The Effect of Caffeic Acid Administration on the Antioxidant Status of the Seminal Vesicle in a High Fructose-Streptozotocin in a Diabetic Male Wistar Rat
Main Article Content
Abstract
Diabetes mellitus is a metabolic disease associated with oxidative stress, which impairs the histoarchitecture of seminal vesicles and impairs male reproductive activity. The aim of the study was to examine the protective properties of caffeic acid on diabetes-induced injury in male Wistar rat seminal vesicles. Twenty (20) adult rats were utilized with twenty controls having normal glucose levels and ten rats having diabetes induced by a single intraperitoneal injection of streptozotocin (50 mg/kg). A digital glucometer was used to measure the blood glucose levels 48 hours after induction, and a diagnosis of diabetes was made at a level of greater than 250 mg/dl, when the glucose level was found to be at fasting levels. The experimental groups (experimental, control, fructose-streptozotocin (FRUC-STZ), fructose-streptozotocin combined with caffeic acid (FRUC-STZ + CA)) were assigned randomly to the animals. The diabetic groups were fed with 10% fructose solution and caffeic acid (50 mg/kg) was given orally. Control group was treated with citrate buffer. The body weight and the level of blood glucose were monitored during the study. At the conclusion of the experimental period, animals were euthanized, and blood samples were taken to be tested by hormonal and biochemical analyses, and seminal vesicles were taken to be studied by a histological technique. Findings indicated that diabetic rats had high blood glucose levels, low insulin levels, and severe distortion of seminal vesicle structure. Nonetheless, these changes were greatly reduced upon treatment using caffeic acid to restore antioxidant status and promote tissue morphology. The results indicate that caffeic acid alleviates oxidative stress, improves the insulin activity, and maintains seminal vesicle integrity in diabetic circumstances.
Article Details
Copyright (c) 2026 Grace Ojonugwa Adige, Tolaniawo Oluwaleke Ogunleye, Mercy Omolola Olukoya, Elijah Olawatosin Olopade, Oluyemi Anthonia Agboola, Kayode Adedapo (Author)
This work is licensed under a Creative Commons Attribution 4.0 International License.
Adeyemi, D. O., Ukwenya, V. O., Obuotor, E. M., & Adewole, S. O. (2014). Anti-hepatotoxic activities of Hibiscus sabdariffa L. in an animal model of streptozotocin diabetes-induced liver damage. BMC complementary and alternative medicine, 14(1), 1-11. DOI:10.1186/1472-6882-14-277 DOI: https://doi.org/10.1186/1472-6882-14-277
Agunloye, O.M., Oboh, G., Ademiluyi, A.O., Ademosun, A.O., Akindahunsi, A.A., Oyagbemi, A.A., Temidayo, O.O., Temitayo, O.A., & Adeolu, A.A. (2019). Cardio-protective and antioxidant properties of caffeic acid and chlorogenic acid: mechanistic role of angiotensin converting enzyme, cholinesterase, and arginase activities in cyclosporine-induced hypertensive rats. Biomedical Pharmacothermal. 109:450–8. doi: 10.1016/j.biopha.2018.10.044 . DOI: https://doi.org/10.1016/j.biopha.2018.10.044
Al-Awar, A., Kupai, K., Veszelka, M., Szűcs, G., Attieh, Z., Murlasits, Z., & Varga, C. (2016). Experimental diabetes mellitus in different animal models. Journal of diabetes research. 2016;2016:9051426.DOI:10.1155/2016/9051426 DOI: https://doi.org/10.1155/2016/9051426
Al Faris, N.A., Al Sawadi, A.D., & Alokail, M.S. (2010). Effect of Samh seeds supplementation (Mesembryanthemum forsskalei Hochst) on liver enzymes and lipid profiles of streptozotocin (STZ) induced diabetic Wistar rats. Saudi Journal of Biological Sciences; 17(1), 23–8. doi: 10.1016/j.sjbs.2009.12.004 DOI: https://doi.org/10.1016/j.sjbs.2009.12.004
Anuradha, C. V. (2009). Amino acid support in the prevention of diabetes and diabetic complications. Current Protein & Peptide Science, 10(1), 8–17. DOI: https://doi.org/10.2174/138920309787315194 DOI: https://doi.org/10.2174/138920309787315194
Ashwal, E., & Hod, M. (2015). Gestational diabetes mellitus: where are we now? Clinica Chimica Acta, 451(Pt A), 14-20. DOI:10.1016/j.cca.2015.01.021 DOI: https://doi.org/10.1016/j.cca.2015.01.021
Asmat, U., Abad, K., & Ismail, K. (2016). Diabetes mellitus and oxidative stress—A concise review. Saudi Pharmaceutical Journal, 24(5), 547-553. DOI:10.1016/j.jsps.2015.03.013 DOI: https://doi.org/10.1016/j.jsps.2015.03.013
Bădescu, S. V., Tătaru, C., Kobylinska, L., Georgescu, E. L., Zahiu, D.M., Zăgrean, A.M., & Zăgrean, L. (2016). Effects of caffeine on locomotor activity in streptozotocin-induced diabetic rats. Journal of medicine and life, 9(2), 120-125.
