Biomedical and Pharmacological significance of marine macro algae-review

Review Article

Biomedical and Pharmacological significance of marine macro algae-review

V. Mariya & Vinoth S. Ravindran^*

Suganthi Devadason Marine Research Institute, 44, Beach Road, Tuticorin 628 001, India

*[Email:vinothravindran@rediffmail.com]

Received 17 May 2012; revised 13 August 2012

Seaweeds are a group of non-flowering marine plants commonly referred to as marine macroalgae. Taxonomically, they are classified into Rhodophyta (red algae), Phaeophyta (brown algae) and Chlorophyta (green algae) depending on their pigments and/or chemical composition¹. Seaweeds contain various inorganic and organic substances which can benefit mankind. Various compounds with biological activities have been isolated^2,3 and they possess pharmacological activities such as Antibiotic, Anticoagulant, Antioxidant, Antiproliferative, Antitumoral, Anticomplementary, Antiinflammatory, Antibacterial, Antifungal, Antiviral, Antihelminthic, Antiprotozoan, Antipeptic, Hypolipidemic, Antiadhesive and Antifouling activities^4-13. The present paper reviews the biomedical and pharmacological properties of seaweeds.

[Keywords: Algae, antioxidant, Seaweed, biomedical, Liquids, corotenoids].

Antioxidant compounds

Free radicals are highly reactive molecules with an unpaired electron and are produced by radiation or as byproducts of metabolic processes. They initiate chain reactions which lead to disintegration of cell membranes and cell compounds, including lipids, proteins and nucleic acids. Antioxidant compounds scavenge free radicals such as peroxide, hydroperoxide or lipid peroxyl and reduce the level of oxidative stress and slow/prevent the development of complications associated with oxidative stress-related diseases

. Many synthetic antioxidants have shown toxic and mutagenic effects in contrast to the naturally occurring antioxidants. Seaweeds have been recognized to have antioxidants

such as ascorbate, glutathione, carotenoids, mycosporine-like amino acids and catechins, gallate, phlorotannins, eckol, ascorbic acid and tocopherols

.

Laminaria digitata and Himanthalia elongata have been reported to exhibit antioxidant activity comparable with those of vitamin E and Butylhydroxyl Toluene (BHT)

. Antioxidant activity has also been reported from Sargassum siliquastrum

, Rhodomela confervoides and Symphyocladia latiuscula

, Sargassum micracanthum

, Kappaphycus alvarezzi

, Gelidiella acerosa

, Fucus vesiculosus

, Ishige okamurae

, Undaria pinnatifida

, Sargassum pallidum

, Enteromorpha compressa, Capsosiphon fulvescens, Chaetomorpha moniligera, and Ulva pertusa

, Halimeda incrassata

, Eisenia bicyclis,

Kjellmaniella crassifolia, Alaria crassifolia, Sargassum horneri and Cystoseira hakodatensis

. Astaxanthin, an antioxidant obtained from Haematococcus pluvialis is marketed

.

Antimicrobial activity

Antibacterial halogenated compounds, such as

bromophenols, have been isolated from many

seaweeds

. Antibacterial activity of Ulva fasciata,

Caulerpa cupressoides against Bacillus subtilis,

Staphylococcus epidermidis, S. aureus, C. freundii

;

Ulva lactuca, Ulva fasciata, Sargassum fluitans against

E. coli and Staphylococcus aureus

; Gracilaria

corticata, Ulva fasciata, Enteromorpha compressa

against Vibrio alginolyticus, Pseudomonas aeruginosa,

P. fluorescens, Aeromonas hydrophila, and

Enteromorpha tarda

; Ulva rigida, Enteromorpha

linza, Padina pavonica, Colpomenia sinuosa, Dictyota

linearis, Dictyopteris membranacea against Candida

sp., E. faecalis, Staphylococcus aureus, S. epidermidis,

Pseudomonas aeruginosa and E. coli

; Caulerpa

scalpeliformis against Salmonella typhi, Micrococcus

sp. and Shigella bodii

; Cheatomorpha aerea against

Pseudomonas aeruginosa, Salmonella typhii and

Micrococcus sp

; Haliptilon virgatum, Corallina

elongata, Ceramium indica, Enteromorpha intestinalis,

Ulva lactuca, Gracilaria corticata, Sargassum sp.,

Laurentia pedicullata, Padina gymnospora, Caulerpa

racemosa, C. scalpelliforrmis, Spathoglossum

variabile, Halimeda tuna, Gelidiopsis gracilis,

Iyengaria stellata, Gelidium sp., Udotea indica,Gastroclonium iyengarii, Heterosiphonia against Bacillus cereus, M. flavus, Klebsiella pneumoniae Pseudomonas testosterone and C. freundii

; Cystoseira barbata, Dictyota dichotoma, Halopteris filicina, Cladostephus spongiosus F. verticillatus and Ulva rigida against Staphylococcus aureus

; Enteromorpha compressa against Shigella sonii and Mucor sp.

