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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5264_Библиотеки_им_академика_М_И_Перельмана.pdf
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Plant-based Foods and their Implications in Brain Health
both at the C- 24 position. Plant cell walls contain phytosterols, which are structurally like human
cholesterol [64]. Plants produce more than 250 phytosterols, and each plant species has a different
are campesterol, stigmasterol, and sitosterol. The C- 5 and C- 6 carbon positions in phytosterols’
and a functional group called hydroxyl. These compounds were initially created as fatty acids,
barrier (BBB) and build up in the brain. As a result, they may play a crucial part in altering several
brain circuits related to neurodegeneration [65]. Some of the derivatives of phytosterols are given
in Figure 12.4.
12.2.6 CardiaC glyCoSide
These secondary metabolites of bioactive phytocompounds have a steroid backbone connected by
a lactone ring at carbon position C- 17b and a sugar moiety and sugar unit at carbon position 3- b
(Figure 12.5). The varied class of naturally occurring substances known as cardiac glycosides is
well- known for its capacity to bind to and block the salt pump. Aldehyde, hydroxyl, and methyl
functional groups are attached to the steroid nucleus and are responsible for their biological activity
[66]. Cardiac glycosides and their derivatives have long been utilized to treat atrial arrhythmia
and heart failure (Figure 12.5) [67]. Recent research describes additional sodium pump signal-
ling pathways and links cardiac glycosides to control numerous critical physiological functions,
68].
12.3 PHYTOCHEMICAL EXTRACTION TECHNIQUES
extracted from medicinal plants and herbs to separate them from their matrix, inert or inactive
FIGURE 12.3 Basic molecular structure and derivatives of terpenoids.
245
Plant Phytochemicals as Therapeutics in Neurological Disorders
material is called extraction [69]. Several methods are used to extract these metabolites, including
maceration, infusion, decoction, percolation, digestion, Soxhlet extraction, ultrasound- assisted
extraction, microwave- assisted, hydrodistillation, and enzyme- assisted extraction [70]. Using thin-
layer chromatography (TLC), high- performance liquid chromatography (HPLC), and gas chro-
FIGURE 12.4 Phytosterols and their derivatives.
FIGURE 12.5 Major cardiac glycosides.
246
Plant-based Foods and their Implications in Brain Health
ratio all play a role in determining the optimum extraction procedure [71, 72]. Thus, the commonly
used conventional and modern methods in the extraction of medicinal plants are:
12.3.1 Conventional methodS for extraCtion
Maceration:
such as leaves, stem bark and root taken in a container. The solvent or menstruum is poured into it
which completely dissolves the powdered material. The solution is kept for few days and agitated
regularly on some time intervals to speed up the extraction process. Filtration or decantation is used
at the extraction end to separate the micelle from the marc (unwanted or insoluble substances). In
an oven or on top of a water bath, the micelle is evaporated to separate it from the menstruum. This
approach is practical and appropriate for phytochemicals that are thermolabile in nature [73].
Infusion: This is a method of extraction similar to maceration, where the drug substance is
reduced to a powder form and put into a clean container. The drug material is covered with the hot
or cold extraction solvent, which is then left to soak for a brief time. This technique works well for
extracting easily soluble bioactive components. It is also a suitable method for making fresh extract
before usage. Depending on the intended purpose, the solvent- to- sample ratio is typically 4:1 or
16:1 [70, 69].
Digestion: With this extraction technique, the extraction procedure uses a modest amount of
heat. Powdered material is added to a clean container after the extraction solvent. At a tempera-
ture of around 50
°
C, the mixture is put over a water bath or in an oven. Throughout the extraction
procedure, heat was used to reduce the solvent’s viscosity and improve the removal of secondary
metabolites. Plant materials that are easily soluble lend themselves to this approach well [74].
Decoction: This procedure uses the given amount of water as a solvent for continuous hot extrac-
tion. Plant material that has been dried, processed and powdered is added to a spotless container.