Baynes, H. W. (2015). Classification, pathophysiology, diagnosis, and management of diabetes mellitus. Journal of Diabetes Metabolism, 6(5), 1-9. https://doi.org/10.4172/2155-6156.1000541 DOI: https://doi.org/10.4172/2155-6156.1000541
Baz, B., Riveline, J.-P., & Gautier, J.-F. (2016). Gestational diabetes mellitus: definition, aetiological and clinical aspects. European Journal of Endocrinology, 174(2), R43-51. DOI:10.1530/EJE-15-0378 DOI: https://doi.org/10.1530/EJE-15-0378
Birková, A. (2020). Caffeic acid: a brief overview of its presence, metabolism, and bioactivity. Bioactive Compounds in Health and Disease, 3(4), 74-81. DOI:10.31989/bchd.v3i4.692 DOI: https://doi.org/10.31989/bchd.v3i4.692
Birowo, P., Uckert, S., Kedia, G.T., Scheller, F., & Meyer, M. (2009). Evaluating the role of the serotonergic system in the control of human seminal vesicle smooth muscle – An in vitro approach. Journal of Sexual Medicine; 6: 2672–9. DOI:10.1111/j.1743-6109.2009.01423.x DOI: https://doi.org/10.1111/j.1743-6109.2009.01423.x
Bispo, V.S., Dantas, L.S., Chaves Filho, A.B., Pinto, I.F.D., Silva Rp, D.A., & Otsuka, F.A.M. (2017). Reduction of the DNA damages, hepatoprotective effect, and antioxidant potential of the coconut water, ascorbic, and caffeic acids in oxidative stress mediated by ethanol. An Acad Bras Cienc, 89, 1095–9. https://doi.org/10.1590/0001-3765201720160581 DOI: https://doi.org/10.1590/0001-3765201720160581
Bromfield, J.J., Schjenken, J.E., Chin, P.Y, Care, A.S., & Jasper, M.J. (2014). Maternal tract factors contribute to paternal seminal fluid's impact on metabolic phenotype in offspring. Production National Academic Science, 111(6), 2200-2205. DOI:10.1073/pnas. 1305609111 DOI: https://doi.org/10.1073/pnas.1305609111
Boštjan Martinc. (2026). Oxidative stress biomarkers in type 2 diabetes: Pathophysiological insights, clinical relevance, and implications for diabetes complications. Diabetes Research and Clinical Practice, 235, 113197. https://doi.org/10.1016/j.diabres.2026.113197 DOI: https://doi.org/10.1016/j.diabres.2026.113197
Celik, S., & Erdogan, S. (2008). Caffeic acid phenethyl ester (CAPE) protects the brain against oxidative stress and inflammation induced by diabetes in rats. Molecular and Cellular Biochemistry, 312(1–2), 39–46. https://doi.org/10.1007/s11010-008-9719-3 DOI: https://doi.org/10.1007/s11010-008-9719-3
Chao, P.-c., Hsu, C.-c., & Yin, M.-c. (2009). Anti-inflammatory and anti-coagulatory activities of caffeic acid and ellagic acid in cardiac tissue of diabetic mice. Nutrition & metabolism, 6(1), 1-8. DOI:10.1186/1743-7075-6-33 DOI: https://doi.org/10.1186/1743-7075-6-33
