Pemanfaatan Zebrafish sebagai Model High-Throughput Screening untuk Penemuan dan Pengembangan Obat Anti-inflamasi

Authors

  • Yuni Antika Jenderal Soedirman University
  • Zulfa Nur Azizah
  • Khesya Gizzani Supratman
  • Nabila Adini Putri
  • Rachel Angelin Situmorang
  • Muhammad Izzan Syawaluddin

Keywords:

zebrafish, inflammatory model, drug discovery, high-throughput screening

Abstract

The development of anti-inflammatory drugs requires test models capable of presenting comprehensive immune responses, and zebrafish have become one of the most widely used animal models due to their mammalian-like immune system and compatibility with high-throughput in vivo screening. This study aims to identify, review, and compare various methods for inducing inflammation in zebrafish through a literature analysis of PubMed, ScienceDirect, SpringerLink, MDPI, and Google Scholar over the past ten years using keywords related to “zebrafish,” “inflammation,” “inflammation model,” “high-throughput screening,” “drug discovery,” and “anti-inflammatory agents.” Three main approaches to inducing inflammation in zebrafish were identified: wounding-induced, chemically-induced, and mutation-induced. Chemically induced models are the most commonly applied because they are easy to standardize and suitable for testing large numbers of compounds, whereas wounding-induced models enable real-time observation of leukocyte migration, and mutation-induced models are used to investigate chronic inflammation and specific molecular pathways. Overall, zebrafish represent an effective and relevant biological model for inflammation research and drug discovery, with diverse induction approaches that enhance sensitivity, screening throughput, and the capacity to study cellular mechanisms and pharmacological effects, thereby potentially accelerating the preclinical development of anti-inflammatory drugs.

References

Bernal-Bermúdez, B., Martínez-López, A., Martínez-Morcillo, F. J., Tyrkalska, S. D., Martínez-Menchón, T., Mesa-del-Castillo, P., Cayuela, M. L., Mulero, V., & García-Moreno, D. (2023). A zebrafish model of Ifih1-driven Aicardi–Goutières syndrome reproduces the interferon signature and the exacerbated inflammation of patients. Frontiers in Immunology, 14, 1294766. https://doi.org/10.3389/fimmu.2023.1294766

Bousquet, M. S., Ratnayake, R., Pope, J. L., Chen, Q.-Y., Zhu, F., Chen, S., Carney, T. J., Gharaibeh, R. Z., Jobin, C., Paul, V. J., & Luesch, H. (2020). Seaweed natural products modify the host inflammatory response via Nrf2 signaling and alter colon microbiota composition and gene expression. Free Radical Biology and Medicine, 146, 306–323. https://doi.org/10.1016/j.freeradbiomed.2019.09.013

Carletti, A., Cardoso, C., Lobo-Arteaga, J., Sales, S., Juliao, D., Ferreira, I., Chainho, P., Dionísio, M. A., Gaudêncio, M. J., Afonso, C., Lourenço, H., Cancela, M. L., Bandarra, N. M., & Gavaia, P. J. (2022). Antioxidant and Anti-inflammatory Extracts From Sea Cucumbers and Tunicates Induce a Pro-osteogenic Effect in Zebrafish Larvae. Frontiers in Nutrition, 9, 888360. https://doi.org/10.3389/fnut.2022.888360

Doke, S. K., & Dhawale, S. C. (2015). Alternatives to animal testing: A review. Saudi Pharmaceutical Journal, 23(3), 223–229. https://doi.org/10.1016/j.jsps.2013.11.002

Duarte Da Silva, K. C., Carneiro, W. F., Virote, B. D. C. R., Santos, M. D. F., De Oliveira, J. P. L., Castro, T. F. D., Bertolucci, S. K. V., & Murgas, L. D. S. (2024). Evaluation of the Anti-Inflammatory and Antioxidant Potential of Cymbopogon citratus Essential Oil in Zebrafish. Animals, 14(4), 581. https://doi.org/10.3390/ani14040581

Furman, D., Campisi, J., Verdin, E., Carrera-Bastos, P., Targ, S., Franceschi, C., Ferrucci, L., Gilroy, D. W., Fasano, A., Miller, G. W., Miller, A. H., Mantovani, A., Weyand, C. M., Barzilai, N., Goronzy, J. J., Rando, T. A., Effros, R. B., Lucia, A., Kleinstreuer, N., & Slavich, G. M. (2019). Chronic inflammation in the etiology of disease across the life span. Nature Medicine, 25(12), 1822–1832. https://doi.org/10.1038/s41591-019-0675-0