; Haligra sp.

against Staphylococcus aureus

; Dictyota acutiloba against methicillin resistant S. aureus, methicillin susceptible Staphylococcus aureus, Enterobacter sp., P. aeruginosa, S. typhi, B. subtilis, K. pneumoniae, C. albicans, A. niger

; Ulva lactuca, Padina gymnospora, Sargassum wightii, Gracilaria edulis against Staphylococcus aureus

; Ulva fasciata against Vibrio parahaemolyticus, V. alginolyticus, V. vulnificus

has been reported.

Antiviral activity

Studies indicate seaweeds to possess antiviral activity due to the presence of sulphated polysaccharides

. Sulphated polysaccharides of marine macroalgae inhibit replication of the Human Immuno Deficiency Virus (HIV) invitro

. A sulphated polysaccharide from Schizymenia pacifica inhibits HIV reverse transcriptase, a later stage in HIV replication in vitro

. λ -carrageenan isolated from Acanthophora spicifera has shown antiviral activities

. Chondriamide A from Chondria atropurpurea has shown antiviral activity against Herpes Simplex Virus (HSV) type II

. A sulphated xylomannan obtained from Nothogenia fastigiata was found to inhibit the replication of type 1 HSV-1, type 2, Human Cyto MegaloVirus (HCMV), Respiratory Syncytial Virus (RSV), influenza A and B virus, Junin and tacaribe virus and simian immunodeficiency virus

. A galactan sulphate from Aghardhiella tenera

and xylomannan sulphate from Nothogenia fastigiata

have shown activity against HIV, HSV types 1 and 2 and RSV. λ-carrageenan and partially cyclized µ/´ı-carrageenan from Gigartina skottsbergii have potent antiviral effects against different strains of HSV types 1 and 2 during the virus adsorption stage

. Antiviral activity has been reported from Gelidium spinosum and Polysiphonia denudata

. In addition, the water extracts of Gelidium rubrum and Polysiphonia denudata inhibited reproduction of HSV-1 and HSV-2 in cell cultures

Carrageenans of Stenogramme interrupta have shown antiherpetic activity

.

A carrageenan-based vaginal microbicide called Carraguard has been shown to block HIV and other sexually transmitted diseases in vitro

and it has entered into phase III clinical trials

. Inhibitory activity against HIV type 1, Reverse Transcriptase (RT) and HIV-1integrase (IN) has been reported from a Korean macroalgae

. Agaroids obtained from Gracilaria corticata

and polysaccharide fractions from Caulerpa sp., Corallina sp., Hypnea charoides, Padina arborescens and Sargassum patens

and fucoidans of Adenocystis utricularis

, sulfated polysaccharides from Gymnogongrus griffithsiae and Cryptonemia crenulata

extracts of Hydroclathrus clathratus and Lobophora variegata

have antiviral properties against HSV types I and II.

Polysaccharides of Gymnogongrus griffithsiae and Cryptonemia crenulata have shown inhibition against multiplication of Dengue Virus (DENV) in Vero cells

. Kahalalide A

and F

from Bryopsis have shown in vitro activity against Mycobacterium tuberculosis. Kahalalide F is extracted from Bryopsis sp. noted for its anti HIV qualities

. Fucoidan of seaweeds has potent antiviral properties towards viruses such as RSV

, HIV

, HSV types I and II and HCMV

. Carrageenan extracted from red seaweed inhibits Human Papiloma Virus (HPV) infection

. Antitumor activity

Most of the anticancer drugs currently used in chemotherapy are cytotoxic to normal cells and cause immunotoxicity

. Many studies have focused on water soluble antitumor active substances from marine algae. Due to the biological properties of seaweeds viz., reduction of plasma cholesterol, binding of biliary steriods, inhibition of carcinogenic faecal flora, binding of pollutants, stimulation of the immune system, and the protective effects of beta- sitosterols seaweed is suggested as a breast cancer anticarcinogen

. Certain algae have long been used in traditional Chinese herbal medicine in the treatment of cancer

. The habit of consuming seaweeds among the Japanese could be an important factor for lower breast cancer rates reported in Japan.

Sulfated polysaccharides, including fucoidans and

carrageenans, inhibit tumor mestastasis in rat test

systems by inhibiting the action of the tumor cell-

derived heparanases involved in membrane crossing

.

