal tissue were calculated before and after the incubation with Cranberry-E. Results: Erectile responseswere significantly reduced in diabetic animals as compared to controls (p<0.001), whichwas normalized after the intracavernous administration of Cranberry-E. There was no difference in the relaxation responses to Cranberry-E between the control and diabetic groups. Cranberry-E induced the relaxation of cavernosal tissue, which remained unaltered in the presence of L-NAME and ODQ. Relaxation responses to Cranberry decreased after KCl-induced precontraction (p<0.001). The relaxation of cavernosal tissue increased after Cranberry-E incubation. Conclusion: Cranberry-E improved diabetes-induced ED and induced relaxation of cavernosal tissue via a nitric oxide-independent mechanism. Thus, cranberry consumption is likely to be effective as a potential strategy to prevent diabetes-induced ED.

Keywords

• Cranberry-E
• Corpus cavernosum
• diabetes
• erectile function
• ericaceae
• Vaccinium oxycoccos L.

References

1. Anhe, F. F., Roy, D., Pilon, G., Dudonne, S., Matamoros, S., Varin, T. V., . . . Marette, A. (2015). A polyphenol-rich cranberry extract protects from diet-induced obesity, insulin resistance and intesti-nal inflammation in association with increased Akkermansia spp. population in the gut microbiota of mice. Gut, 64(6), 872-883. doi:10.1136/gutjnl-2014-307142 google scholar
2. Auger, C., Kim, J. H., Trinh, S., Chataigneau, T., Popken, A. M., & Schini-Kerth, V. B. (2011). Fruit juice-induced endothelium-dependent relaxations in isolated porcine coronary arteries: eval-uation of different fruit juices and purees and optimization of a red fruit juice blend. Food & Function, 2(5), 245-250. doi:10.1039/c1fo10040h google scholar
3. Blumberg, J. B., Camesano, T. A., Cassidy, A., Kris-Etherton, P., How-ell, A., Manach, C., . . . Vita, J. A. (2013). Cranberries and their bioactive constituents in human health. Advances in Nutrition, 4(6), 618-632. doi:10.3945/an.113.004473 google scholar
4. Bukhari, S., Chiragh, S., Tariq, S., Alam, M. A., Wazir, M. S., & Suleman, M. (2015). In Vitro Activity of Vaccinium Macrocarpon (Cranberry) on Urinary Tract Pathogens in Un-complicated Urinary Tract Infection. Journal of Ayub Med-ical College Abbottabad, 27(3), 660-663. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/26721034 google scholar
5. Delpino, F. M., Figueiredo, L. M., Goncalves da Silva, T., & Flo-res, T. R. (2022). Effects of blueberry and cranberry on type 2 diabetes parameters in individuals with or without diabetes: A systematic review and meta-analysis of randomized clini-cal trials. Nutrition, Metabolism & Cardiovascular Diseases, doi:10.1016/j.numecd.2022.02.004 google scholar
6. Ebeigbe, A. B., & Aloamaka, C. P. (1987). Role of endothelium in magnesium-induced relaxation of rat aorta. Research in Experi-mental Medicine, 187(1), 25-31. doi:10.1007/BF01854965 google scholar
7. Hsia, D. S., Zhang, D. J., Beyl, R. S., Greenway, F. L., & Khoo, C. (2020). Effect of daily consumption of cranberry beverage on insulin sensitivity and modification of cardiovascular risk factors in adults with obesity: a pilot, randomised, placebo-controlled study. British Journal of Nutrition, 124(6), 577-585. doi:10.1017/S0007114520001336 google scholar
8. eszka-Skowron, M., Zgola-Grzeskowiak, A., Stanisz, E., & Wask-iewicz, A. (2017). Potential health benefits and quality of dried fruits: Goji fruits, cranberries and raisins. Food Chemistry, 221, 228-236. doi:10.1016/j.foodchem.2016.10.049 google scholar

