120 Marine Macro- and Microalgae: An Overview
The most frequently used assays to evaluate the anti-inflammatory activity of natural compounds can
be divided into in vitro and in vivo tests. The in vitro tests involve the (i) assessment of effects on the AA
metabolism (COX and lipoxygenase [LOX] pathways), and/or the (ii) presence of different eicosanoids
(prostaglandins [PGs] and leukotrienes [LTs]) in various cells; (iii) the effects on cytokines production
(lipopolysaccharide [LPS]-induced IL-1β and TNF-α); (iv) the modulation of pro-inflammatory gene
expression of NO, and isoforms of the NO synthase (NOS): constitutive (cNOS), endothelial (eNOS),
the inducible (iNOS) NOS; and also (v) signalling pathways where the NF-κB transcription factor and
mitogen-activated protein kinases (MAPKs) play an important role (Miguel 2010). The in vivo models
include, among others, granuloma models and oedema induction via, for example, carrageenan (Souto
et al. 2011).
Natural products and folk medicine are an important field in the search for bioactive compounds
and development of drugs for the treatment of inflammation (Gautam and Jachak 2009). Algal natural
products have already been shown to inhibit pro-inflammatory mediators, suggesting their potential in
the inflammation treatment (Pangestuti and Kim 2011). As algae are normally exposed to high light and
oxygen concentrations, which can trigger the accumulation of inflammatory molecules (NO and ROS)
in vertebrate cells, it is likely that they have evolved biochemical mechanisms for their own protection
against external stressors. This fact makes them a potential source of antioxidant and anti-inflammatory
compounds (Heo et al. 2010). Table 2 provides an overview of compounds displaying anti-inflammatory
properties identified in different marine algae. A set of 9 groups of compounds was identified in 20 species
belonging to 9 different families. Among these biochemicals, pigments are one of the most representative
group of bioactive compounds namely pheophytin, fucoxanthin, and a fucoxanthin derivative, which
have been shown to reduce the production of NO, PGE 2 , and pro-inflammatory cytokines. These
pigments were isolated from five species belonging to four different families (Table 2). Crude sulphated
polysaccharides, such as fucan and fucoidan, isolated from the Sargassaceae and Lessoniaceae families,
also displayed anti-inflammatory activity measured by the carregenan permeability oedema (CPO) and
vascular permeability tests, NO production in LPS-induced macrophages and transcriptional analysis
of inflammatory mediator assays (Ananthi et al. 2010; Dore et al. 2012; Lee et al. 2012). Furthermore,
the sesquiterpenes pacifenol and prepacifenol found in three species of the Laurencia genus were able
to inhibit leukotriene B4 (LTB4) and thromboxane B2 (TXB2) production, modulate the COX pathway,
and inhibit phospholipase A 2 (D’Orazio et al. 2012). In addition, the anti-inflammatory flavonoids
catechol, hesperidin, rutin, and stypotriol triacetate were found in the rhodophyte Porphyra dentata and
the ochrophyte Stypopodium flabelliforme (Kazłowska et al. 2010; Jaswir and Monsur 2011; D’Orazio
et al. 2012).
Anti-proliferative activity
The balance between cell division and cell death is a basic feature in the development and maintenance
of the body homeostasis. Disturbances in this balance can cause disease: too much cell death can cause
injury, but too little of it is a prerequisite for cancer development (Elmore 2007). Thus, a tight control
of the equilibrium between cell survival and death is necessary. Under typical conditions, this balance is
maintained by tightly regulating both processes. However, when one or both processes are deregulated,
cancer may ensue.
Andreeff et al. (2003) state that cancer is primarily the accumulation of clonal cells, leading
to therapies that consist in (1) trying to reduce the number of tumour cells and (2) preventing their
accumulation, either by stimulating cancer cell death (preferentially by apoptosis) or via cytostatic
effects. There is a need for improving existing therapies as well as searching for new drugs that provide
higher survival rates and lower the impact of side effects.
Several biomolecules with proved anti-proliferative activity are presented in Table 3. These
molecules act via different cell mechanisms, described below, and present a diverse array of chemical
structures, including phenols, alkaloids, terpenoids, polyesters and other secondary metabolites (Cabrita
et al. 2010; El Gamal 2010; Güven et al. 2010; Liu et al. 2011; Wijesekara et al. 2011).
