Seaweeds as an alternative therapeutic source for aquatic disease management

S. Thanigaivel, Natarajan Chandrasekaran, Amitava Mukherjee, John

Thomas

PII: S0044-8486(16)30400-8
DOI: doi: 10.1016/j.aquaculture.2016.08.001
Reference: AQUA 632260

To appear in: Aquaculture

Received date: 13 June 2016

Revised date: 29 July 2016
Accepted date: 1 August 2016

Please cite this article as: Thanigaivel, S., Chandrasekaran, Natarajan, Mukherjee, Ami-
tava, John Thomas, Seaweeds as an alternative therapeutic source for aquatic disease
management, Aquaculture (2016), doi: 10.1016/j.aquaculture.2016.08.001

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 ACCEPTED MANUSCRIPT

Seaweeds as an alternative therapeutic source for aquatic disease management

S. Thanigaivel, Natarajan Chandrasekaran, Amitava Mukherjee, John Thomas*

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Centre for Nanobiotechnology, VIT University, Vellore, Tamil Nadu

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*Corresponding author.
Dr. John Thomas
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Centre for Nanobiotechnology, VIT University, Vellore, Tamil Nadu

Tel-: +91 416 2202876; fax: +91 416 2243092

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E-mail address: john.thomas@vit.ac.in, th_john28@yahoo.co.in

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Abstract
Aquaculture is one of the principal sources to increase the world’s fish production.
Outbreak of diseases is a major problem in aquaculture. Chemotherapeutic approaches have been
used for the treatment and prevention of disease outbreaks. The use of various chemicals has

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harmful effects on the environment and human health. The prolonged use of antibiotics causes
antibiotic resistance. Natural products such as medicinal plants, marine algae, herbs and their

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extracted compounds are being studied for disease management in fishes and prawns. In this

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review, the use of seaweeds and their importance in aquaculture health and disease management
to control the bacterial infections against the pathogenic bacteria which affect freshwater fishes

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is explained. Application can either be by a single compound or a combination of two different
compounds or as feed additives. Administering the compounds obtained from the extracts in the
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form of encapsulated beads was found to be more effective.
Statement of Relevance
Seaweeds have good antioxidant capacity and act as a natural medicine. Bacterial fish pathogens
affect the health of aquatic organisms. The bioactive compounds from sea weed extracts showed
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good antibacterial activity. They can be used for treating bacterial infection in aquaculture and as
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prophylactis. This kind of prophylactic treatment can be used as an alternative to synthetic since
they cause resistance.
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Keywords
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Aquaculture; Disease resistance; Pathogens; Antibacterial activity of seaweed extracts; Fish

diseases; treatment

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1. Introduction

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Aquaculture provides protein supplements through the fish food. In addition to the non-
food products as such as pearls, seashells and decorative items, aquaculture includes "Food fish"

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which are vertebrates and invertebrates produced for human consumption. Enormous quantities

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of farmed aquatic plant varieties such as seaweeds and cultivable organisms have been produced.
In addition nearly forty-three million tons of fishes have been utilized as a food source and

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0.0135 billion tons of marine algae have been used for various purposes (FAO 2014). Farmed
fishes account for the primary production of nearly 43 % of the total 158 million tons produced.
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The global fish meal production is mainly from the fish residues. Production of algae accounts
for about 25 million tons of seaweeds harvested annually (FAO 2014). Fishery trade and export
is considered to be a significant economic activity in the developing nations and accounted for
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about 10% of total agricultural transportation in 2012. In the last five decades, the global fish
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production has grown enormously at 3.2% per annum compared to the 1.6 percent population
growth based on an FAO report (FAO 2014). This increase and development have been
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determined by an amalgamation of growth of population, increasing incomes, and urbanizations

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(FAO 2014). China is mainly responsible for this enormous increase in fish availability and
production. Fish consumption in the developing countries tends to increase the production of
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seasonally available fishes (FAO 2014).

