1. INTRODUCTION:

Seaweeds are a heterogeneous group of phytoplankton that generally occurs in the intertidal and subtidal region of marine habitat where a very little photosynthetic light is available. On the basis of chemical composition they are classified into green algae (Chlorophyceae), red algae (Rhodophyceae) and brown algae (Phaeophyceae). The red and green algae have rich source of carbohydrates and brown algae are rich in soluble fibre and iodine¹. Many types of seaweed are rich source of proteins, vitamins and minerals and have been established as healthy food materials all over the world. In China, since 300 BC seaweeds has been used for human consumption. Several countries like Malaysia, Singapore, Thailand, Korea etc the seaweeds were used in preparation of salad, jelly, soup etc.

In coastal states of Tamilnadu and Kerala Gracilaria species and Acanthophora species has been used for the preparation of porridge². Apart from human consumption, seaweeds have long been recognized as an effective source for the production of bioactive compounds that are beneficial to all the living organisms as well.

Brown seaweeds are the second most abundant group of seaweeds and it belong to a very large group³. Most brown seaweeds contain carotenoid pigment fucoxanthin, which is responsible for the predominant brown colouration. This also contains polysaccharides such as alginates, laminarin, fucans, cellulose etc apart from a range of components with unique secondary metabolites such as phlorotannins, phloroglucinol, terpenes and tocopherol⁴. Several species of brown seaweeds contains wide range of applications with antimicrobial, anticancer, antioxidant, anti-diabetic and anti-inflammatory properties. In the present review we focuses on the important bioactive compounds identified in the brown seaweeds as well as emphasis on active metabolites that could be of pharmaceutical and medicinal values.

2. BIOACTIVE METABOLITES IN BROWN ALGAE:

2.1. Polysaccharides:

Polysaccharides are a class of macromolecules, polymers of monosaccharides present primarily in the cell walls conferring strength and flexibility, which are increasingly gaining attention in the biochemical and medical areas due to their immunomodulatory and anticancer effects. The composition of polysaccharides varies according to the extrinsic and intrinsic factors, season, area, age, species and geographic location. In addition they act as a food reserve to withstand wave action and maintain ionic equilibrium in the cell. Laminarans and fucoidans are the main water-soluble polysaccharides of brown algae whereas alginic acids are alkali soluble polysaccharides¹. Some of the polysaccharides present in brown macroalgae with very few properties are mentioned below:

Alginic acid or alginate is the major structural components of linear polysaccharides containing 1, 4-linked β-D-mannuronic and α-L-guluronic acid⁵. Alginate that are present on brown seaweed, produced in the form of sodium and calcium alginate, is widely used in the food and pharmaceutical industries due to their ability to chelate metal ions¹. Mannitol is a sugar alcohol corresponding to mannose produced by photosynthesis and is universally found in brown algae and can account for 20–30% dry weight in some Laminaria spp. Mannitol can be used in a variety of foods, candies and chocolate-flavoured compound coatings because it can replace sucrose to make sugar-free compound coatings. It is used as a flavour enhancer because of its sweet and pleasantly cool taste. Laminarin appears to be the food reserve of all brown algae and is increasingly recognised for its biofunctional activity. Laminarin is a water-soluble polysaccharide containing 20-25 glucose units which are composed of (1, 3)-β-D-glucan with β (1, 6) branching⁶. Fucoidan is a type of complex sulfated polysaccharide, mainly found in the cell-wall matrix of various brown seaweed species. It contains substantial percentages of l-fucose and sulfate ester groups. In the past few years, several fucoidans structures have been isolated, and many aspects of their biological activity have also been reported⁷. Furthermore, the constituents of fucoidan also differ with the species by small proportions of D-mannose, D-xylose, D-galactose, and uronic acid⁸. Sulfated polysaccharides has been discovered in almost all of the brown algae investigated so far, but seems to be absent in green algae, red algae, as well as in freshwater algae and terrestrial plants⁹.

