Therapeutic effects of Citrullus colocynths nanoparticles on Streptozotocin-induced diabetic rats: Improvement of pancreatic histology

Document Type : Research Paper

Author

College of Health and Medical Technique, Middle Technical University, Baghdad. Iraq.

Abstract

Objective
Diabetes mellitus is a chronic metabolic disorder. This disorder occurs when insulin secretion is insufficient or insulin function is impaired, and blood sugar levels increase. Continuously elevated blood sugar levels cause oxidative stress and structural damage in pancreatic tissue. This damage is most commonly seen in beta cells of the islets of Langerhans. One of the medicinal plants with antidiabetic properties is colocynthia (Citrullus colocynthis). Therefore, our aim was to study the therapeutic effects of colocynthia nanoparticles (CCNPs) on pancreatic histology, insulin levels, oxidative stress markers, and blood glucose levels in streptozotocin (STZ)-induced diabetic rats.
Materials and methods
Four groups of male Wistar rats were randomly selected. These four groups included the control group, untreated diabetic rats, diabetic rats treated with colocynthia (Citrullus colocynthis) extract, and diabetic rats treated with CCNPs. We used an intraperitoneal injection of streptozotocin (STZ) to induce diabetes. The treatment period was 28 days. We used standard biochemical methods to measure blood glucose and serum insulin levels. We measured the antioxidant effect of the treatments using oxidative stress parameters. We examined pancreatic tissues histologically to examine structural changes in the islets of Langerhans.
Results
Treatment with CCNPs significantly reduced blood glucose levels. In the other groups, namely the untreated diabetic and extract-treated groups, insulin levels increased significantly. Oxidative stress markers improved in the CCNP group mice. In these mice, beta cell density increased, pancreatic islet architecture was restored, and cellular destruction was reduced. On the other hand, in untreated diabetic animals, pancreatic islets were severely shrunk and beta cells were damaged. Therefore, it can be said that the therapeutic efficacy of the nanoparticle formulation is greater than that of the crude plant extract.
Conclusion
Our experimental results confirmed the protective and restorative role of Citrullus colocynthis nanoparticles on pancreatic tissue in diabetic mice. CCNPs improved blood sugar control. In addition, their use increased insulin secretion and reduced oxidative stress. Therefore, it can be concluded that the use of nanoparticle-based formulations from medicinal plants may potentially provide a promising and innovative approach for diabetes management.