2. Overview about the cultivation of Seaweeds
According to FAO reports all cultivable aquatic algae recorded under different groups
have been classified into several sets based on the environment in which they are found and their
potential uses (FAO 2014). The species composition of the worlds farmed seaweed production
increased mainly in the tropical and subtropical marine species (FAO 2014). Seaweed species are
categorized according to their various properties based on their fundamental structural and
functional characteristics. For example, the brown seaweeds are predominantly used for different
syntheseis, while Gracillaria species are commonly used for the production of feeds. It also has
health benefits and is used in drug formulations. Wakame and Porphyraarefarmed for human
consumption. In the past few decades, seaweeds and their extracts are being increasingly used as

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prophylactic and therapeutic agents, and in aquaculture for aquatic health management. Most
seaweeds have antimicrobial activity against harmful fish, and shrimp pathogens particularly in
India. Two examples are Asparagopsis species. (red algae) andSargassum sp (brown algae)
which have exhibited a broad range of antimicrobial activity against pathogens (Vatsos et al.

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2014). The extraction of the compound responsible for their antimicrobial properties depends on
various factors like the use of solvents. Organic solvents are more efficient than others.

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This review focuses on the use of bioactive compounds from the seaweeds that have

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biological activities especially those which can be used for their antibacterial activities
responsible for the prevention of fish diseases. Studies on the constituents of marine algae have

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been carried out. Seaweed extracts are a potential source for sustainable aquaculture (Smit 2004).
The use of chemical compounds and components identified from the bioactive compounds are
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used as tools in medical research (Kris-Etherton et al. 2002; Mayer and Lehmann 2000).
2.1. Importance of seaweed extracts in aquaculture
Aquaculture products represent a rich source of protein supplements. World fish food
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supply has grownenormously in recent years. However, aquaculture is highly vulnerable to

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disease causing microorganisms resulting in high economic losses. This has a major impact on
aquaculture production (Bondad-Reantaso et al. 2005). Change in temperature, inadequate water
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treatment, and reduced nutritional levels lead to stress and immune suppression in aquatic
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animals (Reverter et al.2014). Moreover, stocking of fishes and lack of hygiene facilitates the
spread of infections and causes enormous mortality (Quesada et al. 2013; Cabello 2006; Naylor
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et al.2000). There are several ancient control measures that have been followed to evade
economic losses. A few veterinary drugs have been used to control disease outbreaks in
aquaculture (Reverter et al. 2014).
Commercial use of antibiotics and veterinary drugs are restricted for use in aquaculture to
control the bacterial and other opportunistic infections. The use of a bio-based eco- friendly
approach to control infections and thus promote growth has attracted more attention (fig 1), since
the use of synthetic and commercial antibiotics causes antibiotic resistance.(Seyfried et al. 2010;
Mirand and Zemelman 2002) reported that the presence of antibiotics in residual form has
significant impact on humans (Ormazábal et al. 2012; Cabello2006).
3. Potential uses of marine algae in aquaculture

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Seaweed extracts showed awide range of beneficial properties such as antioxidant, promoting
growth rate, anti stress, appetite stimulus, immune stimulation, boost of tonicity, and
physiological benefits. Enhancement of aphrodisiac and anti pathogen properties due to the
presence of bioactive compounds or essential oils have been reported in aquaculture

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(Chakraborty and Hancz 2011; Thanigaivel et al. 2015a; Citarasu 2010). Besides, the use of such
secondary metabolites is cost efficient and also easily biodegradable when compared to synthetic

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particles (Logambal et al. 2000; Blumenthal et al. 2000).