After that, water is added and mixed. The extraction is then accelerated by using heat throughout the
process. The procedure just takes a few minutes typically around 15 minutes to complete. Typically,
the ratio of solvent to crude medication is 4:1 or 16:1. It is employed to extract plant material that is
both heat- and water- soluble [75, 69].
Percolation: The tool used in this procedure is a percolator, a thin glass jar with openings on
extraction solvent. Filtration is used to separate the extract, followed by decantation. After the marc
has been expressed, the remaining solvent is added to get the necessary volume.
Soxhlet extraction: The glass- based device is known as a Soxhlet extractor which is a round-
with the extraction solvent before the thimble is placed within the extraction chamber. The solvent is
extraction chamber, and by coming into touch with the drug, extracts it. As a result, the solvent and
reaches the top of the syphon. The entire procedure is repeated up until the point at which a solvent
running out of the extraction chamber leaves no trace of any residual medication. Plant materials
with insoluble contaminants, as well as plant materials that are only partially soluble in the selected
solvent, can be used in this approach. For plant materials that are thermolabile, it is an inadequate
approach. A tiny amount of solvent can be used to extract a lot of medication. Plant materials that
technique is inappropriate for materials that are thermolabile and regular shaking is not achievable
[76, 70].
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Plant Phytochemicals as Therapeutics in Neurological Disorders
12.3.2 modern methodS for extraCtion
Microwave- assisted extraction: The method employs the displacement of charged ions found in the
solvent and drug material as well as the dipole rotation and ionic transfer mechanisms. This tech-
MHz and 300 GHz and wavelengths between 1 cm and 1 m is used in this process. Energy produced
by the microwaves started from 300 W and ranged up to 1 kW. The process exposes an object to
microwave radiation, which has the potential to absorb electromagnetic energy and convert it to
heat. The heat created as a result makes it easier for the solvent to enter the drug matrix. The micro-
wave extraction assembly comprises four primary elements: a magnetron/ microwave generator for
microwave production, a Wave Guide for directing microwaves from the source to the microwave
cavity, an applicator for holding the sample holder containing the sample, and a circulator for regu-
lating the forward propagation of microwaves. Dipole rotation and ion migration that boost solvent
penetration and aid in the extraction process happen when the polar solvent is utilized (Figure 12.6).
Nonpolar solvents are not recommended for this procedure since they will reduce the amount of
heat produced by the microwave radiation when employed. Microwave- assisted extraction provides
involved, substances like tannins and anthocyanins may be destroyed [79, 78, 77].
FIGURE 12.6 Microwave- assisted extraction system [77]. Copyright ©Saifullah et al. (2021), Processes,
2021, 9(12), 2212; https:// doi.org/ 10.3390/ pr9122 212.
248
Plant-based Foods and their Implications in Brain Health
Ultrasound- assisted extraction. In this method, sound energy is used at a very high frequency of
more than 20 kHz to damage plant cell walls and increase the drug’s surface area for solvent pene-
tration. Secondary metabolites will consequently be released. In this procedure, plant material must
then placed into the ultrasonic extractor along with a suitable solvent for extraction. By lowering the
amount of heat needed, the high sound energy speeds up the extraction process. Advantages. Small
samples can be extracted using ultrasound; it maximizes yield while cutting down on extraction time
and solvent use. It is challenging to replicate this procedure, because using much energy may cause
the phytochemical to deteriorate by generating free radicals [82, 80, 81].
12.3.2.1 Supercritical Fluid Extraction
When separate liquid and gas phases do not exist, any material above its critical temperature and
gas and then dissolve substances like typical liquids. The density- dependent selectivity of super-
83]. In their sub- and supercritical forms, ethanol, water, butane, propane, and
and non- polluting, as well as being readily available, carbon dioxide is recommended for utilisa-
tion. Due to the fact that CO
2
is a gas at standard temperature and pressure and is therefore readily
eliminated after the extraction, using pressurized CO
2
ensures that there are no chemical leftovers
in the extract [84].
