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154
Plant-based Foods and their Implications in Brain Health
According to
[23]
, In 2019, 132 agents were enrolled in 156 anti- AD therapy trials, with 28 in
phase III, 74 in phase II, and 30 in phase I. 19 Agents targeted cognitive enhancement, 14 targeted
neuropsychiatric and behavioural indications, and 96, the common, aimed to convert a DMT with
amyloid as their primary target.
In 42 phase III clinical studies, 28 drugs are currently being evaluated. Eight drugs (AVP- 786,
nabilone, escitalopram, AXS- 05, methylphenidate, brexpiprazole, zolpidem, and mirtazapine) target
neuropsychiatric symptoms such apathy, agitation, and sleep disturbances, while three molecules
are being explored as symptomatic cognitive enhancers (guanfacine, octohydroaminoacridine
succinate, ginkgo biloba). Three have neuroprotective qualities (E- EPA, ACB101, BHV4157),
atorvastatin) in relation to DMT. Nine of the drugs are anti- amyloid (aducanumab, solanezumab,
cad106, gantenerumab, crenezumab, E2609, etc.), one is anti- tau (TRx0237), and one is both anti-
amyloid and anti- tau
[23]
.
Drug development in AD has centred on DMT therapies in recent years, with the goal of changing
the disease process by affecting distinctive brain alterations. Several entrants failed to go through
FIGURE 8.1 Five medicines have been licenced for the treatment of Alzheimer’s disease: Tacrine, Donepezil,
Galantamine, and Rivastigmine, are four acetylcholinesterase inhibitors (AChEI). Memantine, an NMDA
receptor antagonist.
155
Marine Plant Species: Nutritional and Medicinal Value
clinical trials, and no DMTs were found to make a substantial alteration in phase III clinical trials
or acquired marketing authorisation
[24]
. The amyloid hypothesis is the most researched; however,
approaches, like combination therapy
[23]
approach
[25]
. The methodologies for identifying a promising treatment for Alzheimer’s disease will
be explored in this chapter. Marine natural products (MNPs) have outperformed other types of nat-
ural products (NPs) in clinical trials. Two further emerging techniques in AD medication research,
polypharmacology and drug repurposing, will be highlighted together with the most promising
MNPs in the pipeline for AD treatment. There will also be examples of drugs from this approach
that have shown to have potential activity and are currently being researched.
8.12 MARINE NATURAL PRODUCTS
The seas, which span 70% of the earth’s surface and are a source of primary minerals and bioactive
compounds with a wide range of applications, are the cradle of life and home to a broad range
of marine species
[35,36]
. More than 10,000 natural compounds with biotechnological potential have
micro- and macroalgae, bacteria, sponges, gorgonians, bryozoans, sea cucumbers, nudibranchs,
tunicates, and sea hares, among other marine organisms)
[37]
. As secondary metabolites involved in
defensive/ offensive mechanisms, these bioactive chemicals are the product of these species’ required
[38]
. Microorganisms such as bacteria, protozoa, fungi,
and microalgae currently account for 38% of marine chemicals with pharmacological action
[31]
. About
20% comes from marine sponges and corals, with a focus on the Porifera phylum, which includes
[39]
.
Secondary metabolites from both terrestrial and marine organisms are valuable sources for
novel medication development. Approximately half of all medications put into the market in the
last 20 years were derived straight from tiny molecules of natural origin
[28]
. Current research has
discovered that, midst NP’s many biological actions, neuroprotective activity is a particularly bene-
[10]
. The popular medications derived
from natural creatures come from land- based bases
[28]
. Marine species, on the other hand, can be
regarded as the most recent source of bioactive chemicals from an industrial standpoint. Because
of the connection of a vast genetic variety of species with an enormous molecular and ecological
diversity, oceans offer an exclusive and abundant basis of valuable active chemicals, notably for
the pharmaceutical company. Marine creatures must constantly adjust to changing physicochemical
qualities like pressure, salt content, temperature, radiation exposure, light penetration, and oxygen
concentration in order to thrive. As a result, they can produce a wide range of metabolites, from
simple molecules to more complicated compounds such as peptides and enzymes, which are com-
monly utilised to immobilise and trap predators
[29]
.