9. Johannes, C. B., Araujo, A. B., Feldman, H. A., Derby, C. A., Kleinman, K. P., & McKinlay, J. B. (2000). In-cidence of erectile dysfunction in men 40 to 69 years old: longitudinal results from the Massachusetts male aging study. Journal of Urology, 163(2), 460-463. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/10647654 google scholar
10. Jurikova, T., Skrovankova, S., Mlcek, J., Balla, S., & Snopek, L. (2018). Bioactive Compounds, Antioxidant Activity, and Biological Ef-fects of European Cranberry (Vaccinium oxycoccos). Molecules, 24(1). doi:10.3390/molecules24010024 google scholar
11. Karakaya, S., Yilmaz Oral, D., Gur, S., Duman, H., & Kilic, C. S. (2019). Effect of Extracts of the Aerial Parts and Roots from Four Ferulago Species on Erectile Dysfunc-tion in Rats with Streptozotocin-Induced Diabetes. Turk-ish Journal of Pharmaceutical Sciences, 16(3), 317-325. doi:10.4274/tjps.galenos.2018.26879 google scholar
12. Liska, D. J., Kern, H. J., & Maki, K. C. (2016). Cranberries and Urinary Tract Infections: How Can the Same Evidence Lead to Conflicting Advice? Advances in Nutrition, 7(3), 498-506. doi:10.3945/an.115.011197 google scholar
13. Maher, M. A., Mataczynski, H., Stefaniak, H. M., & Wilson, T. (2000). Cranberry juice induces nitric oxide-dependent vasodi-lation in vitro and its infusion transiently reduces blood pressure in anesthetized rats. Journal of Medicinal Food, 3(3), 141-147. doi:10.1089/jmf.2000.3.141 google scholar
14. Mazzilli, R., Elia, J., Delfino, M., Benedetti, F., Scordovillo, G., & Mazzilli, F. (2015). Prevalence of Diabetes Mellitus (DM) in a population of men affected by Erectile Dysfunction (ED). Clinical Therapeutics, 166(5), e317-320. doi:10.7417/T.2015.1885 google scholar
15. Mojaverrostami, S., Bojnordi, M. N., Ghasemi-Kasman, M., Ebrahimzadeh, M. A., & Hamidabadi, H. G. (2018). A Review of Herbal Therapy in Multiple Sclerosis. Advanced Pharmaceutical Bulletin, 8(4), 575-590. doi:10.15171/apb.2018.066 google scholar
16. Nemr, E., El Helou, E., Mjaess, G., Semaan, A., & Chebel, J. A. (2020). Prospective Multicenter Open-Label One-Arm Trial Investigating a Pumpkin Seed, Isoflavonoids, and Cranberry Mix in Lower Urinary Tract Symptoms/Benign Prostatic Hy-perplasia: A Pilot Study. Advanced in Urology, 2020, 6325490. doi:10.1155/2020/6325490 google scholar
17. Nemzer, B. V., Al-Taher, F., Yashin, A., Revelsky, I., & Yashin, Y. (2022). Cranberry: Chemical Composition, Antioxidant Activ-ity and Impact on Human Health: Overview. Molecules, 27(5). doi:10.3390/molecules27051503 google scholar
18. Olas, B. (2017). The multifunctionality of berries to-ward blood platelets and the role of berry phenolics in cardiovascular disorders. Platelets, 28(6), 540-549. doi:10.1080/09537104.2016.1235689 google scholar
19. Onder, A., Yilmaz-Oral, D., Jerkovic, I., Akdemir, A. O., & Gur, S. (2019). Evaluation of relaxant responses properties of cin-namon essential oil and its major component, cinnamaldehyde on human and rat corpus cavernosum. The International Brazil-ian Journal of Urology, 45(5), 1033-1042. doi:10.1590/S1677-5538.IBJU.2019.0016 google scholar
