Nanoemulsion of Curcuma longa Extract Improves the Developmental Process in High Glucose-Induced Zebrafish (Danio rerio) Embryos
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Gestational diabetes mellitus (GDM) is hyperglycemia during pregnancy, which can increase oxidative stress and reactive oxygen species (ROS). This oxidative stress can adversely affect fetal developmental processes, including body length, ocular development, blood flow, and heart rate. Curcuma longa extract, containing curcumin, has been shown to possess antidiabetic and antioxidant properties. Nanoemulsions have demonstrated efficacy in enhancing the pharmacokinetics and pharmacodynamics of herbal compounds. This study aimed to evaluate the effect of a nanoemulsion of Curcuma longa extract on body length, ocular apoptosis, blood flow, and heart rate in zebrafish (Danio rerio) embryos exposed to high glucose concentrations. Zebrafish has many benefits as it has 70% orthologous genes with humans, high fecundity, and rapid embryogenesis. Nanoemulsions were prepared using the self-nanoemulsifying drug delivery system (SNEDDS) technique. Embryos were allocated to five groups: control, 3% glucose, and 3% glucose with 1.25, 2.5, or 5 µg/mL nanoemulsion of Curcuma longa extract. The results showed that a 1.25 µg/mL nanoemulsion of Curcuma longa extract reduced phosphoenolpyruvate carboxykinase (PEPCK) expression, increased body length, and mitigated developmental process disorders by decreasing ocular apoptosis and maintaining blood flow and heart rate in high glucose-induced zebrafish embryos. These findings suggest that a nanoemulsion of Curcuma longa extract may have potential therapeutic applications in managing the adverse effects of hyperglycemia on fetal development in GDM.
Al-Biltagi, M., El razaky, O., & El Amrousy, D. (2021). Cardiac Changes in Infants of Diabetic Mothers. World Journal of Diabetes, 12(8), 1233–1247. https://doi.org/10.4239/wjd.v12.i8.1233
Berberoglu, Z. (2019). Pathophysiology of Gestational Diabetes Mellitus. EMJ Diabet, 7(1), 97–106. Retrieved from: https://www.emjreviews.com/wp-content/uploads/2019/11/Pathophysiology-of-Gestational-Diabetes-Mellitus.pdf
Brearley, M. C., Daniel, Z. C. T. R., Loughna, P. T., Parr, T., & Brameld, J. M. (2020). The Phosphoenolpyruvate Carboxykinase (PEPCK) Inhibitor, 3-Mercaptopicolinic Acid (3-MPA), Induces Myogenic Differentiation in C2C12 Cells. Scientific Reports, 10(1), 1-10. https://doi.org/10.1038/s41598-020-79324-9
Choudhury, A. A., & Rajeswari, V. D. (2021). Gestational diabetes mellitus-A metabolic and reproductive disorder. Biomedicine & Pharmacotherapy, 143, 112183. https://doi.org/10.1016/j.biopha.2021.112183
Chuengsamarn, S., Rattanamongkolgul, S., Luechapudiporn, R., Phisalaphong, C., & Jirawatnotai, S. (2012). Curcumin Extract For Prevention of Type 2 Diabetes. Diabetes Care, 35(11), 2121–2127. https://doi.org/10.2337/dc12-0116
El-Bahr, S. M. (2013). Curcumin Regulates Gene Expression of Insulin Like Growth Factor, B-Cell CLL/Lymphoma 2 and Antioxidant Enzymes in Streptozotocin Induced Diabetic Rats. BMC Complementary and Alternative Medicine, 13(368), 1-11. https://doi.org/10.1186/1472-6882-13-368