Cheng, J.T., Liu, I.M., Tzeng, T.F., Chen, W.C., Hayakawa, S., & Yamamoto, T. (2003). Release of beta-endorphin by caffeic acid to lower plasma glucose in streptozotocin-induced diabetic rats. Hormonal Metabolism Reservation 35(8), 251–258. DOI:10.1055/s-2003-39482 DOI: https://doi.org/10.1055/s-2003-39482
Damasceno, S. S., Dantas, B. B., Ribeiro-Filho, J., Araújo, D. A. M., & da Costa, J. G. M. (2017). Chemical properties of caffeic and ferulic acids in biological systems: Implications in cancer therapy. A review. Current Pharmaceutical Design, 23(20), 3015–3023. doi: 10.2174/1381612822666161208145508 DOI: https://doi.org/10.2174/1381612822666161208145508
Dena, S. M., Adeleye, A. O., Mohlala, K., Langa, B. C., & Opuwari, C. S. (2025). The Impact of Diabetes Mellitus-Related Oxidative Stress on Male Fertility: A Review. Journal of Diabetes, 17(10), e70157. https://doi.org/10.1111/1753-0407.70157 DOI: https://doi.org/10.1111/1753-0407.70157
Eroschenko, V. P., & Fiore, M. S. H. di. (2013). DiFiores Atlas of Histology with Functional Correlations (12th ed.). Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. 409-423.
Frost, P. A., Chen, S., Mezzles, M. J., Voruganti, V. S., Nava‐Gonzalez, E. J., Arriaga‐Cazares, H. E., & Grayburn, P. A. (2015). Successful pharmaceutical‐grade streptozotocin (STZ)‐induced hyperglycemia in a conscious tethered baboon (Papio hamadryas) model. Journal of Medical Primatology,44(4), 202-217. https://doi.org/10.1111/jmp.12182 DOI: https://doi.org/10.1111/jmp.12182
Giacco, F. & Brownlee, M. (2010). Oxidative stress and diabetic complications. Circulation Research, 107(9), 1058–1070. DOI:10.1161/CIRCRESAHA.110.223545 DOI: https://doi.org/10.1161/CIRCRESAHA.110.223545
Goud, B. J., Dwarakanath, V., & Swamy, B. K. C. (2015). Streptozotocin - A diabetogenic agent in animal models. International Journal of Pharmacy and Pharmaceutical Research, 3(1), 253-269. https://doi.org/10.1080/15569543.2022.2150646 DOI: https://doi.org/10.1080/15569543.2022.2150646
Herr, R. R., Jahnke, H. K., & Argoudelis, A. D. (1967). Structure of streptozotocin. Journal of the American Chemical Society, 89(18), 4808–4809. https://doi.org/10.1021/ja00994a053 DOI: https://doi.org/10.1021/ja00994a053
Hsu, F.L., Chen, Y.C., & Cheng, J.T. (2000). Caffeic acid as an active principle from the fruit of Xanthium strumarium to lower plasma glucose in diabetic rats. Planta Medicine 66(3),228–230. DOI:10.1055/s-2000-8561 DOI: https://doi.org/10.1055/s-2000-8561
Hussain, T., Tan, B., Yin, Y., Blachier, F., Tossou, M.C., & Rahu, N. (2016). Oxidative stress and inflammation: what polyphenols can do for us?.Oxidative Medicine and Cellular Longevity. 2016;2016:7432797. doi: 10.1155/2016/7432797. DOI: https://doi.org/10.1155/2016/7432797
