Brown macroalgae

Besides red macroalgae, brown macroalgae also provide useful additional therapy for treating several enveloped viruses infections. Fucoidans, a complex sulfated polysaccharide found mainly in brown macroalgae, have been reported in many papers for their anti-HSV activities. Feldman and colleagues isolated fucoidan fractions (Ee, Ec, and Ea) from Leathesia difformis and determined their selective antiviral abilities against HSV-1 and HSV-2 (Feldman et al., 1999). Fucoidan Ea was shown to be the most active agent, with IC50 value in the range of 0.5-1.9 mg/ml. Continually, fucoidans were found in different marine brown macroalgae due to their anti-HSV property, including Adenocystis utricularis, Sargassum horneri, Cystoseira indica, Stoechospermum marginatum, and Sargassum tenerrimum (Adhikari et al., 2006; Mandal et al., 2007; Ponce et al., 2003; Preeprame et al., 2001; Sinha et al., 2010). Noticeably, Undaria pinnatifida, the most commonly eaten brown seaweed in Japan, contains sulphated polyanions and other components with appreciable anti-HSV effect. Galactofucan, the major component of an aqueous extract of U. pinnatifida, was evaluated for antiviral activity against 32 clinical strains of HSV, including 12 ACV-resistant strains (4 HSV-1 and 8 HSV-2) and 20 ACV-susceptible strains (10 HSV-1 and 10 HSV-2). The median IC50 of galactofucan for the 14 strains of HSV-1 and 18 strains of HSV-2 was 32 and 0.5 mg/ml, respectively. The mode of action of the galactofucan was shown due to the inhibition of viral binding and entry into the host cell (Thompson and Dragar, 2004). In addition, a fucoidan from sporophyll of U. pinnatifida (Mekabu) was examined for its antiviral activity. The IC50 values for HSV-1 and HSV-2 were 2.5 and 2.6, respectively, under conditions in which the fucoidan was added at the same time as viral infection (Lee et al., 2004a). In the in vivo conditions, ingestion of fucoidan from U. pinnatifida was associated with increased healing rates in patients with active infections (Cooper et al., 2002). Moreover, oral administration of the fucoidan from U. pinnatifida could protect mice from infection with HSV-1 as judged from the survival rate and lesion scores (Hayashi et al., 2008). Substantially, natural killer and cytotoxic T lymphocytes activity in HSV-1-infected mice was enhanced by oral administration of the fucoidan. The production of neutralizing antibodies in the mice inoculated with HSV-1 was significantly promoted during the oral administration of the fucoidan for 3 weeks. According to these results, fucoidan from U. pinnatifida was suggested as a topical microbicide for the prevention of transmission of HSV through direct inhibition of viral replication and stimulation of both innate and adaptive immune defense functions.

In recent years, anti-HSV activity of brown macroalgae was known due to their diterpene and glycolipid components. Two compounds of diterpenes, 8,10,18-trihydroxy-2,6-dolabelladiene (1) and (6R)-6-hydroxy-dichotoma-4,14-diene-1,17-dial (2), were isolated from Dictyota pfaffii and Dictyota menstrualis (Abrantes et al., 2009). It was observed that compounds 1 and 2 inhibited HSV-1 replication in a dose-dependent manner at EC50 values of 5.10 and 5.90 pM, respectively. Similarly, the dolastane diterpenes 4-hydroxy-9,14-dihydroxydolasta-1(15),7-diene and 4,7,14-tri-hydroxydolasta 1(15),8-diene isolated from Canistrocarpus cervicornis also exposed the suppressive effect on replication of HSV-1 (Vallim et al., 2010). In an investigation of El-Baroty et al. (2011), they revealed that glycolipid achieved from brown alga Dilophys fasciola possessed noticeable effect against HSV-1. At concentration range of 25-100 mg/ml, glyco-lipid of D. fasciola caused remarkably inhibition % of HSV-1 with various degrees (78.5-100%). The IC50 value was 10 mg/ml, compared to that 55 mg/ml for acyclovir. A suggestion for active mechanism of glycolipid might involve in the binding of the virus glycoprotein to algal glycolipid and cause an irreversible denaturation that blocks the viral infectivity. In general, many of natural lipid classes have been shown to have high virucidal activity and are being developed as microbicidal ingredient in drug formulas to kill viruses (Hilmarsson et al., 2006).

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