Fucoidan improves serum lipid levels and atherosclerosis through hepatic SREBP-2-mediated regulation

Abstract

Hyperlipidemia is associated with increased risk of the development of cardiovascular diseases. Although a great deal of attention has been paid to the hypolipidemic activity of fucoidan, complex polysaccharides from brown seaweeds, the underlying mechanism is still unclear. This study was performed to investigate whether and how fucoidan has lipid-lowering potential in poloxamer-407 (P407)-induced hyperlipidemic mice. Fucoidan treatment 2 h after acute administration of P407 in these mice significantly reduced serum total cholesterol, triglycerides, and LDL cholesterol levels, but increased the levels of HDL cholesterol. In HepG2 hepatocytes and the liver, fucoidan decreased the expression of FAS and ACC mRNA with no or only a moderate inhibitory effect on SREBP-1c mRNA expression. Furthermore, fucoidan attenuated the hepatic expression of mature SREBP-2 protein with a subsequent decrease in hepatic HMG-CoA reductase mRNA expression and an increase in hepatic LDL receptor mRNA expression. In addition, atherosclerotic lesions in the aorta of chronically P407-treated mice were also reduced by fucoidan. These findings indicate that fucoidan improves serum lipid levels by regulating the expression of key enzymes of cholesterol and triglyceride syntheses in the liver through modulation of SREBP-2.

Phytochemical Screening and Toxicological Evaluation of <i>Sargassum wightii</i> Greville in Wistar Rats

“…Another study correlated the hypolipidemic effect of fucoidan to reduction in HMG CoA reductase expression and an upregulation of LDL receptor. 41 Thus these results are consistent with previous studies available on the hypoglycemic property of sulfated polysaccharides, which are expected to be the major compounds present in S. wightii extract. 42…”

Algal Polysaccharides as Therapeutic Agents for Atherosclerosis

“…After 12 weeks, the atherosclerotic lesion area of their aortas was significantly lower in the mice treated with fucoidan (Figures 4A,B ) ( 11 ). These results were also supported by a study in which poloxamer-407 (P-407) was used to induce atherosclerotic lesions and hyperlipidemia in mice through lipid derangement ( 12 , 13 ). Lesion formation in the aorta was significantly reduced by intraperitoneal administration of 50 mg/kg of fucoidan every third day for 16 weeks ( 12 ).…”

“…Sterol regulatory element-binding protein 1 (SREBP1) regulates expression of lipogenic genes acetyl-CoA-carboxylase (ACC) and fatty acid synthetase (FAS). In the same study, SREBP1 was found to be downregulated by fucoidan treatment (Figures 4C–F ) ( 11 ) but unchanged in human hepatoma cells and the P-407 mice, although ACC and FAS had decreased expression ( 12 ). The bile acid synthesis pathway, controlled by Cytochrome P450 Family 7 Subfamily A Member 1 (CYP7A1) and induced by SREBP1, was also downregulated after treatment with fucoidan ( 11 ).…”

“…One potential mechanism of action for fucoidan's activity on atherosclerosis is the alteration in lipid uptake and metabolism. Total cholesterol, triglycerides and low density lipoprotein (LDL) levels in the serum were significantly reduced while high density lipoprotein (HDL) levels were increased starting from doses of 30 mg/kg in mice ( 10 – 12 ) and 100 mg/kg in rats ( 14 – 16 ). Due to fucoidan's additional effect on dyslipidemia, the liver has been identified as a possible target with research focusing on hepatic lipid metabolism.…”

Effect of γ-oryzanol on hyperlipidemia and thrombus formation in mice treated with poloxamer-407

“…28,29 Oxidative stress occurs when antioxidant/prooxidant homeostasis is imbalanced and reactive oxygen species (ROS) production is elevated. 30 Lipid peroxidation leads to the production of MDA as a byproduct 31 which is detrimental to body. Poloxamer-407 has been reported to aggravate oxidative damage and formation of oxi-LDL.…”