Effect of Stichopus hermanii extract on interleukin-6 levels in a high-fat diet-induced rat model of inflammation

Diah Purwaningsari; Sihning Endah J. Tehupuring; Nita Pranitasari; Lestari Dewi

doi:10.35814/jifi.v24i1.2030

Penulis

Diah Purwaningsari Department of Anatomy and Histology, Faculty of Medicine, Hang Tuah University, Surabaya, 60111, Indonesia
Sihning Endah J. Tehupuring Department of Anatomy and Histology, Faculty of Medicine, Hang Tuah University, Surabaya, 60111, Indonesia
Nita Pranitasari Department of Anatomy and Histology, Faculty of Medicine, Hang Tuah University, Surabaya, 60111, Indonesia
Lestari Dewi Department of Pharmacology, Faculty of Medicine, Hang Tuah University, Surabaya, 60111, Indonesia

DOI:

https://doi.org/10.35814/jifi.v24i1.2030

Kata Kunci:

Atherosclerosis, interleukin-6, sea cucumber, Stichopus hermanii

Abstrak

Atherosclerosis is a major contributor to cardiovascular diseases and is increasingly recognized as a chronic low-grade inflammatory disorder involving oxidative stress and immune-mediated mechanisms. Interleukin-6 (IL-6) is a key proinflammatory cytokine that links oxidative stress and immune responses and has been widely associated with the progression of inflammation-related vascular conditions and the acceleration of atherosclerosis. The adverse effects of current pharmaceuticals have driven interest in herbal alternatives with fewer side effects. Sea cucumbers are recognized as potent biomedical resources with bioactivities against atherosclerotic pathways. This study aimed to identify the effects of Stichopus hermanii extract on IL-6 levels in a rat model of atherosclerosis induced by a high-fat diet. An experimental in vivo study utilizing a post-test-only control group design was performed on 32 Wistar rats, categorized into four groups: negative control (standard diet), positive control (high-fat diet), and two treatment groups administered Stichopus hermanii extract at dosages of 35 mg and 40 mg per 200 g body weight. IL-6 concentrations were markedly increased in rats subjected to a high-fat diet compared to those in the conventional diet group (p<0.05). Stichopus hermanii extract at both dosages markedly diminished IL-6 concentrations compared to the positive control group. The 40 mg dose reinstated IL-6 levels to those similar to the negative control group, signifying a dose-dependent anti-inflammatory effect. The extract of Stichopus hermanii successfully regulated IL-6 levels in rats with atherosclerosis induced by a high-fat diet, indicating its potential as a natural anti-inflammatory and cardioprotective agent for managing atherosclerosis.

Referensi

[1] World Heart Federation, World Heart Report 2023: Confronting the World’s Number One Killer. Geneva: World Heart Federation, 2023.

[2] K. Malekmohammad, R. D. E. Sewell, and M. Rafieian-Kopaei, “Antioxidants and Atherosclerosis: Mechanistic Aspects,” Biomolecules, vol. 9, p. 301, 2019, doi: 10.3390/biom9080301.

[3] D. Wolf and K. Ley, “Immunity and Inflammation in Atherosclerosis,” Circ. Res., vol. 124, no. 2, pp. 315–327, 2019, doi: 10.1161/CIRCRESAHA.118.313591.

[4] S. Zhang, L. Li, W. Chen, S. Xu, X. Feng, and L. Zhang, “Natural products: The role and mechanism in low-density lipoprotein oxidation and atherosclerosis,” Phytother. Res., vol. 35, no. 6, pp. 1–23, 2020, doi: 10.1002/ptr.7002.

[5] Y. N. Fawzya, N. A. Putra, A. B. Witarto, and G. Patantis, “Golden Sea Cucumber: Identification and the Antioxidant Activity of Its Collagen Hydrolysates,” SQUALEN Bull. Mar. Fish. Postharvest Biotechnol., vol. 15, no. 3, p. 119, 2020, doi: 10.15578/squalen.v15i3.511.

[6] D. Pringgenies, S. Rudiyanti, and E. Yudiati, “Exploration of Sea Cucumbers Stichopus hermanii from Karimunjawa Islands as Production of Marine Biological Resources,” IOP Conf. Ser. Earth Environ. Sci., vol. 116, no. 1, p. 012039, 2018, doi: 10.1088/1755-1315/116/1/012039.

[7] M. Khan et al., “Interleukin-6 and Cardiovascular Events in Healthy Adults,” JACC Adv., vol. 3, no. 8, p. 101063, 2024, doi: 10.1016/j.jacadv.2024.101063.

[8] R. Cau and L. Saba, “Interlinking pathways: a narrative review on the role of IL-6 in cancer and atherosclerosis,” Cardiovasc. Diagn. Ther., vol. 14, no. 6, pp. 1186–1201, 2024, doi: 10.21037/cdt-24-344.

[9] A. Ghadiri-anari, J. Behjati, A. Esteghamati, F. Esfahanian, Z. Khazaiipoor, and M. Nakhjavani, “Correlation between oxidized-LDL and interleukin-6 in type 2 diabetic patients,” Iran. J. Diabetes Lipid Disord., vol. 10, pp. 1–7, 2011.

[10] S. Kim and Y. Jang, “Inflammation in Atherosclerotic Cardiovascular Diseases: Biomarkers to Therapeutics in Clinical Settings,” J. Cardiovasc. Interv., vol. 3, no. 4, pp. 199–215, 2024, doi: 10.54912/jci.2024.0014.

[11] P. Libby, “Inflammation and the pathogenesis of atherosclerosis,” Vascul. Pharmacol., vol. 154, p. 107255, 2024, doi: 10.1016/j.vph.2023.107255.

[12] Y. Zhu et al., “Research Progress on the Relationship between Atherosclerosis and Inflammation,” Biomolecules, vol. 8, no. 3, p. 80, 2018, doi: 10.3390/biom8030080.

[13] N. N. Mehta, E. DeGoma, and M. D. Shapiro, “IL‑6 and Cardiovascular Risk: A Narrative Review,” Curr. Atheroscler. Rep., vol. 27, p. 12, 2025, doi: 10.1007/s11883-024-01259-7.

[14] E. V Gerasimova, T. V Popkova, I. G. Kirillova, D. A. Gerasimova, E. L. Nasonov, and A. M. Lila, “Interleukin-6: Cardiovascular Aspects of Long-Term Cytokine Suppression in Patients with Rheumatoid Arthritis,” Int. J. Mol. Sci., vol. 25, p. 12425, 2024, doi: 10.3390/ijms252212425.

[15] G. K. Hansson, P. Libby, and I. Tabas, “Inflammation and plaque vulnerability,” J. Intern. Med., vol. 278, no. 5, pp. 483–493, 2016, doi: 10.1111/joim.12406.Inflammation.

[16] D. W. Damaiyanti, “Characterization Of Water Extract Gold Sea Cucumber (Stichopus hermanii),” Dent. J. Kedokt. Gigi, vol. 9, no. 1, pp. 74–81, 2015.

[17] L. Ding et al., “Saponins of sea cucumber attenuate atherosclerosis in ApoE−/− mice via lipid-lowering and anti-inflammatory properties,” J. Funct. Foods, vol. 48, pp. 490–497, 2018, doi: 10.1016/j.jff.2018.07.046.

[18] D. A. Chistiakov, A. A. Melnichenko, A. V Grechko, V. A. Myasoedova, and A. N. Orekhov, “Potential of anti-inflammatory agents for treatment of atherosclerosis,” Exp. Mol. Pathol., vol. 104, no. 2, pp. 114–124, 2018, doi: 10.1016/j.yexmp.2018.01.008.