Document Type : Original Article


1 Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran

2 Department of Anatomical Sciences, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

3 Connective Tissue Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran


About a third of human infertility is related to male factors. Of these, idiopathic-related infertility is not curable. Diabetes mellitus is a metabolic disorder affecting male impotence and fertility by increased production of free radicals and oxidative stress. Saponin, a glycosidic compound found in many plants, improves sperm parameters. The present study investigated the effect of saponin on sperm oxidative stress and testicular structure in streptozotocin (STZ)-induced diabetic mice. The diabetes was induced by the administration of 150 mg kg-1 STZ via a single intra-peritoneal injection. All experimental mice were allocated to the following groups: Control group, diabetic control group, diabetic group administrated 100 mg kg-1 saponin daily and one healthy group administrated saponin daily for 56 days. At the end of the treatment period, serum levels of insulin, glucose and oxidative stress markers were measured. A histological evaluation of testicles was performed. Treatment of diabetic mice with saponin ameliorated testicular tissue damage as well as serum glucose and insulin concentrations. Furthermore, in the diabetic group, the serum concentration of malondialdehyde was increased; while, the activity of superoxide dismutase and glutathione peroxidase enzymes was reduced. The mean Johnsen's score and the diameter and thickness of seminiferous tubules were lower in the diabetic mice than control ones. However, these parameters were higher in the saponin-treated mice than controls. Overall, saponin administration rectified all examined parameters. The anti-oxidant role of saponin improves sperm parameters and diabetes-induced testicular oxidative damage.


