Red macroalgae

The importance of red macroalgae as a source of novel anti-HSV agents has been recognized and reported by many researchers. According to Serkedjieva (2000), the water extract of Polysiphonia denĂºdate exhibited selective inhibition on the reproduction of HSV-1 and HSV-2 at their effective concentration 50% (EC50) range of 8.7-47.7 mg/ml. The inhibition affected adsorption as well as intracellular stages of viral replication. Likewise, methanol extract of Symphyocladia latiuscula and its fractions was effective against acyclovir and phosphonoacetic acid-resistant HSV-1 (APr HSV-1), thymidine kinase deficient HSV-1 (TK HSV-1), and wildtype HSV-1 in vitro without cytotoxicity (Park et al., 2005). Specially, the major component of CH2Cl2-soluble fraction, 2,3,6-tribromo-4,5-dihy-droxybenzyl methyl ether (TDB), inhibited wild-type HSV-1, as well as (APr HSV-1) and (TK HSV-1) with their inhibitory concentration 50% (IC50) values of 5.48, 4.81, and 23.3 mg/ml, respectively. Moreover, the oral administrations of TDB significantly delayed the development of skin lesions and suppressed virus yields in HSV-1-infected mice. In another study, Persian Gulf Gracilaria salicornia was elucidated for its capability against HSV-2 (Zandi et al., 2007). The antiviral activity of water extract from G. salicornia displayed not only before attachment and entry of virus to the Vero cells but also on post attachment stages of virus replication. Accordingly, the extracts of marine red macroalgae can be a rich source of potential antiviral components. Interestingly, it has known that marine red macroalgae contain significant quantities of sul-fated polysaccharides that may be responsible for anti-HSV properties (Damonte et al., 2004).

Indeed, numerous sulfated polysaccharides from red macroalgae have been determined to possess significant inhibition on herpes virus. Xylo-mannan, a sulphated polysaccharide from Nothogenia fastigiata, was found to inhibit efficiently the replication of HSV-1 and HSV-2 under various experimental conditions (Damonte et al., 1994; Pujol et al., 1995). Further, the xylomannan sulfate of Scinaia hatei exhibited potent antiviral activity against reference strains, syncytial formation, and TK acyclovir-resistant strains of HSV-1 and HSV-2 at IC50 range of 0.5-4.6 mg/ml (Mandal et al., 2008). Additionally, the sulfated xylomannan from Sebdenia polydactyla was identified to have a stronger inhibition than the known sulfated xylomannan with IC50 range of 0.35-2.8 mg/ml (Ghosh et al., 2009). The appreciable inhibition produced by sulfated xylomannan was similar to that of standard antiherpetic polysulfates, such as heparin and dextran sulfate. Notably, the inhibitions of in vitro HSV replication by these xylomannans were observed at concentrations, which did not have any effect on cell viability. These sulfated xylomannans represent a potential candidate for further clinical studies.

Similar to xylomannan, galactans were found to be highly selective antiviral substances against the replication of the different strains of herpes viruses. Remarkably, Gymnogongrus griffithsiae and Cryptonemia crenulata have known to represent an interesting source of galactans with selective and potent antiviral action against reference strains, syncytial variants, and acyclovir-resistant strains of HSV-1 and HSV-2 at IC50 values in the range of 0.5-5.6 mg/ml (Talarico et al., 2004). The active galactans that extracted from C. crenulata exhibited a more effective antiviral action higher than the reference compounds heparin and dextran sulfate. Further, the crude galactan of C. crenulata showed a significant protective effect in vivo against HSV-2 vaginal infection in a murine model, suggesting the potential use of this low-cost product, easy to obtain in large quantities, for prophylaxis of virus infection. On the other hand, the strong antiherpetic activity of galactan sulfate obtained from Grateloupia indica has been shown in recent study (Chattopadhyay et al., 2007). The isolated galactan exhibited potent anti-HSV effect on reference strains, syncytial variants, and TK ACV-resistant strains at low value of IC50 (0.12-1.06 mg/ml), mainly affecting virus adsorption to the host cells.

The natural carrageenans isolated from the red seaweed have recently identified as potent and selective inhibitors of HSV-1 and HSV-2. Carra-geenans isolated from Meristiella gelidium were found to be among the most potent sulfated polysaccharides obtained from red seaweeds according to their inhibitory activity against herpes virus. The most active fraction obtained from M. gelidium showed a selectivity index against HSV-2 of 25,000, a value high enough to regard this carrageenan as a potential agent to be evaluated for the treatment of genital HSV-2 infection (De S-F-Tischer et al., 2006). Additionally, the inhibition of in vivo HSV by carrageenan has been investigated in model of murine infection (Carlucci et al., 2004; Pujol et al., 2006). Among them, the 1-carrageenan extracted from the red seaweed Gigartina skottsbergii revealed 100% protection against HSV-2 mortality and replication in a very strict model of murine infection at a high dose of virus. Further, virus or neutralizing antibodies against HSV-2 was not detected in serum of 1-carrageenan-treated animals until 3 weeks after infection. These evidences warrant the availability of 1-carrageenan to protect the whole infectable surface of the mouse vagina.

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