-
ural sources
[30]
. Since new sample collection techniques, spectrometric techniques, and separation
procedures have been developed, the exploration of the marine environment has increased
[31]
.
Marine chemicals are increasingly being studied, foremost for the development of novel chem-
[28,32]
.
Alkaloids, phenolic chemicals, terpenoids, carotenoids, sterols, and polysaccharides derived
from bacteria, fungi, algae, and weeds have a variety of biological activity and health advantages.
Tables 8.1, 8.2, and 8.3 show the structure of various chemical compounds isolated from marine
156
Plant-based Foods and their Implications in Brain Health
TABLE 8.1
The structure of various chemical compounds isolated from marine sources of bacteria
Bacteria
Marine source
Scientific
name Source of collection
Chemical
compound isolated Nature of chemical Chemical structure Mechanism of action Results of animal studies References
marine bacteria Rapidithrix
thailandica
isolated from a decomposed
wood, which was collected from
the Andaman Sea in Thailand
Marinoquinoline A Alkaloids (quinoline
derivative)
strains TISTR
1742
R. thailandica isolated from a submerged
sea grass blade, which was
collected from the Andaman
Sea
3- (2´- aminophenyl)-
pyrrole
Alkaloids (pyrrole
derivatives)
SH5.13.2 isolated from a submerged sea
grass blade, from a debris,
which was collected from the
Gulf of Thailand
2,2- dimethylpyrrolo-
1,2- dihydroquinoline
marine bacteria Saccharomonos-
pora sp.
isolated from the saline culture of
a marine bacteria
saccharochlorines A Phenolics (chlorinated
phenolic metabolites)
saccharochlorines B
marine
cyanobacterium
Symploca sp. Tasiamide B Peptides (containing
eight amino acid
residues)
157
Marine Plant Species: Nutritional and Medicinal Value
show an effective AChE
inhibitory activity, IC
50
= 4.9 µM (IC
50
of galantamine = 0.6 µM)
127
enzyme inhibition showed = < 30 %
at 0.1 g/ L)
127
Showed weak inhibition of
BACE- 1 activity = 42.4% and
32.0% inhibition, respectively
concentration was 50 µM
128
showed inhibition of BACE- 1 with
IC
50
= 353 nM
129, 130
(continued)
158
Plant-based Foods and their Implications in Brain Health
Bacteria
Marine source
Scientific
name Source of collection
Chemical
compound isolated Nature of chemical Chemical structure Mechanism of action Results of animal studies References
marine
cyanobacterium
Lyngbya sp Tasiamide F Peptides (containing
eight amino acid
residues)
Streptomyces
griseus
isolated from a deep- sea sediment
which was collected from the
Canary Basin
benzoxacystol 1,4- benzoxazine in vitro inhibitory activity
Gram- positive
bacteria
Amycolatopsis,
Salinispora
Rifamycin predictable anti- infectious activity,
Streptomyces Anhydroexfolia-
mycin
Undecylprodi-
gioisin
Phylum
Actinobacteria
Streptomyces
caniferus
Caniferolide A Polyol macrolides
TABLE 8.1 (Continued)
The structure of various chemical compounds isolated from marine sources of bacteria
159
Marine Plant Species: Nutritional and Medicinal Value
inhibited BACE- 1 activity (IC
50
= 690
nM)
131
with IC
50
= 1.35 µM
132
also displayed substantial
neuroprotective activity in several
experiments
133, 134
In an oxidative
damage model, their effects were
demonstrated in primary cortical
neurons, suggesting
their capacity to decrease the levels of
reactive oxygen species (ROS) and
to improve the
antioxidant defences via elevation of
the glutathione levels and catalase
activity.
135
action.
