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Polyphenols: A Potential New Strategy for the Prevention and Treatment of Anxiety and Depression

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Following recent evidence that disturbances in oxidative metabolism are involved in anxiety disorders, high anxiety levels and depression, the use of antioxidants has been proposed as a novel approach for the prevention or treatment of these conditions. Polyphenols are naturally-occurring antioxidant substances which can have pharmacological actions on the central nervous system. This mini-review aims to examine the current evidence for the potential use of dietary polyphenols as neuroprotective agents to reduce anxiety and to manage depression. I will outline recent findings which demonstrate that polyphenols have anti-anxiety effects at higher doses (300/60/30/20 mg/kg body weight) as well as at lower doses (2-4 mg/kg); this can be compared to conventional anxiolytics, which only have anxiolytic effects at lower doses (1-5 mg/kg). To circumvent problems associated with polyphenols (e.g., quercetin) having difficulty crossing the blood-brain barrier and to effectively reduce the active dose, intranasal administration in the form of liposomes could be an interesting approach. I also suggest that dietary polyphenols could be a new alternative approach to treat depression, because they exhibit antidepressant activity with relatively lower doses (0.3-2 mg/kg) than commonlyused antidepressants such as imipramine (10 mg/kg). The polyphenols discussed in this mini-review are found in vegetables and fruits such as apples, plums, cherries, onions and tea. Therefore, a varied diet that is rich in naturallyoccurring polyphenols could be an effective means to prevent (or delay) anxiety, depression and other diseases linked to oxidative stress.
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Current Nutrition & Food Science, 2010, 6, 13-18 13
1573-4013/10 $55.00+.00 © 2010 Bentham Science Publishers Ltd.
Polyphenols: A Potential New Strategy for the Prevention and Treatment
of Anxiety and Depression
Jaouad Bouayed*
Department Environment and Agro-Biotechnologies, Centre de Recherche Public - Gabriel Lippmann, 41 rue du Brill,
4422 Belvaux, Luxembourg
Abstract: Following recent evidence that disturbances in oxidative metabolism are involved in anxiety disorders, high
anxiety levels and depression, the use of antioxidants has been proposed as a novel approach for the prevention or
treatment of these conditions. Polyphenols are naturally-occurring antioxidant substances which can have pharma-
cological actions on the central nervous system. This mini-review aims to examine the current evidence for the potential
use of dietary polyphenols as neuroprotective agents to reduce anxiety and to manage depression. I will outline recent
findings which demonstrate that polyphenols have anti-anxiety effects at higher doses (300/60/30/20 mg/kg body weight)
as well as at lower doses (2-4 mg/kg); this can be compared to conventional anxiolytics, which only have anxiolytic
effects at lower doses (1-5 mg/kg). To circumvent problems associated with polyphenols (e.g., quercetin) having difficulty
crossing the blood-brain barrier and to effectively reduce the active dose, intranasal administration in the form of
liposomes could be an interesting approach. I also suggest that dietary polyphenols could be a new alternative approach to
treat depression, because they exhibit antidepressant activity with relatively lower doses (0.3-2 mg/kg) than commonly-
used antidepressants such as imipramine (10 mg/kg). The polyphenols discussed in this mini-review are found in
vegetables and fruits such as apples, plums, cherries, onions and tea. Therefore, a varied diet that is rich in naturally-
occurring polyphenols could be an effective means to prevent (or delay) anxiety, depression and other diseases linked to
oxidative stress.
Keywords: Polyphenols, antioxidants, oxidative stress, neuroprotective, anxiety and depression.
INTRODUCTION
In the past decade, increasing evidence has been
presented that links disturbances of oxidative metabolism to
anxiety disorders [1,2], high anxiety levels [3-6] and
depression [7-9]. Anxiety may coexist with depression, in
what is defined in psychiatric nosography as an anxio-
depressive syndrome that makes coping more difficult
[10,11]. Anxiety is a psychological state in which the feeling
of fear is disproportionate to the nature of the threat [12].