Sulfated polysaccharides from Sargassum

kjellmanianam

inhibited mouse S-180 tumor growth

and carrageenan, while not active alone, significantly

potentiated the effect of mitomycin against leukemia-

1210 ascites tumor in mice

. Carrageenan has also been found to stimulate lectin dependent cell mediated cytotoxicity against HEp-2 human epipharynx carcinoma cells

. Various brown algae viz., Scytosiphon lomentaria, Lessonia nigrescens, Laminaria japonica, Sargassum ringgoldianum, the red algae, Porphyra yezoensis and Eucheuma gelatinae and the green alga, Enteromorpha prolifera have shown antitumor activity against Meth-A fibrosarcoma

. Fucoidans isolated from Sargassum thunbergii and S. kjellmanianum have proven for antitumor activity

. Ulvan extracted from Ulva lactuca has shown cytotoxicity against human colon cell line

. Facosterols of Turbinaria conoides have displayed cytotoxicity against Murine(MU) and Human(HU) cell lines

. Caulerpenyne of Caulerpa taxifolia has exhibited antitumour activity against HU neuroblastoma cell line by inhibiting microtubule assembly and tubulin aggregation

. Compounds of dihydroxysargaquinone and sargatriol from Sargassum tortile and diterpene from S. crispum are known for their cytotoxic activities

.

Cytotoxicity of Sargassum polycystum against some human cancer cell lines

in vitro, antitumor and antiproliferative activity of Hydroclathrus clathrus

, antitumor activity of Gracilaria corticata against Jurkat and molt-4 human cancer cell lines

, Spyridia filamentosa against human prostate carcinoma epithelium like cell lines DU-145

, Sargassum swartzii, Cystoseira myrica and Colpomenia sinuosa against Colon carcinoma (HT-29), colorectal adenocarcinoma (Caco-2), breast ductal carcinoma (T47D), tamoxifen resistant breast ductal carcinoma (T47D-T.R), and estrogen independent breast carcinoma (MDAMB468) cell lines

and of Arthrospira platensis, Dunaliella salina and Aphanizomenon flosaquae and Haematococcus pluvialis against the growth of human leukemia cell line HL-60 and the biphenotypic B myelomonocytic leukemia cell line MV-4-11

has been reported.

Anti-inflammatory activity

Inflammation can result to genetic defects and immunoregulation and mechanism defects can lead to tissue damage

. Due to several side effects of anti- inflammatory drugs and resistance of pathogens to the drug, safe biological sources are now been considered

. Previous studies report the presence of anti-inflammatory compounds in seaweeds

. Anti-inflammatory compounds of seaweeds have been reviewed earlier

.

The anti inflammatory effect of Sagarssum hemiphyllum against Phorbol 12-myristate 13-acetate (PMA) and A23187-induced IL-8 and on TNF- α secretionfrom human mast cells (HMC-1)

, Galaxaura marginata against Croton oil induced mouse ear edema

, Sargassum thunbergii and S. fulvellum against Taphorbol myriste acetate- induced ear edema, erythema, and blood flow

, Sargassum micracanthum against LPS induced RAW 264.7 macrophage

, Phorphyra dentate against LPS induced RAW 264.7 macrophages

, Petalonia binghamiae against ethyl acetate LPS induced RAW 264.7 macrophages

, Sargassum swartzii and Ulva reticulata against Carrageenan-induced hind paw edema in rats and Peritonitis for acute and chronic inflammatory models

, Dichotomaria obtusata, against water-ear edema induced by TPA and writhing induced by acetic acid

, Turbinaria conoides against carrageenin-induced hind paw edema

has been reported.

Anticoagulant and antithrombic activity

In recent years, algal polysaccharides have been demonstrated to exhibit anticoagulant activity

. They contain a variety of sulfated L-fucans with anticoagulant activity

. Anticoagulant activity of algal polysaccharides was first reported in Iridaea laminariodes

. Several studies have reported the anticoagulant activity of fucans from brown algae

. Anticoagulant activity was also reported in Grateloupia indica

, Gigartina skottsbergii

, Spatoglossum schroederi

, Sargassum stenophyllum

, Codium cylindricum

, Dictyota menstrualis

, Padina gymnospora

, Codium fragile and Sargassum horneri

, Grateloupia filicina and G. lithophila

, Ecklonia cava

, Pachymeniopsis elliptica

, Chaetomorpha antennina

, Laminaria japonica149, Caulerpa cupressoides

. Sulphated fucans from Fucus vesiculosus and Ascophyllum nodosum have been patented as anticoagulant substances

.

Heparin, one of the most effective anticoagulant therapeutics. Heparin-like an anticoagulant has been isolated from seaweeds

. A novel sulfated galactofucan isolated from Spatoglossum schroederi showed potent antithrombotic activity

. A fucan sulfate isolated from Ecklonia kurome

and Spatoglossum schroederi exhibited antithrombin activity

.

