Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5367_Библиотеки_им_академика_М_И_Перельмана
.pdf
186
https://t.me/medicina_free
Yin, Haitao, Yun Zhou, Cuixia Wen, Chong Zhou, Wei Zhang, Xiang Hu, Lifeng Wang,
Chuanwen You, and Junfei Shao. 2014. “Curcumin Sensitizes Glioblastoma to
Temozolomide by Simultaneously Generating ROS and Disrupting AKT/MTOR
Signa l ing.” Oncology Reports 32 (4): 1610–16. https://doi.org/10.3892/or.2014.3342.
Zang, Xinlong, Mingyang Cheng, Xiaoxu Zhang, and Xuehong Chen. 2021. “Quercetin
Nanoformulations: A Promising Strategy for Tumour Therapy.” Food and Function.
Royal Society of Chemistry. https://doi.org/10.1039/d1fo00851j.
Zhang, Yong, Shao Xiang Wang, Ji Wei Ma, Hai Ying Li, Jie Cheng Ye, Si Ming Xie, Bin
Du, and Xue Yun Zhong. 2015. “EGCG Inhibits Properties of Glioma Stem-Like Cells
and Synergizes With Temozolomide Through Downregulation of P-Glycoprotein
Inhibition.” Journal of Neuro-Oncology 121 (1): 41–52. https://doi.org/10.1007/s11060-
014-1604 -1.
NeuroPhytomedicine
Eugenol as
https://t.me/medicina_free
10
Neuro-Phytomedicine
Recent Trends Pertaining
to the Treatment of
Neurological Disorders
Bhagawati Saxena
10.1 INTRODUCTION
Neurological disorders are medically described as conditions that impact the brain,
spinal cord, and body’s nerves. The most frequent neurological conditions include
Alzheimer’s disease (AD), Parkinson’s disease (PD), brain and spinal cord injury,
epilepsy, migraines, multiple sclerosis, stroke, etc. Recently, there has been an
upsurge in the frequency of neurological disorders. Treatment of various neurological illnesses presents a myriad of challenges, one of which is the delivery of drugs to
the brain (Bhavsar et al, 2022). According to reports, phytochemicals derived from
medicinal plants have therapeutic and pharmacological effects that were neuroprotective, making them possible treatments for neurological illnesses. The blood-brain
barrier (BBB), which encircles and protects the brain, hinders a signicant number
of drugs from entering the brain. Eugenol is a widely used researched molecule.
Eugenol appears to pass through the BBB and act in situ when consumed orally
due to its hydrophobic characteristic. Eugenol demonstrates a variety of biological
effects while having a rather simplistic chemical composition. It is renowned for its
anti-microbial (Marchese et al, 2017), antioxidant, and anti-inammatory properties
(Barboza et al, 2018). According to earlier experimental ndings, eugenol has been
proven to be protective against the neurotoxicity caused by chlorpyrifos (Singh and
Panwar, 2014), aluminium (Mesole et al, 2020; Said and Rabo, 2017), acrylamide
(Prasad and Muralidhara 2013), 6-hydroxydopamine (6-OHDA) (Kabuto et al, 2007;
Kabuto and Yamanushi, 2011) and scopolamine (Garabadu and Sharma, 2019).
Eugenol can be utilised to treat several neurological or neurodegenerative problems
due to its chemical properties such as hydrophobicity as well as a wide range of
pharmacological features, such as antioxidative, anti-inammatory activities, etc.
Eugenol continues to be of great interest to researchers because of its multidirectional
impact, which makes it a practical component in therapies with therapeutic potential
against many brain disorders. The present level of knowledge on the neuroprotective
properties and uses of eugenol and its derivatives in neurological disorders such as
187D OI: 10.1201/9781003389781-10
188 NeuroPhytomedicine
https://t.me/medicina_free
depression, AD, Parkinson’s diseases, stress and stress-related disorders, stroke, and
traumatic brain injury (TBI) are emphasised in this chapter in the following sections.