Anxiety is not a unitary phenomenon but can be divided into
various forms including ‘normal’ and ‘pathological’ anxiety
[13]. Anxiety is a normal emotional response to a threat or
potential threat [6,12]. When this aversive emotion is
inappropriate, extreme and persistent, it is classified as
pathological [12,14]. It is estimated that one-eighth of the
total population worldwide suffers from inappropriate
anxiety [15]. Depression is a common mental disorder in
which sufferers exhibit depressed mood, loss of interest or
pleasure, feelings of guilt or low self-worth and disturbed
sleep or appetite [16]. It is estimated that at least 20% of all
individuals suffer from a depressive episode at least once in
their lifetime [17]. Research on anxiety and depression has
predominantly focused on the regulatory systems, including
gamma-aminobutyric acidergic (GABAergic) and serotoni-
nergic systems among others [6,18]. The most popular drugs
*Address correspondence to this author at the Department Environment and
Agro-Biotechnologies, Centre de Recherche Public - Gabriel Lippmann, 41
rue du Brill, 4422 Belvaux, Luxembourg; Tel: + 352-470-261-436;
E-mail: bouayed@lippmann.lu
used to treat anxiety and depression are benzodiazepines
[13,19] and selective serotonin reuptake inhibitors (SSRIs)
[18,20], respectively. Benzodiazepines, agonists of the
benzodiazepine site on GABAA receptors, exert their thera-
peutic effects by potentiating chloride flux through the
GABAA receptor ion channel complex [19,21,22]. Both
classical antidepressants and many of the novel generation of
antidepressants such as SSRIs stabilize the mood of depres-
sive patients by increasing the availability of serotonin,
noradrenalin and/or dopamine in the synaptic cleft [23-25].
However, the recent findings of a link between oxidative
stress and both psychological stress [1-6] and mood
disorders [7-9] have introduced new perspectives for the
prevention and/or treatment of anxiety and depression.
Accordingly, the potential use of antioxidants has emerged
as a novel approach to prevent or treat anxiety and depres-
sion. In support of this approach, some authors have
examined the antioxidant effects of anxiolytic treatments
such as citalopram and other antidepressants [7,26,27].
Additionally, it has been revealed that vitamin E deficiency
in the mouse brain significantly increases both the levels of
central oxidative stress markers and anxiogenic behavior of
mice [28]. Souza et al. [29] pointed out that imbalanced
nutrition (diet enriched with sucrose) induces brain oxidative
stress and anxious behavior in rats. Recently it has been
demonstrated that mice treated with vitamin C showed an
antidepressant-like effect in the tail suspension test [30].
Overall, these recent findings raise the possibility that
anxiety and depression could be prevented or treated either
by a diet rich in naturally-occurring antioxidants or by daily
14 Current Nutrition & Food Science, 2010, Vol. 6, No. 1 Jaouad Bouayed
antioxidant supplementation. Polyphenols such as flavonoids
and phenolic acids are well known for their high antioxidant
activity and are the major class of antioxidants derived from
the diet [31-34]. The use of these phytochemical secondary
metabolites could be an interesting approach to prevent and
treat anxiety and depression [19,22,35,36]. These natural
antioxidants have received considerable attention because
they have been reported to exhibit a wide range of beneficial
biological actions, such as antibacterial, antiviral [37], anti-
inflammatory, antiallergenic [37,38], vasodilatory [37,39],
antimutagenic [40], antidepressant [35,36] and anti-anxiety
effects [41,42].
In this mini-review, I present a brief insight into the
metabolism of oxygen and the links between disturbance of
this process and certain diseases. I then highlight the
cytoprotective effects of dietary polyphenols, which may
play a key role in antioxidant compensatory mechanisms in
living organisms. Finally, I examine recent work that
demonstrates the anxiolytic and antidepressant effects of
dietary polyphenols and discuss the underlying mechanisms
of their actions.
