Fucoidan and Cancer: A Multifunctional Molecule with Anti-Tumor Potential

There is a wide variety of cancer types yet, all share some common cellular and molecular behaviors. Most of the chemotherapeutic agents used in cancer treatment are designed to target common deregulated mechanisms within cancer cells. Many healthy tissues are also affected by the cytotoxic effects of these chemical agents. Fucoidan, a natural component of brown seaweed, has anti-cancer activity against various cancer types by targeting key apoptotic molecules. It also has beneficial effects as it can protect against toxicity associated with chemotherapeutic agents and radiation. Thus the synergistic effect of fucoidan with current anti-cancer agents is of considerable interest. This review discusses the mechanisms by which fucoidan retards tumor development, eradicates tumor cells and synergizes with anti-cancer chemotherapeutic agents. Challenges to the development of fucoidan as an anti-cancer agent will also be discussed.     

Effect of Extraction Temperature on Pressurized Liquid Extraction of Bioactive Compounds from Fucus vesiculosus

This study was aimed at investigating the effect of low polarity water (LPW) on the extraction of bioactive compounds from Fucus vesiculosus and to examine the influence of temperature on the extraction yield, total phenolic content, crude alginate, fucoidan content, and antioxidant activity. The extractions were performed at the temperature range of 120–200 °C with 10 °C increments, and the extraction yield increased linearly with the increasing extraction temperature, with the highest yields at 170–200 °C and with the maximum extraction yield (25.99 ± 2.22%) at 190 °C. The total phenolic content also increased with increasing temperature. The extracts showed a high antioxidant activity, measured with DPPH (2,2-Diphenyl-1-picrylhydrazyl) radicals scavenging and metal-chelating activities of 0.14 mg/mL and 1.39 mg/mL, respectively. The highest yield of alginate and crude fucoidan were found at 140 °C and 160 °C, respectively. The alginate and crude fucoidan contents of the extract were 2.13% and 22.3%, respectively. This study showed that the extraction of bioactive compounds from seaweed could be selectively maximized by controlling the polarity of an environmentally friendly solvent.     

海蒿子岩藻聚糖结构特征及其抗流感病毒活性

采用热水提取法从海蒿子中提取粗多糖,再用Q-Sepharose Fast Flow和Sepharose 4B Fast Flow纯化得到一种硫酸化岩藻聚糖,命名为SF0。通过逐步部分酸水解,该岩藻聚糖SF0被进一步分为3种次级多糖SF1、SF2和SF3,硫酸基团的含量和相对分子质量依次降低。通过单糖组成、傅里叶红外光谱(FT-IR)和¹³C-NMR谱分析了4种多糖的结构特征,并探究了其抗甲型流感(H1N1)病毒的活性。结果表明,SF0主要由甘露糖、葡萄糖醛酸、葡萄糖、半乳糖、木糖和岩藻糖组成,摩尔比为10.8∶8.3∶3.0∶21.1∶21.2∶35.6,相对分子质量为628.1 ku,由α-D-1,2-Manp和β-D-1,4-GlcAp双糖重复单元构成核心骨架。抗甲型流感(H1N1)病毒检测表明,4种多糖都可以抑制MDCK细胞中的H1N1病毒复制。低分子量组分SF3比未降解岩藻聚糖抗病毒活性更好。初步认为该岩藻聚糖的抗H1N1病毒活性与其精细结构和分子量有关。     

Effect of Fucoidan on the Mitochondrial Membrane Potential (ΔΨm) of Leukocytes from Patients with Active COVID-19 and Subjects That Recovered from SARS-CoV-2 Infection

Fucoidan is a polysaccharide obtained from marine brown algae, with anti-inflammatory, anti-viral, and immune-enhancing properties, thus, fucoidan may be used as an alternative treatment (complementary to prescribed medical therapy) for COVID-19 recovery. This work aimed to determine the ex-vivo effects of treatment with fucoidan (20 µg/mL) on mitochondrial membrane potential (ΔΨm, using a cationic cyanine dye, 3,3′-dihexyloxacarbocyanine iodide (DiOC₆(3)) on human peripheral blood mononuclear cells (HPBMC) isolated from healthy control (HC) subjects, COVID-19 patients (C-19), and subjects that recently recovered from COVID-19 (R1, 40 ± 13 days after infection). In addition, ex-vivo treatment with fucoidan (20 and 50 µg/mL) was evaluated on ΔΨm loss induced by carbonyl cyanide 3-chlorophenylhydrazone (CCCP, 150 µM) in HPBMC isolated from healthy subjects (H) and recovered subjects at 11 months post-COVID-19 (R2, 335 ± 20 days after infection). Data indicate that SARS-CoV-2 infection induces HPBMC loss of ΔΨm, even 11 months after infection, however, fucoidan promotes recovery of ΔΨm in PBMCs from COVID-19 recovered subjects. Therefore, fucoidan may be a potential treatment to diminish long-term sequelae from COVID-19, using mitochondria as a therapeutic target for the recovery of cellular homeostasis.     

海带岩藻聚糖硫酸酯对四氯化碳致肝损伤小鼠的保护作用

对小鼠分别灌胃200、400、800 mg/(kg·d)的海带岩藻聚糖硫酸酯(简称FLJ,利用酶解法制备),于第7天腹腔注射四氯化碳制备小鼠急性肝损伤模型,以200 mg/(kg·d)的联苯双酯做阳性对照.测定血清丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)活性及肝组织中丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性,并观察肝组织形态学变化,研究FLJ对CCl_4诱导急性肝损伤小鼠的保护作用.结果表明:FLJ各剂量均能抑制肝损伤小鼠血清ALT、AST活性的升高,且中、高剂量组达到显著水平,并能显著提高肝组织中SOD活力、降低MDA含量,减轻由对肝细胞的病理损伤.FLJ对CCl_4造成的小鼠急性肝损伤具有一定的保护作用.     

