HISTOPROTECTIVE EFFECTS OF MALE PAPAYA FLOWERS (Carica papaya L.) DECOCTION ON THE DUODENUM OF DIABETIC MICE INDUCED BY STREPTOZOTOCIN-NICOTINAMIDE
Main Article Content
Abstract
This study aimed to investigate the protective effects of male papaya flower decoction on the histological structure of the duodenum in female albino mice with diabetes induced by Streptozotocin combined with Nicotinamide. The experimental groups included: a healthy control group, an untreated diabetic group, a diabetic group treated with Metformin, diabetic groups treated with the decoction at doses of 12.4 mg/mL and 22.22 mg/mL, and a non-diabetic group receiving the decoction at 12,4 mg/mL. Histological analysis revealed that the untreated diabetic mice exhibited severe duodenal damage, including mucosal erosion, necrosis, hemorrhage, and a significant reduction in wall thickness. In contrast, treatment groups—particularly the group receiving the 22.22 mg/mL dose of the decoction—showed substantial restoration of normal histoarchitecture and an increase in duodenal wall thickness, with effects equivalent to those observed in the Metformin-treated group. These findings suggest the potential of male papaya flower decoction as a supportive therapeutic agent for duodenal injury associated with diabetes. Further studies are warranted to elucidate its mechanism of action and assess long-term safety for potential application in managing diabetic enteropathy.
Keywords
duodenum histology, histoprotective effect, Male papaya flower decoction, Metformin, Streptozotocin-Nicotinamide-induced diabetes
Article Details
References
Ali, A. M., Gabbar, M. A., Abdel-Twab, S. M., Fahmy, E. M., Ebaid, H., Alhazza, I. M., & Ahmed, O. M. (2020). Antidiabetic Potency, Antioxidant Effects, and Mode of Actions of Citrus reticulata Fruit Peel Hydroethanolic Extract, Hesperidin, and Quercetin in Nicotinamide/Streptozotocin-Induced Wistar Diabetic Rats. Oxidative Medicine and Cellular Longevity, 2020, 1-21. https://doi.org/10.1155/2020/1730492
AL-Ishaq, R. K., Mazurakova, A., Kubatka, P., & Büsselberg, D. (2022). Flavonoids’ Dual Benefits in Gastrointestinal Cancer and Diabetes: A Potential Treatment on the Horizon? Cancers, 14(24), Article 6073. https://doi.org/10.3390/cancers14246073
Brandt, A., Hernández-Arriaga, A., Kehm, R., Sánchez, V., Jin, C. J., Nier, A., Baumann, A., Camarinha-Silva, A., & Bergheim, I. (2019). Metformin attenuates the onset of non-alcoholic fatty liver disease and affects intestinal microbiota and barrier in small intestine. Scientific Reports, 9(1), Article 6668. https://doi.org/10.1038/s41598-019-43228-0
Chen, B., Jia, Y., Lu, D., & Sun, Z. (2021). Acute glucose fluctuation promotes in vitro intestinal epithelial cell apoptosis and inflammation via the NOX4/ROS/JAK/STAT3 signaling pathway. Experimental and Therapeutic Medicine, 22(1), Article 688. https://doi.org/10.3892/etm.2021.10120