Gómez-Abenza, E., Ibáñez-Molero, S., García-Moreno, D., Fuentes, I., Zon, L. I., Mione, M. C., Cayuela, M. L., Gabellini, C., & Mulero, V. (2019a). Zebrafish modeling reveals that SPINT1 regulates the aggressiveness of skin cutaneous melanoma and its crosstalk with tumor immune microenvironment. Journal of Experimental & Clinical Cancer Research, 38(1), 405. https://doi.org/10.1186/s13046-019-1389-3

Gómez-Abenza, E., Ibáñez-Molero, S., García-Moreno, D., Fuentes, I., Zon, L. I., Mione, M. C., Cayuela, M. L., Gabellini, C., & Mulero, V. (2019b). Zebrafish modeling reveals that SPINT1 regulates the aggressiveness of skin cutaneous melanoma and its crosstalk with tumor immune microenvironment. Journal of Experimental & Clinical Cancer Research, 38(1), 405. https://doi.org/10.1186/s13046-019-1389-3

Gong, L., Yu, L., Gong, X., Wang, C., Hu, N., Dai, X., Peng, C., & Li, Y. (2020). Exploration of anti-inflammatory mechanism of forsythiaside A and forsythiaside B in CuSO4-induced inflammation in zebrafish by metabolomic and proteomic analyses. Journal of Neuroinflammation, 17(1), 173. https://doi.org/10.1186/s12974-020-01855-9

Guo, D.-L., Chen, J.-F., Tan, L., Jin, M.-Y., Ju, F., Cao, Z.-X., Deng, F., Wang, L.-N., Gu, Y.-C., & Deng, Y. (2019). Terpene Glycosides from Sanguisorba officinalis and Their Anti-Inflammatory Effects.

He, M., Halima, M., Xie, Y., Schaaf, M. J. M., Meijer, A. H., & Wang, M. (2020). Ginsenoside Rg1 Acts as a Selective Glucocorticoid Receptor Agonist with Anti-Inflammatory Action without Affecting Tissue Regeneration in Zebrafish Larvae. Cells, 9(5), 1107. https://doi.org/10.3390/cells9051107

Hernández-Silva, D., Cantón-Sandoval, J., Martínez-Navarro, F. J., Pérez-Sánchez, H., De Oliveira, S., Mulero, V., Alcaraz-Pérez, F., & Cayuela, M. L. (2022). Senescence-Independent Anti-Inflammatory Activity of the Senolytic Drugs Dasatinib, Navitoclax, and Venetoclax in Zebrafish Models of Chronic Inflammation. International Journal of Molecular Sciences, 23(18), 10468. https://doi.org/10.3390/ijms231810468

Husnul Khotimah, Fathina Zahrani Rahmaniar, Fatimah Az Zahra, Rabjhany Anaqah, Shahdevi Nandar Kurniawan, Masruroh Rahayu, & Hikmawan Wahyu Sulistomo. (2024). Diverse perspectives in zebrafish seizure models: An exploration of chemical inducers. World Journal of Advanced Research and Reviews, 21(3), 865–877. https://doi.org/10.30574/wjarr.2024.21.3.0734

Kabadi, A., McDonnell, E., Frank, C. L., & Drowley, L. (2020). Applications of Functional Genomics for Drug Discovery. SLAS Discovery, 25(8), 823–842. https://doi.org/10.1177/2472555220902092

Kim, H., Alten, R., Avedano, L., Dignass, A., Gomollón, F., Greveson, K., Halfvarson, J., Irving, P. M., Jahnsen, J., Lakatos, P. L., Lee, J., Makri, S., Parker, B., Peyrin-Biroulet, L., Schreiber, S., Simoens, S., Westhovens, R., Danese, S., & Jeong, J. H. (2020). The Future of Biosimilars: Maximizing Benefits Across Immune-Mediated Inflammatory Diseases. Drugs, 80(2), 99–113. https://doi.org/10.1007/s40265-020-01256-5

Koga, R. D. C. R., De Souza, A. A., Sales, P. F., Ferreira, A. M., De Souza, G. C., & Carvalho, J. C. T. (2025). Anti-Inflammatory and Antinociceptive Potential of Hydroethanolic Extract of Bauhinia guianensis Aubl. In Zebrafish (Danio rerio). Nutraceuticals, 5(3), 25. https://doi.org/10.3390/nutraceuticals5030025