THE METABOLISM OF OXYGEN: BENEFICIAL
AND DELETERIOUS EFFECTS
Oxygen is a free biradical because each atom of this
molecule contains one unpaired electron in its external
orbital [43-46]. In vivo, the one electron reduction of oxygen
results in formation of the superoxide radical (O2·), which is
considered to be the precursor of reactive oxygen species
(ROS) [43-47]. Indeed, the superoxide anion (O2·) is the
source of ROS which are either non-radicals (molecules with
no unpaired electrons such as hydrogen peroxide (H2O2),
hypochlorous acid (HOCl), and singlet oxygen (1O2)), or
oxyradicals (free radicals with one unpaired electron, such as
hydroxyl radical (OH·), alkoxyl radical (RO·), and peroxy-
radical (ROO·) among others) [43-47]. The principal cellular
pathways that consume oxygen and are responsible for
generating the largest portion of ROS are: mitochondrial
respiration (in which 85% of oxygen is metabolized), and
processes catalyzed by NAD(P)H oxidase (especially the
oxidative burst stimulated by phagocytosis in immune cells)
and xanthine oxidase [43-48].
In vivo, the antioxidant defense system is divided into
enzymatic antioxidants (including superoxide dismutase,
catalase, glutathione peroxidase, etc) and non-enzymatic
antioxidants (which includes both the endogenous reducers
of cells such as glutathione and uric acid, and also exo-
genous reducers which are provided especially from nutri-
tion such as vitamins, polyunsaturated fatty acids, poly-
phenols and carotenoids) [32,43-48]. In this regard, it is
interesting to note that polyphenols are the major class of
antioxidants derived from the diet [32].
ROS are well recognized for playing a dual role as both
beneficial and deleterious species [43,45,46]. The beneficial
role of ROS is established when there is a balance between
oxidant production and antioxidant protection [43,45,46].
The balance between antioxidation and oxidation is believed
to be critical to maintain a healthy biological system
[43,45,46]. However, when the ROS concentration exceeds
the antioxidative capacity of an organism, cells enter a state
termed oxidative stress in which the excess ROS induces
oxidative damage of cellular components [6,43-48]. In the
oxidative stress state there are differences in gene expres-
sion, protein conformation and cellular signaling [6,43-48].
For these reasons, disturbances in oxidative metabolism have
been implicated in a large number of acute and chronic
diseases, including cancer, diabetes, male infertility, auto-
immune diseases, atherosclerosis and cardiovascular disor-
ders [6,43-49]. Oxidative stress in the brain may affect
overall brain activity, in particular by causing alterations in
neurotransmission and neuronal function, disruptions in
membrane integrity, and sometimes even neuronal cell death
[6,43,45,46]. As a result, oxidative stress is also known to be
involved in specific diseases of the nervous system, such as
neurodegenerative diseases and neuropsychiatric diseases
such as schizophrenia, depression and anxiety disorders
[6,27,43,45,46]. Overall, it is estimated that oxidative stress
is associated with in excess of 100 human diseases [50].
Until recently, it was unclear whether oxidative stress is the
pathogenic factor for diseases such as depression and
anxiety, or whether the oxidative imbalances result from the
pathology [6,50]. Nevertheless, the available data are
consistent with the theory that oxidative stress is one of the
causal factors for the genesis of anxiety [6].
ANTIOXIDANT ACTIVITY OF POLYPHENOLS
Polyphenols are a large class of chemicals that can be
divided into a number of varieties including stilbenes,
lignans and flavonoids [31,51,52]. Certain authors consider
(poly)phenols to be all secondary phytochemicals that have
at least two phenol subunits [51,53]. However, Kim et al.
[52] define (poly)phenols as all secondary metabolites with
an aromatic benzene ring that is substituted with at least two
hydroxyl groups, including their functional derivatives.
Moreover, in their classification Manach et al. [31] include
even those phenolic acids that bear only one hydroxyl group
on the aromatic ring and acrylic acid, such as coumaric
acids. It is worth noting that the high antioxidant activity of
polyphenols has been well documented [31-34]. Antioxi-
dants are chemical compounds that detoxify reactive oxygen
species (ROS) (such as superoxide radical (O2·), hydrogen
peroxide (H2O2), hydroxyl radical (OH·), peroxyradical
(ROO·)), and prevent oxidative damage such as lipid
peroxidation, and protein and DNA oxidation [32,43].
