Rosmarinus officinalis and Centella asiatica Affect Interleukin-6 Zebrafish Larvae Induced High Glucose


  • Fajar Dwi Prastiwi Master Program of Midwifery, Faculty of Medicine, Brawijaya University, Indonesia
  • Sutini Lamadi Master Program of Midwifery, Faculty of Medicine, Brawijaya University, Indonesia
  • Husnul Khotimah Department of Biomedical, Faculty of Medicine, University of Brawijaya, Indonesia
  • I Wayan Arsana Wiyasa Department of Obstetrics and Gynecology, Faculty of Medicine, University of Brawijaya, Indonesia
  • Tri Yudani M. Raras Department of Biomedical, Faculty of Medicine, University of Brawijaya, Indonesia



Centella, Hyperglycemia, Interleukin-6, Rosmarinus


Gestational Diabetes Mellitus (GDM) is diabetes that occurs during pregnancy. GDM is characterized by hyperglycemia. Hyperglycemia causes an inflammatory response characterized by the excretion of pro-inflammatory cytokines, one of which is IL-6. Centella asiatica and Rosmarinus officinalis are known as anti-diabetic and anti-inflammatory. This study aims to study the effect of the combination of nanoemulsion Centella asiatica and Rosmarinus officinalis on the expression of Interleukin-6 in Zebrafish larvae induced by 3% glucose. Hyperglycemia is known from increased levels of Phosphoenolpyruvate carboxykinase in Zebrafish larvae. Phosphoenolpyruvate carboxykinase and Interleukin-6 expression were measured by conventional PCR method. The combination of Rosmarinus officinalis nanoemulsion and Centella asiatica was given with three different doses, namely at a concentration of 2.5, 5 and 10 µg/mL. The statistical analysis used was One Way ANOVA to measure Interleukin-6 expression levels. The results of this study prove that the combination of Rosmarinus officinalis and Centella asiatica nanoemulsions reduces the expression of Interleukin-6. The dose closest to the negative control was at a concentration of 5 μg/mL, although the final result was statistically significant (p<0.05). In conclusion, combining nanoemulsion Centella asiatica and Rosmarinus officinalis with the right dose reduced levels of Interleukin 6 in zebrafish larvae induced by high glucose.


Althurwi, H. N., Soliman, G. A., Abdel-Rahman, R. F., Abd-Elsalam, R. M., Ogaly, H. A., Alqarni, M. H., Albaqami, F. F., & Abdel-Kader, M. S. (2022). Vulgarin, a Sesquiterpene Lactone from Artemisia judaica, Improves the Antidiabetic Effectiveness of Glibenclamide in Streptozotocin-Induced Diabetic Rats via Modulation of PEPCK and G6Pase Genes Expression. International Journal of Molecular Sciences, 23(24), 1–16.

Amirian, A., Mahani, M. B., & Abdi, F. (2020). Role of interleukin-6 (IL-6) in predicting gestational diabetes mellitus. Obstetrics and Gynecology Science, 63(4), 407–416.

Benincá, J. P., Dalmarco, J. B., Pizzolatti, M. G., & Fröde, T. S. (2011). Analysis of the anti-inflammatory properties of Rosmarinus officinalis L. in mice. Food Chemistry, 124(2), 468–475.

Blotsky, A. L., Rahme, E., Dahhou, M., Nakhla, M., & Dasgupta, K. (2019). Gestational diabetes associated with incident diabetes in childhood and youth: A retrospective cohort study. Cmaj, 191(15), E410–E417.

Borges, R. S., Keita, H., Ortiz, B. L. S., dos Santos Sampaio, T. I., Ferreira, I. M., Lima, E. S., de Jesus Amazonas da Silva, M., Fernandes, C. P., de Faria Mota Oliveira, A. E. M., da Conceição, E. C., Rodrigues, A. B. L., Filho, A. C. M. P., Castro, A. N., & Carvalho, J. C. T. (2018). Anti-inflammatory activity of nanoemulsions of essential oil from Rosmarinus officinalis L.: in vitro and in zebrafish studies. Inflammopharmacology, 26(4), 1057–1080.

Borges, R. S., Lima, E. S., Keita, H., Ferreira, I. M., Fernandes, C. P., Cruz, R. A. S., Duarte, J. L., Velázquez-Moyado, J., Ortiz, B. L. S., Castro, A. N., Ferreira, J. V., da Silva Hage-Melim, L. I., & Carvalho, J. C. T. (2018). Anti-inflammatory and antialgic actions of a nanoemulsion of Rosmarinus officinalis L. essential oil and a molecular docking study of its major chemical constituents. Inflammopharmacology, 26(1), 183–195.

Chamoun, L. B. S., Filho, J. R., Corte, V. B., Perin, I. T. D. A. L., Fernandes, C. P., Cruz, R. A. S., & França, H. S. (2021). A nanoemulsion of Rosmarinus officinalis L. essential oil with allelopathic effect against Lactuca sativa L. seeds / Uma nanoemulsão a partir do óleo essencial de Rosmarinus officinalis L com efeito alelopático em sementes de Lactuca sativa L. Brazilian Journal of Development, 7(9), 86752–86771.

