Potential And Actual Therapeutic and Medicinal Applications o

Seaweeds are a natural renewable resource, they are also a naturally, rich with structurally unique and diverse secondary metabolites. From the point of convenience, seaweeds are grossly grouped as the Chlorophyta, Phaeophyta and Rhodophyta on the basis of their major photosynthetic pigments. The seaweeds are a source of chemical diversity including pigments, polysaccharides, organic, and inorganic compounds, some of which find uses as animal fodder, food, nutraceuticals, pharmaceuticals, and cosmeceutical. Therapeutically, selected marine macro algae have the potential to be utilized in the treatments of: cardiovascular diseases, diabetes, obesity, viral diseases (especially HPV and HIV), cancers, and disorder of the gastro-intestinal tract (GIT), hepatic diseases, anti-inflammatory issues, some seaweeds have high levels of calcium carbonate (especially coralline algae) so applicable to treat the osteoporosis and some seaweed are used to make cosmetics which is applicable to treat the skin disease as well as normally used for glowing and taking care of normal skin health. Certain seaweeds have high levels of antioxidants such as poly phenolics, vitamins and fatty acids (especially omega-3 fatty acids) and these inhibit the oxidation of the low lipoproteins in the cell membrane. Vitamins from some seaweed act as immune-stimulants and are also known to help in bone development. Some red algae have been shown to have more antihypertensive activity than that reported for both brown and green algae. Some seaweed also has been reported for having anti-coagulating and anti activities. Due to presence of high micronutrients and | Volume – 1 | Issue – 6 | Sep Oct 2017 6470 | www.ijtsrd.com | Volume Journal of Trend in Scientific and Development (IJTSRD) International Open Access Journal f Marine Macro Algae: A Review in Marine P. Anantharaman Centre of Advanced Study (C.A.S) in Marine Biology, Faculty of Marine Sciences, Annamalai University, Tamilnadu

Seaweeds are a natural renewable resource, they are also a naturally, rich with structurally unique and diverse secondary metabolites. From the point of convenience, seaweeds are grossly grouped as the , Phaeophyta and Rhodophyta on the basis of their major photosynthetic pigments. The seaweeds are a source of chemical diversity including pigments, polysaccharides, organic, and inorganic compounds, some of which find uses as animal ticals, pharmaceuticals, and cosmeceutical. Therapeutically, selected marine macro algae have the potential to be utilized in the treatments of: cardiovascular diseases, diabetes, obesity, viral diseases (especially HPV and HIV), intestinal tract inflammatory issues, some seaweeds have high levels of calcium carbonate (especially coralline algae) so applicable to treat the osteoporosis and some seaweed are used to make licable to treat the skin disease as well as normally used for glowing and taking care of normal skin health. Certain seaweeds have high levels of antioxidants such as poly phenolics, vitamins 3 fatty acids) and bit the oxidation of the low-density lipoproteins in the cell membrane. Vitamins from stimulants and are also known to help in bone development. Some red algae have been shown to have more antihypertensive rted for both brown and green algae. Some seaweed also has been reported for coagulating and anti-hemorrhagic activities. Due to presence of high micronutrients and minerals in some specific seaweed, diet supplement with that particular seaweeds increase haemoglobins in blood and directly reduce anaemia. Some seaweed composed cosmetics find place as herbal skin care product in market. The aim of this review is to accumulate in brief, the therapeutics and medicinal uses of seaweed on the mentio Keywords: Marine macro algae, seaweeds, therapeutics applications, medicinal uses