Technically, several methods were employed in the extraction of medicinal herbs, while some
more recent techniques are still developing, and those already in use are changing. The selec-
tion of an effective extraction method is crucial and, in certain situations, relies on the intended
application of an extract [85]. Heat- stable plant material is extracted using Soxhlet or microwave-
assisted extraction, whereas plant materials that are not heat- stable are extracted using maceration
or percolation. If the solvent of extraction is water, maceration is a suitable method, but for vola-
tile solvents, percolation and Soxhlet extraction are more appropriate. Cheap drugs are extracted
using maceration, whereas costly drugs are preferably extracted using percolation. Maceration
is suitable for plant material requiring long exposure to the menstruum, whereas microwave- or
ultrasound- assisted extraction techniques are used for a shorter duration. Large- volume products
such as tinctures are prepared by maceration, whereas concentrated products are produced by perco-
lation or Soxhlet extraction. Extracts intended for consumption by humans are usually prepared by
maceration, whereas products intended for experimental testing are prepared using other methods in
addition to maceration [86, 87, 88].
12.4 PROMISING PHYTOCHEMICALS FOR PROMINENT DRUG TARGET IN
NEUROLOGICAL DISORDERS
12.4.1 phytoChemiCalS aS aCetylCholineSteraSe (aChe) and butyrylCholineSteraSe
(bChe) inhibitorS in alzheimer’S diSeaSe (ad)
Inhibiting the activity of the cholinesterase enzymes (AChE and BuChE) is the principal purpose
of cholinesterase inhibitors. This contributes to raising the ACh levels in the brain, which enhances
central cholinergic activity. The cholinergic synapses are the primary location of the acetylcholin-
esterase (AChE) and Butrylcholinterase (AChE) enzymes, and as AChE levels fall and BChE level
rises, the progression of Alzheimer’s disease advances. BChE has less impact in controlling acetyl-
choline levels compared to AChE but is still a crucial part of the pathogenesis of AD. Therefore, the
inhibition of cholinesterase enzymes is one of the prime treatments for the suppression or delaying
of Alzheimer’s disease progression, as shown in Figure 12.7 [89, 90].
249
Plant Phytochemicals as Therapeutics in Neurological Disorders
Bioactive phytocompounds group alkaloids have been extensively studied for their cholinesterase
inhibition activity, which leads to the suppression of Alzheimer’s disease. A six- membered aromatic
of heterogeneous secondary metabolites known as indole alkaloids that inhibit the activity of AChE.
Berberine, a benzylisoquinoline alkaloid isolated from Berberis darwinii, was found to inhibit the
91].
Indole alkaloids like rescinnamine, obtained from Rauvola reexa and harmane, 3- Hydroxylated
harmine, harmol, harmine, 1- Hydroxy- 7- methoxy- carboline, and harmaline, obtained from Peganum
harmala were found to be potent cholinesterase inhibitors with having the IC50 1.21 µM to higher
than10 µM [92, 93]. Eserine, another alkaloid obtained from Physostigma venenosum Balf., is
94]. The alkaloids
galantamine, caranine, N- demethylgalanthamine, and lycoramine obtained from the leaves, roots,
and bulbs of Zephyranthes, Habranthus, and Crinum have shown their inhibitory activity for acetyl-
cholinesterase enzyme [95
conjugate, rutin, have been reported for the cholinesterase inhibition, suppression of Fe
2+
- induced
lipid peroxidation and radical scavenging activities in rat brain homogenates in the concentration
range 0.06 to 0.6 mM. Quercetin has shown higher AChE and BChE inhibition activities than rutin.