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3.1. Antioxidant activity
Several antioxidant defense systems help in restoring the normal architecture of cells

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which have become cancerous. These antioxidant defence systems prevent macromolecular cell
damage by oxidation. Studies suggested that tumors are more vulnerable in humans and animals
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when it generates more free radicals during the pro-oxidant state (Boopathy et al. 2013).
Oxidative macromolecular damages are primarily responsible for cancer (Hajiliadis 1997;
Huang 2003). The formation of oxidative species leads to the proliferation of cells, cell cycle
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arrest and apoptosis. There are few antioxidant molecules which scavenge free radicals.They are
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are exogenous and endogenous and complement each other to control cellular redox in cancer
treatment and prevention. The primary source of oxidative substances are; reactive oxygen
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species (ROS) and reactive nitrogen species (RNS).These substances known as hydroxyl
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radicals (•OH).Hydrogen peroxide (H2O2), superoxide (O2 •-), nitric oxide (NO•) and
Peroxynitrite (ONOO-) also damage proteins, lipids and DNA (Orrenius et al. 2007; Jun et al.
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2001). Therefore, it is important to characterize the isolated natural antioxidants and their
potential capabilities to ascertain the side effects before commercilization (Matsukawa et al.
1997; Athukorala et al. 2003; Lim et al. 2002).
3.2. Antipathogenic activities
Different seaweeds screened for antimicrobial property by extracting their active
compounds with various solvents like (ethanol, methanol, chloroform, petroleum ether &
dichloromethane, etc.,) exhibited various antimicrobial activities. (Shanab 2007) reported more
anti bacterial activity in the red algal species than the brown alga Sargassum dentifolium. Total
chlorophylls, carotenoids, free phenolics, saturated and unsaturated fatty acids in the seaweed
extracts were reported to be the active substances responsible for the antioxidant and
antimicrobial activity in the red alga species (Shanab 2007). Phenolic content was found to be

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higher in the ethanolic extracts because of its polarity, and these phenolics were present most
abundantly in rhodophytes. The antibacterial property of marine algae (J. corniculata& L.
papillosa) was reported to be due to the presence of fatty acids such as (Tetradecanoic,
Hexadecanoic, and Octadecanoic) and (Hexadecenoic, 9-octadecenoic and Tetracosenoic). A

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higher percentage of fatty acids was detected in L. papillosa and J. corniculata (Rice-Evans et al.
1997; Wei et al. 2003; Kang et al. 2004; Yuan et al. 2005).This was also reported by (Daoud and

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Foster 1993; Kimura and Yokota 2004). Nagayama et al. 2002, Kubo et al. 1992, Alam et al.

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1994 reported that these fatty acid compounds exhibited potent antimicrobial activity against
different bacterial and fungal species.

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3.3. Immunostimulation property of extracts
Immuno stimulants are protective agents which induce non-specific immune responses
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towards disease resistance. Some immune stimulants which are derivatives of biological
compounds of bacterial and animal origin are reported to have immune stimulation properties.
The immunostimulants used in the fish and shrimp aquaculture farms are derived from barley,
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glucan, chitosan, saponin, and plant extracts, lipopolysaccharides, peptidoglycans, etc.,

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(Rajasekar et al. 2011). Most of the fishes depend on either specific or non-specific mechanism
to defend themselves against attacking pathogens just like humans. In fish, the primary defensive
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lines are skin and mucous membranes as a nonspecific system. During the entry of invading
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pathogens, thesystem activates phagocytosis. This process is considered as the principal mediator
of non-specific immunity against various virulent pathogens in fish. However, some of the
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immune stimulants could not be used because of various dis advantages, on the other hand,
medicinal plants are used as immune stimulants for several diseases (Duke 1987;Mentle et al.
2000; Zarkovic et al. 2001; Verpoorte et al. 1999).
The use of immune stimulants in medicinal plants as immune prophylactics has been
studied as an alternative strategy to the antibiotics. Nowadays there is growing interest in
seaweeds, and their extracts and various formulated combinations of extracts promoting
activities such as growth, immunity, antibacterial and antiviral properties against host pathogens
(Van Hai 2015).
3.4. Immuno stimulants for prevention of fish diseases
The (WHO 2002) has recommended the use of preventive natural plant-based approaches
for illness management, mainly in agriculture and aquaculture (Verschuere et al. 2000). This has

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stimulated research on the control of foreign protein contents which harm the environment. One
of the methods of controlling foreign proteins is immunotherapy which deals with the pathogenic
and immune pathogenic responses towards the invader organism by controlling the action of a
particular pathogen by stimulating the overall immune response of the foreign protein (Sordello