Diass, K., Brahmi, F., Mokhtari, O., Abdellaoui, S., & Hammouti, B. (2021). Biological and pharmaceutical properties of essential oils of Rosmarinus officinalis L. And Lavandula officinalis L. Materials Today: Proceedings, 45, 7768–7773.

Feng, M., Liu, F., Xing, J., Zhong, Y., & Zhou, X. (2021). Anemarrhena saponins attenuate insulin resistance in rats with high-fat diet-induced obesity via the IRS-1/PI3K/AKT pathway. Journal of Ethnopharmacology, 277, 114251.

Filardi, T., Catanzaro, G., Mardente, S., Zicari, A., Santangelo, C., Lenzi, A., Morano, S., & Ferretti, E. (2020). Non-coding RNA: Role in gestational diabetes pathophysiology and complications. International Journal of Molecular Sciences, 21(11).

Garcia, C., Ladeiras, D., & Reis, C. P. (2018). Rosmarinus officinalis L.: an update review of its phytochemistry and biological activity. 4.

Gonçalves, C., Fernandes, D., Silva, I., & Mateus, V. (2022). Potential Anti-Inflammatory Effect of Rosmarinus officinalis in Preclinical In Vivo Models of Inflammation. Molecules, 27(3).

Kementerian Kesehatan Republik Indonesia. (2017). Wanita dan Diabetes - Direktorat P2PTM.Accessed 4-01-2023.

Negara KS. (2015). Skrining Diabetes melitus gestasional. SMF Obstetri dan Ginekologi RSUP Sanglah, FK Universitas Udayana.

Khotimah, H., Alita, S. N. P., Aninditha, D., Weningtyas, A., Prima, W. 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.

Khotimah, H., Prima, W. E., Weningtyas, A., Aninditha, D., Alita, S. N. P., Kalsum, U., Shahdevi, K., Rahayu, M., & Handayani, D. (2021). 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.

Kusumastuti, S. A., Nugrahaningsih, D. A. A., & Wahyuningsih, M. S. H. (2019). Centella asiatica (L.) extract attenuates inflammation and improve insulin sensitivity in a coculture of lipopolysaccharide (LPS)-induced 3T3-L1 adipocytes and RAW 264.7 macrophages. Drug Discoveries & Therapeutics, 13(5), 261–267.

Lee, Y., Choi, H. K., N’deh, K. P. U., Choi, Y. J., Fan, M., Kim, E. K., Chung, K. H., & An, J. H. (2020). Inhibitory effect of Centella asiatica extract on DNCB-induced atopic dermatitis in HaCaT cells and BALB/c mice. Nutrients, 12(2).

Liu, T. Y., Shi, C. X., Gao, R., Sun, H. J., Xiong, X. Q., Ding, L., Chen, Q., Li, Y. H., Wang, J. J., Kang, Y. M., & Zhu, G. Q. (2015). Irisin inhibits hepatic gluconeogenesis and increases glycogen synthesis via the PI3K/Akt pathway in type 2 diabetic mice and hepatocytes. Clinical Science, 129(10), 839–850.

McIntyre, H. D., Catalano, P., Zhang, C., Desoye, G., Mathiesen, E. R., & Damm, P. (2019). Gestational diabetes mellitus. Nature Reviews Disease Primers, 5(1).

Plows, J. F., Stanley, J. L., Baker, P. N., Reynolds, C. M., & Vickers, M. H. (2018). The pathophysiology of gestational diabetes mellitus. International Journal of Molecular Sciences, 19(11), 1–21.

Pusat Kajian Hortikultura Tropika (IPB). (n.d.). Pegagan (Centella asiatica(L.) Urban). accessed 4-01-2023.

Rahbardar, M. G., & Hosseinzadeh, H. (2020). Therapeutic effects of rosemary (Rosmarinus officinalis L.) and its active constituents on nervous system disorders. Iranian Journal of Basic Medical Sciences, 23(9), 1100–1112.

Sharma, A. K., Singh, S., Singh, H., Mahajan, D., Kolli, P., Mandadapu, G., Kumar, B., Kumar, D., Kumar, S., & Jena, M. K. (2022). Deep Insight of the Pathophysiology of Gestational Diabetes Mellitus. Cells, 11(17), 1–19.

Siddiqui, S., Waghdhare, S., Goel, C., Panda, M., Soneja, H., Sundar, J., Banerjee, M., Jha, S., & Dubey, S. (2019). Augmentation of IL-6 production contributes to development of gestational diabetes mellitus: An Indian study. Diabetes and Metabolic Syndrome: Clinical Research and Reviews, 13(2), 895–899.

Sweeting, A. N., & Ross, G. P. (2020). An update on gestational diabetes mellitus. Medicine Today, 21(11), 33–42.

Teh, L. K., Salleh, M. Z., & Adenan, M. I. (2020). Inhibitory Effects of Raw-Extract Centella asiatica. Molecules, 25(892), 1–20.




How to Cite

Prastiwi, F. D., Lamadi, S., Khotimah, H., Wiyasa, I. W. A., & Raras, T. Y. M. (2024). Rosmarinus officinalis and Centella asiatica Affect Interleukin-6 Zebrafish Larvae Induced High Glucose. Medical Laboratory Technology Journal.




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