10.2 EUGENOL AND ITS PROPERTIES
Eugenol (C10H12O2) is chemically 4-allyl-2-methoxy phenol. It is an aromatic phenolic compound. It is frequently used as a scent in fragrances and soaps. Eugenol has an
oily viscosity, a clear to light yellow colour, and a pungent scent. Inorganic solvents
are the best solubilisers of eugenol, while it is sparingly soluble in water. Eugenol
isunstable chemically and vulnerable to oxidation and other chemical reactions. It is
quickly absorbed by several organs when taken orally and metabolised by the liver.
Common sources of it are plants from the Lauraceae, Lamiaceae, Myristicaceae,
and Myrtaceae families’ natural essential oils. It is reported to occur in a variety
of concentrations depending on the species (Table 10.1). However, eugenol is the
primary ingredient in the clove oil extract, that is, 70%–90% (Eugenia caryophyl-
lata, Syzygium aromaticum). Cloves, in addition to being a common spice used to
avour foods and drinks, can also be applied locally to alleviate toothaches. It is
also taken orally, however less frequently to treat digestive and respiratory issues.
Cinnamon, nutmeg, and other aromatic spices also contain eugenol, albeit in smaller
amounts (Charan Raja, 2015; Khalil et al, 2017). Since eugenol is a key component
of the three spices like clove, cinnamon, nutmeg, etc., it is commonly regarded as
safe and employed as a natural food avouring and preservative by the U.S. Food
and Drug Administration (FDA) (Burt, 2004; National Toxicology Program, 1983).
Eugenol’s antimicrobial (Hu et al, 2018; Marchese et al, 2017) properties have led
to its usage as a pesticide. Eugenol has broad-spectrum antibacterial activity against
TABLE 10.1
Eugenol Occurrence and Concentration in Various Plants (Charan Raja,
2015; Khalil et al, 2017).
Plant Common Name Family Part
Syzygium aromaticum Clove, clovetree Myrtaceae Flower, ower
Syzygium aromaticum Clove pepper Myrtaceae Fruit 36
Pepper betel Betel pepper Piperaceae. Leaf 17.85
Daucus carota Carrot Apiaceae or
Ocimum tenuiorum Tulsi Lamiaceae Leaf 4.2–4.97
Cinnamomum verum Ceylon cinnamon, cinnamon Lauraceae Bark 3.52
Curcuma longa Turmeric Zingiberaceae Leaf, essential oil 2.1
Laurus nobilis Bay, bay laurel Lauraceae Leaf 1.34
Zingiber ofcinale Chinese ginger Zingiberaceae Rhizome 0.4
Myristica fragrans Nutmeg Myristicaceae Seed 0.32
Origanum vulgare Small-owered oregano Lamiaceae Shoot 0.055–0.125
Concentration
(mg/g)
1809
buds, leaf, stem
Seed 7.0
Umbelliferae
Eugenol as Neuro-Phytomedicine
https://t.me/medicina_free
microorganisms (Burt, 2004). Eugenol is traditionally been used in dentistry as a
dental analgesic. It is used as an analgesic and an antimicrobial in a variety of root
canal lling products (Diaz and Sembrano, 1985; Pramod et al, 2016).
189
10.3 NEUROPROTECTIVE EFFECTS AND MECHANISMS OF
EUGENOL IN VARIOUS NEUROLOGICAL DISORDERS
10.3.1 DePression
The exceedingly high frequency of depression in the community qualies it as one of
the most signicant neurological illnesses. Moreover, depression frequently coexists
with neurodegenerative illnesses such as PD and AD (Chung et al, 2003; Lyketsos
and Lee, 2004). Depression is a mood condition that affects many people and frequently results in major psychosocial issues including suicide (Wong and Licinio,
2001). The “monoamine theory” has been the most signicant of the pathogenic
explanations for depression. Monoamine levels (serotonin, dopamine (DA), and
noradrenaline) in post-synaptic areas are markedly diminished in individuals with
depression for a plethora of reasons. Symptoms associated with depression should
improve if these monoamines are restored. The current line of medications for the
treatment of depression includes inhibitors of monoamine oxidase (MAO), serotonin
noradrenaline receptor inhibitors (SNRIs), and selective serotonin receptor inhibitors (SSRIs). However, chronic and recurrent depression is still prevalent despite
the introduction of these medicines (Gelenberg et al, 2003). This raises the need
of developing a new therapy for depression. The anti-depressive effects of eugenol
on rats were assessed in the earlier study. Results show that oral administration of
eugenol to animals reduced the depression comparable to imipramine administration (Irie et al, 2004).