Introduction:
Some edible seaweed serves as food items and ingredients of various foods for huge population of people, in different parts of the World Ireland and Wales (Mouritsen et al. 2013). Historically, it has been reported that some seaweed are often been used as food for sick people due to their therapeutic benefits (Chapman et al. 1980). It has been reported that some seaweed spe used for human consumptions and medicinal purposes since 300 BC in China, Korea and Japan and these two countries are the main contributors of edible and medicinally important seaweeds in the world production-consumption scenario. Some edibl seaweed such as Gracilaria spp, cava, Porphyra spp. have been used in jelly, soup and salad in some countries such as Malaysia, Thailand, Korea, Singapore, and Indonesia. seaweeds have been used as folk medicine as remedy for intestinal worms, due to the presence of domoic and kainic acids in the red seaweeds as vermifuge substances. In India, Acanthophora sp. are consumed as porridge along some coastal areas (Dhargalkar et al. 2005). The seaweeds find place in 20% of Asian diets due to their unique and enchanting flavour, but only just as food additives of western diet (Carvalho et al. 2009). The biochemical constituents of seaweeds are used as to treat the world's top 10 chronic diseases such as coronary artery disease or ischemic heart disease, stroke, chronic obstructive pulmonary disease, lower respiratory infection; trachea, bronchus and lung cancers, Human Immunodeficiency Virus (HIV/AIDS), diarrheal diseases, diabetes mellitus, preterm birth complication and tuberculosis (FAO, 2012). More than 7000 marine natural products have already been isolated, 25% of which are from marine macro algae. With tremendous increase in the climate change induced severity of human diseases, it is critical to analyse the data available about the pharmacologically active metabolites from the seaweeds for better utility (Kijjoa et al. 2004).

Anti-allergic activities:
Codium fragile and Ulva japonica inhibit degranulation of both RBL-2H3 cells and mouse eosinophils (Kimiya et al. 2008). Enteromorpha compressa reduces serum IgE level and proves its potential anti-anaphylactic and anti-allergic activities (Raman et al. 2004).

Leishmania
donovani and Mycobacterium tuberculosis. The crude seaweed extracts have no activity against M. tuberculosis, but anti-protozoal activity against at least two protozoan species. All the algal extracts tested are active against T. brucei rhodesiense. Of the extracts, C. rupestris is the most potent one (IC 50 value 3.7 µg/ml), whilst C. rupestris and U. lactuca have moderate trypanocidal activity against T. cruzi (IC 50 values 80.8 and 34.9 µg/ml). All the four extracts have leishmanicidal activity with IC 50 values ranging between 12.0 and 20.2 µg/ml (Spavieri et al. 2010). Ulva extract is moderately active (IC 50 = 34.9 µg/ml) against Trypanosoma cruzi but active as leishmanicidal (IC 50 (Simopoulos 1991;Hassan et al. 2011;Bocanegra et al. 2009). The crude polysaccharides of Ulva lactuca have antiperoxidative and anti-hyperlipidemic activities, as proved in rats induced with hepatitis by Dgalactosamine. The crude polysaccharides also reduce the atherogenic index in plasma which suggests its potential protection against cerebrovascular and ischemic cardiovascular diseases (Pengzhan et al. 2003). The polysaccharides extracted from Ulva pertusa in hot water followed by precipitation with ethanol at low dose of 125 mg kg−1 exhibit optimal effect on triglycerides, but less impact on total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C). Similarly, when rats are fed with dried Ulva rigida exhibits low levels of low density lipoprotein (LDL) cholesterol (Taboada et al. 2010).