Epidemiological and scientific research has identified the
key role of dietary antioxidants for maintaining human
health [54-59]. Epidemiological studies have described the
beneficial effects of consuming fruits and vegetables with
high phenolic content for preventing manifold human
diseases such as cardio- and cerebrovascular diseases [54-56]
and cancer [57-59]. The protective effects provided by fruits
and vegetables against these diseases, which are markedly
associated with oxidative stress, has been attributed to their
antioxidant compounds [60,61]. The main antioxidant
capacity of fruits, vegetables and plants is not only derived
from vitamin C, vitamin E or -carotene, but is also due to
other compounds such as polyphenols [62]. In this regard,
many studies have suggested that polyphenolic compounds
in fruits, vegetables and medicinal plants provide substantial
antioxidant activity. This assumption was based on the direct
and statistically significant relationships found either
Polyphenols Current Nutrition & Food Science, 2010, Vol. 6, No. 1 15
between total phenolic or flavonoid contents and the total
antioxidant capacities of fruits, vegetables and medicinal
plants [33,34,52,63-65]. Chlorogenic acid, quercetin and its
derivatives such as rutin (quercetin 3-rutinoside) are the most
common polyphenols found in fruit and vegetables such as
plums, cherries, apples and onions [31,33,34,41,52,63,65].
Using acellular tests such as a 2-2’-Azino-bis (3ethyl-
benzothiazoline-6-sulfonic acid) (ABTS) test, a 1,1-
diphenyl-2 picrylhydrazyl (DPPH) test or an oxygen radical
absorbance capacity (ORAC) test, it has been demonstrated
that chlorogenic acid, quercetin and rutin possess antiradical
actions [34,65,66]. Using cellular assays, we have
demonstrated that these polyphenols have the capacity to
scavenge ROS and to protect cells against H2O2-induced
oxidative stress [34,41]. In vivo, we have demonstrated that
quercetin fully reverses epirubicin-induced oxidative stress
toxicity in rats [67]. In vivo, it has also been revealed that
rutin prevents oxidative injury in the rat mesenteric
ischemia-reperfusion injury model [68]. In conclusion, there
is good agreement between different researchers that dietary
polyphenols play a key role in antioxidant compensatory
mechanisms and protect against both oxidative stress and
related diseases.
POLYPHENOLS: ANTI-ANXIETY AND ANTI-
DEPRESSANT ACTIVITIES
Prompted by the link between oxidative stress and
anxiety [3-6], we conducted a study to test the effects of an
antioxidant on emotional stress [41]. We used chlorogenic
acid as the antioxidant model because it is one of the most
abundant polyphenols in the human diet and is found in
apples, plums and cherries (Table 1) [33,34,41,65]. We
found that chlorogenic acid significantly decreased anxiety
in mice, without altering locomotion [41]. The dose-res-
ponse curve of chlorogenic acid appeared to have an inverted
U-shape in the light/dark choice test: 20 mg/kg was effec-
tive, but 2, 10 and 40 mg/kg were not [41]. In psycho-
pharmacology, the dose–response curve is usually explained
by the fact that the drug likely acts on different systems
(stimulant, depressant) with different thresholds of
sensitivity [69]. In the elevated plus maze, we confirmed the
anxiolytic-like effect of the active dose of chlorogenic acid
[41]. Combination of flumazenil (5mg/kg, intraperitoneal
injection), a benzodiazepine receptor antagonist, with chloro-
genic acid (20 mg/kg, intraperitoneal injection) reversed the
anti-anxiety effect of chlorogenic acid. This result suggested
that chlorogenic acid diminishes anxiety in mice by acting as
a benzodiazepine receptor agonist [41]. This result
seemingly disproved our initial hypothesis that the anxiolytic
effect of chlorogenic acid is due to its antioxidant potential.