Cruz, P. L., Moraes-Silva, I. C., Ribeiro, A. A., Machi, J. F., de Melo, M. D. T., Dos Santos, F., da Silva, M. B., Strunz, C. M. C., Caldini, E. G., & Irigoyen, M.-C. (2021). Nicotinamide attenuates streptozotocin-induced diabetes complications and increases survival rate in rats: Role of autonomic nervous system. BMC Endocrine Disorders, 21(1), Article 133. https://doi.org/10.1186/s12902-021-00795-6
Daryabor, G., Atashzar, M. R., Kabelitz, D., Meri, S., & Kalantar, K. (2020). The Effects of Type 2 Diabetes Mellitus on Organ Metabolism and the Immune System. Frontiers in Immunology, 11, Article 1582. https://doi.org/10.3389/fimmu.2020.01582
Dong, J., Liang, W., Wang, T., Sui, J., Wang, J., Deng, Z., & Chen, D. (2019). Saponins regulate intestinal inflammation in colon cancer and IBD. Pharmacological Research, 144, 66-72. https://doi.org/10.1016/j.phrs.2019.04.010
Du, Y. T., Rayner, C. K., Jones, K. L., Talley, N. J., & Horowitz, M. (2018). Gastrointestinal Symptoms in Diabetes: Prevalence, Assessment, Pathogenesis, and Management. Diabetes Care, 41(3), 627-637. https://doi.org/10.2337/dc17-1536
Dwivedi, M. K., Sonter, S., Mishra, S., Patel, D. K., & Singh, P. K. (2020). Antioxidant, antibacterial activity, and phytochemical characterization of Carica papaya flowers. Beni-Suef University Journal of Basic and Applied Sciences, 9(1), Article 23. https://doi.org/10.1186/s43088-020-00048-w
Ferraz, C. R., Carvalho, T. T., Manchope, M. F., Artero, N. A., Rasquel-Oliveira, F. S., Fattori, V., Casagrande, R., & Verri, W. A. (2020). Therapeutic Potential of Flavonoids in Pain and Inflammation: Mechanisms of Action, Pre-Clinical and Clinical Data, and Pharmaceutical Development. Molecules, 25(3), Article 762. https://doi.org/10.3390/molecules25030762
Feyisayo, A. K., & Durojaye, A. M. (2018). Anti-hyperglycaemic, anti-inflammatory and anti-oxidant activities of Carica papaya and Citrullus lanatus seeds. Ife Journal of Science, 20(2), Article 2. https://doi.org/10.4314/ijs.v20i2.1
Juárez-Rojop, I. E., Díaz-Zagoya, J. C., Ble-Castillo, J. L., Miranda-Osorio, P. H., Castell-Rodríguez, A. E., Tovilla-Zárate, C. A., Rodríguez-Hernández, A., Aguilar-Mariscal, H., Ramón-Frías, T., & Bermúdez-Ocaña, D. Y. (2012). Hypoglycemic effect of Carica papaya leaves in streptozotocin-induced diabetic rats. BMC Complementary and Alternative Medicine, 12, Article 236. https://doi.org/10.1186/1472-6882-12-236
Lam, T. K. P., Truong, H. B., & Nguyen, T. T. H. (2025). Khao sat nong do cua nuoc sac hoa du du duc len da day chuot dai thao duong [Investigation of male Carica papaya L. flower infusion concentration on the gastric histology of mice]. Ho Chi Minh City Open University Journal of Science Engineering and Technology, 20(2), 5-19. https://journalofscience.ou.edu.vn/index.php/tech-vi/article/view/4056
Le, D. T., Duong, T. T. T., Nguyen, T. T. X., Le, T. A. T., Nguyen, V. T. T., Hoang, T. H. T., Pham, H. P. L., & Tran, H. P. (2013). Xây dựng mô hình chuột tiểu đường và khảo sát hiệu quả hạ đường huyết của cây Hoàng Liên (Copis teeta Wall) trên mô hình động vật [Construction of diabetic mouse model and investigation of hypoglycemic effect of Copis teeta Wall on animal model]. Ho Chi Minh City Open University Journal of Science, Engineering and Technology, 8(1), 62-69.
