Kappaphycus alvarezii supplementation regulates hepatic gene expression involved in cholesterol metabolism in high-sodium fat diet-fed rat
K. alvarezii and Hepatic Cholesterol Metabolism
DOI:
https://doi.org/10.22146/ijp.25703Keywords:
Functional Food, Hypercholesterolaemia, HMG CoA R, Red SeaweedAbstract
Kappaphycus alvarezii (K. alvarezii), is a local red seaweed, claimed to be able to attenuate hypercholesterolaemia, one of CVD risk factors. However, the potential molecular mechanisms of K. alvarezii in regulating cholesterol synthesis and homeostasis remain unknown. Therefore, this study investigates the effect of supplementation of K. alvarezii on the hepatic mRNA gene expression involved in cholesterol metabolism in high sodium-fat diet (HSFD) induced hypercholesterolemic-hypertensive rat models. Twenty-four male Sprague-Dawley rats were fed with prepared HSFD, while control rats were fed with standard chow diet. After 6 weeks of feeding, induction rats were received K. alvarezii 5% (w/w) or 10% (w/w) mixed in the diet, or HFSD + captopril-simvastatin (25mg/kg/day - 1.8mg/kg/day), or HSFD for 4 weeks. Rats supplemented with K. alvarezii significantly reduced body weight, normalized blood pressure, reduced relative liver weight, liver lipid and total cholesterol compared with HSFD-induced rats (p<0.05). Histopathological examination of the liver found K. alvarezii attenuates the presence of steatosis and downregulated hepatic mRNA gene expression of three limiting enzymes that are involved in cholesterol synthesis and homeostasis: sterol regulatory element-binding protein-2 (SREBP-2), acetyl-CoA acetyltransferase-2 (ACAT-2), and 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR). Remarkable upregulation of cholesterol 7 alpha-hydroxylase (CYP7A1) mRNA expression was observed in K. alvarezii supplemented groups (p<0.05). As a conclusion, K. alvarezii attenuates hypercholesterolemia via inhibiting SREBP-2 signaling pathway activation and decreases cholesterol synthesis, reduces hepatic cholesterol esterification and modulates bile acids synthesis. The finding provides a novel idea on how this functional food maintains cholesterol levels for clinical application.
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Cherry, P., O’Hara, C., Magee, P. J., McSorley, E. M., & Allsopp, P. J. (2019). Risks and benefits of consuming edible seaweeds. Nutrition Reviews, 77(5), 307–329. https://doi.org/10.1093/nutrit/nuy066
Cian, R. E., Betancur, D., Garzón, G. A., & Drago, S. (2018). Hydrolyzates from Pyropia columbina seaweed have antiplatelet aggregation, antioxidant and ACE inhibitory peptides. LWT - Food Science and Technology, 64(2), 881–888. https://doi.org/10.1016/j.lwt.2015.06.043
Cui, D., Yu, X., Guan, Q., Zhang, X., Li, J., Chen, W., Chen, H., Liu, X., & Wu, J. (2025). Cholesterol metabolism: Molecular mechanisms, biological functions, diseases, and therapeutic targets. Molecular Biomedicine, 6(1), 72. https://doi.org/10.1186/s43556-025-00321-3
Dousip, A., Matanjun, P., Rosni, S., Song, T., Beng, H. O., & Ping, L. T. (2014). Effect of seaweed mixture intake on plasma lipid and antioxidant profile of hypercholesterolemic rats. Journal of Applied Phycology, 26, 999–1008. https://doi.org/10.1007/s10811-013-0128-y
Fadahunsi, O. S., & Olorunnisola, O. S. (2024). High-salt–fat diet: A risk factor for elevated blood pressure associated with dyslipidemia, perturbation in cardio-renal antioxidant and pro-inflammatory status in Wistar rats. Journal of Basic and Applied Zoology, 85(1), 62. https://doi.org/10.1186/s41936-024-00399-1