Keywords


Alsalihi, M. E., Awlqadr, F. H., Saeed, M. N., Faraj, A. M., Qadir, S. A., & Salih, T. H. (2025). Antidiabetic and antioxidant effects of topically applied Citrullus colocynthis extract in type 2 diabetes: A clinical and phytochemical study. Metabolism Open, 28, Article 100401. https://doi.org/10.1016/j.metop.2025.100401
Dhir, R., Chauhan, S., Subham, P., Kumar, S., Sharma, P., Shidiki, A., & Kumar, G. (2024). Plant-mediated synthesis of silver nanoparticles: Unlocking their pharmacological potential—A comprehensive review. Frontiers in Bioengineering and Biotechnology, 11, Article 1324805. https://doi.org/10.3389/fbioe.2023.1324805
Ghorbani, A. (2005). Studies on pharmaceutical ethnobotany in the region of Turkmen Sahra, north of Iran (Part 1): General results. Journal of Ethnopharmacology, 102(1), 58–68. https://doi.org/10.1016/j.jep.2005.05.035
Hafeez, R., Kanwal, Z., Raza, M. A., Rasool, S., Riaz, S., Naseem, S., Rabani, S., Haider, I., Ahmad, N., & Alomar, S. Y. (2023). Role of Citrullus colocynthis and Psidium guajava mediated green synthesized silver nanoparticles in disease resistance against Aeromonas hydrophila challenge in Labeo rohita. Biomedicines, 11(9), Article 2349. https://doi.org/10.3390/biomedicines11092349
Heidarpour, F., Mohammadabadi, M. R., Zaidul, I. S. M., Maherani, B., Saari, N., Hamid, A. A., Abas, F., Manap, M. Y. A., & Mozafari, M. R. (2011). Use of prebiotics in oral delivery of bioactive compounds: A nanotechnology perspective. Pharmazie, 66(5), 319–324. https://doi.org/10.1691/ph.2011.0279
Kanwugu, O. N., Glukhareva, T. V., Danilova, I. G., & Kovaleva, E. G. (2022). Natural antioxidants in diabetes treatment and management: Prospects of astaxanthin. Critical Reviews in Food Science and Nutrition, 62(18), 5005–5028. https://doi.org/10.1080/10408398.2021.1881434
Karunakaran, S., & Hari, R. (2022). Comparative antioxidant and anti-gout activities of Citrullus colocynthis loaded fruit silver nanoparticles with its ethanolic extract. Avicenna Journal of Medical Biotechnology, 14(4), 303–309. https://pubmed.ncbi.nlm.nih.gov/36504570/
Kooti, W., Farokhipour, M., Asadzadeh, Z., Ashtary-Larky, D., & Asadi-Samani, M. (2016). The role of medicinal plants in the treatment of diabetes: A systematic review. Electronic Physician, 8(1), 1832–1842. https://doi.org/10.19082/1832
Lenzen, S. (2008). The mechanisms of alloxan- and streptozotocin-induced diabetes. Diabetologia, 51(2), 216–226. https://doi.org/10.1007/s00125-007-0886-7
Liu, M., Wang, R., Hoi, M. P. M., Wang, Y., Wang, S., Li, G., Vong, C. T., & Chong, C. M. (2025). Nano-based drug delivery systems for managing diabetes: Recent advances and future prospects. International Journal of Nanomedicine, 20, 6221–6252. https://doi.org/10.2147/IJN.S508875
Maritim, A. C., Sanders, R. A., & Watkins, J. B., III. (2003). Diabetes, oxidative stress, and antioxidants: A review. Journal of Biochemical and Molecular Toxicology, 17(1), 24–38. https://doi.org/10.1002/jbt.10058
Matough, F. A., Budin, S. B., Hamid, Z. A., Alwahaibi, N., & Mohamed, J. (2012). The role of oxidative stress and antioxidants in diabetic complications. Sultan Qaboos University Medical Journal, 12(1), 5–18. https://doi.org/10.12816/0003082
Mohammadabadi, M. R., & Mozafari, M. R. (2018). Enhanced efficacy and bioavailability of thymoquinone using nanoliposomal dosage form. Journal of Drug Delivery Science and Technology, 47, 445–453. https://doi.org/10.1016/j.jddst.2018.08.019
Mohammadabadi, M. R., El-Tamimy, M., Gianello, R., & Mozafari, M. R. (2009). Supramolecular assemblies of zwitterionic nanoliposome-polynucleotide complexes as gene transfer vectors: Nanolipoplex formulation and in vitro characterization. Journal of Liposome Research, 19(2), 105–115. https://doi.org/10.1080/08982100802547326
Mortazavi, S. M., Mohammadabadi, M. R., & Mozafari, M. R. (2005). Applications and in vivo behaviour of lipid vesicles. In M. R. Mozafari (Ed.), Nanoliposomes: From fundamentals to recent developments (pp. 67–76). Elsevier.
Mubeen, B., Rasool, M. G., Ullah, I., Rasool, R., Imam, S. S., Alshehri, S., Ghoneim, M. M., Alzarea, S. I., Nadeem, M. S., & Kazmi, I. (2022). Phytochemicals mediated synthesis of AuNPs from Citrullus colocynthis and their characterization. Molecules, 27(4), Article 1300. https://doi.org/10.3390/molecules27041300
Ostovan, F., Gol, A., & Javadi, A. (2017). Investigating the effects of Citrullus colocynthis pulp on oxidative stress in testes and epididymis in streptozotocin-induced diabetic male rats. International Journal of Reproductive Biomedicine, 15(1), 41–48. https://pmc.ncbi.nlm.nih.gov/articles/PMC5340138/
Ostovar, M., Akbari, A., Anbardar, M. H., Iraji, A., Salmanpour, M., Hafez Ghoran, S., Heydari, M., & Shams, M. (2020). Effects of Citrullus colocynthis L. in a rat model of diabetic neuropathy. Journal of Integrative Medicine, 18(1), 59–67. https://doi.org/10.1016/j.joim.2019.12.002
Rasool, S., Raza, M. A., Manzoor, F., Kanwal, Z., Riaz, S., Iqbal, M. J., & Naseem, S. (2020). Biosynthesis, characterization and anti-dengue vector activity of silver nanoparticles prepared from Azadirachta indica and Citrullus colocynthis. Royal Society Open Science, 7(9), Article 200540. https://doi.org/10.1098/rsos.200540
Sabu, M. C., & Kuttan, R. (2002). Anti-diabetic activity of medicinal plants and its relationship with their antioxidant property. Journal of Ethnopharmacology, 81(2), 155–160. https://doi.org/10.1016/S0378-8741(02)00034-X
Salehi, B., Ata, A., Anil Kumar, N. V., Sharopov, F., Ramírez-Alarcón, K., Ruiz-Ortega, A., Ayatollahi, S. A., Tsouh Fokou, P. V., Kobarfard, F., Amiruddin Zakaria, Z., Iriti, M., Taheri, Y., Martorell, M., Sureda, A., Setzer, W. N., Durazzo, A., Lucarini, M., Santini, A., Capasso, R., Atta-ur-Rahman, Choudhary, M. I., Cho, W. C., & Sharifi-Rad, J. (2019). Antidiabetic potential of medicinal plants and their active components. Biomolecules, 9(10), Article 551. https://doi.org/10.3390/biom9100551
Sarkhel, S., Shuvo, S. M., Ansari, M. A., Mondal, S., Kapat, P., Ghosh, A., Sarkar, T., Biswas, R., Atanase, L. I., & Carauleanu, A. (2024). Nanotechnology-based approaches for the management of diabetes mellitus: An innovative solution to long-lasting challenges in antidiabetic drug delivery. Pharmaceutics, 16(12), Article 1572. https://doi.org/10.3390/pharmaceutics16121572
Souto, E. B., Souto, S. B., Campos, J. R., Severino, P., Pashirova, T. N., Zakharova, L. Y., Silva, A. M., Durazzo, A., Lucarini, M., Izzo, A. A., & Santini, A. (2019). Nanoparticle delivery systems in the treatment of diabetes complications. Molecules, 24(23), Article 4209. https://doi.org/10.3390/molecules24234209
Zarrabi, A., Alipoor Amro Abadi, M., Khorasani, S., Mohammadabadi, M., Jamshidi, A., Torkaman, S., Taghavi, E., Mozafari, M. R., & Rasti, B. (2020). Nanoliposomes and tocosomes as multifunctional nanocarriers for the encapsulation of nutraceutical and dietary molecules. Molecules, 25(3), Article 638. https://doi.org/10.3390/molecules25030638