Fiorentino, T. V., Prioletta, A., Zuo, P., & Folli, F. (2013). Hyperglycemia-induced oxidative stress and its role in diabetes mellitus related cardiovascular diseases. Current pharmaceutical design, 19(32), 5695–5703. https://doi.org/10.2174/1381612811319320005
Giussani, D. A. (2016). The Fetal Brain Sparing Response to Hypoxia: Physiological Mechanisms. Journal of Physiology, 594(5), 1215–1230. https://doi.org/10.1113/JP271099
Harwansh, R. K., Deshmukh, R., & Rahman, M. A. (2019). Nanoemulsion: Promising nanocarrier system for delivery of herbal bioactives. Journal of Drug Delivery Science and Technology, 51, 224-233. https://doi.org/10.1016/j.jddst.2019.03.006
International Diabetes Federation. (2021). IDF Diabetes Atlas 10th edition 2021. Belgium: International Diabetes Federation. Retrieved from: https://www.ncbi.nlm.nih.gov/books/NBK581934/
Jaiswal, M., Dudhe, R., & Sharma, P. K. (2015). Nanoemulsion: An Advanced Mode of Drug Delivery System. 3 Biotech, 5(2), 123–127. https://doi.org/10.1007/s13205-014-0214-0
Jeevanandam, J., Chan, Y. S., & Danquah, M. K. (2019). Zebrafish As A Model Organism to Study Nanomaterial Toxicity. Emerging Science Journal, 3(3), 195–208. https://doi.org/10.28991/esj-2019-01182
Kang, G. G., Francis, N., Hill, R., Waters, D., Blanchard, C., & Santhakumar, A. B. (2020). Dietary Polyphenols and Gene Expression in Molecular Pathways Associated With Type 2 Diabetes Mellitus: A Review. International Journal of Molecular Sciences, 21(1), 1-26. https://doi.org/10.3390/ijms21010140
Khotimah, H., Prima, W. E., Weningtyas, A., Aninditha, D., Alita, S. N. P., Kalsum, U., Nandar, S. K., Rahayu, M., & Handayani, D. (2022). Neuroprotective Activity and Antioxidant Effect of Salacca zalacca Peel Ethanol Extract on High Glucose Induced Zebrafish (Danio rerio) Embryo. Tropical Journal of Natural Product Research, 5(12), 2079–2084. https://doi.org/10.26538/tjnpr/v5i12.6
Khotimah, H., Alita, S. N., Aninditha, D., Weningtyas, A., Wahyu, P. E., Kalsum, U., Rahayu, M., Handayani, D., & Nandar, S.K. (2021). Ethanolic Extract of Salacca Zalacca Peel Reduce IL-1β and Apoptosis in High Glucose Induced Zebrafish Embryo. GSC Biological and Pharmaceutical Sciences, 16(3), 024–033. https://doi.org/10.30574/gscbps.2021.16.3.0213
Kowluru, R. A., & Mishra, M. (2015). Oxidative Stress, Mitochondrial Damage and Diabetic Retinopathy. In Biochimica et Biophysica Acta - Molecular Basis of Disease, 1852(11) 2474–2483. https://doi.org/10.1016/j.bbadis.2015.08.001
Kumar, R., Patel, S. K., Rami Reddy, B. V., Bhatt, M., Karthik, K., Gandham, R. K., ... & Dhama, K. (2015). Apoptosis and other alternate mechanisms of cell death. Asian J. Anim. Vet. Adv, 10(10), 646-668. https://doi.org/10.3923/ajava.2015.646.668
Larasati, Y. A., Yoneda-Kato, N., Nakamae, I., Yokoyama, T., Meiyanto, E., & Kato, J. Y. (2018). Curcumin Targets Multiple Enzymes Involved in The ROS Metabolic Pathway to Suppress Tumor Cell Growth. Scientific Reports, 8(1), 1-13. https://doi.org/10.1038/s41598-018-20179-6
Łuczak, A., Madej, M., Kasprzyk, A., & Doroszko, A. (2020). Role of the eNOS uncoupling and the nitric oxide metabolic pathway in the pathogenesis of autoimmune rheumatic diseases. Oxidative Medicine and Cellular Longevity, 2020(1), 1-15. https://doi.org/10.1155/2020/1417981
