Fucoidan (CAS: 9072-19-9) Biological Activities: Tumor Suppression, Immune Activation, and Metabolic Enhancement

Fucoidan, also referred to as brown algae polysaccharide, is a functional polysaccharide rich in sulfate groups, found exclusively in marine environments. It primarily consists of L-fucose and sulfate groups, along with minor components such as mannose, xylose, galactose, and glucuronic acid. Its main chain typically features α-1,3 or α-1,4 linked fucosidic bonds. Fucoidan exhibits a wide range of biological activities, including immunomodulation, anti-tumor effects, antioxidant properties, anticoagulant activity, lipid-lowering effects, as well as antibacterial, antiviral, anti-arthritic actions, gastric ulcer prevention, neuroprotection, regulation of fat metabolism, and mitigation of diabetic complications.

Discovered by Swedish professor Kylin in 1913, fucoidan has been extensively studied for its structure, properties, and applications. In 1996, at the 55th Annual Meeting of the Japanese Cancer Association, a report highlighting fucoidan’s ability to induce apoptosis in cancer cells garnered significant attention within the academic community.

In terms of extraction methods, fucoidan is typically obtained from brown algae through water extraction, acid extraction, or ultrasonic extraction techniques, all of which preserve its original chemical structure and biological activity. Its molecular structure exhibits considerable heterogeneity, with variations in sulfation degree and monosaccharide composition influenced by factors such as the species of brown algae and their growing seasons. For example, the sulfation patterns of fucoidan from different species, such as Fucus vesiculosus and Undaria pinnatifida, occur at different carbon positions, resulting in distinct biological activities.

Basic Information

CAS No.: 9072-19-9

Molecular formula: C7H14O7S

Molecular weight: 242.24686

EINECS number: 618-634-7

MDL No.: MFCD00131109

Bioactive Functions

The anti-tumor activity of fucoidan is closely linked to its immunomodulatory functions. Fucoidan stimulates macrophages and splenocytes to produce cytokines and chemokines, thereby enhancing the body's overall immune response. It directly inhibits or kills tumor cells, boosts lymphokine activity, and induces macrophages to produce tumor necrosis factor (TNF). These combined effects enable fucoidan to exhibit significant anti-tumor properties.

Fucoidan’s antioxidant activity is influenced by its sulfate ester content, molecular weight, fucose levels, and other structural parameters. A higher sulfate ester content enhances its antioxidant properties. Low molecular weight fucoidan significantly inhibits Cu²⁺-induced oxidation of low-density lipoproteins (LDL). However, highly sulfated low molecular weight fucoidan and those rich in fucose, sulfate esters, and small amounts of uronic acid show limited capacity to neutralize superoxide radicals. Overall, the antioxidant activity of fucoidan depends on a complex interplay of factors such as monosaccharide composition, sulfate group content, and molecular weight.

Fucoidan  possesses remarkable anticoagulant properties, surpassing commonly used sodium citrate in potency and remaining unaffected by calcium ions. Its anticoagulant effects primarily stem from the activation of antithrombin III and other anticoagulant factors, significantly inhibiting the activity of coagulation factors in a manner similar to heparin. Unlike heparin, fucoidan’s anticoagulant efficacy is less impacted by blood pH, and it exhibits a thrombolytic activity that heparin lacks, potentially offering advantages in specific clinical contexts.

In addition to these effects, fucoidan helps regulate blood lipids and blood sugar. It significantly reduces cholesterol (TC) and triglyceride (TG) levels in hyperlipidemic rats while increasing high-density lipoprotein cholesterol (HDL-C). This lipid regulation is crucial for preventing cardiovascular conditions like atherosclerosis and coronary heart disease. Fucoidan also demonstrates strong hypoglycemic effects, comparable to the commonly prescribed metformin hydrochloride when administered at higher doses.

Moreover, fucoidan provides significant protection for the kidneys. It helps restore the negative charge barrier of damaged glomerular basement membranes, reduces matrix proliferation, and alleviates glomerulosclerosis, thereby mitigating kidney damage in certain disease models like doxorubicin-induced nephropathy. In patients with chronic renal failure, fucoidan effectively lowers uremic toxins and improves renal function, positioning it as a safe and effective natural agent for managing uremia.

Fucoidan is beneficial for improving intestinal health, helping alleviate constipation and treat enteritis. In a clinical trial involving 30 constipation patients, the experimental group took 1g of fucoidan daily, while the control group took a placebo. After two months, the experimental group saw their average weekly defecation frequency increase from 2.7 to 4.6 days, with notable improvements in stool volume and softness. In another study, fucoidan-based polysaccharides effectively treated enteritis in mice.

Additionally, fucoidan has a unique ability to eradicate Helicobacter pylori. Studies indicate that fucoidan exhibits strong antibacterial activity, completely inhibiting the proliferation of Helicobacter pylori at concentrations of 100 μg/mL. The sulfate groups in fucoidan’s molecular structure specifically bind to the binding proteins on the surface of Helicobacter pylori, preventing its adhesion to the gastric mucosa.