Ferrell, J. M., Boehme, S., Li, F., & Chiang, J. Y. L. (2016). Cholesterol 7α-hydroxylase-deficient mice are protected from high-fat/high-cholesterol diet-induced metabolic disorders. Journal of Lipid Research, 57(7), 1144–1154. https://doi.org/10.1194/jlr.M064709
Fitzgerald, C., Aluko, R. E., Hossain, M., Rai, D. K., & Hayes, M. (2014). Potential of a renin inhibitory peptide from the red seaweed Palmaria palmata as a functional food ingredient following confirmation and characterization of a hypotensive effect in spontaneously hypertensive rats. Journal of Agricultural and Food Chemistry, 62(33), 8352–8356. https://doi.org/10.1021/jf500983n
Gao, M., Xin, G., Qiu, X., Wang, Y., & Liu, G. (2017). Establishment of a rat model with diet-induced coronary atherosclerosis. Journal of Biomedical Research, 31(1), 47–55. https://doi.org/10.7555/JBR.31.20160020
Gómez-Guzmán, M., Rodríguez-Nogales, A., Algieri, F., & Gálvez, J. (2018). Potential role of seaweed polyphenols in cardiovascular-associated disorders. Marine Drugs, 16(8), 250. https://doi.org/10.3390/md16080250
Hannan, M. A., Sohag, A. A. M., Dash, R., Haque, M. N., Mohibbullah, M., Oktaviani, D. F., & Moon, I. S. (2020). Phytosterols of marine algae: Insights into the potential health benefits and molecular pharmacology. Phytomedicine, 69, 153201. https://doi.org/10.1016/j.phymed.2020.153201
Ipsen, D. H., Lykkesfeldt, J., & Tveden-Nyborg, P. (2018). Molecular mechanisms of hepatic lipid accumulation in non-alcoholic fatty liver disease. Cellular and Molecular Life Sciences, 75(18), 3313–3327. https://doi.org/10.1007/s00018-018-2860-6
Kumar, V., Sharma, P., Bairagya, H. R., Sharma, S., Singh, T. P., & Kaul, P. (2019). Inhibition of human 3-hydroxy-3-methylglutaryl CoA reductase by peptides leading to cholesterol homeostasis through SREBP2 pathway in HepG2 cells. Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, 1867(6), 604–615. https://doi.org/10.1016/j.bbapap.2019.04.002
Lasker, S., Rahman, M. M., & Parvez, F. (2019). High-fat diet-induced metabolic syndrome and oxidative stress in obese rats are ameliorated by yogurt supplementation. Scientific Reports, 9, 200–226. https://doi.org/10.1038/s41598-019-56538-0
Liu, S. H., Hung, H. I., Yang, T. H., Pan, C. L., & Chiang, M. T. (2021). Polysaccharide-rich red algae (Gelidium amansii) hot-water extracts ameliorate the altered plasma cholesterol and hepatic lipid homeostasis in high-fat diet-fed rats. Journal of Food and Drug Analysis, 29(1), 46–56. https://doi.org/10.38212/2224-6614.1181
Makkar, F., & Chakraborty, K. (2017). Antioxidative sulphated polygalactans from marine macroalgae as angiotensin-I converting enzyme inhibitors. Natural Product Research, 32(17), 2100–2106. https://doi.org/10.1080/14786419.2017.1363756
Matanjun, P., & Muhammad, K. (2010). Comparison of cardiovascular protective effects of tropical seaweeds, Kappaphycus alvarezii, Caulerpa lentillifera, and Sargassum polycystum, on high-cholesterol/high-fat diet in rats. Journal of Medicinal Food, 13(4), 1–10. https://doi.org/10.1089/jmf.2008.1212
Montero, L., Sánchez-Camargo, A. D. P., Ibáñez, E., & Gilbert-López, B. (2018). Phenolic compounds from edible algae: Bioactivity and health benefits. Current Medicinal Chemistry, 25(37), 4808–4826. https://doi.org/10.2174/0929867324666170523120101
Oyeleye, S. I., Olasehinde, T. A., Ademosun, A. O., & Akinyemi, A. J. (2019). Moringa oleifera seed and leaf inclusive diets modulate activities of enzymes linked with hypertension and lipid metabolites in high-fat fed rats. PharmaNutrition, 7, 100–141. https://doi.org/10.1016/j.phanu.2018.100141
Ozkan-Nikitaras, T., Grzesik, D. J., Romano, L. E., Chapple, J. P., King, P. J., & Shoulders, C. C. (2024). N-SREBP2 provides a mechanism for dynamic control of cellular cholesterol homeostasis. Cells, 13(15), 1255.