2.2. Carotenoids:

They are colourful natural pigments synthesized in plants, seaweeds and other photosynthetic organisms as well in some non-photosynthetic bacteria and are involved in photosynthesis, hormonal synthesis, photoprotection and photomorphogenesis¹⁰. Carotenoids can usually be divided in two main subclasses: nonpolar carotenes (containing only carbon and hydrogen atoms) and polar xanthophylls (which have at least one oxygen atom). β-carotene is the most common group belongs to the carotene, while lutein, fucoxanthin and violaxanthin belong to the xanthophylls class. Fucoxanthin is one of the most abundant pigments found both in microalgae as well as in macroalgae mainly in brownseaweeds and its contents varies depending upon the seasons. Some studies have suggested that the dietary combination of fucoxanthin in brown seaweeds and edible oil or lipid could increase the absorption rate of fucoxanthin, and thus it might be a promising marine drug¹¹.

2.3. Phlorotannin:

The algal polyphenols are termed as phlorotannins and they are secondary metabolites consist of diverse groups of chemical compounds. Phlorotannin are mostly present in brown seaweeds, where the concentration may vary depending upon the species¹. They are stored in special vesicles (physodes) and are thought to be the defense compounds in brown seaweeds. The concentration of phlorotannins in brown algae is reported to be highly variable among different taxa of brown seaweeds as well as among different geographical areas. Phlorotannins may constitute up to 15% of the dry weight and medicinal values of the brown algae are also related to the presence of this phenolic compound. Phlorotannins from brown algae are more potent free radical scavenger due to interconnected rings than other polyphenols derived from terrestrial plants¹². Having vast range of biological activities, phlorotannins are believed to be the most promising candidates to be developed as pharmaceuticals. Phloroglucinol is a polyphenolic compound that chemical structure includes an aromatic phenyl ring with three hydroxyl groups.

3. THERAPEUTIC POTENTIAL OF BROWN SEAWEEDS:

3.1. Polysaccharides as antibacterial, antitumor and antidiabetic property

Many carbohydrate polymers have been shown to be responsible for various biological effects. Due to the presence of varying amount of sulphate groups sulphated polysaccharides are well-known to have biological activities. Very few reports of the prominent effects proved by the polysaccharides were mentioned here. The fucoidan and alginates isolated from Sargassum siliquosum were investigated for its chemopreventive potential using in vitro assays and displayed significant antiproliferative activity in both Hep G2 and renal carcinoma cells¹³. Mannitol exhibits hydrating and antioxidant properties used in numerous cosmetic and pharmaceutical applications¹⁴.

Fucoidan possessed significant antibacterial activities against some bacterial ornamental fish pathogens¹⁵. The oral intake of the fucoidans present in dietary brown seaweed might take the protective effects through direct inhibition of viral replication and stimulation of the immune system (innate and adaptive) functions¹⁶. Some of the fractions of the polysaccharide extracts from Sargassum latifolium explored cytotoxic potential against lymphoblastic leukemia 1301 cells¹⁷. Apart from antibacterial and cytotoxic properties one of the edible seaweed Laminaria japonica exhibited antiobesity and antidiabetic properties¹⁸.

3.2. Carotenoids as anti-inflammatory, anticancer and antiocular property

It was reported that fucoxanthin isolated from Sargassum siliquastrum appears to have the potential to prevent inflammatory diseases and may act as a modulator of macrophage activation¹⁹. A study demonstrates that pretreatment with fucoxanthin from Undaria pinnatifida improves the chemotherapeutic efficacy of cisplatin by enhancing the inhibition of cell proliferation of human hepatoma HepG2²⁰. Shiratori et al., studied the antiocular inflammatory effect of fucoxanthin on lipopolysaccharide-induced uveitis in male Lewis rats, and found that fucoxanthin suppressed the development of the uveitis²¹.

3.3. Phlorotannin as antioxidant, antidiabetic, antiviral, antiallergic and photoprotective property

Phlorotannins have secondary functions as defensive compounds and primary roles in cell-wall construction²². Like other phenolic compounds, phloroglucinol shows a variety of biological activities such as antioxidant, antiinflammatory, antidiabetic antimicrobial, anti-allergic, and anti- HIV, by which has attracted attention for the development of new^23-28. It was also reported that out of six phlorotannins isolated from brownalga Eisenia bicyclis, phlorofucofuroeckol-A (PFF) exhibited anti-MRSA activity against methicillin-resistant Staphylococcus aureus (MRSA) and showed antiallergic properties^{29, 30}. Angiogenesis is the process where new blood vessels are made to facilitate the invasion of cancers, and fucodiphloroethol-G from Ecklonia cava has inhibited this process in an angiogenesis-induced cellular model³¹. One of the phloroglucinol derivative dioxinodehydroeckol brown alga Ecklonia cava has a potential inhibitory effect on proliferation of human breast cancer cell lines MCF-7³². Ko et al., have also studied on the photoprotective effect of dieckol from Ecklonia cava using human epithelial keratinocytes (HaCat) and have found that dieckol treatment induces the survival of cells³³.