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et al. 1997). The use of immune stimulants is considered as an alternative method to control or
prevent the fish diseases (Sakai 1999). (Thanigaivel et al. 2014, 2015a) reported the possibility

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of using seaweed extracts for controlling diseases in both shrimp and fishes, opening up the

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possibility of using seaweed extracts as a source of immune stimulants. For the past two
decades, numerous chemotherapeutics have been used to treat various bacterial infections in

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cultured fishes and shrimps, but the occurrence of multiple drug-resistant bacteria is a major
problem (Aoki 1992). The administration of an active vaccine may also preclude fish diseases. A
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supplementary practical method of controlling bacterial diseases in aquaculture appears to be
enhancement of natural disease resistance by using immune stimulants (Sakai 1999).
4. Beneficial properties of Seaweed extracts
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`The Rhodophyta seem to be an attractive and potentially usefulsource of food because of

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its amino acid compositions, presence of high level of food proteins. In Europe, the emergence of
food varieties developed from the seaweeds has increased, in particular the protein-rich species.
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The role of protein is vital in the human nutrition. Anessentialprotein Phycoerythrin (PE) derived
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from Rhodophyceae has biotechnological applications (dye in immune fluorescence reaction)

(Gantt and Lipschultz 1974). Algae with high protein levels could also be used in aqua farming
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as food. It is one of the active applications of the marine resources according to (Mustafa et al.
1995). These bioactive diets appeared to improve body weight of the host organisms and
enhance the triglyceride levels in consumers and protein deposition in muscles. Supplementary
benefits of use of seaweed extracts as fish feed with different formulations have been reported.
These algal diets also enhanced the disease resistance in fishes (Mustafa et al. 1995; Nakagawa
et al. 1987). Thus, the algal diversity seen in different seaweeds can be used as a complementary
and beneficial alternative source of protein for mammalian nutrition.
A literature survey carried from the Aquaculture and Fisheries Resources database,
identified seaweed with biological and pharmaceutical activity. Algae which are presently
receiving maximum attention include Deliseapulchra which has antiviral property due to the
presence of sulphated polysaccharides, halogenated furanonesand antifouling compounds

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(Smit2004). The chemical compounds that are present in algae are potentially useful for the
development of natural antifouling agents, antimicrobials, and novel UV-sunscreens.
The active compounds isolated from the seaweeds possess a broad range of biological
activities, and some have a high potential for production of environment-friendly pesticides,

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agrochemical compounds, and drugs for biochemical, pharmaceutical and medical research (Smit
2004). Our review will focus on the renewed interest in secondary metabolites in seaweeds, and

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perhaps prompt researches to discover the ecologically important active compounds of many of

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the seaweeds for aquatic disease management.
4.1. Nutritional value and protein content of seaweeds

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Seaweedsare used as sources of human and animal nutrition in various forms. Their
protein levels differ from species to species. Not much of information on the nutritive seaweed
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proteins, specifically, on important bioactive compounds responsible for decreasing their
digestibility and in some case the potential use of algal proteins as additives is available
(Fleurence 1999). The use of seaweeds proteins varies from country to country. In Europe,
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brown algae are most commonly utilized for additive preparations or as a feed in animal nutrition
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(Indergaard and Minsaas 1991). Brown seaweeds have the lowest protein fraction of (3±15% of
the dry weight DW) associated with the Chlorophyta and Rhodophyta (nearly 11% of the DW)
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(Arasaki and Arasaki 1983). An exception is the species Undaria pinnatifida, which contains a
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protein level of eleven and twenty-four percentage (DW). In some green Ulva sp, the amount of
protein content is between ten and twenty-six percent (dry weight) of the algae. For example, the
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species Ulva pertusa, which is most frequently obsessive, has high protein content between
twenty and twenty-six percentage. Higher protein levels were recorded in Porphyra tenera
(forty-seven percent of dry mass) (Arasaki and Arasaki 1983; Morgan et al. 1980) reported
greater protein levels were recorded at the end of the Winter period. Annual monitoring of the
seaweeds in spring showed that protein content in the marine algae from French Atlantic coast
varies from 9% to 25% (dry weight) (Abdel-Fattah and Sary 1987; Augier and Santimone 1978).
The cultivation of fishes with seaweeds naturally increases the production and development of
environmentally sustainable aquaculture (Winberg et al. 2009). Sustainable plant derived diets
are able to enhance fish growth and flesh. According to a report seaweeds collected from the
Portuguese coast are used in the diet of tilapia. Research and development for the formulation of
functional foods will help in modifying the growth performance of fish with higher yieldand