The most frequently used assays to evaluate the anti-inflammatory activity of natural compounds can
be divided into in vitro and in vivo tests. The in vitro tests involve the (i) assessment of effects on the AA
metabolism (COX and lipoxygenase [LOX] pathways), and/or the (ii) presence of different eicosanoids
(prostaglandins [PGs] and leukotrienes [LTs]) in various cells; (iii) the effects on cytokines production
(lipopolysaccharide [LPS]-induced IL-1β and TNF-α); (iv) the modulation of pro-inflammatory gene
expression of NO, and isoforms of the NO synthase (NOS): constitutive (cNOS), endothelial (eNOS),
the inducible (iNOS) NOS; and also (v) signalling pathways where the NF-κB transcription factor and
mitogen-activated protein kinases (MAPKs) play an important role (Miguel 2010). The in vivo models
include, among others, granuloma models and oedema induction via, for example, carrageenan (Souto
et al. 2011).
Natural products and folk medicine are an important field in the search for bioactive compounds
and development of drugs for the treatment of inflammation (Gautam and Jachak 2009). Algal natural
products have already been shown to inhibit pro-inflammatory mediators, suggesting their potential in
the inflammation treatment (Pangestuti and Kim 2011). As algae are normally exposed to high light and
oxygen concentrations, which can trigger the accumulation of inflammatory molecules (NO and ROS)
in vertebrate cells, it is likely that they have evolved biochemical mechanisms for their own protection
against external stressors. This fact makes them a potential source of antioxidant and anti-inflammatory
compounds (Heo et al. 2010). Table 2 provides an overview of compounds displaying anti-inflammatory
properties identified in different marine algae. A set of 9 groups of compounds was identified in 20 species
belonging to 9 different families. Among these biochemicals, pigments are one of the most representative
group of bioactive compounds namely pheophytin, fucoxanthin, and a fucoxanthin derivative, which
have been shown to reduce the production of NO, PGE 2 , and pro-inflammatory cytokines. These
pigments were isolated from five species belonging to four different families (Table 2). Crude sulphated
polysaccharides, such as fucan and fucoidan, isolated from the Sargassaceae and Lessoniaceae families,
also displayed anti-inflammatory activity measured by the carregenan permeability oedema (CPO) and
vascular permeability tests, NO production in LPS-induced macrophages and transcriptional analysis
of inflammatory mediator assays (Ananthi et al. 2010; Dore et al. 2012; Lee et al. 2012). Furthermore,
the sesquiterpenes pacifenol and prepacifenol found in three species of the Laurencia genus were able
to inhibit leukotriene B4 (LTB4) and thromboxane B2 (TXB2) production, modulate the COX pathway,
and inhibit phospholipase A 2 (D’Orazio et al. 2012). In addition, the anti-inflammatory flavonoids
catechol, hesperidin, rutin, and stypotriol triacetate were found in the rhodophyte Porphyra dentata and
the ochrophyte Stypopodium flabelliforme (Kazłowska et al. 2010; Jaswir and Monsur 2011; D’Orazio
et al. 2012).
Anti-proliferative activity
The balance between cell division and cell death is a basic feature in the development and maintenance
of the body homeostasis. Disturbances in this balance can cause disease: too much cell death can cause
injury, but too little of it is a prerequisite for cancer development (Elmore 2007). Thus, a tight control
of the equilibrium between cell survival and death is necessary. Under typical conditions, this balance is
maintained by tightly regulating both processes. However, when one or both processes are deregulated,
cancer may ensue.
Andreeff et al. (2003) state that cancer is primarily the accumulation of clonal cells, leading
to therapies that consist in (1) trying to reduce the number of tumour cells and (2) preventing their
accumulation, either by stimulating cancer cell death (preferentially by apoptosis) or via cytostatic
effects. There is a need for improving existing therapies as well as searching for new drugs that provide
higher survival rates and lower the impact of side effects.
Several biomolecules with proved anti-proliferative activity are presented in Table 3. These
molecules act via different cell mechanisms, described below, and present a diverse array of chemical
structures, including phenols, alkaloids, terpenoids, polyesters and other secondary metabolites (Cabrita
et al. 2010; El Gamal 2010; Güven et al. 2010; Liu et al. 2011; Wijesekara et al. 2011).