It has also shown a strong Fe
2+
chelating ability and higher radical scavenging capacity than rutin. It
has been suggested that the control of oxidative stress- induced neurodegeneration may be aided by
96]. Other phenolic
compounds like resveratrol, curcumin, gallocatechin, cinnamic acid, and caffeic acid were found
97, 98, 99, 100, 101,
102
acetylcholinesterase inhibition. Abietane diterpenoids compounds, 12- O- demethylcrptojaponol and
FIGURE 12.7 An overview of the cholinesterase hypothesis and inhibition of AChE and BuChE [90].
Copyright©Lai Shi Min et al. (2022), Biology 2022, 11(2), 307. https:// doi.org/ 10.3390/ biol ogy1 1020 307.
250
Plant-based Foods and their Implications in Brain Health
6- hydroxydemethylcryptojaponol obtained from Caryopteris mongolica have shown inhibitory
activities against AChE and BuChE in which 6- hydroxydemethylcryptojaponol inhibited both AChE
and BuChE (AChE IC50 = 50.8 µM, BuChE IC50 = 70.1 µM) while 12- O- demethylcrptojaponol
militrone, cryptotanshinone, 1,2- didehydromiltirone Caryopteris mongolica, Perovskia atriplicifolia,
Salvia Glutinosa, and Lycopodiastrum Casuarinoides have demonstrated notable AChE and BuChE
inhibition activities [104, 105]. The phytosterols did not seem to contribute much to the cholin -
esterase activity since the mature fronds’ BChE inhibitory impact was >10 times less than that of the
impact on either AChE or BuChE [106].
12.4.2 phytoChemiCalS aS nrf2 aCtivatorS in autiSm SpeCtral diSorder (aSd)
The autism spectrum disorder is a complicated illness with behavioural side effects and comorbid
conditions, including anxiety, epilepsy, gastrointestinal issues leading to gut dysbiosis, oxidative
stress, mitochondrial dysfunction, and biochemical changes [107
ties have the potential to exacerbate biochemical and behavioural issues. No therapeutic cure has
been recognized to treat the disease, but signs like self- mutilation, animosity, monotonous and
stereotyped behaviours, carelessness, hyperactivity, and resting disarranges can be treated util-
izing medications [108
dative dysfunction stress all impact the development of ASD [109]. Nrf2 (nuclear factor erythroid
2 related factors 2), a universal master transcription factor, controls the production of antioxidant
enzymes and cytoprotective proteins via the antioxidant response elements (AREs) pathway. Cell
survival and defence are the results of this transcriptional factor. Chemoprevention and defence
against cardiovascular, renal, and pulmonary illnesses depend on Nrf2 stimulation of gene expres-
sion [110, 111].
One method of activating Nrf2 requires cysteine oxidation at particular Keap1 sites to break the
homodimer’s attachment to it. The target genes’ antioxidant response element (ARE) sequence is
bound by free Nrf2, which then enters the nucleus and forms a dimer with small musculoaponeurotic
-
chondrial dysfunction, is one of the hallmarks of neurodegenerative pathologies. It is a target
for altering Nrf2/ ARE signalling and the transcriptional activity of certain genes to prevent or
postpone the onset of age- related and hereditary neurogenerative disorders [112]. Numerous
including lower levels of methylcobalamin (III) in the brain. Nuclear factor erythroid 2- related
factor 2 (Nrf2) stimulates the expression of many antioxidant genes (MeCbl) [113]. When used as
a neurotherapeutic, phytochemicals can help to reduce the oxidative stress that leads to mitochon-
drial dysfunction in ASD. Phenolic compounds such as quercetin reduced mitochondrial damage
and increased the expression of genes linked to mitochondrial DNA copy number. Additionally,
quercetin supported Nrf2 activation, and elevated heme oxygenase- 1 gene expression leads to an
effective therapeutic compound in autism [114
in the Citrus genus that induced higher levels of high- energy phosphates, improved mitochondrial
ANT transport activity, and increased mitochondrial membrane potential; all suggest that this com-
pound could help with mitochondrial dysfunction [115]. Naringenin also reduced the rate of cell
death and enhanced cell viability. These results showed that NAR activated the Nrf2/ ARE signal-
ling pathway in neurons, which reduced oxidative stress and improved mitochondrial dysfunction,
obtained from Curcuma longa, has demonstrated exceptional therapeutic effect in suppressing
as a
neurotherapeutic to treat the neurobehavioral, biochemical, and molecular changes associated with
251
Plant Phytochemicals as Therapeutics in Neurological Disorders
ASD [116]. Sulforaphane, a member of the isothiocyanate group, is produced when myrosinase
catalyses glucoraphanin. Sulforaphane reduces oxidative stress and mitochondrial dysfunction
linked to Nrf2 activation [117].