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alsominimize pathogenic bacteria spreading in aquaculture farms. However, we lack complete

information on the quantitative nutrient requirements of most fish (Oliva‐Teles 2012)

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5. Bacterial pathogens and its influence in the aqua farming
5.1. Fish bacterial pathogen

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Seaweed extracts are very rich in essential bioactive metabolites which have various

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biological activities like anti-inflammatory, antiviral and antibacterial. Many seaweed extracts
and active fractions were studied for their antibacterial activity (Thanigaivel et al. 2015b). These

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algal extracts were found to be effective against several types of the Gram negative and Gram
positive fish pathogens. (Lu et al. 2008; Vatsos 2014; Genovese et al. 2012; Bansemiret al. 2004,
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2006; Cavallo et al. 2013;Ganeshamurthy et al. 2012; Vairappan and Suzuki 2000; Singh et al.
2012; Thomas et al. 2014; Dubber and Harder 2008; Rebecca et al. 2012), carried out a study on
antimicrobial activities of the marine algae Ulva clathrata. This was found to be effective agaisnt
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Vibrio anguillarium
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5.2. Virulence of bacterial pathogens in shrimp

All the major studies discussed in this review have mainlyfocused on the bioactive
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benefits of algae and their extracts as antimicrobial agent against various opportunistic
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pathogens. These in vivo models have focused on the bacterial genus Vibrio sp(Baleta et al.
2011; Selvin et al. 2011; Cavalo et al. 2013; Silva et al. 2013; Defoirdt et al. 2006; Sivakumar et
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al. 2014; Manilal et al. 2012; Thanigaivel et al. 2014; Dashtiannasab et al. 2012). Thebio-
actively enriched seaweed extracts were administered to the shrimps, through the enriched
medicated formulation of Artemia dry feeds (Defoirdt et al. 2006). In our earlier study
(Thanigaivel et al. 2014) the extracts of medicated Chaetomorpha antennina were added to water
containing infected shrimp to demonstrate the use of algal extracts as alternatives to commercial
antibiotics used in farms against Vibrio paraheamolyticus. We have examined both the natural
antioxidant and antibacterial properties of the ethanolic extract of the green alga C. antenninato
assess its bioactivity and also determined its free radical scavenging activity to up-regulate the
stress and infection caused by the pathogenic Vibrio. To assess its antibacterial properties,
shrimps (12 g) experimentally infected with V. parahaemolyticus were
challengedthroughdispersion method for 12–48 h. This immersion method resulted in ninety-

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eight percentage of survival in treated shrimps. We have also used the intramuscular injection
method of (Thomas et al. 2013) to study its effects on the pathogen by administering 25
microliters of the seaweed extract per shrimp. These studies illustrated the protective efficacy of
the extract on to the shrimps when they were subsequently being infected with the pathogen.