In patients suffering from depression, the hippocampus area is relatively smaller
(Bremner et al, 2000; Brosch et al, 2022). This decrease in the hippocampal region
is recovered as the patients receive antidepressant therapy and their clinical condition improves (Malberg et al, 2000). One of the neuronal growth factors in the
brain that is crucial for the process of neurogenesis is called brain-derived neurotrophic factor (BDNF). Previous animal research shows that BDNF supplementation
can alleviate depression associated with BDNF deciency (Shirayama et al, 2002).
Additionally, recent research showed that the neurogenic benets of antidepressants
were eliminated when this neurogenesis was disrupted by X-ray irradiation in the
brain (Santarelli et al, 2003). Thus, it is determined that regenerated neurons are
responsible for an antidepressant’s therapeutic benet (Malberg et al, 2000). The
elevation of BDNF expression in the hippocampus promotes the antidepressantinduced regeneration of neurons (Björkholm and Monteggia, 2016; Shirayama et al,
2002). It was discovered that eugenol elevated BDNF expression in the hippocampus
as with imipramine (Irie et al, 2004). Eugenol also promotes hippocampus neurogenesis, which is seen with other antidepressants (Akbar et al, 2021; Irie, 2006).
In contrast to treatment with imipramine, eugenol enhances the expression of
the metallothionein-III (MT-III) gene in the hippocampus (Irie et al, 2004). MT-III
is a member of the MT family that is particular to the brain and shields cells and
190
https://t.me/medicina_free
organs from numerous harmful events. It is thought that MT-III functions in the
brain to promote neurogenesis and neuroprotection (Irie and Keung, 2001; Tanji
et al, 2003). These results imply that eugenol’s ability to induce neurogenesis may
be mediated through MT-III expression. Certain study shows that eugenol and its
analogues inhibit MAO, preferentially MAO-A (Tao et al, 2005); however, another
study reported that eugenol neither inhibits MAO-A nor inhibits MAO-B (Kong
et al, 2004). This difference in observation may be owing to various experimental
circumstances.
NeuroPhytomedicine
10.3.2 Alzheimer’s DiseAse
AD is a neurodegenerative disease that occurs due to the atrophy of cholinergic
neurons mainly in the cerebral cortex and hippocampus region. The most prevalent
type of dementia is AD. The prevalence of AD is rising globally as the proportion of
elderly people increases worldwide (Citron, 2002). The majority of AD cases occur
sporadically, that is, without genetic origins, however, some familial cases of AD
have been well-described, that is, genetic anomalies in the genes (PS1, PS2, APP,
etc.) (Selkoe and Schenk, 2003). Pathogenesis of AD is multifactorial. The two hallmarks of AD’s pathogenesis include interneuronal accumulation of amyloid β (Aβ)
plaques and intra-neuronal accumulation of neurobrillary tangles (NFTs). Studies
have demonstrated that Aβ plaques result in the death of neuronal cells through several mechanisms (Choi et al, 2019; Gschwind and Huber, 1995; Orellana et al, 2011).
Aβ plaque and NFT exert their neurotoxicity through a range of mechanisms. First,
the reactive oxygen species (ROS) are generated as a consequence of Aβ plaque
deposition. Generated ROS results in direct damage to cell membranes and DNA
to cause atrophy of neurons (Behl et al, 1994; Cheignon et al, 2018; Wang et al,
2010). Second, NFT and Aβ plaque have been linked to promoting excitotoxicity by
allowing an excessive inux of calcium ions via NMDA receptor into the neuronal
cells (Pallo et al, 2016). Insoluble deposits of Aβ plaques between neurons result
in the activation of microglia, an innate immune cell within the brain. Activated
microglia have two distinct tasks in the pathogenesis of AD. Through phagocytic
action, it initially provides neuroprotective effects by eliminating Aβ deposits, but
with time, it releases cytotoxic chemicals and pro-inammatory cytokines, causing gradual neurodegeneration (Mandrekar-Colucci and Landreth, 2010). Although
microglia express all toll-like receptor (TLR) subtypes, TLR2 and TLR4 are particularly abundant (Fiebich et al, 2018). TLR4 is crucial in the identication of the
Aβ plaques by microglia, which is believed to be a part of inammatory reactions
in AD pathogenesis (Papageorgiou et al, 2016). In AD, TLR4 is crucial for the initiation of neuroinammation which in turn results in neurodegeneration (Chavali
et al, 2020; Saxena and Chavali, 2019; Walter et al, 2007).