Marton, L. T., Pescinini-e-Salzedas, L. M., Camargo, M. E. C., Barbalho, S. M., Haber, J. F. dos S., Sinatora, R. V., Detregiachi, C. R. P., Girio, R. J. S., Buchaim, D. V., & Cincotto dos Santos Bueno, P. (2021). The Effects of Curcumin on Diabetes Mellitus: A Systematic Review. Frontiers in Endocrinology, 12(669448), 1-12. https://doi.org/10.3389/fendo.2021.669448
Millward, D. J. (2017). Nutrition, Infection and Stunting: The Roles of Deficiencies of Individual Nutrients and Foods, and of Inflammation, As Determinants of Reduced Linear Growth of Children. In Nutrition Research Reviews, 30(1), 50–72. https://doi.org/10.1017/S0954422416000238
Mugoni, V., Camporeale, A., & Santoro, M. M. (2014). Analysis of Oxidative Stress in Zebrafish Embryos. Journal of Visualized Experiments, 89, 1-11. https://doi.org/10.3791/51328
Naseema, A., Kovooru, L., Behera, A. K., Kumar, K. P., & Srivastava, P. (2021). A critical review of synthesis procedures, applications and future potential of nanoemulsions. Advances in Colloid and Interface Science, 287, 102318. https://doi.org/10.1016/j.cis.2020.102318
Nguyen, C. L., Pham, N. M., Binns, C. W., Van Duong, D., & Lee, A. H. (2018). Prevalence of Gestational Diabetes Mellitus in Eastern and Southeastern Asia: A Systematic Review and Meta-Analysis. Journal of Diabetes Research, 2018), 1-10. https://doi.org/10.1155/2018/6536974
Nijs, H., & Benhalima, K. (2020). Gestational diabetes mellitus and the long-term risk for glucose intolerance and overweight in the offspring: a narrative review. Journal of clinical medicine, 9(2), 599. https://doi.org/10.3390/jcm9020599
Phoswa, W. N., & Khaliq, O. P. (2021). The role of oxidative stress in hypertensive disorders of pregnancy (preeclampsia, gestational hypertension) and metabolic disorder of pregnancy (gestational diabetes mellitus). Oxidative medicine and cellular longevity, 2021(1), 5581570. https://doi.org/10.1155/2021/5581570
Prakash, G. T., Das, A. K., Habeebullah, S., Bhat, V., & Shamanna, S. B. (2017). Maternal and Neonatal Outcome in Mothers With Gestational Diabetes Mellitus. Indian Journal of Endocrinology and Metabolism, 21(6), 854–858. https://doi.org/10.4103/ijem.IJEM_66_17
Pratiwi, H., Winarso, D., & Handoyo, D. N. (2016). Effect of Turmeric Etanol Extract (Curcuma Longa L) on Low Density Lipoprotein Level and Liver Histopathology Image in Type 1 Diabetes Mellitus Rat Model Induced by Streptozotocin. Jurnal Ilmu dan Teknologi Hasil Ternak, 11(1), 1-7. https://doi.org/10.21776/ub.jitek.2016.011.01.1
Safitri, N.P.D., Charles, S., & Siahaan, S.CP.T. (2022). Hubungan Diabetes Melitus Gestasional dengan Preeklamsia dan Luaran Neonatal di Rumah Sakit Kristen Mojowarno. NJM, 8(1), 18-24. Retrieved from: https://dspace.uc.ac.id/handle/123456789/8052
Puspita, O. E., Suwaldi, S., & Nugroho, A. K. (2016). Optimization of self-nanoemulsifying drug delivery system for pterostilbene. Journal of Food and Pharmaceutical Sciences, 4(2), 18-24. Retrieved from: https://journal.ugm.ac.id/jfps/article/view/12184
Raut, S. K., Singh, G. B., Rastogi, B., Saikia, U. N., Mittal, A., Dogra, N., Singh, S., Prasad, R., & Khullar, M. (2016). miR-30c and miR-181a Synergistically Modulate p53–p21 Pathway in Diabetes Induced Cardiac Hypertrophy. Molecular and Cellular Biochemistry, 417(1–2), 191–203. https://doi.org/10.1007/s11010-016-2729-7