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5.3. Seaweed extracts as an alternative source to control pathogens in aquaculture
Seaweeds exhibit significant antimicrobial activity, but the level of efficacy varies from

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the species to species. Extracts of various species showed antibacterial properties against various

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virulence factors of fishes and shrimps. However, A. sparagopsi sspp (red seaweed) and
Sargassum sp (brown algae) exhibit a broader range of antibacterial properties. In fish, almost all

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published information on bacterial virulence focused only on in vitro screenings. Our findings
reported the use of extract based treatment through immersion and intramuscular methods
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against P. aeruginosa and A. solmonicida infection in tilapia. In general, most of the bacterial
pathogens of fish were susceptible to the extracts of different seaweeds.
The method of controlling various disease causing pathogens affecting the farmed fishes
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relies on the efficient use of prophylactics. Different studies have demonstrated the use of
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various chemotherapeutics for the treatment of the several diseases in aquaculture although with
increased risks for both humans and aquatic animals (Vatsos and Rebours 2014; Burridge et al.
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2010). It is well known, for instance, that use of different degradable and non-bio degradable
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chemicals induces an intense selective pressure and multi-drug resistance to the pathogens,
through the horizontal exchange of genetic material. Antibiotics produce only transient and local
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challenges in microbial communities, whereas antibiotic resistance genes present in gene transfer
units can spread in nature which can affect human health and the evolution of environmental
microbiota (Martinez 2009).
5.4. Antibiotic resistance in aquatic pathogens
The regular exposure of opportunistic pathogen to antibiotics in aquaculture and other
agricultural products results in development of the resistant strains of the pathogen. This type of
drug resistance causes various health-associated risks. There is a growing awareness towards the
proper use of the antibiotics and care to be taken when using them in aqua farming. This
approach up-regulates the use of prophylactic use of antibiotics, for the further sustainable
development of the aquaculture industry. This kind of prophylaxis mediated natural biobased
novel methodologies is now being followed to control bacterial infections. Nowadays, alternative

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effective alternative disease controlling methods have emerged with the use of seaweed extracts
(Defoirdt 2011).
Based on the recommendation of the FAO, the use of antibiotics in aquaculture practices
has been revised and banned in some countries particularly in Europe, North American and

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Japan. There are rules governing the use of antibiotics. Some are strictly prohibited while very
few are permitted for use in commercial aquaculture (Smith 2008). However, there was a

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significant rise in aqua production where there are no such valid rules Individual governments

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have monitored the Maximum Residue Levels (MRLs) in aquaculture production and usage
levels (FAO). The countries which export the products have to implement the requirement of

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Hazard Analysis Critical Control Point (HACCP) system for international trade (FAO).
Karunasagar and colleagues studied the multiple drug resistance mechanisms. For instance, huge
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mortality in larvae of (P. monodon) was caused by Vibrio harveyi (Karunasagar et al. 1994).
Indeed, resistant genes were found on transferable plasmids of pathogenic bacteria like
Aeromonas spp., Citrobacter spp., Edwardsiella spp., Photobacterium sp. and Vibrio sp.(Ishida
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et al. 2010; Sorum 2006; Cabello 2006). Various methods currently employed in aquaculture for
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protection against pathogenic bacteria avoid the use of antibiotics (Bondad-Reantaso et al. 2005).
6. Bacterial fish treatment and application strategy
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Bacterial fish disease treatment using seaweed extracts have been already reported in our
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previous studies (Thanigaivel et al. 2014, 2015a). This method involves the mixing of two
different seaweed extracts namely the aqueous and ethanol extracts obtained from Gracillaria
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folifera and Sargassum longifolium.They were mixed in the different ratios to enhance the
bioactive efficacy against the pathogen. This mixture was effective against A. salmonicida
infection in O. mossambicus (Tilapia). The extracts from the two plants studied revealed that
they were rich in marine bioactive compounds with the antibacterial property. This mixture was
used to treat fishes subsequently; since it does not have any toxic effects on the fishes. Moreover,
it does not have any adverse effects on the aquatic environment. Another study also reported that
the use of ethanol extract of the red seaweed Gracilaria fisheri is not toxic to the shrimps
(Kanjana et al. 2011). (Reverter et al. 2014; Takaoka et al. 2011; Thanigaivel et al. 2014)
reported that extracts of some seaweeds are responsible for the enhancement of the physiological
and immunological defense mechanisms of aquatic animals. This effective, low-cost method of

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treatment can be used in aquaculture industries for the sustainable aquaculture production. This
can also be used as prophylactics and therapeutics.
6.1. Seaweed extracts and its mechanisms against pathogens
Seaweeds and bioactive antimicrobial compoundsderived from themhave an essential

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role in its antibacterial properties against various pathogens. In general, these substances interact
in the cells and membranes of the causative microorganisms and disrupt the uptake of

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intracellular substances and its transportation (Mohamed et al. 2012; Hierholtzer et al. 2013).

