Fruit Extract of Black Pepper (Piper Nigrum L.) Ameliorates Male Reproductive Dysfunction in Alloxan-Induced Diabetic Rats
Urology Journal,
Vol. 23 No. 02 (2026),
20 June 2026
,
Page 60-66
https://doi.org/10.22037/uj.v23i00.8546
Abstract
Purpose: Diabetes mellitus is a chronic hyperglycemic condition leading to metabolic problems that cause organ damage and result in serious complications. Long-term complications of diabetes can cause serious health problems, such as sexual and reproductive dysfunction in men and women. Black pepper (Piper nigrum L.) is a medicinal plant proven to increase testosterone hormone levels, sexual function (libido), and spermatogenesis parameters in male rats. In this study, the effect of black pepper fruit extract on sexual function and reproductive function (fertility) in alloxan-induced diabetic male rats was evaluated.
Materials and Methods: A total of 30 male Sprague Dawley rats (Rattus norvegicus), aged 2.5 to 3 months and weighing 100-150 g, were divided into five groups of 6 individuals each. Group I consisted of rats given only standard feed. Group II consisted of alloxan-induced hyperglycemic rats given standard feed. Groups III and IV were alloxan-induced hyperglycemic rats given black pepper extract at 122.5 and 245 mg/kg BW, respectively, for 8 days. Group V consisted of alloxan-induced hyperglycemic rats given sildenafil therapy or zinc plus ascorbic acid. After 8 days of treatment, the erectile function and libido of the rats were assessed, followed by an evaluation of spermatozoa and testicular histology. Data were analyzed using ANOVA with significance set at p < 0.05.
Results: Alloxan-induced diabetic rats showed significant impairment in erectile function, libido, sperm quality, and testicular histology (p < 0.001 vs. control). Administration of black pepper extract at a dose of 122.5 mg/kg BW increased total penile reflexes (9.33 ± 1.03 vs. 6.00 ± 1.26 in the diabetes group, p = 0.002) and improved libido, with a decrease in courtship latency (5.50 ± 0.55 s vs. 21.00 ± 9.47 s, p = 0.013) and an increase in mounting frequency (18.05 ± 5.99 vs. 7.17 ± 1.83, p = 0.009). The extract dose of 245 mg/kg BW increased sperm concentration (158.16 ± 29.80 vs. 12.6 ± 1.3 ×10⁶, p < 0.001), progressive sperm motility (65.0 ± 35% vs. 27.0 ± 30%, p = 0.006), and normal sperm morphology (82.9 ± 5.7% vs. 35.0 ± 10.8%, p < 0.001). The number of Leydig cells increased significantly in the 122.5 mg/kg BW extract group (59.33 ± 4.08 vs. 30.50 ± 3.86; p < 0.001) compared to the diabetes group. There was no significant difference in spermatogonia count (640 ± 86.5 vs. 491 ± 37.0; p = 0.119).
Conclusion: Piper nigrum fruit extract ameliorates sexual dysfunction and reproductive impairment in alloxan-induced diabetic rats, particularly at 122.5 mg/kg BW, with significant improvements in erectile function, libido, sperm quality, and testicular histology. These findings suggest its potential as a natural therapeutic agent for diabetes-related male reproductive dysfunction.
- diabetes mellitus
- hyperglycemia
- black pepper
- piper nigrum
- erectile function
- libido
- spermatozoa count
- spermatogonia count
How to Cite
References
1. Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of Hyperglycemia in Type 2 Diabetes: A Patient-Centered Approach: Position Statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2012;35:1364-1379.
2. International Diabetes Federation. IDF Diabetes Atlas. 11th ed. Brussels International Diabetes Federation; 2025.
3. Mansour A, Mousa M, Abdelmannan D, Tay G, Hassoun A, Alsafar H. Microvascular and macrovascular complications of type 2 diabetes mellitus: Exome wide association analyses. Microvascular and macrovascular complications of type 2 diabetes mellitus: Exome wide association analyses. 2023; 14:1143067.
4. Defeudis G, Mazzilli R, Tenuta M, et al. Erectile dysfunction and diabetes: A melting pot of circumstances and treatments. Diabetes/Metabolism Research and Reviews. 2021;38(2):e3494.
5. Huang R, Chen J, Guo B, Jiang C, Sun W. Diabetes-induced male infertility: potential mechanisms and treatment options. Molecular Medicine (Cambridge, Mass). 2024; 15;30:11
6. Grossmann M, Thomas MC, Panagiotopoulos S, et al. Low Testosterone Levels Are Common and Associated with Insulin Resistance in Men with Diabetes. The Journal of Clinical Endocrinology & Metabolism. 2008;93:1834-1840.
7. Yao Q, Wang B, An X, Zhang J, Ding L. Testosterone level and risk of type 2 diabetes in men: a systematic review and meta-analysis. Endocrine Connections. 2018;7:220-231.
8. Corona G, Maggi M. The role of testosterone in male sexual function. Reviews in Endocrine and Metabolic Disorders. 2022;23:1159-1172.
9. Smith LB, Walker WH. The regulation of spermatogenesis by androgens. Seminars in Cell & Developmental Biology. 2014;30:2-13.
10. Ghosal S. The Side Effects Of Metformin - A Review. Diabetes & Metabolic Disorders. 2019;6:1-7.
11. Atal S, Atal S, Vyas S, Phadnis P. Bio-enhancing effect of Piperine with Metformin on lowering blood glucose level in Alloxan induced diabetic mice. Pharmacognosy Research. 2016;8:56..
