Peran Fucoidan Terhadap Angiogenesis

Muhammad Yusran, Muhammad Irsan Saleh, Ernawati Sinaga, Ramzi Amin

Sari


ABSTRACT

 

Angiogenesis is a tightly regulated biological process that supports tissue growth and wound healing. Dysregulation of this process may lead to various pathological conditions, including cancer, cardiovascular diseases, and diabetic retinopathy. Fucoidan is a sulfated polysaccharide derived from several marine species, such as brown seaweeds and sea cucumbers. Fucoidan has been reported to possess therapeutic potential in diseases associated with angiogenesis.To elucidate the role of fucoidan in the modulation of angiogenesis, both as a pro-angiogenic and anti-angiogenic agent across various pathological conditions. This article was prepared through a literature search conducted in EMBASE/Elsevier, Google Scholar, PubMed, ScienceDirect, and the Cochrane Review for publications from 2015 to 2025. The search terms included “angiogenesis”, “fucoidan”, “fucoidan AND (pro-angiogenic OR proangiogenic)”, and “fucoidan AND (anti-angiogenic OR antiangiogenic)”. Inclusion criteria comprised English-language, relevant full-text publications (2015–2025), including both original research articles and review papers. The synthesized evidence indicates that the effects of fucoidan on angiogenesis are influenced by molecular weight, degree of sulfation, source material, extraction methods, dosage, and disease context. Low-molecular-weight fucoidan tends to exert pro-angiogenic effects by enhancing endothelial cell proliferation and migration through the PI3K/AKT and AKT/Nrf2/HIF-1α signaling pathways, thereby potentially accelerating wound healing. In contrast, high-molecular-weight fucoidan may exhibit anti-angiogenic properties by suppressing VEGF and HIF-1α expression, inhibiting vascular tube formation, and modulating mechanisms associated with tumor progression, suggesting its potential application as a therapeutic target in cancer. Fucoidan is a context-dependent modulator of angiogenesis that may exert either pro- or anti-angiogenic effects depending on its physicochemical characteristics and biological context.

 

Keywords: Angiogenesis, Fucoidan, Pro-Angiogenik, Anti-Angiogenik.

 

 

ABSTRAK

 

Angiogenesis merupakan proses biologis yang diatur secara ketat untuk mendukung pertumbuhan jaringan dan proses penyembuhan luka. Adanya disregulasi pada proses ini dapat menyebabkan berbagai kondisi patologis seperti kanker, penyakit kardiovaskular dan retinopati diabetik. Fucoidan adalah polisakarida sulfat yang berasal dari beberapa spesies laut, seperti ganggang cokelat dan teripang. Fucoidan dilaporkan memiliki potensi terapeutik pada penyakit yang terkait dengan angiogenesis. Untuk menguraikan peran fucoidan dalam modulasi angiogenesis, baik sebagai agen pro-angiogenik maupun anti-angiogenik pada berbagai kondisi patologis. Penulisan artikel ini dilakukan melalui penelusuran literatur pada EMBASE/Elsevier, Google Scholar, PubMed, ScienceDirect, dan Cochrane Review untuk publikasi tahun 2015–2025. Kata kunci yang digunakan meliputi “angiogenesis”, “fucoidan”, “fucoidan AND (pro-angiogenic OR proangiogenic)”, dan “fucoidan AND (anti-angiogenic OR antiangiogenic)”. Kriteria inklusi mencakup publikasi berbahasa Inggris dengan full-text yang relevan (2015–2025), termasuk artikel original maupun review. Hasil sintesis menunjukkan bahwa efek fucoidan terhadap angiogenesis dipengaruhi oleh berat molekul, derajat sulfatasi, sumber bahan, metode ekstraksi, dosis, serta kondisi penyakit. Fucoidan dengan berat molekul rendah cenderung bersifat pro-angiogenik melalui peningkatan proliferasi dan migrasi sel endotel melalui jalur PI3K/AKT dan AKT/Nrf2/HIF-1α, sehingga berpotensi mempercepat penyembuhan luka. Sebaliknya, fucoidan dengan berat molekul tinggi dapat bersifat anti-angiogenik, dengan menekan ekspresi VEGF dan HIF-1α, menghambat pembentukan tabung vaskular, serta memodulasi mekanisme yang terkait progresivitas tumor, sehingga berpotensi dimanfaatkan sebagai target terapi kanker. Fucoidan merupakan modulator angiogenesis yang dapat bersifat pro- maupun anti-angiogenik tergantung karakteristik dan konteks biologisnya.

