Nerdy Nerdy, Linta Meliala, Bunga Rimta Barus, Puji Lestari, Selamat Ginting, Peny Ariani, Vriezka Mierza, Tedy Kurniawan Bakri


Male infertility has occurred rapidly in the last few decades, primarily in developing countries. An antioxidant, hesperetin is a flavonoid that
is found in abundance in orange peels. The aims of this research were to determine the effect of hesperetin on blood sugar levels, spermatozoa
quality, and spermatozoa quantity. The research structure included induction of diabetes mellitus and treatment for 8 weeks, followed by
determination of blood sugar levels, spermatozoa quality, and spermatozoa quantity. Hesperetin has the ability to restore blood sugar levels, spermatozoa quantity, seminiferous tubules diameter, and testicular weight, volume, and germinal epithelial layer thickness with significant difference from the normal control group. Hesperetin did not fully restore spermatozoa motility, viability, and morphology with significant difference from the normal control group, nor from the positive control group. However, overall, hesperetin decreased blood glucose levels, increased spermatozoa quantity, and improved the spermatozoa quality in alloxan-induced diabetes mellitus mice. Dose-dependent activity was observed with the optimum dose at 200 mg/kg body weight.


alloxan, blood glucose, diabetic, hesperetin, spermatozoa


Abdelhamid M.H.M., M. Walschaerts, G. Ahmad, R. Mieusset, L. Bujan, S. Hamdi. 2019. Mild experimental increase in testis and epididymis temperature in men - effects on sperm morphology according to spermatogenesis stages. Transl. Androl. Urol. 8(6):651-665.

Ahmed O.M., A.M. Mahmoud, A. Abdel-Moneim, and M.B. Ashour. 2012. Antidiabetic effects of hesperidin and naringin in type 2 diabetic rats. Diabetol. Croat. 41(2)2:53-67.

Al-Ishaq R.K., M. Abotaleb , P. Kubatka, K. Kajo, and D. Büsselberg. 2019. Flavonoids and their anti diabetic effects - cellular mechanisms and effects to improve blood sugar levels. Biomolecules. 9(9):430.

Al-Saeed M.H., M.A. Kadhem, and A.H. Al-Saeed. 2019. Study the effect of ethanolic extract of Ceratonia siliqua, glimepiride and metformin on semen fluid quality in diabetic male guinea pig induced by alloxan. Bas. J. Vet. Res. 18(2):208-233.

Alahmar A.T. 2019. Role of oxidative stress in male infertility - an updated review. J. Hum. Reprod. Sci. 12(1):4-18.

Altoe P.M., E.D. Tatsuo, D.N.S. Paulo, R. Jarske, M. Milagres, I.D. Loureiro. 2014. Effects of human chorionic gonadotropin on the normal testicular tissue of rats. Acta Cir. Bras. 29(5): 292-298.

Aryal S., M.K. Baniya, K. Danekhu, P. Kunwar, R. Gurung, and N. Koirala. 2019. Total phenolic content, flavonoid content and antioxidant potential of wild vegetables from western nepal. Plants. 8(4):96.

Bahar A., F. Elyasi, M. Moosazadeh, G. Afradi, and Z. Kashi. 2020. Sexual dysfunction in men with type 2 diabetes. Caspian J. Int. Med. 11(3):295-303.

Banjarnahor S.D.S., and N. Artanti. 2014. Antioxidant properties of flavonoids. Med. J. Indones. 23(4):239-244.

Benko F., V. Palkovičová, M. Ďuračka, J. Árvay, N. Lukáč, and E. Tvrdá. 2019. Antioxidant effects of marigold (Calendula officinalis) flower extract on the oxidative balance of bovine spermatozoa. Contemp. Agric. 68(3-4): 92-102

Biagi M., D. Noto, M. Corsini, G. Baini, D. Cerretani, G. Cappellucci, and E. Moretti. 2019. Antioxidant effect of the Castanea sativa Mill. leaf extract on oxidative stress induced upon human spermatozoa. Oxid. Med. Cell. Longev. 2019:8926075.

Caro-Ordieres T., G. Marín-Royo, L. Opazo-Ríos, L. Jiménez-Castilla, J.A. Moreno, C. Gómez-Guerrero, and J. Egido. 2020. The coming age of flavonoids in the treatment of diabetic complications. J. Clin. Med. 2020, 9(9):346.

Das N., and T.R. Kumar. 2018. Molecular regulation of follicle stimulating hormone synthesis, secretion and action. J. Mol. Endocrinol. 60(3):R131-R155.