Anti-inflammatory activities:
Biologically active steroid (3-O-β-D-glucopyranosyl cholesterol) from Ulva lactuca reduces oedema and acts as promising anti-inflammatory agent (Awad, 2000;Margret et al. 2009). In humans, phospholipase A2 (PLA2) involves in developing inflammatory diseases, and hence the compounds with inhibitory effect on PLA2 act as anti-inflammatory drugs, as reported in the case of Caulerpa prolifera (Mayer et al. 1993). Caulerpenyne, major secondary metabolite, a sesquiterpene which involves in the chemical defence of Caulerpa taxifolia acts as antiinflammatory agent (Figure-3). Caulerpenyne induces an inhibition of SK-N-SH cell proliferation. After observation, on Immune-fluorescence microscopic examination has proved that no blockage in G2/M phase and there is an increase in cell death. Caulerpenyne affects the microtubule network in SK-N-SH cell line and causes a loss of neurites and a compaction of the microtubule network at the cell periphery (Barbier et al. 2002). Methanol extracts of Ulva conglobata and U. lactuca are proved to have anti-inflammatory effects in murine hippocampal HT22 cell line (Jin et al. 2006). Aqueous and methanol extracts of Caulerpa mexicana exhibit antinociceptive and anti-inflammatory activities (Bitencourt et al. 2011), and these activities are also shown by lectin and sulphated polysaccharide from Caulerpa cupressoides (Vanderlei et al. 2010).
International Journal of Trend in Scientific Research and Development (IJTSRD) ISSN: 2456 @ IJTSRD | Available Online @ www.ijtsrd.com Caulerpenyne from Caulerpa sp. is reported to have anticancer, anti-tumour, and anti properties (Fischel et al. 1995). The poly phenols such as catechin, epicatechin, epigallocatechin, gallate and gallic acid of Halimeda sp. show anti-cancer activity (Yoshie et al. 2002). The methanolic extract of lactuca is active in regulating the tumour genesis ). Cladophoropsis sp. has cytotoxicity to human cervical adenocarcinoma cell line (Murugan, 2011). Glycoprotein of Capsosiphon fulvescens induces apoptosis in human gastric cancer cells ). The extracts from Ulva fasciata cytotoxicity against colon cancer cell line and the HCT116 human colon cancer cell line by inhibiting by 50% at 200μg/ml. This also induces apoptosis through alteration in Bcl2 family protein expression, increases mitochondrial membrane permeability, and activates caspase 9 and 3 (Ryu et al. 2013).

Potentiality for Immunomodulation:
Ulvans act as immunostimulant. Sulphated polysaccharides from Ulva rigida induce a two increase of expression of several chemokines and interleukins that result in nitrite production, prostaglandin secretion and that accelerate macrophage activities for the immunity in the host systems (Leiro et al. 2007

Therapeutics and medicinal utilities of brown seaweeds:
Generally, brown seaweeds have excellent therapeutic and medicinal properties against deadliest disease such as cardiovascular disease, diabetes, HIV and immune disease etc. (Gamalbrown seaweeds are composed of chlorophylls a, c, carotene, proteins, amino acids, peptides, poly phenols, fatty acids, free manitol, minerals including iodine and minerals polysaccharide, alginic acid and alginate, cellulose, manitol and sulphated polysaccharides such as fucoidans, fucoxanthin and laminarins (Chapman et al. 1980). Alginates are the principle cell wall acidic polysaccharides widely distributed in brown algae including hyperborea, Laminaria digitata, Laminaria japonica, Ascophyllum nodosum, and Alginates are linear anionic polysaccharides, composed of a main backbone of poly acid (G blocks) and poly-D blocks), together with D-guluronic acid and D mannuronic acid (GM blocks) (Draget et al. 2006 andWang et al. 2012). consist of a backbone of (insoluble) β glucopyranoses of which some carry β glucose residues. Mannitol, the alcohol form of mannose, is the first product of brown macro algae. Primarily, fucoidans from Laminariaceae are composed of a backbone of α linked-L-fucopyranose residues with sulphate substitutions at C-4 and occasionally at the   (Jung et al., 2006). The intravenous applications of fucogalactan fractions extracted from Undaria reduce lipid clearance time indirectly and minimise the risk of cardiovascular disease development (Mori et al. 1982). Fucoidans recognize blocking of the macrophage scavenger receptor with uptake of low density lipoprotein (Yokota et al. 1988). An aqueous ethanolic extract of Ascophyllum nodosum inhibits rat intestinal a-glucosidase (IC50 = 77 mg/mL) and stimulates basal glucose uptake into 3T3-L1 adipocytes during a 20-minute incubation by about 3fold (at 400 mg/ml extract) (Zhang et al. 2007). Alginate tends to bind with toxins including heavy metals and radioactive isotopes in the intestines and helps to flush out the toxins from the host system. Likewise, alginate reduces cholesterol from the liver, thereby alleviating fatty liver conditions. Fucoxanthin absorbs 75% of ingested fat; Saccharina latissima has high sugars and mannitol which is a blood sugar balancer 2.6. Active potentiality against various cancers: Brown seaweeds have been proved to have anticancer activities on different cell lines. Laminaria, Macrocystis, Nereocystis have anti-cancer activity to liver carcinoma (HepG2) human cell lines (Murugan, 2011). Two polysaccharide fractions, SP31 and SP32 from Sargassum pallidum, display significant in-vitro antitumor activity against HepG2 cells, A549 cells 2.6. b. Colorectal cancer: According to the World Health Organization, it is the second most common cancer worldwide, after lung cancer. Colorectal cancer is one of the most common cancers in men and women and it is particularly prevalent in developed countries. The worldwide incidence of this cancer has increased steadily in recent years, and attributes to rapid changes in dietary patterns and preferences. Dietary habits influence the risk for colorectal cancer (WCRF/AICR, 2009) and search for preventive food component for tumour genesis process will be effective measure for curing colorectal cancer (Kim et al. 2010 There is a nine fold lower incidence of breast cancer in the Japanese population and an even lower incidence in the Korean population due to seaweeds consumption, as compared to the incidence in the West (Lawson et al. 2001;Teas, 1983