 

Kata Kunci: Angiogenesis, Fucoidan, Pro-Angiogenik, Anti-Angiogenik.


Teks Lengkap:

Download Artikel.

Referensi


Aspriţoiu, V. M., Stoica, I., Bleotu, C., & Diaconu, C. C. (2021). Epigenetic Regulation Of Angiogenesis In Development And Tumors Progression: Potential Implications For Cancer Treatment. In Frontiers In Cell And Developmental Biology (Vol. 9). Https://Doi.Org/10.3389/Fcell.2021.689962

Bae, H., Lee, J. Y., Yang, C., Song, G., & Lim, W. (2020). Fucoidan Derived From Fucus Vesiculosus Inhibits The Development Of Human Ovarian Cancer Via The Disturbance Of Calcium Homeostasis, Endoplasmic Reticulum Stress, And Angiogenesis. Marine Drugs, 18(1). Https://Doi.Org/10.3390/Md18010045

Bouvard, C., Galy-Fauroux, I., Grelac, F., Carpentier, W., Lokajczyk, A., Gandrille, S., Colliec-Jouault, S., Fischer, A. M., & Helley, D. (2015). Low-Molecular-Weight Fucoidan Induces Endothelial Cell Migration Via The Pi3k/Akt Pathway And Modulates The Transcription Of Genes Involved In Angiogenesis. Marine Drugs, 13(12). Https://Doi.Org/10.3390/Md13127075

Dipietro, L. A. (2016). Angiogenesis And Wound Repair: When Enough Is Enough. Journal Of Leukocyte Biology, 100(5). Https://Doi.Org/10.1189/Jlb.4mr0316-102r

Dörschmann P, Bittkau Ks, Neupane S, Roider J, Alban S, Klettner A.(2019). Effects Of Fucoidans From Five Different Brown Algae On Oxidative Stress And Vegf Interference In Ocular Cells. Marine Drugs. 17(5):258

Falcao, M. (2012). Diabetic Retinopathy: Understanding Pathologic Angiogenesis And Exploring Its Treatment Options. The Open Circulation & Vascular Journal, 3(1). Https://Doi.Org/10.2174/1877382601003010030

Huerta, M., Tejada, M., & Nieto, F. R. (2024). Fucoidan As A Promising Drug For Pain Treatment: Systematic Review And Meta-Analysis. Marine Drugs, 22(7), 1–17. Https://Doi.Org/10.3390/Md22070290

Jayson, G. C., Kerbel, R., Ellis, L. M., & Harris, A. L. (2016). Antiangiogenic Therapy In Oncology: Current Status And Future Directions. In The Lancet (Vol. 388, Issue 10043). Https://Doi.Org/10.1016/S0140-6736(15)01088-0

Jeong, S., Lee, S., Lee, G., Hyun, J., & Ryu, B. (2024). Systematic Characteristics Of Fucoidan: Intriguing Features For New Pharmacological Interventions. International Journal Of Molecular Sciences, 25(21). Https://Doi.Org/10.3390/Ijms252111771

Kim, B. S., Park, J. Y., Kang, H. J., Kim, H. J., & Lee, J. (2014). Fucoidan/Fgf-2 Induces Angiogenesis Through Jnk- And P38-Mediated Activation Of Akt/Mmp-2 Signalling. Biochemical And Biophysical Research Communications, 450(4). Https://Doi.Org/10.1016/J.Bbrc.2014.06.137

Kwak, J. Y. (2014). Fucoidan As A Marine Anticancer Agent In Preclinical Development. In Marine Drugs (Vol. 12, Issue 2). Https://Doi.Org/10.3390/Md12020851

La Mendola, D., Trincavelli, M. L., & Martini, C. (2022). Angiogenesis In Disease. In International Journal Of Molecular Sciences (Vol. 23, Issue 18). Https://Doi.Org/10.3390/Ijms231810962

Laeliocattleya, R. A., Yunianta, Suloi, A. F., Gayatri, P. P., Putri, N. A., & Anggraeni, Y. C. (2020). Fucoidan Content From Brown Seaweed (Sargassum Filipendula) And Its Potential As Radical Scavenger. Journal Of Physics: Conference Series, 1430(1). Https://Doi.Org/10.1088/1742-6596/1430/1/012023

