Seaweeds: A novel, untapped source of drugs from sea to combat

Infectious diseases

S. Chanda*, Dave R, Kaneria M and Nagani K

Phytochemical, Pharmacological and Microbiological Laboratory, Department of Biosciences, Saurashtra University,

Rajkot 360 005, Gujarat, India

* author for correspondence email:svchanda@gmail.com

The discovery and development of antibiotics are among the most powerful and successful achievements of modern

science and technology for the control of infectious diseases. Prolonged usage of broad – spectrum antibiotics has led to

the emergence of drug resistance. There is a tremendous need for novel antimicrobial agents from different sources. The

biodiversity of marine ecosystem provides an important source of chemical compounds which have many therapeutic

applications. Seaweeds or marine algae have been reported to contain many important compounds which act as antibiotics,

laxatives, anticoagulants, anti-ulcer products and suspending agents in radiological preparations. Many substances

obtained from marine algae such as alginate, carrragenean and agar as phycocolliods have been used for decades in

medicine and pharmacy. More and more chemist and biologist pay attention to the constituents of the algae; if their natural

products are explored, they may lead to an efficient lead for the discovery of new drug molecules against several

pathogens causing infectious diseases.

Key words: Infectious diseases; seaweeds; antimicrobial; marine algae

1. Synthetic dominance: growing threat of antimicrobial resistance

Mankind's discovery of antibiotics ushered in a new age of medicine during the 19th

century, an age wherein many

predicted an end to diseases that had plagued the mankind for centuries with the appearance of penicillin during World

War II as the first miracle drug [1]. From 1940s to almost 1980s many classes of antibiotics discovered have helped

tame many of the terrors of human health. The use of these "wonder drugs", combined with improvements in sanitation,

housing, nutrition, and the advent of widespread immunization programmes, led to a dramatic drop in deaths from

diseases that were previously widespread, untreatable, and frequently fatal. Over the years, antimicrobials have saved

the lives and eased the suffering of millions of people.

Advances in synthetic chemistry for identification of many key chemical molecules offered more opportunities to

develop novel compounds. Numerous drugs like sulphonamides, isoniazid, anti-psychotics, anti-histamines and

penicillin were developed from thousands of chemicals [2]. Emergence of modern pharmaceutical industry is an

outcome of all these different activities that developed potent single molecules with highly selective activity for a wide

variety of ailments. These successes resulted in reduced interest in natural products drug discovery. Thus, herbal

medicines became the domain of 'old wives tales'.

It was not until the 1970s that antibiotic resistance was considered to be a real threat. In the past, medicine and

science were able to stay ahead of this natural phenomenon through the discovery of potent new classes of

antimicrobials, a process that flourished from 1930-1970 and has since slowed to a virtual standstill, partly because of

misplaced confidence that infectious diseases had been conquered, at least in the industrialized world. In just the past

few decades, the development of resistant microbes has been greatly accelerated by several concurrent trends like

urbanization, pollution, AIDS epidemic, etc. These have worked to increase the number of infections and thus expand

both the need for antimicrobials and the opportunities for their misuse.

Recently, infections have become the leading cause of death world-wide which has led to an increase in antibacterial

resistance, making it a global growing problem [3]. More and more bacteria are developing resistance to antibiotics

conferred by randomly mutated genes [4]. Each year infectious diseases cause 14 million deaths worldwide, with

mortality increasing even in the United States at an annual rate of 4.8 percent. In 2000, the World Health Organization

(WHO) estimated that pneumonia, diarrhoeal disease, and tuberculosis accounted for more than half the deaths due to

infectious disease worldwide. The problem is worsened by antibiotic resistance, as well as the emergence of new

pathogens with the potential for rapid global spread [5]. In addition to this problem, antibiotics are sometimes

associated with adverse effects on the host including hypersensitivity, immume-supression and allergic reactions [6].