12.4.3 role of phytoChemiCalS targeting α- SynuClein aggregation in parkinSon’S
diSeaSe
Parkinson’s disease (PD) is the second most prevalent chronic neurodegenerative illness that
impairs both motor and cognitive function [118]. The standard treatment strategies for managing PD
only effectively treat symptoms [119]. Numerous environmental and genetic risk factors have been
linked to the development of Parkinson’s disease, including ambient air pollution and pesticides,
especially organochlorines [120, 121
a 140- residue presynaptic protein that controls the rate of releasing neurotransmitters in synaptic
ways. However, most preferably, it has been predicted cellular homeostasis disturbance and neur-
onal death through impacts on a variety of intracellular targets, including synaptic function, are
122, 124]. Lewy
bodies and synuclein aggregations are characteristics of both familial and sporadic types of PD.
-
tion, leading to the pathogenesis of PD [127, 125, 126]. Thus, the progression of PD is linked with
-
ment. Phytochemicals have been used to treat neurodegenerative disorders and have demonstrated
128]. Zhu et al. (2013) demonstrated that
the oxidized quercetin species like benzyfuranone, chalcantrione, and quercetinchinone with other
polarity and hydrophilicity than quercetin [128]. In an experiment, Li et al. (2017) demonstrated that
its propagation in neurons [129]. Epigallocatechin gallate (epigallocatechin- 3- gallate), a phenolic
compound of the catechin sub- class, was found to inhibit the size and adverse effects due to oligo-
130]. Polyphenol, brazilin isolated from red cedarwood trees, was
(2017) reported that diarylheptanoids like alpinin a and alpinin b isolated from Alpinia ofcinarum
131]. Ghanem et al. (2021) reported that the results
from Th- S assays demonstrated six out of nine alkaloid compounds from Chinese herbs: cytisine,
harmine, hupehenine, koumine, synephrine, and trigonelline were found to be potent inhibitors of
132
Abrus precatorius133].
12.4.4 phytoChemiCalS promote γ- amino butyriC aCid (gaba) in hungtinton’S
diSeaSe
A neurodegenerative condition called Huntington’s disease (HD) or Huntington’s chorea is
characterized by increasing motor dysfunction, such as chorea and dystonia, as well as emotional
problems, memory problems, and weight loss. Huntington’s disease primarily affects the medium
spiny neurons in the brain and striatum [134]. Along with changes in N- methyl- D- aspartate (NMDA)
receptors, HD also results in the loss of enkephalin and gamma- aminobutyric acid (GABA) neurons
from the basal ganglia. By attaching to gamma- aminobutyric acid receptors, which are found either
pre- or postsynaptically, that controls neuronal function [135]. The mammalian central nervous
252
Plant-based Foods and their Implications in Brain Health
system primarily uses the amino acid GABA for inhibitory purposes. The GABAergic system is
made up of structures that are involved in the release or binding of GABA as a neurotransmitter.