Le, T. T., Nguyen, D. T. P., Pham, T. N. T., Quach, H. T., Le, N. T. V., Nguyen, T. T., Tran, D. L., Nguyen, T. V., & Le, T. D. (2019). Saponin, polyphenol, flavonoid content and α-glucosidase inhibitory activity, antioxidant potential of Launaea sarmentosa leaves grown in Ben Tre province, Vietnam. IOP Conference Series: Materials Science and Engineering, 542(1), Article 012036. https://doi.org/10.1088/1757-899X/542/1/012036
Min, X., Yu, T., Qing, Q., Yuan, Y., Zhong, W., Chen, G., Zhao, L., Deng, N., Zhang, L., & Chen, Q. (2014). Abnormal differentiation of intestinal epithelium and intestinal barrier dysfunction in diabetic mice associated with depressed Notch/NICD transduction in Notch/Hes1 signal pathway. Cell Biology International, 38(10), 1194-1204. https://doi.org/10.1002/cbin.10323
Nakamura, T., Terajima, T., Ogata, T., Ueno, K., Hashimoto, N., Ono, K., & Yano, S. (2006). Establishment and pathophysiological characterization of type 2 diabetic mouse model produced by streptozotocin and nicotinamide. Biological & Pharmaceutical Bulletin, 29(6), 1167-1174. https://doi.org/10.1248/bpb.29.1167
Napolitano, A., Miller, S., Nicholls, A. W., Baker, D., Van Horn, S., Thomas, E., Rajpal, D., Spivak, A., Brown, J. R., & Nunez, D. J. (2014). Novel Gut-Based Pharmacology of Metformin in Patients with Type 2 Diabetes Mellitus. PLoS ONE, 9(7), Article e100778. https://doi.org/10.1371/journal.pone.0100778
Nguyen, M.-N. T., & Ho-Huynh, T.-D. (2016). Selective cytotoxicity of a Vietnamese traditional formula, Nam Dia long, against MCF-7 cells by synergistic effects. BMC Complementary and Alternative Medicine, 16(1), Article 220. https://doi.org/10.1186/s12906-016-1212-z
Pegah, A., Abbasi-Oshaghi, E., Khodadadi, I., Mirzaei, F., & Tayebinia, H. (2021). Probiotic and resveratrol normalize GLP-1 levels and oxidative stress in the intestine of diabetic rats. Metabolism Open, 10, Article 100093. https://doi.org/10.1016/j.metop.2021.100093
Qin, J., Li, Y., Cai, Z., Li, S., Zhu, J., Zhang, F., Liang, S., Zhang, W., Guan, Y., Shen, D., Peng, Y., Zhang, D., Jie, Z., Wu, W., Qin, Y., Xue, W., Li, J., Han, L., Lu, D., … Wang, J. (2012). A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature, 490(7418), 55-60. https://doi.org/10.1038/nature11450
Sun, H., Saeedi, P., Karuranga, S., Pinkepank, M., Ogurtsova, K., Duncan, B. B., Stein, C., Basit, A., Chan, J. C. N., Mbanya, J. C., Pavkov, M. E., Ramachandaran, A., Wild, S. H., James, S., Herman, W. H., Zhang, P., Bommer, C., Kuo, S., Boyko, E. J., & Magliano, D. J. (2022). IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Research and Clinical Practice, 183, Article 109119. https://doi.org/10.1016/j.diabres.2021.109119
Wegeberg, A.-M., & Brock, C. (2024). Diabetes and the gastrointestinal tract. Medicine, 52(5), 304-310. https://doi.org/10.1016/j.mpmed.2024.02.013
AL-Ishaq, R. K., Mazurakova, A., Kubatka, P., & Büsselberg, D. (2022). Flavonoids’ Dual Benefits in Gastrointestinal Cancer and Diabetes: A Potential Treatment on the Horizon? Cancers, 14(24), Article 6073. https://doi.org/10.3390/cancers14246073
Brandt, A., Hernández-Arriaga, A., Kehm, R., Sánchez, V., Jin, C. J., Nier, A., Baumann, A., Camarinha-Silva, A., & Bergheim, I. (2019). Metformin attenuates the onset of non-alcoholic fatty liver disease and affects intestinal microbiota and barrier in small intestine. Scientific Reports, 9(1), Article 6668. https://doi.org/10.1038/s41598-019-43228-0
