130 Marine Macro- and Microalgae: An Overview
infusion in patients with advanced pre-treated solid tumours is now complete (Pardo et al. 2008). A dose
limit was set due to the occurrence of toxicity symptoms, mainly acute transaminitis, which precluded
the administration of the compound in a weekly fashion; however, administration of this compound
led to the remarkable absence of bone marrow suppression, alopecia, and other organ toxicities. Such
early data suggests lack of cumulative toxicities that may allow chronic therapy. The pharmacokinetic
profile demonstrates a short terminal half-life, a finding supporting additional studies with longer infusion
schedules. Evidence of activity in pre-treated patients with melanoma (Martín-Algarra et al. 2009),
colorectal cancer, and hepatocellular carcinoma has also been reported (Jimeno et al. 2004). A phase II
trial in patients with advanced liver cancer is on-going and further studies in different tumour types has
been planned (Jimeno et al. 2004). A second phase I trial with a schedule of five drug administrations per
day in patients with androgen independent prostate cancer is also on-going and expanding the cohort of
patients at the recommended dose (Rademaker-Lakhai et al. 2005).
Neuroprotective activities
Dementia (from the Latin demens, meaning “without mind”) is a group of symptoms that may accompany
several neurological disorders. It occurs mainly in the elderly population and is characterized by the
progressive and permanent deterioration of neuronal processes and the loss of synaptic connections
(Selkoe 2002; Honer 2003; Parihar and Hemnani 2004; Tanzi 2005; Blennow et al. 2006; Scheff et al.
2006), which results in the decline of multiple cognitive functions, such as memory, language, thinking,
comprehension, and calculation. In 2030 it is estimated that 63 million people will suffer from dementia,
65% of which will be in less developed countries (Wimo et al. 2003). Dementia can be caused by several
degenerative neurological diseases, namely Alzheimer’s (AD), dementia with Lewy bodies, Parkinson’s,
and Huntington’s.
AD is the most common cause of senile dementia, and is estimated to account for 50–60% of
dementia cases among people age 65 or older (Filho et al. 2006). It has no cure and is the fourth leading
cause of death in developed nations, after heart disease, cancer, and stroke (Natarajan et al. 2009).
Pathologically, AD is characterized by extracellular deposits of plasma amyloid beta peptide (Aβ) in
senile plaques, intracellular formation of neurofibrillary tangles, and the loss of neuronal synapses and
pyramidal neurons (Weinreb et al. 2011). The molecular mechanism of AD can be explained by two
major hypotheses: the cholinergic hypothesis and the amyloid cascade hypothesis (Parihar and Hemnani
2004). The amyloid cascade theory suggests that the sequence of events leading to AD is initiated by
the deposition of the amyloid-β peptide in the brain parenchyma (Karran et al. 2011). Conversely, the
cholinergic premise postulates that the renewal of acetylcholine (ACh) levels, the major neurotransmitter
in the central nervous system (CNS), which are progressively lost during the progression of AD, delays the
loss of cognitive function (Filho et al. 2006). Therefore, one of the main strategies for symptomatic relief
of AD is the enhancement of the levels of ACh, which is hydrolized primarily by acetylcholinesterase
(AChE) and secondly by butyrylcholinesterase (BChE). The inhibition of AChE through the use of
AChE inhibitors (AChEi) has so far been considered the main approach for the symptomatic treatment
of several neurological disorders (e.g., AD, Parkinson disease, and myasthenia gravis), associated with
reduced ACh levels in the synapse (Whitehouse et al. 1983; Mukherjee et al. 2007). In fact, several
AChE inhibitors such as tacrine, donzepil, and galanthamine have been approved for the treatment of AD
(Racchi et al. 2004).
The search for new cholinesterase inhibitors (ChEi) among natural resources, especially plants, is
still however a growing area of investigation since the compounds mentioned above can display several
side effects. There are more than 180 natural compounds namely alkaloids, terpenoids, and flavonoids
with a direct relevance to AD therapeutics, mostly from plant origin (reviewed in Williams et al. 2011).
However, knowledge of AChE inhibitors from marine photosynthetic organisms is particularly scarce.