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Quorum sensing mechanism is the process which most of the natural sources possess. Seaweeds
are of particular interest because of the communication of bacterial signals between the bacterial

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populations. The substances released into the extracellular environment during this process were
detected by specific receptors located in the cytoplasm of the cell wall (Cai et al. 2014; Stern et
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al. 1996; Vatsos and Rebours 2014). The active substances released from the seaweeds help in
the defense mechanism, furanones were found to be the active substance released during the
virulence of many pathogenic organisms (Rutherford and Bassler 2012; Manefield et al. 2001).
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During sensing process, the inhibition against particular bacteria have been avoided as most of
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the commercial antibiotics cause resistance against the microorganisms (Defoirdt et al. 2006; Jha
et al. 2013; Dobretsov et al. 2009; Genovese et al. 2012; Cavalo et al. 2013).
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6.2. In vivo treatment using seaweed extracts in aquaculture

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Bacterial infections have been treated using numerous seaweed extracts which are
reported to have good antibacterial activity against most of the aquatic pathogens (Thanigaivel et
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al. 2015c).In vivo treatment with the extracts was carried out, and the survival rate was found to
be 90% during the treatment study. This result agrees with the results of (Thanigaivel et al. 2014,
2015 a, c). In our earlier report the treatment of P. aeruginosa, V. parahemolyticus infection in
fish and shrimp was carried out using seaweed extracts. These studies proved that the algal
extracts couldbe used for controlling the bacterial infection in fishes. Various studies revealed
the action of seaweed extracts against gram-negative bacteria such as A. salmonicida, C. freundii
and P. aeruginosa, V. parahemolyticus, V. harveyi, V. vulnificus and V. anguillarumfor the
treatment of fishes (Manilal et al. 2012; Thanigaivel et al. 2014).
The above-mentioned reports discussed the use of seaweed extracts and their bioactive
compounds for controlling bacterial infections. Among all the solvents used to enhance the yield
of antioxidant compounds, ethanol extract was found to be very effective in improving and

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sustaining the antioxidant activities achieved (Van Hai 2015; Mousavi et al. 2011; Thanigaivel et
al. 2015a). A diet mixture of equal proportions of different seaweed extracts and their
phytocompounds used in the treatment study provides an insight into the improvement of its
immune response and hematological parameters by enhancing the hemocyte counts, phenol

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oxidase, phagocytosis and haemagglutinin activities (Rajeswari et al. 2012; Lin et al. 2006).
The method of treating microbial disease described by (Yu et al. 2008) in fishes is

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problematic and is neither efficient nor cost-effective in some cases. A possible alternative

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method would be the use of bio-encapsulation technique for the treatment. Bio encapsulation
with live feed is an appropriate approach to introducing the extracts into the hosts such as

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Artemia (Immanuel et al. 2004). Artemia enriched with the butanolic extract from Withania
somnifera reduced V. parahaemolyticus and V. damsela infection in prawns (Praseetha 2005;
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Citarasu et al. 2003).
The biological matrices mediated encapsulation enhances the feed quality by improving
the sustainable release of antioxidant and antibacterial activities for prolonged periods by
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ensuring improved immune stimulation in aquatic animal health management. Cultivation of