Role for Negotiation of Diabetes:
Laminaria digitata and Undaria pinnatifida as a food supplement have potent role against type-2 diabetes. Seaweed ingestion as food influences glycemic control, lowers blood lipids, and increases antioxidant enzyme activities. It reduces the risk of cardiovascular diseases to type-II diabetes patients ). Ecklonia stolonifera have strong anti-diabetic and antioxidant properties (Iwai, 2008).
2.9. Role for Neuroprotection: Microglia, a specialized form of macrophage residing with a wide distribution in the brain play a key role in host defence and tissue regeneration in the central nervous system. Dieckol, a hexameric phloroglucinol isolate from Ecklonia cava produce neuroprotective effect by microglia activation ). Transmissible spongiform encephalopathies, or prion diseases, are fatal neurodegenerative disorders that include Creutzfeldt-Jakob disease (CJD) and Gerstmann-Stra¨ussler-Scheinker syndrome in humans and Scrapie, bovine spongiform encephalopathy (BSE), and chronic wasting disease in animals. The daily uptake of fucoidans might be prophylactic against prion diseases caused by ingestion of prioncontaminated materials (Doh-ura et al. 2007). Pheophytin A, purified from the Japanese brown alga Sargassum fulvellum synergizes nerve growth factor (NGF) at 3.9μg/mL by a mechanism that appeared to involve activation of mitogen activated protein kinase signalling (Ina et al. 2007).

Rhodophyta:
Red algae are the most abundant and commercially valuable group of seaweeds. Rhodophyta produce a lot of secondary metabolites with broad spectrum activities which have immense biomedical potential and therapeutic applications. Rhodophyta composed of carbohydrates, protein and lipids, fatty acids, amino acids, and pigments such as chlorophylls a, d, phycoerythrin and phycocyanins, carotenes and a number of unique xanthophylls, starch, xylans, mannans, Floridian cellulose, sulphated polysaccharides, agar, caragennans and porphyrans. The cell wall of red seaweeds accounts for up to 65% (w/w) of dry matter and comprises three domains: fibrillar wall, amorphous matrix and glycoprotein domain. Red seaweeds contain high amount of protein almost 47% w/w of dry matter in contrast, green algae contain moderate amounts (9-26 g protein 100 g−1 dry weight), while brown algae display much lower protein contents (3- 3.2. Role for Hepatoprotection: If the liver cells get damage due to infectious agents or chemicals, then the serum levels of GPT (glutamic pyruvic transaminase) and GOT (Glutamic oxaloacetic transaminase) tend to increase significantly (Recknagel, 1967). Similarly, elevations of Creatinine and Bilurubin have been reported in the Acetaminophen induced hepato-toxicity (Ellenhorn et al. 1997). Gracilaria crassa at 200 mg/kg elevate the levels of total Bilurubin, SGOT, SGPT, LDH and ALP in Aflatoxin but aqueous extract of Gracilaria corticata (250 mg/kg) restorated it to normal level (Manoharan et al. (2008).
3.3. Anti-allergic activities: Some species of red macro algae are also known to be useful additional materials for control of allergic responses. Porphyran, a sulphated polysaccharides isolated from Porphyra tenera have been reported for its anti-allergic activity.
Carpopeltis affinis has preventive role to atopic allergic reaction in vitro. The C. affinis (10 g/ml) significantly alleviates the release of histamine,hexosaminidase, IL-8, and TNF-from mast cells with inhibition rates of 58.  (Kwon and Nam, 2006). A sterol fraction extract of Porphyra dentata, a folk medicine had anti-cancer activity (Kazłowska et al. 2013). Chondria, Palmaria, and Amphiroa have high cytotoxic effect against human cervical adenocarcinoma cell line, murine leukemic cell lines, nasopharyngeal and colorectal cancer cells (Murugan, 2011).
3.6. Role for Immunomodulating: Sulphated polysaccharides isolated from two red algae Porphyra yezoensis and Gracilaria verrucosa stimulate phagocytosis and respiratory burst in mouse macrophages in-vitro and in-vivo (Yoshizawa et al. 1993(Yoshizawa et al. , 1995(Yoshizawa et al. , 1996. Rhamnose moieties of ulvans backbone use to treat skin pathologies specially related with age effect. It helps to tone the skin, promotes the formation of collagen and elastin (Andrès et al. 2006;Faury et al. 2011). Marine algal compounds phlorotannins, sulphated polysaccharides and tyrosinase inhibitor compounds have been reported for its cosmeceutical importance. Oxidative stress produces reactive oxygen species (ROS) which is responsible for skin wrinkling. The methanol extract of Corallina pilulifera (CPM) have preventive ability to reduce UV-induced oxidative stress and also the expression of matrix metalloproteinase (MMPs) -MMP2 and MMP9 in human dermal fibroblast (HDF) cells. It have been suggested that the phenolic compounds from red algae have MMP inhibitory activity (Ryu et al. 2009). Tyrosinase inhibitors are responsible for skin hypo-pigmentation and enzyme catalyzes the rate-limiting step of pigmentation.