Now, Scientists accepted that antibiotics will leave healthcare professionals without effective therapies for bacterial

infections for example Staphylococcus aureus. It is estimated that about half of all strains found in many medical

institutions are resistant to antibiotics such as methicillin [7]; or enterococci, which are resistant to widely effective

antibiotic, vancomycin [8]. Thus, there is an urgent need to discover new antimicrobial compounds with diverse

chemical structures and novel mechanisms of action for new and re-emerging infectious diseases. The new therapeutic

agents should be effective and have a novel mode of action that render them impervious to existing resistance

mechanisms. Not only drugs from natural sources have new structural features, with novel biological activity but

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phytochemicals derived from them are also extremely useful as lead structures for synthetic modification and

optimization of bioactivity.

2. Need of the hour

We are now at the crucial stage where it is essential to explore new strategies in order to combat infectious diseases.

The oceans represent virtually untapped resource from which novel bioactive compounds can be discovered. The

marine environment representing approximately half of the global biodiversity, is an enormous resource for new

compounds. Sea weeds or marine algae are potentially prolific sources of highly bioactive secondary metabolites that

might represent useful leads in the development of new pharmaceutical agents. Many reports have been published about

isolated compounds from algae with biological activity, demonstrating their ability to produce metabolites, with high

complexity and unlimited diversity of pharmacological and/or biological properties.

3. Seaweeds

Seaweeds belong to a group of plants known as algae. Seaweeds are classified as Rhodophyta (red algae), Phaeophyta

(brown algae) or Chlorophyta (green algae) depending on their nutrient, pigments and chemical composition. Like other

plants, seaweeds contain various inorganic and organic substances which can benefit human health [9]. Seaweeds are

considered as a source of bioactive compounds as they are able to produce a great variety of secondary metabolites

characterized by a broad spectrum of biological activities. Compounds with antioxidant, antiviral, antifungal and

antimicrobial activities have been detected in brown, red and green algae [10, 11]. Some promising red, brown and

green algae of Gujarat coast region are shown in Fig. 1.

The environment in which seaweeds grow is harsh as they are exposed to a combination of light and high oxygen

concentrations. These factors can lead to the formation of free radicals and other strong oxidizing agents but seaweeds

seldom suffer any serious photodynamic damage during metabolism. This fact implies that seaweed cells have some

protective mechanisms and compounds [12].

In recent years, several marine bacterial and protoctist forms have been confirmed as important source of new

compounds potentially useful for the development of chemotherapeutic agents. Previous investigations of the

production of antibiotic substances by aquatic organisms point to these forms as a rich and varied source of antibacterial

and antifungal agents. Over 15,000 novel compounds have been chemically determined. Focusing on bioproducts,

recent trends in drug research from natural sources suggest that algae are a promising group to furnish novel

biochemically active substances [13].

Seaweeds or marine macro algae are the renewable living resources which are also used as food and fertilizer in

many parts of the world. Seaweeds are of nutritional interest as they contain low calorie food but rich in vitamins,

minerals and dietary fibres [14]. In addition to vitamins and minerals, seaweeds are also potentially good sources of

proteins, polysaccharides and fibres [15]. The lipids, which are present in very small amounts, are unsaturated and

afford protection against cardiovascular pathogens.

4. Seaweeds - Diversity in marine ecosystem

Algae are known to be comparatively sensitive to chemicals [16]. Their ecological position at the base of the aquatic

food chain and their essential roles in nitrogen and phosphorus cycling are critical to aquatic ecosystems [17].

Moreover, the alternation of species composition in an aquatic community as a result of toxic stress may affect the

structure and function of the whole aquatic ecosystem [18].

The diversity of life in the terrestrial environment is extraordinary; the greatest biodiversity is in the world’s oceans,

with 34 of the 36 phyla of life represented. The oceans cover more than 70% of the earth’s surface and contain more

than 300,000 described species of plants and animals [19, 20]. The marine environment represents a treasure of useful

products awaiting discovery for the treatment of infectious diseases. Ecological pressures, including competition for

space, the fouling of the surface, and predation have led to the evolution of unique secondary metabolites with various

biological activities [21]. The important role of these secondary metabolites in the control of infectious microorganisms

was for many years largely unnoticed.