However, we have concluded that chlorogenic acid possesses
dual effects – cytoprotective and anxiolytic - which may be
beneficial to anxious subjects [41]. It has been demonstrated
that chlorogenic acid is absorbed in the small intestine with
no structural change [70]. This increases the nutritional value
of this polyphenol and suggests that the consumption of
fruits such as apples, plums, cherries, etc should be
promoted. Our findings are in keeping with the results of
Vignes et al. [42], which demonstrated that polyphenols can
interact with the GABAA receptor. These authors found that
green tea polyphenol ()-epigallocatechinn gallate (EGCG)
(Table 1) can be used as a neuroprotective agent to reduce
anxiety [42]. It is interesting to note that the effective
anxiolytic dose of chlorogenic acid (20 mg/kg) and EGCG
(30 and 60 mg/kg) was higher than that of commonly-used
anxiolytics such as diazepam and chlordiazepoxide (1-5
mg/kg) [41,42]. Priprem et al. [71] demonstrated that
quercetin is an anxiolytic polyphenol (Table 1). However,
anxiolysis was obtained only after one-week of daily oral
administration of this flavonoid. In addition, the active dose
of quercetin is very high (300mg/ kg/day) compared to
conventional anxiolytics such as diazepam and chlordia-
zepoxide, which are active at lower doses after only one-
hour of oral administration. These results may be explained
by the very low distribution of orally-administered quercetin
to the brain due to its poor absorption, its rapid metabo-
lization and the difficulty with which it penetrates the blood-
Table 1. Dietary Polyphenols: Anxiolytic-like Effects, Antidepressant-like Effects, Side Effects and Dietary Sources
Polyphenols Activity on the Nervous System Side Effects Dietary Source
Chlorogenic acid Anxiolytic-like effects [41] Many types of fruits and vegetables (apples, plums,
cherries, etc) [31,34]
Rosmarinic acid Anxiolytic-like and antidepressant-
like effects [35,69] Skin of apples [73]
Caffeic acid Antidepressant-like effects [35] Many types of fruits and vegetables (apples, plums,
cherries, kiwi, etc) [31,34]
Quercetin Anxiolytic-like effects [71] Sedative effect [19] Many types of fruits and vegetables (apples, plums,
onions, broccoli, tea) [31,34,74]
Rutin Antidepressant-like effects [36] Many types of fruits and vegetables (apples, plums,
cherries, onions, tomato, etc) [31,34,74]
EGCG Anxiolytic-like effects [42] Sedative and amnesic effects
[42,75] Tea [42,74]
Apigenin Anxiolytic-like effects [19,72] Slight sedative effect [19,72] Parsley and celery [74]
16 Current Nutrition & Food Science, 2010, Vol. 6, No. 1 Jaouad Bouayed
brain barrier [71]. In order to improve the absorption of
quercetin and reduce both the duration of treatment and the
active dose required to treat anxiety, Priprem et al. [71]
adopted several methods including intranasal administration
of quercetin in the form of liposomes. Interestingly, they
found that a single dose of intranasally-administered
quercetin elicited an anxiolytic effect. They estimated that
the dose of quercetin in the liposomes was 20 μg; this was
6000 times less than the oral active dose (300 mg/kg) given
to rats [71]. Therefore, the use of liposomes is a potentially
novel strategy with which to facilitate the delivery of
polyphenols across the blood-brain barrier and also to
effectively reduce the active dose. It is important to note here
that previous research has also demonstrated that
polyphenols can have anxiolytic effects at lower doses
(similar to those required by reference anxiolytics)
[19,69,72]. Moreover, some natural flavonoids such as
apigenin (Table 1) also have a selective and relatively mild
affinity for benzodiazepine receptors. These substances have
a pharmacological profile that suggests a partial agonistic
action that may produce the anxiolytic-like effects of
polyphenols, but without the side-effects [19]. At 3 mg/kg,
apigenin exerts its anxiolytic effect in mice without sedation
or myorelaxant effects. However, a 10-fold increase in
dosage of this flavonoid produced slight sedative effects
[72]. Another example of polyphenols that reduce anxiety at
lower doses is rosmarinic acid (Table 1), which is a natural
polyphenol antioxidant found in apple skins and in many
plants such as Melissa officinalis [69,73]. At lower doses (2-
4 mg/kg), Pereira et al. [69] showed that rosmarinic acid
disinhibited behavior towards the aversive spaces of the
elevated plus maze in rats. The dose–response curve for the
anxiolytic-like effects of rosmarinic acid is an inverted U-
shape; this suggests that it likely acts on different systems
(stimulant, depressant) with different thresholds of