4. CONCLUSION:

This review paper explores and identifies some of the major compounds present in the brown seaweeds, their isolation and identification and outlines the potentially therapeutic effects of some of the extracts or compounds isolated from them. From the above intensive studies it is quite evident that out of many compounds isolated so far only very few with real potency are available. Generous amount of research concerning the toxicity aspects also needs to be carried out before they could actually be used for clinical trials. So future work in the area of bioactive compounds should aim to scrutinize the properties of purified compounds to understand their actual prospective in the medical field for human and animal health applications could also be exploited.

5. REFERENCES:

1. Gupta S and Abu-Ghannam N. Bioactive potential and possible health effects of edible brown seaweeds. Trends in Food Science and Technology. 22 (6); 2011: 315-326.

2. Dhargalkar VK, Pereira N. Seaweed: Promising plant of the millennium. Sci and Cult. 71; 2005: 60-66.

3. Reddy P and Urban S. Meroditerpenoids from the southern Australian marine brown alga Sargassum fallax. Phytochemistry. 70; 2009: 250–255.

4. Subhash R Yende, Uday N Harle, Bhupal B Chaugule. Therapeutic potential and health benefits of Sargassum species. 8 (15); 2014: 1-8.

5. Andrade LR, Salgado LT, Farina M, Pereira MS, Mourao PAS and Amado-Filho GM. Ultrastructure of acidic polysaccharides from the cell walls of brown algae. Journal of Structural Biology. 145; 2004: 216-225.

6. Nelson TE and Lewis BA. Separation and characterization of the soluble and insoluble components of insoluble laminaran. Carbohydrate Research. 33; 1974: 63-74.

7. Li B, Lu F, Wei X, and Zhao R. Fucoidan: Structure and bioactivity. Molecules. 13; 2008: 1671–1695.

8. Yamamoto I, Takahashi M and Suzuki T. Antitumor effect of seaweeds. IV. Enhancement of antitumor activity by sulfation of a crude fucoidan fraction from Sargassum kjellmanianum. Japanese Journal of Experimental Medicine. 54 (4); 1984: 143–151.

9. Shanmugam M and Mody KH. Heparinoid-active sulphated polysaccharides from marine algae as potential blood anticoagulant agents. Current Science. 79; 2000: 1672-1683.

10. Balboa EM, Conde E, Moure A, Falque E, Domínguez H. In vitro antioxidant properties of crude extracts and compounds from brown algae. Food Chem.138; 2013a: 1764–1785.

11. Juan Peng, Jian-Ping Yuan, Chou-Fei Wu, and Jiang-Hai Wang. Fucoxanthin, a Marine Carotenoid Present in Brown Seaweeds and Diatoms: Metabolism and Bioactivities Relevant to Human Health. Mar Drugs. 9(10); 2011: 1806–1828.

12. Hemat RAS. 2007. Fat and muscle dysfunction. In R. A. S. Hemat (Eds), Andropathy. Dublin, Ireland: Urotext, (pp. 83-85).

13. Vasquez RD, Ramos JDA, Bernal SD. Chemopreventive properties of sulfated polysaccharide extracts from Sargassum siliquosum J.G. Agardh (Sargassaceae). International Journal of Pharma and Bio Sciences. 3(3); 2012: B333-345.

14. Iwamoto K, Shiraiwa Y. Salt-regulated mannitol metabolism in algae. Mar Biotech. 7; 2005: 407–415.

15. Thangapandi M and Thipramalai TA. Effect of fucoidan from Turbinaria ornata against marine ornamental fish pathogens. 1 (4); 2013: 282-286.

16. Hayashi L, Yokoya NS, Ostini S, Pereira RTL, Braga ES, Oliveira EC. Nutrients removed by Kappaphycus alvarezii (Rhodophyta, Solieriaceae) in integrated cultivation with fishes in recirculating water. Aquaculture. 277; 2008: 185–191.

17. Gamal-Eldeen AM, Ahmed EF, and Abo-Zeid MA. In vitro cancer chemopreventive properties of polysaccharide extract from the brown alga, Sargassum latifolium. Food and Chemical Toxicology. 47; 2009: 1378–1384.