5. Seaweeds – an anti infectious agent

The revolutionized therapy of infectious diseases by the use of antimicrobial drugs has certain limitations due to

changing patterns of resistance in pathogens and side effects they produce. These limitations demand for improved

pharmacokinetic properties, which necessitates continued research for the search of new antimicrobial compounds for

the development of drugs. Seaweeds are used in traditional remedies in many parts of the world. The production of

inhibitory substances by seaweed was noted as early as in 1917.

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Fig 1. Some promising marine macro algae

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6. Seaweeds – biological activities and bioactive compounds

The extracts and active constituents of various algae have been shown to have antibacterial activity in vitro against

Gram-positive and Gram-negative bacteria; some examples are given in Table 1. The production of antimicrobial

activities was considered to be an indicator of the capacity of the seaweeds to synthesize bioactive secondary

metabolites [22]. There are numerous reports of compounds derived from macroalgae with a broad range of biological

activities, such as antibacterial [23], antivirals [24], antitumorals [25], anticoagulant [26] and antifouling [27].

Compounds with cytostatic, antiviral, antihelminthic, antifungal and antibacterial activities have been detected in green,

brown and red algae [28]. Also, considering their great taxonomic diversity, investigations related to the search of new

biologically active compounds from algae can be seen as an almost unlimited field.

Among the different compounds with functional properties, antioxidants are the most widely studied. Moreover, the

important role of antioxidants in human health has been demonstrated thus increasing the interest in such products and

their demand by consumers. Marine algae serve as important resources for bioactive natural products [29]. Brazilian red

algae have been found to have phenolic substances. Kappaphycus alvarezzi has nutritive and antioxidant property;

different parts of the thalli are also known to differ in their antimicrobial potential [30].

Similarly, some micro-algae contain and/or excrete pharmacologically active compounds. For example, the

dinoflagellates Gymnodinium sp. and Gonyaulax sp. produce an alkylguanidine compound that affects the central

nervous system. Brominated bi-indoles of Rivularia firma show pharmacological activity. Gracilaria lichenoides, a red

alga, excretes prostaglandins and the compound C20 [31]. Seaweeds are known to contain reactive antioxidant

molecules, such as ascorbate and glutathione (GSH) when fresh, as well as secondary metabolites, including

carotenoids (α- and β-carotene, fucoxanthin, astaxanthin), mycosporine-like amino acids (mycosporine-glycine) and

catechins (e.g., catechin, epigallocatechin), gallate, phlorotannins (e.g., phloroglucinol), eckol and tocopherols (α-, χ-, δ-

tocopherols) [32]. Brown-algal polyphenols phlorotannins worked as antioxidants and antibacterial compounds [33].

7. An attempt at integration — Conclusion

Research is a crucial part of the response to new and emerging diseases. A sustained, forward-thinking applied research

programme would enable scientists to identify the weak links in the armour of emerging microbes, create novel ways to

fight microbial foes, and evaluate the preventive power of new approaches. The priority for the next decades should be

focused in the development of alternative drugs and/or the recovery of natural molecules that would allow the consistent

and proper control of pathogen-caused diseases. The general trend to more widespread antibiotic resistance is relentless

and if it continues unabated, deaths from what were previously treatable infections will occur with increasing

frequency. The initiatives must be implemented now because the battle against antibiotic resistance is being lost.

Complacency and delay will have major detrimental effects on future public health. Seaweeds may be an answer to

unsolved and growing problem of resistance, a novel untapped source to combat infectious diseases.

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Table 1 List of some reported algae for antimicrobial activity

No Name of algae Microorganisms Referen

ces

1

Ceramium indica, Enteromorpha

intestinalis, Ulva lactuca, Gelidiella

acerosa, Corallina officinalis, Gracilaria

corticata, Sargassum sp., Galaxaura

oblongata, Grateloupia sp., Ceramium

indica, Laurentia pedicullata, Sargassum

sp., Padina gymnospora, Stoechospermum

marginatum, Cystoseira sp. Caulerpa

racemosa, Caulerpa scalpelliforrmis,

Spathoglossum variabile, Halimeda tuna,

Gelidiopsis gracilis, Iyengaria stellata,

Gelidium sp., Udotea indica,

Gastroclonium iyengarii, Heterosiphonia

sp.