sensitivity. In support of this, at a 8 mg/kg dose, Pereira et
al. [69] found that rosmarinic acid has psychostimulative
effects. Using a mouse model [35], it has been demonstrated
that rosmarinic acid (2 mg/kg) significantly decreased
immobility behavior in the forced swimming test. These
results suggest that rosmarinic acid has antidepressant-like
effects [35]. These authors also found that caffeic acid (4
mg/kg) (Table 1), which is a major metabolite of rosmarinic
acid, significantly increased the anti-resignation behavior of
mice in the forced swimming test, thus suggesting anti-
depressant like effects of this polyphenol [35]. They found
that neither caffeic acid nor rosmarinic acid affected the
uptake of monoamines to synaptosomes or the activity of
mitochondrial monoamine oxidase in the mouse brain. This
suggested that both phenolic acids may produce antide-
pressive-like activity via some mechanism(s) other than the
inhibition of monoamine transporters and monoamine
oxidase [35]. Using the tail suspension test (another beha-
vioral model of depression), it was revealed that rutin (0.3-3
mg/kg, per os) (Table 1) significantly decreased the duration
of immobility behavior of mice; this suggested anti-
depressant like effects of this polyphenol [36]. These authors
examined the mechanism of action of rutin and found that it
likely exerts its an tidepressant-like effect by increasing the
availability of serotonin and noradrenaline in the synaptic
cleft [36]. It is important to note that in contrast to reference
antidepressants (e.g., imipramine or fluoxetine) which are
active at higher doses ( 10 mg/kg, intraperitoneal injection),
the polyphenols rutin, caffeic acid and rosmarinic acid are
active at relatively low doses. As a consequence, these
phenolic compounds could be an interesting approach for the
treatment of depression.
CONCLUSION
Polyphenols are interesting naturally-occurring anti-
oxidant substances that can exert pharmacological effects on
the central nervous system (CNS) [35,36,41,69,71]. Poly-
phenols that have partial agonistic properties at benzo-
diazepine receptors may be promising anxiolytic agents due
to the absence of side effects such as dependency, which are
a feature of full agonists such as benzodiazepines [19]. The
intranasal administration of polyphenols in the form of
liposomes [71] could be an effective strategy both to
facilitate the movement of these substances across the blood-
brain barrier and to effectively reduce the activ e dose. As
some polyphenols have been shown to possess antide-
pressant-like effects [35,36] at lower doses than reference
antidepressants, they can be used to stabilize the mood of
depressive patients. Finally, a varied diet that is rich in natu-
rally-occurring polyphenols could be a good means of pre-
venting (or delaying) anxiety, depression and other diseases
linked to oxidative stress.
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Received: October 7, 2009 Revised: December 3, 2009 Accepted: January 5, 2010
... Both are readily found in plant foods and were shown to influence cerebral blood flow, cellular energy metabolism, and modulate signaling pathways of molecules involved with brain plasticity [52][53][54][55]. Naturally occurring dietary polyphenols, found in apples, plums, cherries, onions, and tea, exhibit antidepressant activity with relatively low doses (0.3-2 mg/kg) and are an effective means to prevent (or delay) both anxiety and depression [53]. ...
... Both are readily found in plant foods and were shown to influence cerebral blood flow, cellular energy metabolism, and modulate signaling pathways of molecules involved with brain plasticity [52][53][54][55]. Naturally occurring dietary polyphenols, found in apples, plums, cherries, onions, and tea, exhibit antidepressant activity with relatively low doses (0.3-2 mg/kg) and are an effective means to prevent (or delay) both anxiety and depression [53]. Quercetin, a polyphenol phytochemical compound found exclusively in plant foods [56,57], is probably the most prominent example. ...
... Quercetin was shown to decrease this neurotransmitter breakdown [58] and prevented depression-like behavior in animal studies [61][62][63]. It is exclusively found in plantfoods; thus, a plant-based eating pattern abundant in fruits, vegetables, and legumes enhances its intake and has been proposed as a promising approach for the prevention and treatment of anxiety and depression [53]. Although quercetin also possesses antiviral properties [64,65], it has not yet been tested in a clinical trial in patients suffering from COVID-19. ...