Seaweeds for Bone development:
Bone is a complex and hierarchical tissue consisting of nano hydroxyapatite and collagen as major portion. Several attempts have been made to prepare the artificial bone so as to replace the autograft and allograft treatment. Tissue engineering is a promising approach to solve the several issues and is also useful in the construction of artificial bone with materials including polymer, ceramics, metals, cells and growth factors (Venkatesan et al. 2014). Alginate, a polysaccharide extracted from brown seaweed (Laminaria hyperborea, Laminaria digitata, Laminaria japonica, Ascophyllum nodosum, and Macrocystis pyrifera) forms 3D hydrogel through ionic crosslink in the presence of Ca2+. Some enzymes decompose calcium alginate by generating non-poison products. So, alginate has been applied as wound cover, drug carrier, bacterial culturing substrate, etc. Calcium alginate hydrogel implant under rat skin and discover a new cartilage development. The disadvantages of calcium alginate is hard to degrade in body, so the composition and purity varies in different products (Fei et  . It has been recently discovered that alginate beads can control the creation of calcium phosphate-one of the skeleton's essential building blocks. Alginates are biopolymers derived from seaweeds. They have the ability to thick, stabilize solutions forming gels, and use in a number of applications in both the food and medical industries. The beads show particular promise in cell transplantation. Calcium phosphate may occur in numerous forms, but inside the alginate beads the scientists find nano-sized crystals of hydroxyapatite. These have many similarities with the mineral found in bones. If the researchers succeed, the living bone mass will be implanted into skeletal injuries, such as in hip replacements, and eventually it will grow to form new functional bones out of living tissue instead of plastic (Olderoy, 2011) . The cell wall material alginate of two seaweed species of Chile such as Lessonia trabeculata and Lessonia nigrescens is suitable for stem cell cultivation: it consists of a highly aqueous gel that is more viscous than honey. It cross link with calcium or barium, it is both stable and flexible like jelly, so, it can insert into the body as artificial bone cells (Zimmermann, et al. 2005). Alginate hydro gels, the polysaccharide use for small chemical drug delivery, tissue regeneration, and stimulation of blood vessel formation, bone and cartilage repair (www.sciencedaily.com). Alginate uses in cosmetics, food manufacturing and more recently in healthcare. Alginate itself use in wound dressings to keep burns moist. It has been found that after three days at a range of temperatures 4-21C up to 90% of the stem cells is viable and available for healing. Medically, 70% viability is considered acceptable. Stem cells translational medicine has been described with low cost seaweed solution and neural fetal abnormalities collectively called cretinism, the condition, result due to low maternal iodine supplies, is difficult to correct postpartum. The treatment is adequate maternal iodine consumption from the mother's initial beginning as an egg in her maternal grandmother (Kazutosi, 2002). Few cases of toxicity have been reported in people with intakes of less than 5000 mcg/d although transient mild effects have been demonstrated in previously in individuals receiving only 150 -200 mcg/d. Normal subjects with intake of 1,000 -2,000 mcg/d shows an increased iodine concentration in the thyroid gland, but no other changes. An intake of 10 -20 mg/d (iodine not seaweed) in Japanese fishermen has been resulted in an incidence of iodine goitre in 6 -12%. Kazutosi, (2002) has been reported that large brown seaweeds Laminaria sp. and kelps (Icelandic kelp, Norwegian kelp, Bullwhip kelp, Sugar kelp, Giant Pacific kelp, and Hijiki), Bladder wrack, Rockweed, Sargassum, Wakame, and Sea Palm, tend to contain more minerals per unit weight than the Red seaweeds (Nori, Irish Moss, Dulse, Grapestone, and Euchemia sp.).
Due to high Iodine, daily diet of brown seaweeds reduces the absorption of radioactive substances by the body. Iodine acts as radiation absorbing agent (Gong et al. 1991 8. Issues about toxic trace metals of seaweeds: The mineral composition and the accumulation of heavy metal change depending on the growth environment and age of seaweeds. Uptakes of adequate amount of seaweeds with diet compensate Iodine and traceelement requirement to human body. Arsenic is considered to be toxic in the form of the inorganic salt when it consume in excess of 2 μg /kg body weight/day but it is also an essential trace element with a recommended minimum intake of 12-50 μg/day (Mohri et al. 1990). Seaweeds contain 10 times more minerals than land plants, so consumption of seaweeds compensates the mineral deficiencies. The high content of omega-3 fatty acids and trace elements in seaweed supports strong mental and physical health (harmonicarts.ca).