Li, G., Gao, J., Ding, P., & Gao, Y. (2025). The Role Of Endothelial Cell–Pericyte Interactions In Vascularization And Diseases. In Journal Of Advanced Research (Vol. 67). Https://Doi.Org/10.1016/J.Jare.2024.01.016

Liu, F., Wang, J., Chang, A. K., Liu, B., Yang, L., Li, Q., Wang, P., & Zou, X. (2012). Fucoidan Extract Derived From Undaria Pinnatifida Inhibits Angiogenesis By Human Umbilical Vein Endothelial Cells. Phytomedicine, 19(8–9). Https://Doi.Org/10.1016/J.Phymed.2012.03.015

Liu, X., Zhang, J., Yi, T., Li, H., Tang, X., Liu, D., Wu, D., & Li, Y. (2025). Decoding Tumor Angiogenesis: Pathways, Mechanisms, And Future Directions In Anti-Cancer Strategies. Biomarker Research, 13(1), 1–29. Https://Doi.Org/10.1186/S40364-025-00779-X

Lomartire, S., & Gonçalves, A. M. M. (2022). Novel Technologies For Seaweed Polysaccharides Extraction And Their Use In Food With Therapeutically Applications—A Review. In Foods (Vol. 11, Issue 17). Https://Doi.Org/10.3390/Foods11172654

Luthuli, S., Wu, S., Cheng, Y., Zheng, X., Wu, M., & Tong, H. (2019). Therapeutic Effects Of Fucoidan: A Review On Recent Studies. In Marine Drugs (Vol. 17, Issue 9). Https://Doi.Org/10.3390/Md17090487

Minhajat, R. (2019). Angiogenesis Dan Perannya Pada Kanker. 1st Ed. Vol. 1. Makasar: Bagian Ilmu Penyakit Dalam Fakultas Kedokteran Unhas

Muz, B., De La Puente, P., Azab, F., & Azab, A. K. (2015). The Role Of Hypoxia In Cancer Progression, Angiogenesis, Metastasis, And Resistance To Therapy. Hypoxia. Https://Doi.Org/10.2147/Hp.S93413

Polverini, P. J. (2002). Angiogenesis In Health And Disease: Insights Into Basic Mechanisms And Therapeutic Opportunities. Journal Of Dental Education, 66(8). Https://Doi.Org/10.1002/J.0022-0337.2002.66.8.Tb03565.X

Rajabi, M., & Mousa, S. A. (2017). The Role Of Angiogenesis In Cancer Treatment. In Biomedicines (Vol. 5, Issue 2). Https://Doi.Org/10.3390/Biomedicines5020034

Rezzola, S., Loda, A., Corsini, M., Semeraro, F., Annese, T., Presta, M., & Ribatti, D. (2020). Angiogenesis-Inflammation Cross Talk In Diabetic Retinopathy: Novel Insights From The Chick Embryo Chorioallantoic Membrane/Human Vitreous Platform. In Frontiers In Immunology (Vol. 11). Https://Doi.Org/10.3389/Fimmu.2020.581288

Saghiri, M. A., Asatourian, A., Orangi, J., Sorenson, C. M., & Sheibani, N. (2015). Functional Role Of Inorganic Trace Elements In Angiogenesis-Part Ii: Cr, Si, Zn, Cu, And S. In Critical Reviews In Oncology/Hematology (Vol. 96, Issue 1). Https://Doi.Org/10.1016/J.Critrevonc.2015.05.011

Santiago, A. R., Boia, R., Aires, I. D., Ambrósio, A. F., & Fernandes, R. (2018). Sweet Stress: Coping With Vascular Dysfunction In Diabetic Retinopathy. In Frontiers In Physiology (Vol. 9, Issue Jul). Https://Doi.Org/10.3389/Fphys.2018.00820

Senthilkumar, K., Manivasagan, P., Venkatesan, J., & Kim, S. K. (2013). Brown Seaweed Fucoidan: Biological Activity And Apoptosis, Growth Signaling Mechanism In Cancer. In International Journal Of Biological Macromolecules (Vol. 60). Https://Doi.Org/10.1016/J.Ijbiomac.2013.06.030

Sharma, R. (2024). Angiogenesis: Mechanisms, Roles, And Implications In Health And Disease. Clinical Investigation, 14(4), 551–553.