Memantine, an NMDA inhibitor of the glutamate receptor, three different cholinesterase blockers (donepezil, galantamine, and rivastigmine), and most recently
Aducanumab, a monoclonal antibody, were the only medications that the US-FDA
approved for treating AD patients (Chauhan et al, 2022; Long and Holtzman, 2019;
Yang and Sun, 2021). Thus, excitotoxicity via glutamate acting on NMDA, as well as
cholinesterase, is found promising target for the new molecule.
191Eugenol as Neuro-Phytomedicine
https://t.me/medicina_free
Eugenol is well known for its antioxidant as well as anti-inammatory activity.
Eugenol can directly neutralise hydroxyl free radicals and lessen oxidative stress
(Taira et al, 1992). Additionally, it was revealed that eugenol’s free radicals scavenging activity (antioxidative effect) is linked to its capacity as a metal transition (Ito
et al, 2005). It is suggested that eugenol prevents lipid peroxidation caused by lipoxygenase (Naidu, 1995). Additionally, earlier reports show that eugenol has inhibitory activity on calcium ion channels (Chung et al, 2008; Seo et al, 2013). Eugenol
prevents excitotoxicity induced by NMDA in cultured neuronal cells by inhibiting
2+
Ca
absorption (Wie et al, 1997). It has also been proven that NMDA receptors
mediate the neurotoxic effects of Aβ deposits (Parks et al, 2001). Hence, it stands to
reasonthat eugenol might counteract the harmful action of Aβ, which is mediated
through the NMDA receptor. TLR4 is a key player in the innate immune responses in
neurodegenerative diseases like AD, PD, etc. We docked eugenol against the human
myeloid differentiation factor-2 (hMD2) co-receptor of TLR4 to better comprehend
the mechanism underlying the anti-inammatory effect. Eugenol has a −6.897 kcal/
mol binding afnity towards the hMD2 active site (Vora et al, 2022). Eugenol dramatically decreased the gene expression of TLR4 indicators, according to a prior
study (Choudhury et al, 2014). Lipopolysaccharide (LPS) is the natural agonist of
TLR4, and eugenol inhibits the production of pro-inammatory mediators generated
by LPS in human macrophages (Lee et al, 2007). Thus, eugenol’s antagonistic action
at TLR4 might be partially responsible for its anti-inammatory effects. Further
research is necessary to corroborate this conclusion. Thus, eugenol is supposed to be
effective against AD by simultaneously acting on multiple pathways.
Eugenol inhibits the aggregation of amyloid protein (Dubey et al, 2017). Eugenol
administration prevented the loss in memory and learning performance against insulin and Aβ-induced AD rat models (Taheri et al, 2019). In vitro study shows that
eugenol has antioxidant activities as well as inhibits MAO, butyrylcholinesterase
(BChE), acetylcholinesterase (AChE), and activities dose-dependently (Adefegha
et al, 2021). Eugenol was also found to alleviate the impairment in the learningmemory ability and augmented oxidative stress in the hippocampus of rats with AD
(Liu et al, 2013). The report shows that eugenol enhanced learning and memory in
the mouse by augmenting neurogenesis as well as dendritic complexity of neurons
in the dentate gyrus (DG) and cornu ammonis 1 (CA1) basal regions of the mouse
brain (Akbar et al, 2021). Additionally, eugenol reduced the memory loss brought
on by scopolamine. Eugenol also lessened the effects of scopolamine on the rat’s
hippocampus cholinergic and mitochondrial dysfunction and glutamate neurotoxicity (Garabadu and Sharma, 2019). Aluminium administration results in dementia,
hastening Aβ plaque formation and accumulation, neuroinammation, and oxidative
stress in the rat’s brain (Chavali et al, 2020; Saxena and Chavali, 2019). It was discovered that eugenol protected against aluminium-induced neurotoxicity (Said and
Rabo, 2017; Mesole et al, 2020). Thus, these pieces of literature show that eugenol
is found effective for treating AD via acting through multiple pathways which are
shown in Figure 10.1.