Conclusion:
The brown seaweed such as Sargassum sp. contains bioactive compounds such as sulphated polysaccharides, plastoquinone, phlorotannins, fucoxanthin, fucoidans, Sargaquinoic acid, sargachromenol, steroids, terpenoid and flavanoid and the various extracts from this species showed significant therapeutic potential and it could be included for the preparation of novel functional component of pharmaceuticals for the treatment or prevention of several disorder. For brown seaweeds, it is remarkable to select some of the brown seaweeds as anti-cancer agent, as they are showing excellent anti-International Journal of Trend in Scientific Research and Development (IJTSRD) ISSN: 2456-6470 @ IJTSRD | Available Online @ www.ijtsrd.com | Volume -1 | Issue -6 | Sep -Oct 2017 Page: 1206 cancer activity. The green seaweeds and some of the red seaweeds have high amount of omega-3 fatty acids, so they have activity against some of the risk factor of cardiovascular disease.
10. Future Prospective: Many studies explore the use of seaweed in the fight against several diseases. Various therapeutic compounds from seaweed are able to induce activity through different pathways and molecular mechanisms to fight against various diseases. However, not all species of algae have health-promoting properties, as some are known to produce toxic metabolites that cause neurodegenerative disorders . So, this review will offer new insights on seaweeds as alternative therapeutic strategies in the treatment of different disease. As this review elaborate the species specific importance of seaweeds, it will be helpful to identify the particular species of seaweed for the progress of future research for specific disease. From this base level information, we can proceeds future research with different aspects. Although marine algae are enormous sources of a wide range of chemicals with remarkable diversity, they are not easy to isolate a large yield of desired compounds. Likely, the combinatorial genetic and metabolic engineering will be the future solution for commercial production of these compounds.

Conflicts of interest:
There are no conflicts of interest to be declared.
12. Acknowledgements: Authors would like to acknowledge their sincere thanks Dean, Faculty of Marine Science, Annamalai University and Director, C.A. S. in Marine Biology, Annamalai University. Authors are also thankful to higher authorities of Annamalai University.