12. Gerfan Patandung. Potential of Black Pepper Extract (Piper Nigrum L) as Antidiabetic and Anticholesterol in Alloxan and Propylthiouracil (PTU) Induced Wistar Rats. Pakistan Journal of Life and Social Sciences (PJLSS). 2024; 22: 20289-20301.
13. Sutyarso, Kanedi M, Rosa E. Effects of Black Pepper (Piper nigrum Linn.) Extract on Sexual Drive in Male Mice. Research Journal of Medicinal Plant. 2015;9:42-47.
14. Sutyarso, Muhartono, Kanedi M. The Effect of Fruit Extracts of Black Pepper on the Fertility Potential of Male Albino Rats. American Journal of Medical and Biological Research. 2016;4:1-4.
15. Sheriff OL, Olayemi O, Taofeeq AO, Riskat KE, Ojochebo DE, Ibukunoluwa AO. A New model for Alloxan-induced diabetes mellitus in rats. Journal of Bangladesh Society of Physiologist. 2020;14:56-62.
16. Balhara YP, Sarkar S, Gupta R. Phosphodiesterase-5 inhibitors for erectile dysfunction in patients with diabetes mellitus: A systematic review and meta-analysis of randomized controlled trials. Indian Journal of Endocrinology and Metabolism. 2015;19:451.
17. Usta M, Gurbuz N, Kol A, Ipekci T, Ates E, Baykal A. Chronic administration of sildenafil improves erectile function in a rat model of chronic renal failure. Asian Journal of Andrology. 2015;17:797.
18. Ajayi AF, Akhigbe RE. Assessment of sexual behaviour and fertility indices in male rabbits following chronic codeine use. Andrology. 2019;8:509-515.
19. Fouche G, Afolayan AJ, Wintola OA, Khorombi TE, Senabe J. Effect of the aqueous extract of the aerial parts of Monsonia angustifolia E. Mey. Ex A. Rich., on the sexual behaviour of male Wistar rats. BMC Complementary and Alternative Medicine. 2015;15:343.
20. Gusti Ayu, Exsa Hadibrata, Andi Eka, Susianti. The Effect Of Black Pepper (Piper nigrum L.) Extract on Male White Rat (Rattus norvegicus) Libido (Sexual Behavior) With Diabetes Mellitus. J Medula. 2025. 14: 1707-1712
21. Kaleem M, Sheema, Sarmad H, Bano B. Protective effects of Piper nigrum and Vinca rosea in alloxan induced diabetic rats. Indian J Physiol Pharmacol. 2005. 49: 65-71
22. He Z, Yin G, Li QQ, Zeng Q, Duan J. Diabetes Mellitus Causes Male Reproductive Dysfunction: A Review of the Evidence and Mechanisms. In Vivo 2021; 35:2503-2511.
23. Sheikh-Ali M, Sultan S, Alamir AR, Haas MJ, Mooradian AD. Hyperglycemia-induced endoplasmic reticulum stress in endothelial cells. Nutrition 2010; 26 : 1146-50.
24. Guo S, Zhao D, Zang Z, Shao D, Zhang K, Fu Q. Effects of endoplasmic reticulum stress on erectile function in rats with cavernous nerve injury. Sex Med 2023; 3;11:qfad050.
25. Du Z, Xu S, Hu S, Yang H, Zhou Z, Sidhu K, et al. Melatonin attenuates detrimental effects of diabetes on the niche of mouse spermatogonial stem cells by maintaining Leydig cells. Cell Death & Disease 2018; 9 : 968
26. Kashyap SR, Roman LJ, Lamont J, Masters BSS, et al., Insulin Resistance Is Associated with Impaired Nitric Oxide Synthase Activity in Skeletal Muscle of Type 2 Diabetic Subjects, The Journal of Clinical Endocrinology & Metabolism 2005; 90 : 1100–1105
27. Maresch CC, Stute DC, Alves MG, Oliveira PF, de Kretser DM & Linn T, Diabetes-induced hyperglycemia impairs male reproductive function: a systematic review, Human Reproduction Update 2018; 24: 86–105.
28. Rahmawati N and Bachri MS. The aphrodisiac effect and toxicity of combination Piper retrofractum L, Centella asiatica, and Curcuma domestica infusion. Health Science Indonesia 2012; 3 : 19-22
29. Rizk PJ, Kohn TP, Pastuszak AW, Khera M. Testosterone therapy improves erectile function and libido in hypogonadal men. Curr Opin Urol 2017; 27 :511-515.
30. Chinta G, Coumar MS, Periyasamy L. Reversible Testicular Toxicity of Piperine on Male Albino Rats. Pharmacogn Mag 2017; 13(Suppl 3):S525-S532.
31. Chen X, Ge F, Liu J, Bao S, Chen Y, Li D, Li Y, Huang T, Chen X, Zhu Q, Lian Q, Ge RS. Diverged Effects of Piperine on Testicular Development: Stimulating Leydig Cell Development but Inhibiting Spermatogenesis in Rats. Front Pharmacol 2018; 28 ;9:244.
32. Ere R, Imasuen J, Ere-Richard A. Additive effect of ethanolic extract of Black Pepper (Piper nigrum) on gonadosomatic weight of testes and testicular histomorphometry: in relation to spermatogenesis in Rabbit bucks. Glob. J. Anim. Sci. Res 2020; 8:18-29.
- Abstract Viewed: 273 times
- 8546/pdf Downloaded: 39 times