Recently, effort has been made to find AChEi from marine origin, namely from macroalgae. The
AChE inhibitory activity was evaluated on methanol extracts of seven macroalgae species (Caulerpa
racemosa var. laetevirens, Codium capitatum, Halimeda cuneata, Ulva fasciata, Amphiroa bowerbankii,
A. ephedraea, and Dictyota humifusa) collected from the east coast of South Africa (Stirk et al. 2007).
infusion in patients with advanced pre-treated solid tumours is now complete (Pardo et al. 2008). A dose
limit was set due to the occurrence of toxicity symptoms, mainly acute transaminitis, which precluded
the administration of the compound in a weekly fashion; however, administration of this compound
led to the remarkable absence of bone marrow suppression, alopecia, and other organ toxicities. Such
early data suggests lack of cumulative toxicities that may allow chronic therapy. The pharmacokinetic
profile demonstrates a short terminal half-life, a finding supporting additional studies with longer infusion
schedules. Evidence of activity in pre-treated patients with melanoma (Martín-Algarra et al. 2009),
colorectal cancer, and hepatocellular carcinoma has also been reported (Jimeno et al. 2004). A phase II
trial in patients with advanced liver cancer is on-going and further studies in different tumour types has
been planned (Jimeno et al. 2004). A second phase I trial with a schedule of five drug administrations per
day in patients with androgen independent prostate cancer is also on-going and expanding the cohort of
patients at the recommended dose (Rademaker-Lakhai et al. 2005).
Neuroprotective activities
Dementia (from the Latin demens, meaning “without mind”) is a group of symptoms that may accompany
several neurological disorders. It occurs mainly in the elderly population and is characterized by the
progressive and permanent deterioration of neuronal processes and the loss of synaptic connections
(Selkoe 2002; Honer 2003; Parihar and Hemnani 2004; Tanzi 2005; Blennow et al. 2006; Scheff et al.
2006), which results in the decline of multiple cognitive functions, such as memory, language, thinking,
comprehension, and calculation. In 2030 it is estimated that 63 million people will suffer from dementia,
65% of which will be in less developed countries (Wimo et al. 2003). Dementia can be caused by several
degenerative neurological diseases, namely Alzheimer’s (AD), dementia with Lewy bodies, Parkinson’s,
and Huntington’s.
AD is the most common cause of senile dementia, and is estimated to account for 50–60% of
dementia cases among people age 65 or older (Filho et al. 2006). It has no cure and is the fourth leading
cause of death in developed nations, after heart disease, cancer, and stroke (Natarajan et al. 2009).
Pathologically, AD is characterized by extracellular deposits of plasma amyloid beta peptide (Aβ) in
senile plaques, intracellular formation of neurofibrillary tangles, and the loss of neuronal synapses and
pyramidal neurons (Weinreb et al. 2011). The molecular mechanism of AD can be explained by two
major hypotheses: the cholinergic hypothesis and the amyloid cascade hypothesis (Parihar and Hemnani
2004). The amyloid cascade theory suggests that the sequence of events leading to AD is initiated by
the deposition of the amyloid-β peptide in the brain parenchyma (Karran et al. 2011). Conversely, the
cholinergic premise postulates that the renewal of acetylcholine (ACh) levels, the major neurotransmitter
in the central nervous system (CNS), which are progressively lost during the progression of AD, delays the
loss of cognitive function (Filho et al. 2006). Therefore, one of the main strategies for symptomatic relief
of AD is the enhancement of the levels of ACh, which is hydrolized primarily by acetylcholinesterase
(AChE) and secondly by butyrylcholinesterase (BChE). The inhibition of AChE through the use of
AChE inhibitors (AChEi) has so far been considered the main approach for the symptomatic treatment
of several neurological disorders (e.g., AD, Parkinson disease, and myasthenia gravis), associated with
reduced ACh levels in the synapse (Whitehouse et al. 1983; Mukherjee et al. 2007). In fact, several
AChE inhibitors such as tacrine, donzepil, and galanthamine have been approved for the treatment of AD
(Racchi et al. 2004).
The search for new cholinesterase inhibitors (ChEi) among natural resources, especially plants, is
still however a growing area of investigation since the compounds mentioned above can display several
side effects. There are more than 180 natural compounds namely alkaloids, terpenoids, and flavonoids
with a direct relevance to AD therapeutics, mostly from plant origin (reviewed in Williams et al. 2011).
However, knowledge of AChE inhibitors from marine photosynthetic organisms is particularly scarce.
Recently, effort has been made to find AChEi from marine origin, namely from macroalgae. The
AChE inhibitory activity was evaluated on methanol extracts of seven macroalgae species (Caulerpa
racemosa var. laetevirens, Codium capitatum, Halimeda cuneata, Ulva fasciata, Amphiroa bowerbankii,
A. ephedraea, and Dictyota humifusa) collected from the east coast of South Africa (Stirk et al. 2007).