The GABAergic system has a role in the control of memory, alertness, anxiety, muscular tension,
and epileptogenic activity [136]. Morphin, the oldest known alkaloid for pain- relieving action, is
content in the synapses [137]. They reported that zerumin A and labdane, diterpenes, and isolated
from Curcuma kwangsiensis were found to have potent GABA receptor modulations [138]. The
methanol extract of Crataeva nurvala
which found to have GABArgic modulating effect in swiss albino mice as reported by [139].
Withanolide isolated from Withania somnifera and purnavin, an alkaloid isolated from Boerhaavia
diffusa L., was reported to have practical modulatory activities in the GABAergic system [140].
12.4.5 phytoChemiCalS aS inhibitorS of the expreSSion of nf- κb Signalling
pathway in Cerebral palSy
The most prevalent motor impairment in children is cerebral palsy (CP), and to date, the exact
of long- term abnormalities of movement and posture development that impair daily activities and
are thought to be caused by non- progressive problems of the fetal or newborn brain. In an animal
141]. The most well- known
-
mation; thus, a prominent pathological feature of neurodegenerative disorders [142]. Many bio-
majority belong to alkaloids, phenolics, terpenoids, and others. Can this- 6- one (CO) alkaloids have
a variety of biological effects, including antimicrobial, anticancer, antifungal, and antiviral were
Ailanthus altissima. The compounds were
found to inhibit the phosphorylation of inhibitor kappa B as well as the transcriptional activation
143].
Gao et al. (2020) reported preskimmianine an alkaloid isolated from the root bark of Dictamnus
dasycarpus
BV- 2 microglial cells [144]. Resveratrol, apigenin, quercetin, and epicatechin polyphenols were
diseases [145, 146, 147, 148], and thus might help treat neurological diseases like cerebral palsy.
12.4.6 role of phytoChemiCalS aS interleukin- 1β (il- 1β) inhibitorS in epilepSy
a sharp change in behaviour brought on by a momentary disturbance in the electrical activity of
the brain [149]. Typically, the brain continuously generates tiny electrical impulses that have a
consistent pattern. Neurotransmitters are the chemical messengers that carry these signals along
neurons, the network of nerve cells in the brain, and throughout the whole body. In epilepsy, the
brain’s electrical rhythms have a tendency to become imbalanced, resulting in recurrent seizures.
Despite the fact that epilepsy is widespread, almost 80% of epileptic patients reside in developing
or low- income nations [150, 151]. The current experimental models suggest that epilepsy involves
cause an increase in IL- 1, but they can also modify a person’s vulnerability to stimuli that cause
253
Plant Phytochemicals as Therapeutics in Neurological Disorders
[149]. Phenolic compounds like rutin, hesperidin, gallic acid, kaempferol, and curcumin were found
-
152, 153, 154]. Gabay et al. (2010) reported stigmasterol’s poten -
in newborn mouse chondrocytes and human osteoarthritis (OA) chondrocytes [155]. Alkaloids
[156, 157]. Therefore, the use of phytoconstituents to treat epilepsy and the comorbidities that it is
linked with gives support for the research and creation of new antiepileptic medicines derived from
herbal remedies.
12.5 CONCLUSION
Neurological disorders are fatal, and they have a profound impact on the overall standard of living
of the patients. These disorders are more often acknowledged as one of the conditions having the
-
tion, aggregation of the protein, and oxidative stress. Phytochemicals comprise an enormous source
we have discussed and reviewed various classes of phytochemicals, their extraction techniques,
and their mode of action in the pathophysiology of neurological disorders. Therefore, in the future,
phytochemicals may be utilized as a treatment for neurological diseases by altering the disease
mechanism, but a profound investigation is needed to explore new compounds and their mechanism
of action to stop disease progression.
CONTRIBUTION OF AUTHORS
Pawan Prabhakar has given the framework, designed, and written the manuscript. Ankit Kumar
has designed, interpreted, and technically corrected the manuscript while Mamoni Banerjee has
CONFLICT OF RESEARCH INTERESTS
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