Lanzarin, G. A. B., Félix, L. M., Monteiro, S. M., Ferreira, J. M., Oliveira, P. A., & Venâncio, C. (2023). Anti-Inflammatory, Anti-Oxidative and Anti-Apoptotic Effects of Thymol and 24-Epibrassinolide in Zebrafish Larvae. Antioxidants, 12(6), 1297. https://doi.org/10.3390/antiox12061297

Latrille, T., Joseph, J., Hartasánchez, D. A., & Salamin, N. (2024). Estimating the proportion of beneficial mutations that are not adaptive in mammals. PLOS Genetics, 20(12), e1011536. https://doi.org/10.1371/journal.pgen.1011536

LeBert, D. C., Squirrell, J. M., Rindy, J., Broadbridge, E., Lui, Y., Zakrzewska, A., Eliceiri, K. W., Meijer, A. H., & Huttenlocher, A. (2015). Matrix metalloproteinase 9 modulates collagen matrices and wound repair. Development, 142(12), 2136–2146. https://doi.org/10.1242/dev.121160

Liu, W., Yu, H., Gurbazar, D., Rinchindorj, D., Kang, W., Qi, C., Chen, H., Chang, X., You, H., Han, Y., Li, Z., R. G., A., & Dong, W. (2024). Anti-inflammatory effects and beneficial effects of the feed additive Urtica cannabina L. in zebrafish. PLOS ONE, 19(7), e0307269. https://doi.org/10.1371/journal.pone.0307269

Lubin, A., Otterstrom, J., Hoade, Y., Bjedov, I., Stead, E., Whelan, M., Gestri, G., Paran, Y., & Payne, E. (2021). A versatile, automated and high-throughput drug screening platform for zebrafish embryos. Biology Open, 10(9), bio058513. https://doi.org/10.1242/bio.058513

Marques Fernandes, S., Watanabe, M., & Fernandes Vattimo, M. D. F. (2021). Inflammation: Improving understanding to prevent or ameliorate kidney diseases. Journal of Venomous Animals and Toxins Including Tropical Diseases. https://doi.org/10.1590/1678-9199-JVATITD-2020-0162

Montero-Lobato, Z., Vázquez, M., Navarro, F., Fuentes, J. L., Bermejo, E., Garbayo, I., Vílchez, C., & Cuaresma, M. (2018). Chemically-Induced Production of Anti-Inflammatory Molecules in Microalgae. Marine Drugs, 16(12), 478. https://doi.org/10.3390/md16120478

Nguyen, T. H., Le, H. D., Nguyen Thi Kim, T., Pham The, H., Nguyen, T. M., Cornet, V., Lambert, J., & Kestemont, P. (2020). Anti–Inflammatory and Antioxidant Properties of the Ethanol Extract of Clerodendrum Cyrtophyllum Turcz in Copper Sulfate-Induced Inflammation in Zebrafish. Antioxidants, 9(3), 192. https://doi.org/10.3390/antiox9030192

Oprişoreanu, A.-M., Ryan, F., Richmond, C., Dzekhtsiarova, Y., Carragher, N. O., Becker, T., David, S., & Becker, C. G. (2023). Drug screening in zebrafish larvae reveals inflammation-related modulators of secondary damage after spinal cord injury in mice. Theranostics, 13(8), 2531–2551. https://doi.org/10.7150/thno.81332

Pratiwi, D. M. N., Yuliani, S. H., & Samirana, P. O. (2024). Studies on anti-inflammatory activity and wound-healing property of secondary metabolite of Anredera cordifolia (Ten.) Steenis leaves: A review. Journal of Applied Pharmaceutical Science. https://doi.org/10.7324/JAPS.2025.206872

Raghupathy, S., Vaidyanathan, L., & Sivaswamy, L. (2017). Adult Zebrafish Model of Wound Inflammation to Study Wound Healing Potency of Curcuma longa Extracts Title changed as suggested by the reviewer. Annual Research & Review in Biology, 18(3), 1–8. https://doi.org/10.9734/ARRB/2017/35910

Rai, M., Sinha, A., & Roy, S. (2024). A Review On The Chemical-Induced Experimental Model Of Cardiotoxicity. International Journal of Pharmacy and Pharmaceutical Sciences, 1–11. https://doi.org/10.22159/ijpps.2024v16i7.51028

Rasmussen, S. K., & Jain, S. M. (2024). Editorial: Mutational breeding: from induced mutations to site-directed mutagenesis. Frontiers in Plant Science, 15, 1511363. https://doi.org/10.3389/fpls.2024.1511363