Eugenol analogue, that is, acetoxy eugenol acetate has shown neuroprotective
activity against cognitive impairment in mice caused by Aβ (Jayasingh Chellammal
et al, 2019). Eugenol-rich grass leaf sweet ag rhizome shields PC-12 cells against
192
https://t.me/medicina_free
NeuroPhytomedicine
FIGURE 10.1 Neuroprotective mechanisms of eugenol in Alzheimer’s disease. Proteolysis
of amyloid precursor protein (APP), a transmembrane glycoprotein occurs by two pathways,
that is, non-amyloidogenic pathway and amyloidogenic pathway. In the non-amyloidogenic
pathway, APP is rst cleaved by alpha-secretase and then by gamma-secretase and thus
leads to the generation of soluble fragments sAPPα. On the other hand, in the amyloidogenic pathway, neurotoxic Aβ formed through cleavage of APP by beta-secretase followed
by gamma-secretase and formed sAPPβ and then Aβ oligomers. Deposition of Aβ plaque
leads to hyperphosphorylation of tau proteins and ultimately leads to the formation of NFTs.
Formation and deposition of Aβ plaque and NFTs results in ROS generation, excessive inux
of calcium ion by activation of NMDA receptors, and activation of neuroinammatory receptors like toll-like receptor 4 (TLR4), which further play role in neurotoxicity and cause neuronal death of cholinergic nerve bres. In scopolamine-induced amnesia, there is an increase
in AchE activity which decreases the level of acetylcholine. Neurodegeneration or decreased
activity of cholinergic system leads to memory loss associated with Alzheimer’s disease.
Eugenol inhibits the formation of ROS, NMDA receptor as well as TLR4. It also blocks the
inux of calcium ions and thus inhibits excitotoxicity. It also inhibits AchE activity and thus
increases the concentration of Ach within the synapse. Thus, eugenol exerts its neuroprotection against Alzheimer’s disease by acting on multiple pathways.
Eugenol as Neuro-Phytomedicine
https://t.me/medicina_free
193
the Aβ peptide’s harmful effects (Liang et al, 2015). Moreover, eugenol containing
Syzygium aromaticum was found to be protective against Aβ
-induced neuro-
25-35
toxicity in neuronal cells (Shekhar et al, 2018). Certain analogues of eugenol, that
is, asaronic acid, o-eugenol, 4-hydroxy-3-methoxybenzylamine, ethyl 4-hydroxy3-methyoxycinnamate, ethyl homovanillate, and 2-methoxy5-nitrophenol greatly
shielded PC-12 cells from the harmful effect of Aβ 1–40 (2.5 mM) (Irie, 2006).
10.3.3 PArkinson’s DiseAse
After AD, PD is the second most typical neurodegenerative condition. PD is caused
by the depletion of DA in the nigrostriatal pathway due to the gradual degeneration
of neurons (dopaminergic) in the substantia nigra pars compacta (SNpc) (Bergman
and Deuschl, 2002). Characteristic features of PD include impairment of the motor
and nonmotor (limbic and cognitive) functions. DA deciency in the SNpc results
in motor symptoms that include resting tremors, stiff joints, akinesia/bradykinesia,
etc (Jankovic, 2008)). The majority of the time, nevertheless, there are no apparent
genetic backgrounds; however, rarely, PD develops as a hereditary condition brought
on by a gene defect (Bergman and Deuschl, 2002). Treatment for PD has advanced
signicantly. Many prospective treatments for PD are developing as a consequence
of advancements in experimental medicines (Ellis and Fell, 2017). The most efcient
drug for treating the signs and symptoms of PD is currently levodopa, but it is also
linked to serious side effects such as the “wearing off” effect including dyskinesias
and other motor problems (Bargiotas and Konitsiotis, 2013). Alternative treatments
for PD include DA agonists, nondopaminergic therapy, and catechol-o-methyltransferase inhibitors. These treatments can be taken in conjunction with levodopa
or alone (Jankovic and Aguilar, 2008).