Antiulcer compounds

Carrageenan interferes with the proteolytic activity

of pepsin, both in-vivo and in-vitro and has been

useful in treating peptic ulcers. A comprehensive review of this activity has been made

. The effect of carrageenan on the peptic and tryptic digestion of casein in-vitro

has been reported. A chromene compound extracted from the seaweed Sargassum micracanthum has been reported to possess antiulcer compounds

.

Antilipemic, hypocholesterolaemic, hypoglycemic, hypotensive and related activities

Carrageenan and other sulfated polysaccharides have been shown to have phyocholesteromic activity

. Unfortunately, large doses of these that are necessary to demonstrate antilipemic activity would be difficult for humans to tolerate. Some macroalgal polysaccharides and fibres such as alginate, carrageenan, funoran, fucoidan, laminaran, porphyran and ulvan have been noted to produce hypocholesterolemic and hypolipidemic responses due to reduced cholesterol absorption in the gut

. This is often coupled with an increase in the faecal cholesterol content and a hypoglycaemic response

. Others have reported lowering of systolic blood pressure (antihypertensive responses)

and lower levels of total cholesterol, free cholesterol, triglyceride and phospholipid in the liver

. Immunoregulator, cellular response modifier activity

Immunopharmacological effects of carregeenan, has been reviewed for understanding the immunoregulatory and cellular response modifier properties of seaweed polysacccharides

. The immune adjuvant properties of carrageenan have been observed and studies have indicated that they have immune stimulant as well as immune suppressant activities

. Carrageenans have been shown to act as human T-cells mitogens

, induce T-cell suppressor activity in mice

, modify lymphocyte migration via specific receptors

, induce production of a granulocyte-macrophage colony-stimulating factor (GM-CSF)

, stimulate population of mouse B cells

and stimulate the release of dialyzable helper factors from mouse spleen cells

. Funcoidan extracted from Laminaria japonica has stimulated murine splenocyte to produce IFN – 7

. Extracts of Hizikia fusiformis and Meristotheca papulosa have shown to enhance Ig production by B cells, Tumor Necrosis Factor (TNF) production by macrophages and stimulate human lymphocytes to proliferate

.

Other activities

Alginate fiber preparations have been used for some time to suppress bleeding associated with surgical

procedures, as wound dressings and as swabs for culture sampling. Calcium alginate dressings accelerate split skin graft donor site healing and permit recropping to take place in half the usual time

.

Sterile dried stripes of Laminaria can be used as cervical dilators in obstetrics and for gynecological examinations

. The stripe or “laminaria tent” is inserted in the cervix and causes dilation. Although it is probably the physical swelling of the polysaccharides contained in the stripe rather than a physiological response that enables this application, this is another example of the varied medical uses of marine algal polysaccharides.

Fucoidan of seaweeds has the capacity to inhibit binding of sperm to the zona pellucida in humans

, thus allowing the compound to be developed into a possible vaginal microbicide with contraceptive properties. Inhibitory activity on sperm motility has been reported from Chaetomorpha antennina, Helimeda gracilis, and Gracilaria edulis due to the presence of spermicidal compounds

.

Medium for microbial growth and gel documentation Macro algal polysaccharides have played a major role in the discovery and development of new, more potent anti inflammatory drugs. The most important current medically oriented use for sulfated seaweed polysaccharides is in biochemical research, where their inflammatory, immune stimulating and suppressing, thrombosis causing, and other properties are used to induce a particular response in model systems for studying and or screening materials for potential therapeutic value. Many anti-inflammatory agents have been discovered using the carrageenan induced, non-inflammatory response, the rat paw edema assay

. The use of this model system for drug screening and studies on the mechanism of edema formation and recession are the subject of a number of publications

. When carrageenan is infused into the lungs of mice and rats, a pleurisy like, inflammatory reaction occurs which can be reversed by anti inflammatory agents

. An arthritis-like model can be generated when carrageenan is injected into the synovial fluid of animals

. This model has been used not only to study the mechanism of the onset and development of arthritis, but also to screen for arthritis-specific anti-inflammatory agents.

Systems for screening potential therapeutic value

190

Koch (1882), formally announced the use of

agar, extracted from seaweeds, as a new solid medium

for microorganisms following his experiments on Mycobacterium tuberculosis. It is still the medium of choice for general microbial growth and identification. Agarose, because of its higher degree of purity and consistency, is being used increasingly by scientists for critical cultures and gel documentation studies

.

Projections for the future

Thus marine alga proves a s a source of novel bioactive metabolites. Many other algal metabolites such as agar, algin and carageenan would be commercialized and available for therapeutic use as new biochemical and biotechnological assays are developed.

Acknowledgement

Authors are thankful to Director, Suganthi Devadason Marine Research Institute (SDMRI), Tuticorin, for providing facilities.

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