Main Subjects

  1. Modaresi M, Mesripour M, Asadi Morghmaleki M, et al. The effect of saffron extract on testis tissue [Persian]. Iran J Med Aroma Plants 2008; 24(2): 237-243.
  2. Ameli M, Moghimian M, Saeb F, et al. The effect of clomiphene citrate and human chorionic gonadotropin on the expression of CatSper1, CatSper2, LHCGR, and SF1 genes, as well as the structural changes in testicular tissue of adult rats. Mol Reprod Dev 2019; 86(6): 738-748.
  3. Durairajanayagam D. Lifestyle causes of male infertility. Arab J Urol 2018; 16(1): 10-20.
  4. Abtahi-Evari SH, Shokoohi M, Abbasi A, et al. Protective effect of Galega officinalis extract on streptozotocin-induced kidney damage and biochemical factor in diabetic rats. Crescent J Med Biol Sci 2017; 4(3):108-114.
  5. Shoorei H, Khaki A, Shokoohi M, et al. Evaluation of carvacrol on pituitary and sexual hormones and their receptors in the testicle of male diabetic rats. Hum Exp Toxicol 2020; 39(8): 1019-1030.
  6. Shoorei H, Banimohammad M, Kebria MM, et al. Hesperidin improves the follicular development in 3D culture of isolated preantral ovarian follicles of mice. Exp Biol Med (Maywood) 2019; 244(5): 352-361.
  7. Shoorei H, Khaki A, Khaki AA, et al. The ameliorative effect of carvacrol on oxidative stress and germ cell apoptosis in testicular tissue of adult diabetic rats. Biomed Pharmacother 2019; 111: 568-578.
  8. Fang JY, Lin CH, Huang TH, et al. In vivo rodent models of type 2 diabetes and their usefulness for evaluating flavonoid bioactivity. Nutrients 2019; 11(3): 530. doi: 10.3390/nu11030530.
  9. Gupta RS, Chaudhary R, Yadav RK, et al. Effect of saponins of Albizia lebbeck (L.) Benth bark on the reproductive system of male albino rats. J Ethnopharmacol 2005; 96(1-2):31-36.
  10. Ji M, Minami N, Yamada M, et al. Effect of proto-panaxatriol saponin on spermatogenic stem cell survival in busulfan-treated male mice. Reprod Med Biol 2007; 6(2): 99-108.
  11. Ventura-Sobrevilla J, Boone-Villa VD, Aguilar CN, et al. Effect of varying dose and administration of streptozotocin on blood sugar in male CD1 mice. Proc West Pharmacol Soc 2011; 54: 5-9.
  12. Shokri F, Shokoohi M, Niazkar HR, et al. investigation the spermatogenesis and testis structure in diabetic rats after treatment with Galega officinalis extract. Crescent J Med Biol Sci 2019; 6(1): 31-36.
  13. Muratoğlu S, Akarca Dizakar OS, Keskin Aktan A, et al. The protective role of melatonin and curcumin in the testis of young and aged rats. Andrologia 2019; 51(3): e13203. doi: 10.1111/and.13203.
  14. Arthur JR, Boyne R. Superoxide dismutase and glutathione peroxidase activities in neutrophils from selenium deficient and copper deficient cattle. Life Sci 1985; 36(16): 1569-1575.
  15. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976; 72: 248-254.
  16. Paglia DE, Valentine WN. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 1967; 70(1): 158-169.
  17. Barghi B, Shokoohi M, Khaki AA, et al. Eugenol improves tissue damage and oxidative stress in adult female rats after ovarian torsion/detorsion. J Obstet Gynaecol 2021; 41(6): 933-938.
  18. Pillion DJ, Amsden JA, Kensil CR, et al. Structure-function relationship among Quillaja saponins serving as excipients for nasal and ocular delivery of insulin. J Pharm Sci 1996; 85(5): 518-524.
  19. Kwon DY, Kim YS, Ryu SY, et al. Platyconic acid, a saponin from Platycodi radix, improves glucose homeostasis by enhancing insulin sensitivity in vitro and in vivo. Eur J Nutr 2012; 51(5): 529-540.
  20. Keller AC, Ma J, Kavalier A, et al. Saponins from the traditional medicinal plant Momordica charantia stimulate insulin secretion in vitro. Phytomedicine 2011; 19(1): 32-37.
  21. Oishi Y, Sakamoto T, Udagawa H, et al. Inhibition of increases in blood glucose and serum neutral fat by Momordica charantia saponin fraction. Biosci Biotechnol Biochem 2007; 71(3): 735-740.
  22. Ameli M, Hashemi MS, Moghimian M, et al. Protective effect of tadalafil and verapamil on testicular function and oxidative stress after torsion/detorsion in adult male rat. Andrologia 2018; 50(8): e13068. doi: 10.1111/and.13068.
  23. Zhang P, Li T, Wu X, et al. Oxidative stress and diabetes: antioxidative Front Med 2020; 14(5): 583-600.
  24. Bian D, Liu M, Li Y, et al. Madecassoside, a triterpenoid saponin isolated from Centella asiatica herbs, protects endothelial cells against oxidative stress. J Biochem Mol Toxicol 2012; 26(10): 399-406.
  25. Akbarizare M, Ofoghi H, Hadizadeh M. In vitro anticancer evaluation of saponins obtained from Spirulina platensis on MDA, HepG2, and MCF7 cell lines. Multidiscip Cancer Investig 2019; 3(4): 25-32.
  26. Hu JN, Yang JY, Jiang S, et al. Panax quinquefolium saponins protect against cisplatin evoked intestinal injury via ROS-mediated multiple mechanisms. Phyto-medicine 2021; 82: 153446. doi: 10.1016/ j.phymed. 2020.153446.
  27. Tremellen K. Oxidative stress and male infertility - - a clinical perspective. Hum Reprod Update 2008; 14(3): 243-258.
  28. Huang JL, Jing X, Tian X, et al. Neuroprotective properties of Panax notoginseng saponins via preventing oxidative stress injury in SAMP8 mice. Evid Based Complement Alternat Med 2017; 2017: 8713561. doi: 10.1155/2017/8713561.
  29. Francisco Javier O, Manuel R, Manuel RR. Regular physical activity increases glutathione peroxidase activity in adolescents with Down syndrome. Clin J Sport Med 2006;16(4): 355-356.
  30. Schoeller EL, Schon S, Moley KH. The effects of type 1 diabetes on the hypothalamic, pituitary and testes axis. Cell Tissue Res 2012; 349(3): 839-847.
  31. Shokoohi M, Khaki A, Shoorei H, et al. Hesperidin attenuated apoptotic-related genes in testicle of a male rat model of varicocoele. Andrology 2020; 8(1): 249-258.
  32. Wankeu-Nya M, Florea A, Bâlici S, et al. Dracaena arborea alleviates ultra-structural spermatogenic alterations in streptozotocin-induced diabetic rats. BMC Complement Altern Med 2013; 13, 71. doi: 10.1186/1472-6882-13-71.
  33. Lim JG, Park HM, Yoon KS. Analysis of saponin composition and comparison of the antioxidant activity of various parts of the quinoa plant (Chenopodium quinoa Willd.). Food Sci Nutr 2019; 8(1): 694-702.
  34. Sainio-Pöllänen S, Henriksén K, Parvinen M, et al. Stage-specific degeneration of germ cells in the seminiferous tubules of non-obese diabetic mice. Int J Androl. 1997; 20(4): 243-253.
  35. Amaral S, Oliveira PJ, Ramalho-Santos J: Diabetes and the impairment of reproductive function: possible role of mitochondria and reactive oxygen species. Curr Diabetes Rev 2008; 4(1): 46-54.
  36. Mallidis C, Agbaje I, McClure N, et al. The influence of diabetes mellitus on male reproductive function: a poorly investigated aspect of male infertility [German]. Urology A 2011, 50(1): 33-37.