6-OHDA and 1-methly-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) are widely
used classic toxins that induce PD in animals (Schober, 2004). Eugenol was proven
to be effective in the 6-OHDA-induced rat model of PD (Moreira Vasconcelos et al,
2020). Further research suggests that eugenol inhibits 6-OHDA-induced DA depletion in the striatum both directly by inhibiting lipid peroxidation and indirectly
through the activation of glutathione (GSH) and L-ascorbate-producing systems.
Additionally, additional GSH by conjugating with the p-quinone created during
6-OHDA auto-oxidation could prevent cell death (Kabuto et al, 2007). According to
a report, eugenol pre-treatment inhibits 6-OHDA-induced DA reduction by halting
lipid peroxidation. On the contrary, eugenol post-treatment enhanced the DA decline
caused by 6-OHDA. According to the study, eugenol pre-treatment reduces lipid
peroxidation, which in turn prevents 6-OHDA’s ability to cause DA depletion in the
striatum. Eugenol post-treatment, however, further enhanced the DA decline. Thus,
depending on when it was administered concerning when the model PD started,
eugenol showed negative consequences (Kabuto and Yamanushi, 2011).
The synthetic neurotoxin MPTP has shown to cause PD-like symptoms in mice,
including dyskinesia (Mustapha and Taib, 2021; Schober, 2004). MPTP, that is, less
toxic is converted to MPP+ (highly toxic) in the mitochondria of the brain by MAO,
particularly MAO-B. MPP+ inhibits the function of mitochondrial complex I, which
causes the production of ROS (Mustapha and Taib, 2021). These facts suggest that
194
https://t.me/medicina_free
MAO-B inhibitors are currently used in therapeutic settings. In the MPTP-induced
PD mouse model, our research demonstrates that pre-treatment with eugenol has
positive effects on behavioural and pathological development. The protective effect
of eugenol against the MPTP-induced PD model is because of its antioxidant effect.
However, post-treatment with eugenol further deteriorates the MPTP-induced alteration in behaviour and pathological progression (Vora et al, 2022).
NeuroPhytomedicine
10.3.4 stress AnD stress-relAteD DisorDers
The level of stress that people sense nowadays appears to have signicantly increased.
Stress leads to numerous other conditions or disorders, including anxiety, depression, cognitive impairment, diabetes, immunosuppression, irritable bowel syndrome,
ulcerative colitis, gastric ulcer, hypertension, and male impotence. Stress is described
as the body’s non-specic reaction to demands placed on it, which are typically
unpleasant (Selye, 1936). The body responds to stress through the process of adaption
(also known as allostasis) by maintaining physiological processes within a predetermined range. However, excessive stress or ineffective allostasis control results in an
allostatic load, which can cause diseases and must thus be managed (McEwen, 2000).
The sympathoadrenal system (SAS), brain monoaminergic systems (BMS), and hypothalamic-pituitary-adrenal (HPA) all have a role in the physiological and psychological reactions to stress. In response to stress, the ulcer index, plasma corticosterone,
and norepinephrine (NE) levels were elevated. Increased plasma corticosterone and
NE are a marker of the stimulated HPA axis and the SAS, respectively. The earlier
report shows that eugenol exerts an anti-stress effect against restraint-induced stress
(Sen et al, 1992). Another study shows that the seven-day pre- treatment with eugenol
showed a selective impact on the HPA axis and thus, reduced the ulcer scoring and
increased corticosterone level in plasma induced by stress but did not inuence the
stress-induced altered levels of NE in plasma (Garabadu et al, 2011). Additionally,
eugenol restored the stress-related alterations in 5-HT levels in the various region of
the brain while NE levels were reversed in the various region of the brain except for
the hippocampus. Results further demonstrated that eugenol has strong anti-stress
activity in the four-hour restraint stress paradigm and that the impact is a consequence of HPA and BMS regulation. Eugenol-rich bark of Cassia zelynicum (cinnamon) (Saxena and Saxena, 2012) and buds of eugenia caryophyllus (clove) (Singh
et al, 2009) were also found to be effective as an anti-stress agent.