Chen, B., Jia, Y., Lu, D., & Sun, Z. (2021). Acute glucose fluctuation promotes in vitro intestinal epithelial cell apoptosis and inflammation via the NOX4/ROS/JAK/STAT3 signaling pathway. Experimental and Therapeutic Medicine, 22(1), Article 688. https://doi.org/10.3892/etm.2021.10120
Cruz, P. L., Moraes-Silva, I. C., Ribeiro, A. A., Machi, J. F., de Melo, M. D. T., Dos Santos, F., da Silva, M. B., Strunz, C. M. C., Caldini, E. G., & Irigoyen, M.-C. (2021). Nicotinamide attenuates streptozotocin-induced diabetes complications and increases survival rate in rats: Role of autonomic nervous system. BMC Endocrine Disorders, 21(1), Article 133. https://doi.org/10.1186/s12902-021-00795-6
Daryabor, G., Atashzar, M. R., Kabelitz, D., Meri, S., & Kalantar, K. (2020). The Effects of Type 2 Diabetes Mellitus on Organ Metabolism and the Immune System. Frontiers in Immunology, 11, Article 1582. https://doi.org/10.3389/fimmu.2020.01582
Dong, J., Liang, W., Wang, T., Sui, J., Wang, J., Deng, Z., & Chen, D. (2019). Saponins regulate intestinal inflammation in colon cancer and IBD. Pharmacological Research, 144, 66-72. https://doi.org/10.1016/j.phrs.2019.04.010
Du, Y. T., Rayner, C. K., Jones, K. L., Talley, N. J., & Horowitz, M. (2018). Gastrointestinal Symptoms in Diabetes: Prevalence, Assessment, Pathogenesis, and Management. Diabetes Care, 41(3), 627-637. https://doi.org/10.2337/dc17-1536
Dwivedi, M. K., Sonter, S., Mishra, S., Patel, D. K., & Singh, P. K. (2020). Antioxidant, antibacterial activity, and phytochemical characterization of Carica papaya flowers. Beni-Suef University Journal of Basic and Applied Sciences, 9(1), Article 23. https://doi.org/10.1186/s43088-020-00048-w
Ferraz, C. R., Carvalho, T. T., Manchope, M. F., Artero, N. A., Rasquel-Oliveira, F. S., Fattori, V., Casagrande, R., & Verri, W. A. (2020). Therapeutic Potential of Flavonoids in Pain and Inflammation: Mechanisms of Action, Pre-Clinical and Clinical Data, and Pharmaceutical Development. Molecules, 25(3), Article 762. https://doi.org/10.3390/molecules25030762
Feyisayo, A. K., & Durojaye, A. M. (2018). Anti-hyperglycaemic, anti-inflammatory and anti-oxidant activities of Carica papaya and Citrullus lanatus seeds. Ife Journal of Science, 20(2), Article 2. https://doi.org/10.4314/ijs.v20i2.1
Juárez-Rojop, I. E., Díaz-Zagoya, J. C., Ble-Castillo, J. L., Miranda-Osorio, P. H., Castell-Rodríguez, A. E., Tovilla-Zárate, C. A., Rodríguez-Hernández, A., Aguilar-Mariscal, H., Ramón-Frías, T., & Bermúdez-Ocaña, D. Y. (2012). Hypoglycemic effect of Carica papaya leaves in streptozotocin-induced diabetic rats. BMC Complementary and Alternative Medicine, 12, Article 236. https://doi.org/10.1186/1472-6882-12-236
Lam, T. K. P., Truong, H. B., & Nguyen, T. T. H. (2025). Khao sat nong do cua nuoc sac hoa du du duc len da day chuot dai thao duong [Investigation of male Carica papaya L. flower infusion concentration on the gastric histology of mice]. Ho Chi Minh City Open University Journal of Science Engineering and Technology, 20(2), 5-19. https://journalofscience.ou.edu.vn/index.php/tech-vi/article/view/4056
Le, D. T., Duong, T. T. T., Nguyen, T. T. X., Le, T. A. T., Nguyen, V. T. T., Hoang, T. H. T., Pham, H. P. L., & Tran, H. P. (2013). Xây dựng mô hình chuột tiểu đường và khảo sát hiệu quả hạ đường huyết của cây Hoàng Liên (Copis teeta Wall) trên mô hình động vật [Construction of diabetic mouse model and investigation of hypoglycemic effect of Copis teeta Wall on animal model]. Ho Chi Minh City Open University Journal of Science, Engineering and Technology, 8(1), 62-69.