Rapacz, M., & Kozera, B. (2013). Reference genes in real-time PCR. Journal of Applied Genetics, 54(4), 391–406.
Saini, R. K., Prasad, P., Shang, X., & Keum, Y. S. (2021). Advances in lipid extraction methods: A review. International Journal of Molecular Sciences, 22(24), 13643. https://doi.org/10.3390/ijms222413643
Shehnaz, S. I., Roy, A., Vijayaraghavan, R., Sharma, R., Kumar, P., Bhatt, S., & Jaiswal, N. (2023). Luteolin mitigates diabetic dyslipidemia in rats by modulating ACAT-2, PPARα, SREBP-2 proteins, and oxidative stress. Applied Biochemistry and Biotechnology, 195(11), 4893–4914. https://doi.org/10.1007/s12010-023-04544-4
Shi, J., Li, R., Liu, Y., Lu, H., Yu, L., & Zhang, F. (2019). Shuangyu Tiaozhi granule attenuates hypercholesterolemia through the reduction of cholesterol synthesis in rats fed a high-cholesterol diet. BioMed Research International, 2019, 1–11. https://doi.org/10.1155/2019/4805926
Sokolova, E. V., Kravchenko, A. O., Sergeeva, N. V., Davydova, V. N., Bogdanovich, L. N., & Yermak, I. M. (2019). Effect of carrageenans on some lipid metabolism components in vitro. Carbohydrate Polymers, 215, 230–242. https://doi.org/10.1016/j.carbpol.2019.115629
Vinelli, V., Biscotti, P., Martini, D., Del Bo’, C., Marino, M., Meroño, T., Nikoloudaki, O., Calabrese, F. M., Turroni, S., Taverniti, V., Unión Caballero, A., Andrés-Lacueva, C., Porrini, M., Gobbetti, M., De Angelis, M., Brigidi, P., Pinart, M., Nimptsch, K., Guglielmetti, S., & Riso, P. (2022). Effects of Dietary Fibers on Short-Chain Fatty Acids and Gut Microbiota Composition in Healthy Adults: A Systematic Review. Nutrients, 14(13), 2559. https://doi.org/10.3390/nu14132559
Ward, N. C., Watts, G. F., & Eckel, R. H. (2019). Statin toxicity: Mechanistic insights and clinical implications. Circulation Research, 124(2), 328–350. https://doi.org/10.1161/CIRCRESAHA.118.312782
Zhao, C., Yang, C., Liu, B., Lin, L., Sarker, S. D., Nahar, L., & Xiao, J. (2018). Bioactive compounds from marine macroalgae and their hypoglycemic benefits. Trends in Food Science and Technology, 72, 1–12. https://doi.org/10.1016/j.tifs.2017.12.001
Published
2026-06-25
How to Cite
Mahadi, M., Eshak, Z. ., Ibrahim, A. H. ., Md Akim , A., & Abdul Rasyid, F. . (2026). Kappaphycus alvarezii supplementation regulates hepatic gene expression involved in cholesterol metabolism in high-sodium fat diet-fed rat: K. alvarezii and Hepatic Cholesterol Metabolism. Indonesian Journal of Pharmacy. https://doi.org/10.22146/ijp.25703
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Research Article