People today experience inescapable chronic stress due to the difcult and
extremely demanding life rhythm. Numerous major health issues, such as anxiety, depression, gastrointestinal dysfunctions consequently irritable bowel syndrome, dysregulations of the neuroendocrine system, etc., are linked to chronic
stress. Studies also show that eugenol is also effective against stress-induced disorders. Study shows that eugenol reduces anxiety brought on by stress in rodents by
inhibiting the expression of glyoxalase 1 (Siyal et al, 2021) and downregulation of
neurokinin-1 receptors (Siyal et al, 2020). The manifestation of emotional behaviours,
such as pathologic anxiety disorders, is critically inuenced by the central amygdala
(CeA). CeA-specic infusion or intraperitoneal injection of methyl eugenol, a derivative of eugenol decreased anxiety-like behaviours in mice. This is most likely a result
Eugenol as Neuro-Phytomedicine
https://t.me/medicina_free
of the methylleugenol’s ability to activate A-type GABA receptors (GABAARs).
Stimulation of GABAARs increases gamma-aminobutyric acid (GABA)ergic inhibitory inuence in the CeA, which lowers anxiety (Liu et al, 2019). Eugenol also
showed a protective effect against gastrointestinal dysfunction caused by constraint
stress. The results of this investigation suggest that eugenol may be used to treat
irritable bowel syndrome (Garabadu et al, 2015). Chronic stress-related hormonal
variations or irregularities and associated psychological and physical effects, including reproductive dysfunction, are more common in women. Stress activates the HPA
axis, elevating blood cortisol levels, which attenuates the release of anti-Mullerian
and oestradiol hormones from the ovary while augmenting anterior pituitary synthesis of luteinising and follicle-stimulating hormones. Stress also results in insulin
resistance, oxidative stress and consequently molecular damage in the ovaries. These
alterations cumulatively result in fertility issues (Bethea et al, 2008). Another study
shows the preventive effects of eugenol against stress-induced infertility in female
rats (Helmy et al, 2022). It’s interesting to note that the injection of eugenol dramatically reduced all of these negative consequences by modifying animal behaviour,
ovarian damage, corticosterone upsurge hormonal abnormalities and thus, ultimately reproductive disturbances.
195
10.3.5 eugenol for the treAtment of stroke
Stroke is one of the most dangerous illnesses endangering people’s health and life. A
stroke occurs when the blood ow to a certain area of the brain is interrupted. This
may result in permanent brain damage, chronic disability, or even death. Ischemic
stroke and haemorrhagic stroke are the two forms of stroke. Ischemic stroke happens when blood arteries get blocked, cutting off the brain’s blood supply whereas
eruption of the blood vessels, results in haemorrhagic stroke, resulting in an inux
of blood into the brain cavity. Up to 60%–80% of all strokes are ischemic, making
them more prevalent (Chugh, 2019). Stroke is the most frequent long-term disability,
the second-leading cause of death, and dementia in those over sixty (Chamorro et al,
2016). The nancial burden of stroke is rising globally due to an ageing population
(Feigin et al, 2016; Forouzanfar et al, 2015). Recombinant tissue plasminogen activator (rt-PA) is the only thrombolytic FDA-approved to date for the treatment of stroke
(Lekoubou et al, 2017). rt-PA may not be used as widely as it might due to its short
therapy windows and adverse effects. Research has indicated that eugenol may protect against brain ischemia damage (Ahmad et al, 2018; Won et al, 1998). Autophagy
is a phenomenon which is induced as a result of ischemic stroke, its signicance
for stroke is yet debatable. Numerous studies indicate that autophagy triggered in
response to ischemia acts as a double-edged sword that can have both advantageous
and detrimental effects on brain neurons (Shi et al, 2021; Wang et al, 2018). However,
certain studies show that autophagy prevents neuronal damage caused by cerebral
ischemia followed by reperfusion. The molecules having the capacity to induce
autophagy are found to prevent cerebral ischemia (Wang et al, 2018; Yao et al, 2019).
The study by Sun and the team shows that by enhancing autophagy, eugenol reduces
the effects of cerebral ischemia-reperfusion injury (Sun et al, 2020). Moreover, it has
been shown that the analogous of eugenol, that is, methyleugenol can reduce brain
Соседние файлы в папке Библиотека им академика М.И. Перельмана