Research into fucoidan as a vaccine adjuvant has found that elderly individuals over 60 years old who took fucoidan daily showed significantly higher antibody production after receiving influenza vaccinations. Their natural killer cell activity was also enhanced. In another study, fucoidan effectively stimulated the activity of dendritic cells in the spleen, promoting cytokine secretion and enhancing the immune response of antigen-specific T cells, highlighting its potential as a powerful vaccine adjuvant.

Beyond these effects, fucoidan exhibits a wide range of other biological activities. It has broad-spectrum antimicrobial effects, including antiviral, antibacterial, and antifungal actions. In terms of organ protection, fucoidan not only safeguards the kidneys but also provides liver protection and protects the gastric mucosa. Additionally, it has neuroprotective and anti-inflammatory properties, making it potentially valuable in the prevention and treatment of neurological diseases. Fucoidan also promotes wound healing, presenting potential applications in both medical and cosmetic fields.

Researchers worldwide have conducted extensive studies on the biological functions of fucoidan. In over 1,000 published papers, fucoidan has been shown to exhibit numerous effects, including anti-tumor, gastrointestinal improvement, immunity enhancement, anti-thrombotic, blood pressure-lowering, and antiviral properties. These findings have laid the foundation for its application in functional foods, health supplements, and other wellness products.

Food Industry

Fucoidan has gained traction in the food industry, particularly in the functional health foods sector, due to its natural origin, safety, and versatility. We have developed various products based on functional foods and beverages, including antioxidant-rich drinks and health supplements aimed at lowering blood sugar and lipid levels. As a food additive, fucoidan enhances food's antioxidant properties, improves immune function, and offers other health benefits. With its antibacterial and antifungal properties, fucoidan can  encapsulate yeast K2 toxin, ensuring food safety, while significantly boosting the shelf life of food and beverages by enhancing biological preservation.

Additionally, fucoidan is frequently combined with other natural ingredients to create composite functional foods that address a range of health needs. Many bioactive compounds have poor solubility, high sensitivity, and limited bioavailability, making fucoidan an ideal material for encapsulation due to its unique physicochemical and biological properties. Its applications include nanoparticles, emulsions, edible films, nanocapsules, and hydrogels, providing various delivery methods for nutritional supplements. For example, loading antimicrobial peptides like nisin into fucoidan particles can enhance antibacterial properties, making them suitable for food preservation and antimicrobial applications.

Moreover, fucoidan's physical and chemical properties—such as gelation, thickening, film formation, stabilization, and emulsification—along with its physiological benefits like antioxidant activity, heavy metal ion adsorption, and gastrointestinal health improvement, make it increasingly important in the field of marine functional foods. China has officially issued a fucoidan food production license, marking its formal entry into the food industry.

Medical field

Significant progress has been made in the research and application of fucoidan in the medical field, particularly in immunomodulation, anti-tumor, and anti-coagulation areas, highlighting its strong potential. Fucoidan is used as an excipient in various drugs and plays a key role in the development of new hypoglycemic and hypolipidemic medications. Its antiviral, antithrombotic, and gastric mucosal protective properties make it an ideal ingredient for treating gastrointestinal disorders, immune-related conditions, and chronic diseases.

Fucoidan exhibits its anti-tumor properties through several complex mechanisms. It can effectively inhibit the cell cycle, particularly blocking tumor cells in the G1 phase, preventing them from entering mitosis, thus significantly reducing tumor cell proliferation. Fucoidan also induces apoptosis by activating the endoplasmic reticulum stress pathway and triggering the caspase cascade. Additionally, it has anti-angiogenic properties, inhibiting the formation of new blood vessels in tumors by downregulating key factors like VEGF, thereby curbing tumor growth and metastasis. By activating immune cells such as NK cells and macrophages, fucoidan significantly enhances the immune system’s ability to recognize and eliminate cancer cells. Moreover, it regulates the Nrf2/ROS signaling pathway, further inhibiting cancer cell proliferation, offering a novel approach to anti-tumor therapy.

Fucoidan plays a comprehensive role in immune regulation, significantly enhancing immune function by improving the activity of immune organs, particularly NK cells. It promotes non-specific immune responses by boosting the phagocytic ability of macrophages, enabling the body to better resist pathogen invasion. In terms of specific immunity, fucoidan increases the number and activity of T cells, enhancing the body’s viral resistance. Its notable anti-inflammatory effects help to control excessive inflammatory responses, maintaining immune balance and preventing unnecessary tissue damage. These multifaceted immunomodulatory mechanisms make fucoidan a powerful tool for strengthening immunity and preventing disease.

