Fucoidan

It is a sulfated fucopolysaccharide and is the subject of extensive research for its anticancer properties. Studies have shown fucoidan to be effective in stopping the growth of tumors, inducing cancer cell apoptosis (programmed cell death) in leukemia, stomach, and colon cancer lines, and in interfering with metastasis by inhibiting interaction between tumor cells and the host tissue basement membrane. Fucoidan from Laminaria angu-stata is composed mainly of fucose/galactose/sulfate (9/1/9) (Kitamura et al., 1991). Fucoidan of L. japonica has anti-RNA and DNA virus functions. The antivirus effects of fucoidan on infection due to poliovirus III, adenovirus III, ECHO6 virus, Coxsackie B3 virus, and Coxsackie A16 are remarkable. Fucoidan can inhibit the development of cytopathic effect and protect cultural cells from infection caused by above viruses (Li et al., 1995). Lu et al. (2007) added a ''novel mechanistic profiling'' of the previously reported sulfated polymannuroguluronate, a polysaccharide with an average molecular weight of 8.0 kDa isolated from the brown alga L. japonica, that has been reported to be in Phase II clinical trials in China as an anti-AIDS drug candidate (Mayer et al., 2011). Fucoidan prevented concanavalin A-induced liver injury by mediating the endogenous inter-leukin (IL)-10 production and the inhibition of proinflammatory cytokine in mice (Saito et al., 2006). The dietary fiber in edible brown seaweeds (Laminaria sp., Sargassum fulvellum, and Eisenia bicyclis) had the repressive effect against d-galactosamine (d-GalN)-induced hepatopathy, and the protective effect was caused at least in part by fucoidan (Kawano et al., 2007a,b). Fucoidans from brown algae of Laminariale order have been also described as inhibitors of the complement (Zvyagintseva et al., 2000).

Antitumor activity of many polysaccharides has been reported in recent years. Fucoidan from L. japonica is effective against sarcoma 180 (Song et al., 2000). It can inhibit hepatoma QGY7703 cells into logarithmic phase in vitro, accordingly restraining the growth of tumor (Shi et al., 2000). It can also restore the immune functions of immunosuppressed mice, and it acts as immunomodulator acting directly on macrophage and T lymphocyte (Wang et al., 1994). It can also promote the recovery of immunologic function in irradiated rats through a mechanism associated with the arrest of lymphocyte apoptosis by fucoidan (Wu et al., 2003, 2004). Japanese scientists found out that the lowest level of cancer in Japan was reported among population of Okinawa Island. They revealed that Okinawa residents consume raw Laminaria, which contains great amount of fucoidan.

Lots of studies show that fucoidan presents significant antioxidant activity in experiments in vitro. It is an excellent natural antioxidant and has great potential for preventing free radical-mediated diseases. Fucoidan from L. japonica can prevent the increase of lipid peroxide in serum, liver, and spleen of diabetic mice obviously. However, no inhibition effect was found on both spontaneous lipid peroxidation of homogenates and that induced by Cys/FeSO4 in vitro (Li et al., 2002). This fucoidan had strong scavenging effect on superoxide radical, its effect on hydroxyl radical was weak, and it had less influence on 1,1-diphenyl-2-picryl-hydrazyl. It inhibited H2O2-induced hemolysis of rat erythrocytes effectively and showed significant protective effect on lipid peroxidation of liver homogenate in rat induced by FeSO4-ascorbic acid (Zhang et al., 2003).

Antioxidant activity relates to the molecular weight and sulfate content of fucoidan. Fucoidan fractions from L. japonica had excellent scavenging capacities on superoxide radical and hypochlorous acid, except the highly sulfated fraction L-B. In LDL oxidation system, low molecular weight fractions L-A and L-B exhibited great inhibitory effects on LDL oxidation induced by Cu2+; however, F-A and F-B had little inhibitory effects in this system due to their large molecular weights (Zhao et al., 2005). Yoon et al. (2007) reported the purification of a complex and heterogeneous sulfated fucan from the brown alga Laminaria cichorioides. The purified polysaccha-ride had potent anticoagulant activity which is resulted from enhancement of thrombin inhibition by heparin cofactor II, within the same concentration range as the clinically used heparin (Yoon et al., 2007).

Both molecular mass and sulfate content of fucoidan played very important roles in the effects on the azo radicals 2-2'-azobis (2-amidino-propane)dihydrochloride-induced LDL oxidation (Li et al., 2006). The correlation between the sulfate content and scavenging superoxide radical ability was positive, the ratio of sulfate content/fucose was an effective indicator to antioxidant activity of the samples (Wang et al., 2008).

Fucoidan is a kind of active material similar to sialic acid; it can enhance the negative charges of cell surface so as to effect the aggradation of cholesterol in blood, as a result of decreasing the cholesterol in serum. Fucoidan of L. japonica remarkably decreased total cholesterol, triglyceride, and LDL-C; increased HDL-C in serum of mice with hypercholester-olemia and rats with hyperlipidemia; and efficiently prevented the formation of experimental hypercholesterolemia in mice (Li et al., 1999a,b, 2001). It can also remarkably reduce the contents of cholesterol and triglyceride in serum of patients with hyperlipidemia, without side effect of damaging liver and kidney (Wang and Bi, 1994). Low molecular weight sulfated fucan (average Mw = 8000 Da) prepared from L. japonica can distinctly reduce blood lipids of hyperlipidemic rats (Li et al., 1999a, b). Fucoidan oligosaccharides show good antihypertensive effects on renovascular hypertensive rats, and one of the mechanisms underlying the antihypertensive effects might be that they can inhibit the production of plasma angiotensin II (Fu et al., 2004).

The elevated urinary protein excretion and plasma creatinine due to the induction of Heymann nephritis were significantly reduced by fucoi-dan from L. japonica by oral intubation. This indicated that fucoidan has a renoprotective effect on active Heymann nephritis and is a promising therapeutic agent for nephritis (Zhang et al., 2005).

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