Rolfe, E. D. L., França, G. V. A. De, Vianna, C. A., Gigante, D. P., Miranda, J. J., Yudkin, J. S., Horta, B. L., & Ong, K. K. (2018). Associations of Stunting in Early Childhood with Cardiometabolic Risk Factors in Adulthood. PLoS ONE, 13(4), 1-13. https://doi.org/10.1371/journal.pone.0192196
Runtuwene, J., Cheng, K. C., Asakawa, A., Amitani, H., Amitani, M., Morinaga, A., Takimoto, Y., Kairupan, B. H. R., & Inui, A. (2016). Rosmarinic Acid Ameliorates Hyperglycemia and Insulin Sensitivity in Diabetic Rats, Potentially By Modulating The Expression of PEPCK and GLUT4. Drug Design, Development and Therapy, 10, 2193–2202. https://doi.org/10.2147/DDDT.S108539
Sachett, A., Benvenutti, R., Reis, C. G., Gallas-Lopes, M., Bastos, L. M., Aguiar, G. P. S., Herrmann, A. P., Oliveira, J. V., Siebel, A. M., & Piato, A. (2022). Micronized Curcumin Causes Hyperlocomotion in Zebrafish Larvae. Neurochemical Research, 47(8), 2307–2316. https://doi.org/10.1007/s11064-022-03618-9
Salehpour, A., Rezaei, M., Khoradmehr, A., Tahamtani, Y., & Tamadon, A. (2021). Which hyperglycemic model of zebrafish (Danio rerio) suites my type 2 diabetes mellitus research? A scoring system for available methods. Frontiers in cell and developmental biology, 9, 652061. https://doi.org/10.3389/fcell.2021.652061
Shen, J. D., Wei, Y., Li, Y. J., Qiao, J. Y., & Li, Y. C. (2017). Curcumin Reverses The Depressive-Like Behavior and Insulin Resistance Induced By Chronic Mild Stress. Metabolic Brain Disease, 32(4), 1163–1172. https://doi.org/10.1007/s11011-017-0017-1
Singh, A., Castillo, H. A., Brown, J., Kaslin, J., Dwyer, K. M., & Gibert, Y. (2019). High Glucose Levels Affect Retinal Patterning During Zebrafish Embryogenesis. Scientific Reports, 9(1), 1-13. https://doi.org/10.1038/s41598-019-41009-3
Sovia, E., Sukandar, E. Y., Sigit, J. I., Dewi, L., & Sasongko, N. (2011). Efek Rimpang Kunyit (Curcuma longa L.) dan Bawang Putih (Allium sativum L.) terhadap Sensitivitas Insulin pada Tikus Galur Wistar. Bandung Medical Journal, 43(4), 153-159. http://dx.doi.org/10.15395/mkb.v43n4.62
Wijayanti, A. R., Ridlayanti, A., & Muljohadi Ali, H. K. (2021). Protection of Pegagan (Centella asiatica) Extract through Hsp60 and Bax Expression on Stunting Model Zebrafish Larvae (Danio rerio) by Rotenone Inducted. Journal of Physics: Conference Series, 1764(1), 1-8. https://doi.org/10.1088/1742-6596/1764/1/012019
Xiong, X. P., Song, Q., Han, C. C., Gan, W., He, F., Wei, S. H., Liu, H. H., & Xu, H. Y. (2016). Insulin Promotes The Expression of The Gluconeogenic Rate-Limiting Enzymes Phosphoenolpyruvate Carboxykinase (PEPCK) and Glucose 6-Phosphatase (G6pase) Through Pi3k/Akt/Mtor Signaling Pathway in Goose Hepatocytes. Revista Brasileira de Ciencia Avicola, 18(3), 395–400. https://doi.org/10.1590/1806-9061-2015-0080
Zakaria, Z. Z., Benslimane, F. M., Nasrallah, G. K., Shurbaji, S., Younes, N. N., Mraiche, F., ... & Yalcin, H. C. (2018). Using zebrafish for investigating the molecular mechanisms of drug‐induced cardiotoxicity. BioMed research international, 2018(1), 1642684. https://doi.org/10.1155/2018/1642684
Zhang, D. W., Fu, M., Gao, S. H., & Liu, J. L. (2013). Curcumin and diabetes: a systematic review. Evidence‐Based Complementary and Alternative Medicine, 2013(1), 636053. https://doi.org/10.1155/2013/636053
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