Ibrahim, M. N., Asalah, A. K., Abd-Alaleem, D. I., & Moursi, S.M. (2015). Effect of ghrelin on testicular functions in Streptozotocin-induced type 1 diabetic rats.Zagazig University Medical Journal,20(2). doi:10.5923/j.diabetes.20130206.03 DOI: https://doi.org/10.21608/zumj.2014.4358
Iman Akhlaghipour, Arya Nasimi Shad, Vahid Reza Askari, Amirhosein Maharati, Vafa Baradaran Rahimi.(2023). How caffeic acid and its derivatives combat diabetes and its complications: A systematic review, Journal of Functional Foods, Volume 110, 105862, ISSN 1756-4646, https://doi.org/10.1016/j.jff.2023.105862. DOI: https://doi.org/10.1016/j.jff.2023.105862
Jia, Y., Lao, Y., Zhu, H., Li, N., & Leung, S. W. (2019). Is metformin still the most efficacious first‐line oral hypoglycaemic drug in treating type 2 diabetes? A network meta‐analysis of randomized controlled trials.Obesity Reviews,20(1), 1-12. DOI:10.1111/obr. 12753 DOI: https://doi.org/10.1111/obr.12753
Khaki, A., Fathiazad, F., Nouri, M., Khaki, A., Maleki, N. A., Khamnei, H. J., & Ahmadi, P. (2010). Beneficial effects of quercetin on sperm parameters in streptozotocin‐induced diabetic male rats.Phytotherapy Research,24(9), 1285-1291. DOI: https://doi.org/10.1002/ptr.3100 DOI: https://doi.org/10.1002/ptr.3100
Khimmaktong, W., Komolkriengkrai, M., Boonyoung, P., & Anupunpisit, V. (2019). Effects of curcumin on testis microvascular complications in streptozotocin-induced diabetic rats.Functional Foods in Health and Disease,9(1), 34-51. DOI: https://doi.org/10.31989/ffhd.v9i1.542 DOI: https://doi.org/10.31989/ffhd.v9i1.542
Knight, J., & Nigam, Y. (2017). Diabetes management 1: disease types, symptoms, and diagnosis. Nursing Times, 4(113), 4. http://cronfa.swan.ac.uk/Record/cronfa32919
Kochakian, C.D. (1973). Hypotaurine: regulation of production in seminal vesicles and prostate of the guinea pig by testosterone. Nature; 241: 202–3. DOI:10.1038/241202a0 DOI: https://doi.org/10.1038/241202a0
Kotian, S.R., Kumar, A., Mallik, S.B., Bhat, N.P., Souza, A.D., & Pandey, A.K. (2019). Effect of Diabetes on the Male Reproductive System—A Histomorphological Study.Journal of Morphological Sciences,36(01), 017-023. DOI: https://doi.org/10.1055/s-0039-1683405 . DOI: https://doi.org/10.1055/s-0039-1683405
Kowalczyk, A. (2022). The Role of the Natural Antioxidant Mechanism in Sperm Cells.Reprod. Sci.29, 1387–1394. https://doi.org/10.1007/s43032-021-00795-w DOI: https://doi.org/10.1007/s43032-021-00795-w
Kumar, V., Abbas, A.K., Aster, J.C., Robbins, S.L., Cotran, R.S., & Perkins, J.A. (2015). Robbins and Cotran Pathologic Basis of Disease (9th ed.). Philadelphia, Pa: Elsevier/Saunders. 1105-1120
Lal, B. S. (2016). Diabetes: Causes, symptoms, and treatments. In B. S. Lal (Ed.), Public health environment and social issues in India (1st ed., pp. 55–67). Serials Publications.