Shen, H. Y., Li, L. Z., Xue, K. C., Hu, D. D., & Gao, Y. J. (2017). Antitumor Activity Of Fucoidan In Anaplastic Thyroid Cancer Via Apoptosis And Anti-Angiogenesis. Molecular Medicine Reports, 15(5). Https://Doi.Org/10.3892/Mmr.2017.6338

Shi, Z., Yao, C., Shui, Y., Li, S., & Yan, H. (2023). Research Progress On The Mechanism Of Angiogenesis In Wound Repair And Regeneration. In Frontiers In Physiology (Vol. 14). Https://Doi.Org/10.3389/Fphys.2023.1284981

Turrini, E., Maffei, F., & Fimognari, C. (2023). Ten Years Of Research On Fucoidan And Cancer: Focus On Its Antiangiogenic And Antimetastatic Effects. In Marine Drugs (Vol. 21, Issue 5). Https://Doi.Org/10.3390/Md21050307

Ustyuzhanina, N. E., Bilan, M. I., Ushakova, N. A., Usov, A. I., Kiselevskiy, M. V., & Nifantiev, N. E. (2014). Fucoidans: Pro- Or Antiangiogenic Agents? In Glycobiology (Vol. 24, Issue 12). Https://Doi.Org/10.1093/Glycob/Cwu063

Wang, Y., Xing, M., Cao, Q., Ji, A., Liang, H., & Song, S. (2019). Biological Activities Of Fucoidan And The Factors Mediating Its Therapeutic Effects: A Review Of Recent Studies. Marine Drugs, 17(3). Https://Doi.Org/10.3390/Md17030183

Wen, W., Yang, L., Wang, X., Zhang, H., Wu, F., Xu, K., Chen, S., & Liao, Z. (2023). Fucoidan Promotes Angiogenesis And Accelerates Wound Healing Through Akt/Nrf2/Hif-1α Signalling Pathway. International Wound Journal, 20(9). Https://Doi.Org/10.1111/Iwj.14239

Whelan, S. (2022). What Is Angiogenesis? Technology Networks.

Xu, J., Chen, L. J., Yu, J., Wang, H. J., Zhang, F., Liu, Q., & Wu, J. (2018). Involvement Of Advanced Glycation End Products In The Pathogenesis Of Diabetic Retinopathy. In Cellular Physiology And Biochemistry (Vol. 48, Issue 2). Https://Doi.Org/10.1159/000491897

Yang, W.; Yu, X.; Zhang, Q.; Lu, Q.; Wang, J.; Cui, W.; Zheng, Y.; Wang, X.; Luo, D. (2013). Attenuation Of Streptozotocin-Induced Diabetic Retinopathy With Low Molecular Weight Fucoidan Via Inhibition Of Vascular Endothelial Growth Factor. Exp. Eye Res.115, 96–105

Zhang, R., Yao, Y., Gao, H., & Hu, X. (2024). Mechanisms Of Angiogenesis In Tumour. Frontiers In Oncology, 14(March), 1–15. Https://Doi.Org/10.3389/Fonc.2024.1359069

Zhao, Y., Zheng, Y., Wang, J., Ma, S., Yu, Y., White, W. L., Yang, S., Yang, F., & Lu, J. (2018). Fucoidan Extracted From Undaria Pinnatifida: Source For Nutraceuticals/Functional Foods. Marine Drugs, 16(9). Https://Doi.Org/10.3390/Md16090321

Zhu, Y., Zhang, J., Hu, X., Wang, Z., Wu, S., & Yi, Y. (2020). Extracellular Vesicles Derived From Human Adipose-Derived Stem Cells Promote The Exogenous Angiogenesis Of Fat Grafts Via The Let-7/Ago1/Vegf Signalling Pathway. Scientific Reports, 10(1). Https://Doi.Org/10.1038/S41598-020-62140-6




DOI: https://doi.org/10.33024/mahesa.v6i8.24160

Refbacks

  • Saat ini tidak ada refbacks.


Publisher: Universitas Malahayati Lampung

Creative Commons License
Semua artikel dapat digunakan dibawah lisensi Creative Commons Attribution-ShareAlike 4.0 International License