Fucoidan, a polysaccharide, comes from marine sources. Fucoidan’s diverse biological activities, including lipid-lowering, anti-atherosclerosis, and anticoagulation, have made it increasingly popular in recent years. In this blog, I would like to introduce the study, “Application of fucoidan as a treatment for cardiovascular and cerebrovascular diseases” by Ke Wang et al. This study reveals how fucoidan affects the body and could be used to treat cardiovascular and cerebrovascular diseases. Each year, the number of cardiovascular disease (CVD) cases climbs, making CVD the world’s number one killer.
On the other hand, fucoidan is a complex marine acidic polysaccharide with diverse biological activities present in various organisms, which can play an important therapeutic role in all stages of cardiovascular disease, including early hyperlipidemia, fatty streaking of arteries, lipid accumulation, fibrous plaque, atherosclerotic plaque, plaque hemorrhage and rupture, thrombosis, and cerebral infarction. Hyperlipidemia is the cause of many cardiovascular and cerebrovascular diseases, and fucoidan has shown particularly diverse and powerful effects on lipid levels. The potential of fucoidan as a therapeutic agent for cardiovascular and cerebrovascular diseases stems from its ability to combat arteriosclerosis through anti-inflammatory, lipid-lowering, and antioxidant mechanisms.
Studies have shown that fucoidan can complete the efflux of intracellular free cholesterol by upregulating the expression of Scavenger receptor class B type I (SR-B1), Low-density lipoprotein receptor (LDLR), ATP-binding cassette transporter G1 (ABCG1), and ATP-binding cassette transporter A1 (ABCA1) that all of these proteins are involved in reverse cholesterol transport (RCT), a process that helps the body eliminate excess cholesterol in ApoE mice which has atherosclerosis gene and phagocytosing and removing excess peripheral lipids via transport to the liver by HDL.
The elevation of peroxisome proliferator-activated receptor alpha (PPAR α) levels, facilitated by fucoidan, enhances lipoprotein metabolism, stimulates fatty acid oxidation, and promotes cholesterol metabolism and efflux within the liver. Simultaneously, ABCA1 and ATP-binding cassette subfamily G member 8 (ABCG8), crucial for transporting cholesterol and plant sterols, contribute to the degradation and metabolism of cholesterol delivered to the liver. It breaks down cholesterol into bile salts or bile acids. Fucoidan can lower lipid levels and slow the progression of atherosclerosis (AS) by affecting the expression of genes and proteins related to the process of Reverse cholesterol transport (RCT).
Twelve weeks of a high-fat diet supplemented with 1% or 5% fucoidan significantly reduced aortic plaque thickness in ApoE mice, attributable to elevated plasma lipoprotein lipase (LPL) activity. In a mouse model of hyperlipidemia, serum Lecithin-cholesterol acyltransferase (LCAT), hepatic endothelial lipase (HL), and Lipoprotein lipase (LPL) activities were increased after intragastric administration of Sargassoam fucoidan, indicating that fucoidan has a potent lipid-lowering effect acting by promoting the catabolism of total cholesterol (TC) and LDL. Fucoidan induced LPL secretion in a dose- and time-dependent manner in vitro, increased LPL activation in the blood, regulated blood triglyceride (TG) content, and promoted TG clearance.
Atherosclerosis is a disease affecting the cardiovascular system and causing inflammation, linked to endothelial dysfunction. The persistent elevation of blood lipids leads to substantial deposits of proteins, including LDL, LDL-C, and ApoB, within arterial walls. Lipids and inflammatory cytokines accumulate in the arterial intima, triggering inflammatory cascades, local endothelial cell dysfunction, and vascular endothelial cell damage, leading to the progression of atherosclerosis. Fucoidan has demonstrated concentration-dependent antioxidant properties in other studies, including free radical scavenging, antioxidant enzyme enhancement, and protection of endothelial cells from oxidative free radical damage. Fucoidan also reduces the expression of endothelin-1 and the inflammatory cytokines interferon (IFN)-γ and tumor necrosis factor-α (TNF)-α, reducing the intensity of inflammation, improving metabolic disorders, and protecting endothelial cells from damage. Fucoidan also strengthens immune response, decreases inflammatory cytokine release, and reduces endothelial cell damage.
Ross, a pathologist, pioneered the “inflammatory theory” of atherosclerosis, revolutionizing its treatment. Research has shown that fucoidan reduces the inflammatory cytokines TNF-α, IL-1b, and iNOS released by macrophages, significantly reduces the adhesion of Ox-LDL coating to the macrophage surface, and reduces the transformation of macrophages into foam cells.
The process of autophagy is vital for cells and tissues as it helps degrade lipids in foam cells, particularly during the formation of foam cells. Fucoidan enhances the autophagy-lysosomal system in foam cells, increasing cellular autophagy to degrade lipids and play an anti-atherosclerotic defense role. Studies show fucoidan reduces new plaque formation by breaking down lipids in foam cells through autophagy.
Research indicates that the anti-inflammatory and antioxidant characteristics of fucoidan have a regulatory effect on endothelial cells, macrophages, and smooth muscle cells, all of which play a significant role in the development of atherosclerosis.
Further research also revealed that fucoidan potently blocked the intrinsic coagulation pathway by acting on factor Xase. It was shown that fucoidan significantly inhibited both intrinsic and extrinsic coagulation factors involved in the coagulation pathway. Fucoidan was isolated and purified from Sargassum, and mice treated with the highest concentration showed the longest clotting time, and the clotting time of each component was longer than that in the presence of aspirin and clopidogrel. Fucoidan shows great promise as a safer anticoagulant and antithrombotic drug for treating cardiovascular disease.
Fucoidan has been found to have an affinity for P-selectin, which is expressed by activated platelets in thrombi. Research shows that a 3900 Da highly sulfated fucoidan may be a superior antithrombotic drug due to its specific platelet aggregation inhibition, minimal anticoagulant effects, and reduced in vivo bleeding risk.
In a mouse model of hindlimb ischemia, fucoidan’s antioxidant effects safeguard neurons against cerebral oxidative stress from transient ischemia and lessen worsened brain damage in obese mice. It significantly reduces neurological deficits and infarct volume during cerebral ischemia and reperfusion by decreasing inflammation, oxidative stress, and cell apoptosis, while also suppressing the mitogen-activated protein kinase (MAPK) pathway. Fucoidan’s neuroprotective effects stem from its ability to suppress inflammation, oxidative stress, and apoptosis; thus, it shows promise as a treatment to improve outcomes in cardiovascular and cerebrovascular diseases.
Fucoidan has significant therapeutic potential across the spectrum of cardiovascular disease, impacting early stages like hyperlipidemia, the development of arterial fatty streaks and lipid accumulation, the progression to fibrous and atherosclerotic plaques, and the complications of plaque hemorrhage and rupture, thrombosis, and ultimately cerebral infarction. Hyperlipidemia is the cause of many cardiovascular and cerebrovascular diseases, and fucoidan has been shown to exert particularly diverse and powerful effects on lipid levels. Fucoidan’s anti-inflammatory, lipid-lowering, and antioxidant effects may benefit arteriosclerosis treatment, potentially improving cardiovascular and cerebrovascular health.
Source: Ther Adv Chronic Dis. 2022 Apr 12;13:20406223221076891. doi: 10.1177/20406223221076891