Lieberman, M., & Ricer, R.E. (2019). Biochemistry, Molecular Biology, and Genetics. Philadelphia: Lippincott Williams & Wilkins. 145-324
Liu, H., Lin, S., Lv, Q., Yang, Q., Wu, G., Hu, J., & Yang, J. (2017). Taurine recovers testicular steroidogenesis and spermatogenesis in streptozotocin-induced diabetic rats. Adv Exp Med Biol. 975 Pt 2, 801-811. DOI:10.1007/978-94-024-1079-2_62 DOI: https://doi.org/10.1007/978-94-024-1079-2_62
Long, L., Qiu, H., Cai, B., Chen, N., Lu, X., Zheng, S., Ye, X., Li, Y. (2018). Hyperglycemia induced testicular damage in type 2 diabetes mellitus rats exhibiting microcirculation impairments associated with decreased vascular endothelial growth factor via the PI3K/Akt pathway. Oncotarget. 9(4):5321-5336. doi: 10.18632/oncotarget. 23915 DOI: https://doi.org/10.18632/oncotarget.23915
Magnani, C., V. L. B. Isaac, M. A. Correa, H. R. N. Salgado. (2014). Caffeic acid: A review of its potential use in medications and cosmetics. Analytical Methods, 6(10), 3203–3210. DOI:10.1039/c3ay41807c DOI: https://doi.org/10.1039/C3AY41807C
McGraw, L.A, Suarez, S.S, Wolfner, M.F. (2015). On a matter of seminal importance. Bioessays. 37(2), 142-147. DOI: 10.1002/bies. 201400117 DOI: https://doi.org/10.1002/bies.201400117
McKay, A.C., Odeluga, N., Jiang, J., Sharma, S. (2023). Anatomy, Abdomen and Pelvis, Seminal Vesicle. StatPearls Publishing. https://pubmed.ncbi.nlm.nih.gov/29763029
Morrison, J. F., Dhanasekaran, S., Sheen, R., Frampton, C.M., & Mensah Brown, E. (2006). The effect of streptozotocin induced diabetes on the rat seminal vesicle: a possible pathophysiological basis for disorders of ejaculation. Ann N Y Academia Science; 1084: 267–79. DOI:10.1196/annals. 1372.013 DOI: https://doi.org/10.1196/annals.1372.013
Moore, K. L., Persaud, T.V.N. & Torchia, M. G. (2016). The Developing Human, Clinically Oriented Embryology (10th ed.). United States of America: Elsevier. 267-278
Mishra, R., Nikam, A., Hiwarkar, J. T., Nandgude, J. B., & Polshettiwar, S. (2024). Flavonoids as potential therapeutics in male reproductive disorders. Future J Pharm Sci 10, 100. https://doi.org/10.1186/s43094-024-00677-3 DOI: https://doi.org/10.1186/s43094-024-00677-3
Murilo, K., Espíndola ,M., Ferreira, R. G., Eduardo, L., Narvaez, M., Caroline A., Silva R., Hanna A., Gabrielle A., Silva B., Paula A., Vieira O., & Monteiro M. C. (2019). Chemical and Pharmacological Aspects of Caffeic Acid and Its Activity in Hepatocarcinoma. 9(June), 3–5. https://doi.org/10.3389/fonc.00541 DOI: https://doi.org/10.3389/fonc.2019.00541
Muhammad, Abdul Kadar, N. N., Ahmad, F., Teoh, S. L., & Yahaya, M. F. (2021). Caffeic Acid on Metabolic Syndrome: A Review.Molecules,26(18), 5490. https://doi.org/10.3390/molecules26185490 DOI: https://doi.org/10.3390/molecules26185490
Okutan, H., Ozcelikb, N., Yilmazb, H.R., & Uzb, E. (2005). Effects of caffeic acid phenethylester on lipid peroxidation and antioxidant enzymes in diabetic rat heart. Clinical Biochemical 38:191 -196. https://doi.org/10.1016/j.clinbiochem.2004.10.003 DOI: https://doi.org/10.1016/j.clinbiochem.2004.10.003
Oyenihi, A.B., Ayeleso, A.O., Mukwevho, E., & Masola, B. (2015). Antioxidant strategies in the management of diabetic neuropathy. Biomedical Reserve International 2015;515042. DOI:10.1155/2015/515042 DOI: https://doi.org/10.1155/2015/515042
Pavlíková, N. (2023). Caffeic acid and disease mechanisms of action. International Journal of Molecular Sciences, 24(1), 588. https://doi.org/10.3390/ijms24010588 DOI: https://doi.org/10.3390/ijms24010588