20. Petre, G. C., Francini-Pesenti, F., Vitagliano, A., Grande, G., Ferlin, A., & Garolla, A. (2023). Dietary Supplements for Erec-tile Dysfunction: Analysis of Marketed Products, Systematic Review, Meta-Analysis and Rational Use. Nutrients, 15(17), 3677. doi:10.3390/nu1517367 google scholar
21. Rossi, R., Porta, S., & Canovi, B. (2010). Overview on cranberry and urinary tract infections in females. Jour-nal of Clinical Gastroenterology, 44 Suppl 1, S61-62. doi:10.1097/MCG.0b013e3181d2dc8e google scholar
22. Ruan, Y., Li, M., Wang, T., Yang, J., Rao, K., Wang, S., . . . Ye, Z. (2016). Taurine Supplementation Improves Erec-tile Function in Rats with Streptozotocin-induced Type 1 Di-abetes via Amelioration of Penile Fibrosis and Endothelial Dysfunction. The Journal of Sexual Medicine 13(5), 778-785. doi:10.1016/j.jsxm.2016.02.164 google scholar
23. Salahdeen, H. M., Idowu, G. O., Yemitan, O. K., Murtala, B. A., & Al-ada, A. R. (2015). The relaxant actions of ethanolic extract of Tri-dax procumbens (Linn.) on rat corpus cavernosum smooth muscle contraction. Journal of Basic and Clinical Pharmacy, 26(2), 211216. doi:10.1515/jbcpp-2013-0032 google scholar
24. Shin, Y. S., Zhao, C., Zhang, L. T., & Park, J. K. (2015). Current Sta-tus and Clinical Studies of Oriental Herbs in Sexual Medicine in Korea. The World Journal of Men’s Health, 33(2), 62-72. doi:10.5534/wjmh.2015.33.2.62 google scholar
25. Shukitt-Hale, B., Galli, R. L., Meterko, V., Carey, A., Bielinski, D. F., McGhie, T., & Joseph, J. A. (2005). Dietary supplementation with fruit polyphenolics ameliorates age-related deficits in behavior and neuronal markers of inflammation and oxidative stress. Age (Dordr), 27(1), 49-57. doi:10.1007/s11357-005-4004-9 google scholar
26. Skrovankova, S., Sumczynski, D., Mlcek, J., Jurikova, T., & Sochor, J. (2015). Bioactive Compounds and Antioxidant Activity in Differ-ent Types of Berries. International Journal of Molecular Sciences, 16(10), 24673-24706. doi:10.3390/ijms161024673 google scholar
27. Stasiak, M., Zarlok, K., & Tomaszewski, W. (2016). [Erectile dysfunction - treatment with substances of natural origin]. Wiadomosci Lekarskie, 69(3 pt 2), 576-581. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/27717948 google scholar
28. Vidlar, A., Vostalova, J., Ulrichova, J., Student, V., Stejskal, D., Re-ichenbach, R., . . . Simanek, V. (2010). The effectiveness of dried cranberries ( Vaccinium macrocarpon) in men with lower urinary tract symptoms. British Journal of Nutrition, 104(8), 1181-1189. doi:10.1017/S0007114510002059 google scholar
29. Yarnell, E. (2002). Botanical medicines for the urinary tract. The World Journal of Urology, 20(5), 285-293. doi:10.1007/s00345-002-0293-0 google scholar
30. Yilmaz, D., Bayatli, N., Un, O., Kadowitz, P. J., Sikka, S. C., Gur, S. (2014). The effect of intracavernosal avanafil, a newer phosphodiesterase-5 inhibitor, on neonatal type 2 dia-betic rats with erectile dysfunction. Urology, 83(2):508.e7-12. doi: 10.1016/j.urology.2013.10.021. google scholar
31. Yung, L. M., Tian, X. Y., Wong, W. T., Leung, F. P., Yung, L. H., Chen, Z. Y., . . . Huang, Y. (2013). Chronic cranberry juice consumption restores cholesterol profiles and improves endothelial function in ovariectomized rats. European Journal of Nutrition, 52(3), 11451155. doi:10.1007/s00394-012-0425-2 google scholar