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various fishes indirectly helps for the supplementation of nutrients to the seaweeds. Hence, the
seaweedextracts bio-encapsulated feeds support the environmental conditions and eco-friendly
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aquaculture management practices to control the infections in fish and molluscs as an effective
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alternative treatment strategy than the commercially available antibiotics (Citarasu et al. 2003).
Co-cultivation of microalgae is beneficial as it can lead to increased yield and decrease the risk
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of eutrophication by farm waste. For desiccation tolerant intertidal seaweeds such as Porphyra,
epiphyte control is achieved by exposing lines to the air, which kills desiccation tolerant
epiphytes and may enhance the nutrient uptake by the Porphyra upon re-submersion (Harrison
and Hurd 2001). (Immanuel et al. 2004) reported that the seaweed diet enriched Artemia fed to
P. indicus juveniles reduced the bacterial load in various organs (Takaoka et al. 2011) indicated
that the use of extract mixtures promoted the body weight. In another case the use of therapeutic
medication of extracts through the injection enhanced the immune parameters and disease
resistance (Harikrishnan et al. 2009a; Çek et al. 2007). Seaweed extracts are more efficient when
aqueous, and ethanol extracts are administered through immersion method (Rajendiran et al.
2008; Winberg et al. 2009)
7. Future areas which require new research

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Complete information on the quantitative nutrient requirement and disease prevention by

natural products such as bioactive compounds in most fishes is lacking. Therefore this is the hot
spot where future research needs to be carried out. Another important area where further research
need to focused is the controlled release of the bioactive compounds extracted from the seaweeds

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which are encapsulated in the form of effective aqua feeds. Its bioavailability in large scale
farming requires more attention.

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8. Inferences and future perspectives

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This detailed reviewdiscussed an overview of using seaweed extracts as an alternative
strategy to control infections in aquaculture. Marine macro algae which are readily available and

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inexpensive are the most suitable because they are not only useful but also harmless to beneficial
bacteria like probiotics. These natural immune stimulants which induce immune stimulant and
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anti pathogenic activity can be used instead ofsynthetic antibiotics which cause resistance to the
organisms. Hence, this bio-based mediated defense process is helpful when the pathogenic
organisms attack the fishes& shrimps leading to various symptoms and mass mortalities in
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farms. Moreover, the use of seaweed extracts based products for treatments in aqua farms is
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considered as a biodegradable and eco-friendly approach, since it maintains a clean aquatic

environment which directly and indirectly enhances the aquatic animal health. Marine seaweeds
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and their metabolites based treatment can control infections caused by the pathogenic organisms.
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The administration strategy of seaweed extracts depends on the bioactive compounds and its
controlled release in the aquatic environment which is most promisingly by dispersion. However,
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its bioavailability in large scale farming is yet to be studied. The use of seaweed extracts in a
colloidal mixture of two or more beneficial bioactive compounds for the treatment of bacterial
infections was studied in vivo and in-vitro in the laboratory. These substances probably act by
affecting the quorum sensing mechanism of bacteria limiting its growth (Thanigaivel et al.
2015a). While focusing on the prospects for controlling or treating the pathogenic infection in
fish farms and hatcheries, the wide range of bio based natural processes available need to be
given importance to ensure that the aquatic ecosystem remains clean and more productive.
Various bio-encapsulation techniques can also be developed by using the different biologically
synthesized matrices to deliver the desired compounds or secondary metabolites such as protein,
minerals, carbohydrates, fats, fibers and vitamins by integrating them into the models to ensure
that the best nutritional feeds for the growth of various fishes and shellfishes are available.

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Bioactive compounds extracted from the seaweeds which have antibacterial activity are
encapsulated. These extracts are added to the commercially available feeds (live or dry), to
stimulate immune response to act directly against the fish pathogens. This method of
encapsulation of the active fractions of seaweeds and its phyto compounds in the different

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matrices like Sodium caseinate and alginate needs to be popularized. In conclusion, we state that
the bioactive compounds encapsulated in the feed in the form of beads can be used for the

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treating bacterial infection in fish and shellfish aquaculture.

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Acknowledgement

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We thank VIT University, Vellore for providing facility to carry out the work

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Figure legend
Fig 1. Benefits of bio based extracts as a therapeutic approach

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Highlights

Seaweed extracts
Bacterial pathogens
Antioxidant

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Antibacterial

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prophylactics treatment

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