18. Shirosaki M and Koyama T. Laminaria japonica as a food for the prevention of obesity and diabetes. Adv. Food Nutr. Res. 64; 2011: 199–212.

19. Heo SJ, Yoon WJ, Kim KN, Oh C, Choi YU, Yoon KT, Kang DH, Qian ZJ, Choi IW, Jung WK. Anti-inflammatory effect of fucoxanthin derivatives isolated from Sargassum siliquastrum in lipopolysaccharide-stimulated RAW 264.7 macrophage. Food Chem. Toxicol. 50; 2012: 3336–3342.

20. Liu CL, Lim YP, Hu ML. Fucoxanthin enhances cisplatin-induced cytotoxicity via NFkB-mediated pathway and down regulates DNA repair gene expression in human hepatoma HepG2Cells. Mar. Drugs. 11; 2013: 50–66.

21. Shiratori K, Ohgami K, Ilieva I, Jin XH, Koyama Y, Miyashita K, Yoshida K, Kase S, Ohno S. Effects of fucoxanthin on lipopolysaccharide-induced inflammation in vitro and in vivo. Exp. Eye Res. 81; 2005: 422–428.

22. Arnold T M and Targett NM. To grow and defend: lack of trade-offs for brown algal phlorotannins. Oikos. 100; 2003: 406-408.

23. Crockett SL, Wenzig EM, Kunert O, Bauer R. Anti-inflammatory phloroglucinol derivatives from Hypericum empetrifolium. Phytochem. Lett. 1; 2008: 37–43.

24. Daikonya A, Katsuki S, Wu JB, Kitanaka S. Anti-allergic agents from natural sources (4): anti-allergic activity of new phloroglucinol derivatives from Mallotus philippensis (Euphorbiaceae). Chem. Pharm. Bull. 50; 2002: 1566– 1569.

25. Kim MM, Kim SK. Effect of phloroglucinol on oxidative stress and inflammation. Food Chem. Toxicol. 48; 2010: 2925–2933.

26. Sithranga Boopathy N, Kathiresan K. Anticancer drugs from marine flora: an overview. J. Oncol. 2010. doi: 10.1155/2010/214186.

27. Vo TS, Kim SK. Potential anti-HIV agents from marine resources: an overview. Mar. Drugs. 8; 2010: 2871–2892.

28. Wang W, Wang SX, Guan HS. The antiviral activities and mechanisms of marine polysaccharides: an overview. Mar. Drugs. 10; 2012b: 2795–2816.

29. Eom SH, Kim DH, Lee SH, Yoon NY, Kim JH, Kim TH, Chung YH, Kim SB, Kim YM, Kim HW et al., In vitro antibacterial activity and synergistic antibiotic effects of phlorotannins isolated from Eisenia bicyclis against methicillin-resistant Staphylococcus aureus. Phytother. Res. 27; 2013: 1260–1264.

30. Sugiura Y, Matsuda K, Yamada Y, Nishikawa M, Shioya K, Katsuzaki H, Imai K, Amano H. Isolation of a new anti-allergic phlorotannin, phlorofucofuroeckol-B, from an edible brown alga, Eisenia arborea. Biosci. Biotechnol. Biochem. 70; 2006: 2807–2811.

31. Li YX, Li Y, Qian ZJ, Ryu B and Kim SK. Suppression of vascular endothelial growth factor (VEGF) induced angiogenic responses by fucodiphloroethol G. Process Biochem. 46; 2011: 1095–110.

32. Kong CS, Kim JA, Yoon NY, Kim SK. Induction of apoptosis by phloroglucinol derivative from Ecklonia cava in MCF-7 human breast cancer cells. Food Chem. Toxicol. 47; 2009: 1653–1658.

33. Ko, S. C., Cha, S. H., Heo, S. J., Lee, S. H., Kang, S. M., and Jeon, Y. J. (2011). Protective effect of Ecklonia cava on UVB-induced oxidative stress: In vitro and in vivo zebrafish model. J. Appl. Phycol. 23; 2011: 697–708.

Received on 25.03.2016 Modified on 10.04.2016

Research J. Pharm. and Tech. 9(4): April, 2016; Page 369-372

DOI: 10.5958/0974-360X.2016.00066.4