Robertson, A. L., Ogryzko, N. V., Henry, K. M., Loynes, C. A., Foulkes, M. J., Meloni, M. M., Wang, X., Ford, C., Jackson, M., Ingham, P. W., Wilson, H. L., Farrow, S. N., Solari, R., Flower, R. J., Jones, S., Whyte, M. K. B., & Renshaw, S. A. (2016). Identification of benzopyrone as a common structural feature in compounds with anti-inflammatory activity in a zebrafish phenotypic screen. Disease Models & Mechanisms, 9(6), 621–632. https://doi.org/10.1242/dmm.024935

Schwartz, A. V., Sant, K. E., & George, U. Z. (2025). Integrating network analysis and machine learning to elucidate chemical-induced pancreatic toxicity in zebrafish embryos. Toxicological Sciences, 206(2), 330–353. https://doi.org/10.1093/toxsci/kfaf069

Sohail, R., Mathew, M., Patel, K. K., Reddy, S. A., Haider, Z., Naria, M., Habib, A., Abdin, Z. U., Razzaq Chaudhry, W., & Akbar, A. (2023). Effects of Non-steroidal Anti-inflammatory Drugs (NSAIDs) and Gastroprotective NSAIDs on the Gastrointestinal Tract: A Narrative Review. Cureus. https://doi.org/10.7759/cureus.37080

Sreesivasakthi, A., Devi, R., Srinivasan, Dr. R., Jayaramakani, N., David, E. S., & Dhavamanikandan, A. (2024). Zebrafish As A Model Organism For Drug Screening And Development. In Dr. S. Pishawikar, Dr. P. Singh, Mrs. D. Raman, Dr. S. Deshpande, Dr. M. Bhateria, Dr. R. B. Pandit, Mr. C. Nayak, Mrs. N. V. N. Jyothi, Dr. M. Adikwu, Dr. N. Hussain, Dr. M. V. Suryawanshi, & Mrs. S. Desai (Eds), Futuristic Trends in Pharmacy & Nursing Volume 3 Book 16 (First, pp. 132–150). Iterative International Publishers, Selfypage Developers Pvt Ltd. https://doi.org/10.58532/V3BKPN16P1CH12

Varshney, G. K., Pei, W., LaFave, M. C., Idol, J., Xu, L., Gallardo, V., Carrington, B., Bishop, K., Jones, M., Li, M., Harper, U., Huang, S. C., Prakash, A., Chen, W., Sood, R., Ledin, J., & Burgess, S. M. (2015). High-throughput gene targeting and phenotyping in zebrafish using CRISPR/Cas9. Genome Research, 25(7), 1030–1042. https://doi.org/10.1101/gr.186379.114

Wilhelm, K. ‐P., Wilhelm, D., & Bielfeldt, S. (2017). Models of wound healing: An emphasis on clinical studies. Skin Research and Technology, 23(1), 3–12. https://doi.org/10.1111/srt.12317

Xie, Y., Meijer, A. H., & Schaaf, M. J. M. (2021). Modeling Inflammation in Zebrafish for the Development of Anti-inflammatory Drugs. Frontiers in Cell and Developmental Biology, 8, 620984. https://doi.org/10.3389/fcell.2020.620984

Zanandrea, R., Bonan, C. D., & Campos, M. M. (2020). Zebrafish as a model for inflammation and drug discovery. Drug Discovery Today, 25(12), 2201–2211. https://doi.org/10.1016/j.drudis.2020.09.036

Zhang, P., Liu, N., Xue, M., Zhang, M., Xiao, Z., Xu, C., Fan, Y., Liu, W., Qiu, J., Zhang, Q., & Zhou, Y. (2023). Anti-Inflammatory and Antioxidant Properties of Squalene in Copper Sulfate-Induced Inflammation in Zebrafish (Danio rerio). International Journal of Molecular Sciences, 24(10), 8518. https://doi.org/10.3390/ijms24108518

Downloads

Published

2025-12-01

How to Cite

Yuni Antika, Azizah, Z. N., Supratman, K. G., Putri, N. A., Situmorang, R. A., & Syawaluddin , M. I. (2025). Pemanfaatan Zebrafish sebagai Model High-Throughput Screening untuk Penemuan dan Pengembangan Obat Anti-inflamasi. Jurnal Apoteker Indonesia, 2(6), 131–142. Retrieved from https://journal.talentainsan.com/index.php/jai/article/view/89