Delpire E., and K.B. Gagnon. 2018. Water homeostasis and cell volume maintenance and regulation. Curr. Top. Membr. 81:3-52.

Deyhoul N., T Mohamaddoost, and M. Hosseini. 2017. Infertility related risk factors - a systematic review. Int. J. Women's Health and Reprod. Sci.. 5(1):24-29

Ding G.L., Y. Liu, M.E. Liu, J.X. Pan, M.X. Guo, J.Z. Sheng, and H.F. Huang. 2015. The effects of diabetes on male fertility and epigenetic regulation during spermatogenesis. Asian J. Androl. 17(6):948-953.

Dutta S., P. Sengupta, and S. Muhamad. 2019. Male reproductive hormones and semen quality. Asian Pac. J. Repro. 8(5):189-194.

Gandhi G.R., A.B.S. Vasconcelos, D.T. Wu, H.B. Li, P.J. Antony, H. Li, F. Geng, R. Q. Gurgel, N. Narain, and R.Y. Gan. 2020. Citrus flavonoids as promising phytochemicals targeting diabetes and related complications - a systematic review of in vitro and in vivo studies. Nutrients. 12(11):2907.

Gayatri P.R., S.A. Sudjarwo, and R. I'tishom. 2017. Potency of ethanol extract of dayak onion (Eleutherine americana Merr) as protector of testosteron level, diameter and thickness of seminiferous tubule in mice induced with lead acetate. J. of Appl. Sci. and Research. 5(4):43-51.

Gupta P.C., and A. Verma. 2018. Potential parameters in assessment of testicular toxicity. Biomed. J. Sci. & Tech. Res. 7(3):5915-5918.

Gregory S., and N.D. Kelly. 2011. Quercetin. Altern. Med. Rev. 16(2):172-194.

Jakubik-Uljasz J., K. Gil, A. Rosiak-Gill, and M. Piasecka. 2020. Relationship between sperm morphology and sperm DNA dispersion. Transl. Androl. Urol. 9(2):405-415.

Jofré I., M. Cuevas, L.S. de Castro, J.D. de Agostini Losano, M.A. Torres, M. Alvear, E. Scheuermann, A.F.C. Andrade, M. Nichi, M.E.O. Assumpção, and F. Romero. 2019. Antioxidant effect of a polyphenol rich murtilla (Ugni molinae Turcz.) extract and its effect on the regulation of metabolism in refrigerated boar sperm. Oxid. Med. Cell. Longev. 2019:2917513.

Kalwar Q., M. Chu., A.A. Ahmad, X. Ding, X. Wu, P. Bao, and P. Yan. 2019. Morphometric evaluation of spermatogenic cells and seminiferous tubules and exploration of luteinizing hormone beta polypeptide in testis of datong yak. Animals. 10(1):66.

Lenzen S. 2008. The Mechanisms of alloxan and streptozotocin induced diabetes. Diabetologia. 51(2):216-226.

Ligita T., K. Wicking, K. Francis, N. Harvey, and I. Nurjannah. 2019. How people living with diabetes in indonesia learn about their disease - a grounded theory study. Plos One. 10(1371):0212019.

Loeken M.R. 2012. A new role for pancreatic insulin in the male reproductive axis. Diabetes. 61(7):1667-1668

Maiorino M.I., G. Bellastella, K. Esposito. 2014. Diabetes and sexual dysfunction - current perspectives. Diabetes Metab. Syndr. Obes. Targets Ther. 7:95-105.

Mangoli E., A.R. Talebi, M. Anvari, and M. Pourentezari. 2013. Effects of experimentally - induced diabetes on sperm parameters and chromatin quality in mice. Iran J. Reprod. Med. 11(1):53-60.

Martin L.J., and M. Touaibia. 2020. Improvement of testicular steroidogenesis using flavonoids and isoflavonoids for prevention of late onset male hypogonadism. Antioxidants (Basel). 9(3):237.

Meneguzzo F., R. Ciriminna, F. Zabini, and M. Pagliaro. 2020. Review of evidence available on hesperidin rich products as potential tools against covid-19 and hydrodynamic cavitation based extraction as a method of increasing their production. Processes. 8(5):549.

Meneses M.J., M. Sousa, M.G. Alves, and P.F. Oliveira. 2015. The antidiabetic drug metformin and male reproductive function - an overview. Int. J. Diabetol. Vasc. Dis. Res. 3(1e):1-2.

Jalili C., M. Kamani, S. Roshankhah, H. Sadeghi, and M.R. Salahshoor. 2018. Effect of Falcaria vulgaris extracts on sperm parameters in diabetic rats. Andrologia. 50(10):e13130.