B. cereus ATCC11778, M. flavus ATCC10240, K.

pneumoniae NCIM 2719, P. testosteroni NCIM5098,

C. freundii ATCC10787

[23]

2

Corallina officinalis, Cystoseira barbata,

Dictyota dichotoma, Halopteris filicina,

Cladostephus spongiosus f. verticillatus,

Ulva rigida

S. aureus, M. luteus, E. faecalis, E. coli, E. aerogenes,

E. coli O157:H7 [34]

3 Gracilaria tikvahiae, Ulva lactuca, Ulva

fasciata, Sargassum fluitans

E. coli, S. aureus, S. enteriditis, S. epidermidis, P.

aeruginosa, S. faecalis, C. albicans [35]

4 Ulva lactuca, Padina gymnospora,

Sargassum wightii, Gracilaria edulis

S. aureus, V. cholerae, S. dysentriae, S. bodii, S.

paratyphi, P. aeruginosa, K. pneumoniae [36]

5 Trichodesmium erythraeum

B. subtilis MTCC441, E. faecalis ATCC29212, S.

aureus ATCC 25923, E. coli ATCC25922, K.

pneumoniae ATCC15380, P. vulgaris MTCC1771, P.

aeruginosa ATCC27853, E. amylowora MTCC 2760,

S. typhimurium, T. rubrum 57/01, T. mentagrophytes

66/01, T. simii 110/02, Scopulariopsis sp. 101/01, A.

niger MTCC1344, A. flavus, B. cinerea, C. albicans

MTCC227

[37]

6 Sargassum sp. B. subtilis CCR 12, E. coli MTCC 443, S. aureus

MTCC 96 [38]

7 Eucheuma denticulatum S. aureus, S. Pyogenes [39]

8

Ulva rigida, Enteromorpha linza, Padina

pavonica, Colpomenia sniosa, Dictyota

linearis, Dictyopteris membranacea,

Cystoseira mediterranea, Ectocarpus

siliculosus, Ceramium rubrum, Gracilaria

gracilis, Acanthophora nojadiformis

Candida sp., E. faecalis, S. aureus, S. epidermidis, P.

aeruginosa, E. coli [40]

9 Kappaphycus sp., Padina sp.

P. fluorescence, S. aureus, V. cholera, P. mirabilis, B.

megaterium, Citroacitro sp., Entrobacter sp., K.

pneumoniae, E. coli, S. typhimurium, S. fexneri, P.

vulgaris, P. aeruginosa, V. cholera

[41]

10 Sargassum dentifolium, Laurencia

papillosa, Jania corniculata

B. subtilis, S. albus, S. faecalis, E. coli, C. albicans, A.

flavus [42]

11

Colpomenia sinuosa, Dictyota dichotoma,

Dictyota dichotoma var. implexa, Petalonia

fascia, Scytosiphon lomentaria

B. subtilis ATCC6633, S. aureus ATCC6538P, E.

aerogenes ATCC 13048, E. coli ATCC29998, P.

vulgaris ATCC6897, S. typhimurium CCM 583,

methicillin-oxacillin- resistant S. aureus ATCC43300,

E. coli (O157: H7) RSSK 232, C. albicans ATCC10239

[43]

12 Synechocystis sp., Himanthalia elongata S. aureus ATCC25923, E. coli ATCC11775, C.

albicans ATCC 60193, A. niger ATCC16404 [44]