Blockade of the BACE- 1 enzyme.
136
160
Plant-based Foods and their Implications in Brain Health
TABLE 8.2
The structure of various chemical compounds isolated from marine sources of fungus
Fungus
Sl. No. Marine source Scientific name Source of collection Chemical compound isolated Nature of chemical Chemical structure Mechanism of action References
1. TK- 43, an
endophytic fungus
Acrostalagmus
luteoalbus
obtained from a marine green alga
Codium fragile, collected in
Turkey
Acrozines A Alkaloids (N-
Acrozines B anti- AChE
Acrozines C anti- AChE
2. racemic mixture
from a marine-
derived fungus
Penicillium
commune
366606
isolated from seawater, collected in
China
Penicillamine Alkaloids potent anti- AChE activity
3. mangrove
endophytic fungus
Penicillium
chemesinum
ZH$- E2
Isolated from the stem of the
mangrove plant Kandelia candel,
and isolated from the ethyl acetate
extract of cultures, which was
collected from the South China
Sea.
O- desmethylter-
phenyllin
desmethylterphenyllin
desmethylcandidusin B
161
Marine Plant Species: Nutritional and Medicinal Value
methoxyindoledi
ketopiperazine
derivatives)
anti- AChE
activity (IC50 = 9.5 µM)
137
activity (IC50 = 60.7 µM)
activity
(IC50 = 130.5µM)
potent anti- AChE activity
(32.4% inhibition)
138
Phenolics
(p- terphenyls)
inhibitory activity against
AChE with IC
50
= 7.8
and 5.2 µM,
139
(continued)
162
Plant-based Foods and their Implications in Brain Health
Fungus
Sl. No. Marine source Scientific name Source of collection Chemical compound isolated Nature of chemical Chemical structure Mechanism of action References
4. Seaweed allied
fungus
Aspergillus
unguis
DLEP2008001
collected from the South China Sea,
and from the plasma- induced
mutant of the fungus
Aspergillusidone A Phenolics AChE inhibition with
5. marine sponge-
associate fungus
Talaromyces sp.
strain LF458
isolated from
tissues of a marine sponge
Axinella verrucose, extracts of
a culture broth and mycelia,
which was collected at Punta
di Fetovaia, Isle of Elba
(Mediterranean Sea) Italy
Talaromycesone A Phenolics (anti- AChE
Talaroxanthenone Phenolics (isopentenyl
6. deep sea- derived
fungus
Ochroconis sp.
FS449
methanol extract of a fermentation
broth, isolated from a sediment
collected from the Indian Ocean
Ochuscins B Phenolics (highly
Ochuscins D
Ochuscins G
7. Isolated from a
culture of a
mangrove- allied
fungus
Colletotrichum
sp. SCSIO
KcB3- 2
obtained from a mangrove plant
K. candel, which was collected in
Guangdong Province, China
Bisabolanoic acid A Terpenoids (polychiral
8. Isolated from a
culture of an
endophytic fungus
Aspergillus avus isolated from the inner tissue of
a marine red alga Corallina
ofcinalis, which was collected
from the coast of Yantai, China
methoxyergosta- 7,24(28)-
dien- 6- one
Episterol,
(22E,24R)- ergosta- 7,22- dien-
TABLE 8.2 (Continued)
The structure of various chemical compounds isolated from marine sources of fungus
163163
Marine Plant Species: Nutritional and Medicinal Value
AChE inhibition with
IC
50
= 56.8 µM
140
metabolites viz.
oxaphenalenone
dimer)
IC
50
= 7.49 µM 141
xanthenone)
AChE with IC
50
= 1.61
µM
oxygenated usnic
acid derivatives)
displayed moderate anti-
AChE activity, with
IC
50
= 50 to 75 µM
142
bisabolane
sesquiterpene)
moderate inhibition of
AChE activity with
IC
50
= 2.2 µM
143
Terpenoids (Sterols) AChE inhibitory activity 144
(continued)