In Vitro and In Vivo Dendritic Cell Immune Stimulation Effect of Low Molecular Weight Fucoidan from New Zealand Undaria pinnatifida

Low molecular weight fucoidan (LMWF) has been reported to have immunomodulation effects through the increase of the activation and function of macrophages. In this study, the regulating effect of LMWF from Undaria pinnatifida grown in New Zealand on dendritic cells (DCs) was investigated. We discovered that LMWF could stimulate DCs’ maturation and migration, as well as CD4+ and CD8+ T cells’ proliferation in vitro. We proved that this immune promoting activity is activated through TLR4 and its downstream MAPK and NF–κB signaling pathways. Further in vivo (mouse model) investigation showed that LMWF has a strong immunological boosting effect, such as facilitating the proliferation of immune cells and increasing the index of immune organs. These findings suggest that LMWF has a positive immunomodulatory effect and is a promising candidate to supplement cancer immunotherapy.     

Stimulating the Hematopoietic Effect of Simulated Digestive Product of Fucoidan from Sargassum fusiforme on Cyclophosphamide-Induced Hematopoietic Damage in Mice and Its Protective Mechanisms Based on Serum Lipidomics

Hematopoietic damage is a serious side effect of cytotoxic drugs, and agents promoting hematopoiesis are quite important for decreasing the death rate in cancer patients. In our previous work, we prepared the simulated digestive product of fucoidan from Sargassum fusiforme, DSFF, and found that DSFF could activate macrophages. However, more investigations are needed to further evaluate whether DSFF could promote hematopoiesis in the chemotherapy process. In this study, the protective effect of DSFF (1.8–7.2 mg/kg, i.p.) on cyclophosphamide-induced hematopoietic damage in mice and the underlying mechanisms were investigated. Our results show that DSFF could restore the numbers of white blood cells, neutrophils, and platelets in the peripheral blood, and could also retard bone marrow cell decrease in mice with cyclophosphamide-induced hematopoietic damage. UPLC/Q-Extraction Orbitrap/MS/MS-based lipidomics results reveal 16 potential lipid biomarkers in a serum that responded to hematopoietic damage in mice. Among them, PC (20:1/14:0) and SM (18:0/22:0) were the key lipid molecules through which DSFF exerted protective actions. In a validation experiment, DSFF (6.25–100 μg/mL) could also promote K562 cell proliferation and differentiation in vitro. The current findings indicated that DSFF could affect the blood cells and bone marrow cells in vivo and thus showed good potential and application value in alleviating the hematopoietic damage caused by cyclophosphamide.     

The Protective Effect of Fucoidan in Rats with Streptozotocin-Induced Diabetic Nephropathy

Diabetic nephropathy (DN) has long been recognized as the leading cause of end-stage renal disease, but the efficacy of available strategies for the prevention of DN remains poor. The aim of this study was to investigate the possible beneficial effects of fucoidan (FPS) in streptozotocin (STZ)-induced diabetes in rats. Wistar rats were made diabetic by injection of STZ after removal of the right kidney. FPS was administered to these diabetic rats for 10 weeks. Body weight, physical activity, renal function, and renal morphometry were measured after 10 weeks of treatment. In the FPS-treated group, the levels of blood glucose, BUN, Ccr and Ucr decreased significantly, and microalbumin, serum insulin and the β2-MG content increased significantly. Moreover, the FPS-treated group showed improvements in renal morphometry. In summary, FPS can ameliorate the metabolic abnormalities of diabetic rats and delay the progression of diabetic renal complications.     

动物抗凝血酶Ⅲ和褐藻糖胶结合的结构模拟

褐藻糖胶是一种含有硫酸基的水溶性杂多糖,其抗凝血与抗血栓等生理机能与肝素类似。用分子动力学计算,模拟抗凝血酶Ⅲ结合褐藻糖胶的结构变化。抗凝血酶Ⅲ和褐藻糖胶结合时Arg393从抗凝血酶Ⅲ的内部激发到了分子表面,Arg393与凝血酶活性中心的Asp、His、Ser结合,继而进入到四面体的过渡状态。     

Fucoidan regulate blood glucose homeostasis in C57BL/KSJ m+/+db and C57BL/KSJ db/db mice

Type 2 diabetes mellitus is a multisystem disease that is characterized by hyperglycemia and is associated with the dysfunction and failure of various organs. The control of postprandial hyperglycemia is important in the prevention and intervention of type 2 diabetes. Fucoidan has several biological activities in vitro and in vivo. However, the effect of fucoidan on hyperglycemia in non-diabetic and diabetic mice has not been investigated. This study was undertaken to study the effects of different molecular weight forms (5 kilodalton (k), 5-30 k and crude) of fucoidan on oral glucose tolerance tests in non-diabetic mice and on food intake, weight gain, fasting blood glucose and blood biochemistry of db/db mice. Treatment with 200 mg/mL 5 k, 5-30 k and crude fucoidan substantially prevented hyperglycemia according to oral glucose tolerance tests in non-diabetic mice. In addition, fucoidan fractions significantly reduced blood glucose levels in diabetic mice.