Le, T. T., Nguyen, D. T. P., Pham, T. N. T., Quach, H. T., Le, N. T. V., Nguyen, T. T., Tran, D. L., Nguyen, T. V., & Le, T. D. (2019). Saponin, polyphenol, flavonoid content and α-glucosidase inhibitory activity, antioxidant potential of Launaea sarmentosa leaves grown in Ben Tre province, Vietnam. IOP Conference Series: Materials Science and Engineering, 542(1), Article 012036. https://doi.org/10.1088/1757-899X/542/1/012036
Min, X., Yu, T., Qing, Q., Yuan, Y., Zhong, W., Chen, G., Zhao, L., Deng, N., Zhang, L., & Chen, Q. (2014). Abnormal differentiation of intestinal epithelium and intestinal barrier dysfunction in diabetic mice associated with depressed Notch/NICD transduction in Notch/Hes1 signal pathway. Cell Biology International, 38(10), 1194-1204. https://doi.org/10.1002/cbin.10323
Nakamura, T., Terajima, T., Ogata, T., Ueno, K., Hashimoto, N., Ono, K., & Yano, S. (2006). Establishment and pathophysiological characterization of type 2 diabetic mouse model produced by streptozotocin and nicotinamide. Biological & Pharmaceutical Bulletin, 29(6), 1167-1174. https://doi.org/10.1248/bpb.29.1167
Napolitano, A., Miller, S., Nicholls, A. W., Baker, D., Van Horn, S., Thomas, E., Rajpal, D., Spivak, A., Brown, J. R., & Nunez, D. J. (2014). Novel Gut-Based Pharmacology of Metformin in Patients with Type 2 Diabetes Mellitus. PLoS ONE, 9(7), Article e100778. https://doi.org/10.1371/journal.pone.0100778
Nguyen, M.-N. T., & Ho-Huynh, T.-D. (2016). Selective cytotoxicity of a Vietnamese traditional formula, Nam Dia long, against MCF-7 cells by synergistic effects. BMC Complementary and Alternative Medicine, 16(1), Article 220. https://doi.org/10.1186/s12906-016-1212-z
Pegah, A., Abbasi-Oshaghi, E., Khodadadi, I., Mirzaei, F., & Tayebinia, H. (2021). Probiotic and resveratrol normalize GLP-1 levels and oxidative stress in the intestine of diabetic rats. Metabolism Open, 10, Article 100093. https://doi.org/10.1016/j.metop.2021.100093
Qin, J., Li, Y., Cai, Z., Li, S., Zhu, J., Zhang, F., Liang, S., Zhang, W., Guan, Y., Shen, D., Peng, Y., Zhang, D., Jie, Z., Wu, W., Qin, Y., Xue, W., Li, J., Han, L., Lu, D., … Wang, J. (2012). A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature, 490(7418), 55-60. https://doi.org/10.1038/nature11450
Sun, H., Saeedi, P., Karuranga, S., Pinkepank, M., Ogurtsova, K., Duncan, B. B., Stein, C., Basit, A., Chan, J. C. N., Mbanya, J. C., Pavkov, M. E., Ramachandaran, A., Wild, S. H., James, S., Herman, W. H., Zhang, P., Bommer, C., Kuo, S., Boyko, E. J., & Magliano, D. J. (2022). IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Research and Clinical Practice, 183, Article 109119. https://doi.org/10.1016/j.diabres.2021.109119
Wegeberg, A.-M., & Brock, C. (2024). Diabetes and the gastrointestinal tract. Medicine, 52(5), 304-310. https://doi.org/10.1016/j.mpmed.2024.02.013