Nak-Ung S., N. Nakprom, C. Maneengam, S. Nudmamud-Thanoi, and S. Thanoi. 2018. Changes in sperm quality and testicular structure in a rat model of type 1 diabetes. Asian Biomed. 12(4):141-147.

Noda T., and M. Ikawa. 2019. Physiological Function of seminal vesicle secretions on male fecundity. Reprod. Med. Biol. 18(3):241-246.

Noh S., A. Go, D.B. Kim, M. Park, H.W. Jeon, and B. Kim. 2020. Role of antioxidant natural products in management of infertility - a review of their medicinal potential. Antioxidants. 9(10):957.

Oduwole O.O., H. Peltoketo, and I.T. Huhtaniemi. 2018. Role of follicle stimulating hormone in spermatogenesis. Front. Endocrinol. (Lausanne). 9:763.

Olayinka E.T., A. Ore, O.A. Adeyemo, O.S. Ola. 2019. The role of flavonoid antioxidant, morin in improving procarbazine induced oxidative stress on testicular function in rat. Porto Biomed. J. 4(1):e28.

Orieke D., O.C. Ohaeri, I.I. Ijeh, and S.N. Ijioma. 2019. Semen quality, hormone profile and histological changes in male albino rats treated with Corchorus olitorius leaf extract. Avicenna J. Phytomed. 9(6):551-562.

Parhizkar S., S.B. Zulkifli, and M.A. Dollah. 2019. Testicular morphology of male rats exposed to Phaleria macrocarpa aqueous extract. Iran J. Basic Med. Sci. 17(5):384-390.

Petersen P.M., K. Seierøe, and B. Pakkenberg. 2015. The total number of leydig and sertoli cells in the testes of men across various age groups - a stereological study. J. Anat. 226(2):175-179.

Popal W., and Z.P. Nagy. 2013. Laboratory processing and intracytoplasmic sperm injection using epididymal and testicular spermatozoa - what can be done to improve outcomes. Clinics (Sao Paulo). 68(Suppl 1):125-130.

Ramaswamy S., and G.F. Weinbauer. 2014. Endocrine control of spermatogenesis - role of follicle stimulating hormone and luteinizing hormone or testosterone. Spermatogenesis. 4(2): e996025.

Saez F., A. Ouvrier, and J.R. Drevet. 2011. Epididymis cholesterol homeostasis and sperm fertilizing ability. Asian J. Androl. 13(1):11-17.

Salimnejad R., G. Sazegar, M.J.S. Borujeni, S.M. Mousavi, F. Salehi, and F. Ghorbani. 2017. Protective effect of hydroalcoholic extract of Teucrium polium on diabetes induced testicular damage and serum testosterone concentration. Int. J. Reprod. Biomed. 15(4):195-202.

Sarian M.N., Q.U. Ahmed, S.Z.M. So’ad, A.M. Alhassan, S. Murugesu, V. Perumal, S.N.A.S. Mohamad, A. Khatib, and J. Latip. 2017. Antioxidant and antidiabetic effects of flavonoids - a structure activity relationship based study. Biomed. Res. Int. 2017:8386065.

Shi G.J., Y. Li, Q.H. Cao, H.X. Wu, X.Y. Tang, X.H. Gao, J.Q. Yu, Z. Chen, Y. Yang. 2020. In vitro and in vivo evidence that quercetin protects against diabetes and its complications - a systematic review of the literature. Biomed. Pharmacother. 109:1085-1099.

Soliman G.A., A.S. Saeedan, R.F. Abdel-Rahman, H.A. Ogaly, R.M. Abd-Elsalam, and M.S. Abdel-Kader. 2019. Olive leaves extract attenuates type 2 diabetes mellitus induced testicular damage in rats - molecular and biochemical study. Saudi Pharm. J. 27(3):326-340.

Swee D.S., and R. Quinton. 2019. Managing congenital hypogonadotrophic hypogonadism - a contemporary approach directed at optimizing fertility and long term outcomes in males. Ther. Adv. Endocrinol. Metab. 10:2042018819826889.

Tvrda E., P. Straka, D. Galbavy, and P. Ivanic. 2019. Epicatechin provides antioxidant protection to bovine spermatozoa subjected to induced oxidative stress. Molecules. 24(18):3226.

DOI: https://doi.org/10.21157/j.ked.hewan.v15i1.18406

Article Metrics

Abstract view : 0 times


  • There are currently no refbacks.

Indexed by:


p-ISSN: 1978-225X e-ISSN: 2502-5600 Copyright© 2007-2021