Fucoidan regulates blood sugar through multiple mechanisms, improving insulin resistance by increasing basal insulin levels and enhancing insulin sensitivity. In a rat model of type 2 diabetes, fucoidan significantly reduced fasting blood glucose levels, showing promise for diabetes prevention. It also decreased blood sugar and urea nitrogen levels in diabetic mice while increasing serum calcium and insulin levels. Furthermore, it exhibited a restorative effect on pancreatic islet damage caused by alloxan, indicating its potential therapeutic value for diabetes.

Fucoidan has demonstrated significant lipid-lowering and weight loss effects. It reduces serum and liver levels of triglycerides, total cholesterol, and low-density lipoprotein cholesterol (LDL-C), while increasing high-density lipoprotein cholesterol (HDL-C) levels in hyperlipidemic mice, effectively treating dyslipidemia. This effect is partly attributed to fucoidan's ability to regulate lipid metabolism in the liver and small intestine, promoting normal lipid metabolism and excretion. Additionally, by regulating gut microbiota, particularly those related to metabolic diseases, fucoidan helps maintain glucose and lipid homeostasis, offering comprehensive support for blood lipid regulation.

Fucoidan is effective in inhibiting Helicobacter pylori proliferation. In a mouse study, daily doses of 100 mg/kg of fucoidan resulted in an 83.3% eradication rate of H. pylori after two weeks. In a clinical trial involving 42 patients, 300 mg of fucoidan was administered daily for 8 weeks, leading to a 42% reduction in the urea breath test baseline value, along with a significant decrease in serum pepsinogen levels, a marker of chronic atrophic gastritis. In vitro, fucoidan completely inhibited H. pylori growth at 100 μg/mL and reduced urease activity at 1500 pg/mL, showcasing its potential for improving gastric health.

Fucoidan has substantial effects on intestinal health, increasing peristalsis, treating constipation, alleviating intestinal inflammation, and assisting in the treatment of intestinal cancer while minimizing side effects. In a clinical study involving 30 patients, the experimental group taking 1g of fucoidan daily for 8 weeks showed a significant increase in bowel movement frequency, stool volume, and softness, with no adverse effects reported.

Fucoidan has been developed to prevent diseases affecting the heart, brain, kidneys, and blood vessels, achieving satisfactory clinical results. Its potential as a transport carrier for new drugs opens opportunities for applications such as sustained-release coatings, microsphere embolization, nanomedicine, gene therapy, surgical repair, and transdermal drug delivery.

Cosmetics field

The application of fucoidan in the cosmetics industry and its benefits for skin health are primarily seen in the following areas:

Moisturizing and Anti-UV Protection: Fucoidan possesses excellent moisturizing properties, making it a valuable ingredient in cosmetics for deep hydration, helping to maintain skin moisture levels. Additionally, fucoidan protects the skin from UV damage, shielding it from harmful ultraviolet rays.

Antioxidant Effect: As a natural sulfated polysaccharide, fucoidan has potent antioxidant properties. This enables it to neutralize free radicals, slow down the skin's aging process, and contribute to anti-aging effects in cosmetic products.

Antibacterial and Anti-Inflammatory Effects: Fucoidan has been shown to inhibit the growth of certain bacteria and fungi, making it beneficial for reducing the risk of skin infections. It also has anti-inflammatory properties, which can help alleviate skin conditions caused by inflammation.

Promoting Skin Health: Beyond moisturizing and antioxidant effects, fucoidan promotes the regeneration and repair of skin cells, helping to improve overall skin health, resulting in a younger and more vibrant appearance.

Agriculture

Fucoidan has various applications in agriculture, offering benefits such as improving soil health and promoting plant growth. Key areas of application include:

Enhancing Soil Nutrients and Regulating Microbial Activity: Algae resources, including fucoidan, can increase the nutrient content of soil through carbon fixation, nitrogen fixation, and phosphorus solubilization. The extracellular polymers secreted by algae also help combat desertification and salinization of soils while reducing pesticide pollution and increasing fertilizer efficiency.

Promoting Plant Growth: Algal biostimulants, like fucoidan, provide essential nutritional support throughout crop growth, particularly during challenging conditions like drought or salt stress. This growth-promoting effect is linked to the bioactive compounds in fucoidan, which stimulate root development, enhancing both crop yield and quality.

Improving Soil Conditions and Remediating Heavy Metal Pollution: Fucoidan can assist in restoring soils damaged by heavy metal contamination. Its ability to biosorb heavy metal ions helps reduce their harmful effects on plants and the environment.

Antibacterial, Antiviral, and Preservation Functions: Fucoidan exhibits antibacterial and antiviral properties, protecting crops from diseases. It is also used to prepare intestinal prebiotics, enhancing digestion, reducing disease risk, and improving the intestinal flora of livestock. Due to its antioxidant and immunomodulatory effects, fucoidan is a natural alternative to antibiotics in animal feed. Additionally, its preservation function helps extend the shelf life of agricultural products, reducing food waste.

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