13 Microchaete tenera, Nitella tenuissima,

Sphaeroplea annulina

P. vulgaris, B. cereus, E. coli, P. aeruginosa, A. niger,

A. flavus, R. nigricans [45]

14 Ulva fasciata, Caulerpa cupressoides, B. subtilis, S. epidermidis, S. aureus, C. freundii, E. [46]

_______________________________________________________________________________________

Caulerpa prolifera, Gracilaria

domingensis, Gracilaria sp., Amansia

smultifida

coli, E. aerogenes, K. pneumoniae, M. morganii, P.

aeruginosa, S. typhi, S. typhimurium, S. enteritidis, S.

cholerae-suis, S. marcescens, V. cholerae

15

S. marginatum, St. marginatum, P.

tetrastromatica, P. gymnospora, C.

implexa, D. australis, D. bartayresiana, S.

aspermum, Asparagopsis taxiformis,

Amphiroa fragilissima, Jania reubens,

Caulerpa racemosa, Caulerpa peltata,

Caulerpa taxifolia, Codium fragile,

Chlorodesmis fastigiata

B. subtilis, E. coli, Pseudomonas sp., S. pyrogenes, S.

aureus, P. vulgaris, K. pneumoniae, S. morganii, C.

albicans.

[47]

16 Gracilaria corticata, Ulva fasciata,

Enteromorpha compressa

V. alginolyticus, P. aeruginosa, A. hydrophila, E.

tarda, P. fluorescens, A. hydrophila [48]

17

Valonia aegrophila, Ulva pertusa,

Halimeda opumtia, Halimeda tuna,

Caulerpa racemosa, Caulerpa mexicana

S. aureus, B. subtilis, E. coli, C. albicans [49]

18 Cystoseira tamariscifolia S. cerevisiae, C. albicans, Debaryomyces sp.,

Kluyveromyces sp strains), A. flavus, Penicillium sp [50]

19 Spirulina platensis

S. faecalis, B. subtilis, S. aureus, S. epidermidis, P.

aeruginosa, E. aerogenes, E. cloacae, E. coli, S.

typhimurium, P. vulgaris, C. albicans

[51]

20 Dictyopteris membranaceae, Cystoseira

barbata

S. faecalis, B. subtilis, S. aureus, S. epidermidis, P.

aeruginosa, E. cloacae, E. coli, S. typhimurium, C.

albicans

[52]

21 Enteromorpha linza

S. aureus, S. epidermidis, S. fecalis, B. subtilis, S.

typhimurium, P. aeruginosa, E. cloacae, E. coli, C.

albicans

[53]

22 Jania rubens

S. aureus, S. epidermidis, S. faecalis, B. cereus, B.

subtilis, S. typhimurium, P. aeruginosa, E. cloacae, E.

coli, C. albicans

[54]

23 Polysiphonia virgata M. smegmatis, M.tuberculosis, multidrug resistant M.

tuberculosis [55]

24

Ulva lactua, Halimeda gracilis, Gracilaria

edulis, Hypnea musiformis, Turbinaria

conoides, Sargassum myricystum

E. coli, P. aeruginosa, S. aureus, K. pneumoniae, E.

faecalis [56]

25 Gracilaria changii

S. aureus, P. aeruginosa, P. mirabilis, E. coli, A.

calcoaceticus, S. saprophyticus, S. marcescens, K.

pneumoniae, A. nitratus, S. paratyphyi B, B.

licheniformis, Micrococcus sp., S. epidermidis, C.

preundii, E. enterocolitica, S. typhi, B. pseudomallei,

B. subtilis, Erwinia sp., B. cereus, E. aerogenes, C.

albican, R. rubra, C. neoformans, S. cerevisiae, T.

viride, Rhizophus sp., Mucor sp., Penicillium sp.,

Fusarium sp., T. mentagrophytes, F. oxysporium, A.

niger, A. flavus

[57]

26 Ulva fasciata V. parahaemolyticus, V. alginolyticus, V. vulnificus [58]

27 Dictyota acutiloba

methicillin resistant S. aureus, methicillin susceptible S.

aureus, Enterobacter sp., P. aeruginosa, S. typhi, B.

subtilis, K. pneumoniae, C. albicans, A. niger

[59]

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