Poiani, A. (2006). Complexity of seminal fluid: a review. Behavioural Ecology Sociobiology; 60: 289–310. DOI:10.1007/s00265-006-0178-0 DOI: https://doi.org/10.1007/s00265-006-0178-0
Sidoryk, K., Jaromin, A., Filipczak , N., Cmoch, P., & Cybulski, M. (2018). Synthesis and antioxidant activity of caffeic acid derivatives. Molecules. 23:2199. doi: 10.3390/molecules23092199 DOI: https://doi.org/10.3390/molecules23092199
Sun, X.Q., Xu,C., Leclerc,P., Benoît, G., & Giuliano, F. (2009). Spinal neurons involved in the control of the seminal vesicles: a transsynaptic labeling study using pseudorabies virus in rats. Neuroscience; 158: 786–97. doi: 10.1016/j.neuroscience.2008.10.008 DOI: https://doi.org/10.1016/j.neuroscience.2008.10.008
Tripathi, V., & Verma, J. (2014). Different models used to induce diabetes: a comprehensive review. International Journal of Pharmacy and Pharmaceutical Science,6(6), 29-32. epididymal spermatozoa. Biology Reproduction; 59(4), 753–758.DOI:10.1095/biolreprod59.4.753 DOI: https://doi.org/10.1095/biolreprod59.4.753
Tsounapi, P., Honda, M., Dimitriadis, F., Kawamoto, B., & Hikita, K. (2017). Impact of antioxidants on the function of seminal vesicles and fertilizing potential in diabetic rats. 639–646. https://doi.org/10.4103/1008-682X.186871 DOI: https://doi.org/10.4103/1008-682X.186871
Ukwenya, V.O., Olawuyi, T.S., Adelakun, S.A., Ogunsola, O.I., & Ukwenya, M.U. (2020). D-ribose-L-cysteine improves hormonal imbalance , spermatogenic dysregulation , and redox status in streptozotocin-diabetic rats. 25(3):358-367 doi:10.5935/1518-0557.20200109 DOI: https://doi.org/10.5935/1518-0557.20200109
Victor, U. O., Ashaolu, J. O., Adeyemi, A. O., Akinola, O. A., and Caxton-Martins, E. A. (2012). Antihyperglycemic activities of methanolic leaf extract of Anacardium occidentale (Linn.) on the pancreas of streptozotocin-induced diabetic rats. Journal of Cell and Animal Biology, 6(14). https://doi.org/10.5897/AJPS12.028 DOI: https://doi.org/10.5897/AJPS12.028
Xie, J., Yang, F., Zhang, M., Lam, C., Qiao, Y., & Xiao, J. (2017). Antiproliferative activity and SARs of caffeic acid esters with mono-substituted phenylethanols moiety. Bioorganic & Medicinal Chemistry Letters, 27(1), 131–134. DOI:10.1016/j.bmcl.2016.12.007 DOI: https://doi.org/10.1016/j.bmcl.2016.12.007
Xu, Y., Tang, G., Zhang, C., Wang, N., & Feng, Y. (2021). Gallic Acid and Diabetes Mellitus: Its Association with Oxidative Stress.Molecules,26(23), 7115. https://doi.org/10.3390/molecules26237115 DOI: https://doi.org/10.3390/molecules26237115
Yonezawa, A., Ebiko, M., Yoshizumi, M., Ise, S., & Watanabe, C. (2009). Effects of insulin replacement on ejaculatory dysfunction in streptozotocin induced diabetic rats. Int J; 16(2):208-11. DOI:10.1111/j.1442-2042.2008.02214.x DOI: https://doi.org/10.1111/j.1442-2042.2008.02214.x
Watanabe, K., Morinaka, Y., Iseki, K., Watanabe, T., & Yuki S. (2003). Structure activity relationship of 3 methyl 1 phenyl 2 pyrazolin 5 one (edaravone). Redox Reproduction; 8(3), 151–155. DOI:10.1179/135100003225001520 DOI: https://doi.org/10.1179/135100003225001520
Zahran, F., Al-Hussaini, A.S., & El-shehabi, M.E. (2015). ANTIDIABETIC ACTIVITY OF CAFFEIC ACID AND 18β-GLYCYRRHETINIC ACID AND ITS RELATIONSHIP WITH THE ANTIOXIDANT PROPERTY. Asian Journal of Pharmaceutical and Clinical Research, 8, 229-235.
Article Sidebar