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Purpose of Review The SARS-CoV-2-pandemic has caused mortality and morbidity at an unprecedented global scale. Many patients infected with SARS-CoV-2 continue to experience symptoms after the acute phase of infection and report fatigue, sleep difficulties, anxiety, and depression as well as arthralgia and muscle weakness. Summarized under the umbrella term “long-COVID,” these symptoms may last weeks to months and impose a substantial burden on affected individuals. Dietary approaches to tackle these complications have received comparably little attention. Although plant-based diets in particular were shown to exert benefits on underlying conditions linked to poor COVID-19 outcomes, their role with regard to COVID-19 sequelae is yet largely unknown. Thus, this review sought to investigate whether a plant-based diet could reduce the burden of long-COVID. Recent Findings The number of clinical trials investigating the role of plant-based nutrition in COVID-19 prevention and management is currently limited. Yet, there is evidence from pre-pandemic observational and clinical studies that a plant-based diet may be of general benefit with regard to several clinical conditions that can also be found in individuals with COVID-19. These include anxiety, depression, sleep disorders, and musculoskeletal pain. Adoption of a plant-based diet leads to a reduced intake in pro-inflammatory mediators and could be one accessible strategy to tackle long-COVID associated prolonged systemic inflammation. Summary Plant-based diets may be of general benefit with regard to some of the most commonly found COVID-19 sequelae. Additional trials investigating which plant-based eating patterns confer the greatest benefit in the battle against long-COVID are urgently warranted.
... Therefore it's provide and repair a balanced oxidants-antioxidants in human system. 1227 Polyphenol establish the majority of secondary plant metabolites and also of dietary antioxidants (Bouayed, 2010;Bouayed and Bohn, 2010). Anthocyanins represent an important group of phenolic compounds called flavonoids. ...
... They have received the greatest attention for their effects in the treatment and prevention of several diseases. It has been proved that this type of molecule has numerous cardio-protective functions [48]; they can also prevent or delay depression, anxiety, and other diseases related to oxidative stress [49]. Several studies have indicated that polyphenols and their derivatives have shown anticancer capacities and an antioxidant potential for animal and human cervical cancer cells [50]. ...
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Artemisia absinthium L. is one of the plants which has been used in folk medicine for many diseases over many centuries. This study aims to analyze the chemical composition of the Artemisia absinthium ethyl acetate and its aqueous extracts and to evaluate their effect on the pancreatic α-amylase enzyme and the intestinal α-glucosidase enzyme. In this study, the total contents of phe-nolic compounds, flavonoids, and condensed tannins in ethyl acetate and the aqueous extracts of Artemisia absinthium leaves were determined by using spectrophotometric techniques, then the an-tioxidant capacity of these extracts was examined using three methods, namely, the DPPH (2, 2-diphenyl-1picrylhydrazyl) free radical scavenging method, the iron reduction method FRAP, and the β-carotene bleaching method. The determination of the chemical composition of the extracts was carried out using high-performance liquid chromatography-the photodiode array detector (HPLC-DAD). These extracts were also evaluated for their ability to inhibit the activity of the pan-creatic α-amylase enzyme, as well as the intestinal α-glucosidase enzyme, in vitro and in vivo, thus causing the reduction of blood glucose. The results of this study showed that high polyphenol and flavonoid contents were obtained in ethyl acetate extract with values of 60.34 ± 0.43 mg GAE/g and 25.842 ± 0.241 mg QE/g, respectively, compared to the aqueous extract. The results indicated that the aqueous extract had a higher condensed tannin content (3.070 ± 0.022 mg EC/g) than the ethyl acetate extract (0.987 ± 0.078 mg EC/g). Ethyl acetate extract showed good DPPH radical scavenging and iron reduction FRAP activity, with an IC50 of 0.167 ± 0.004 mg/mL and 0.923 ± 0.0283 mg/mL, respectively. The β-carotene test indicated that the aqueous and ethyl acetate extracts were able to delay the decoloration of β-carotene with an inhibition of 48.7% and 48.3%, respectively, which may mean that the extracts have antioxidant activity. HPLC analysis revealed the presence of naringenin and caffeic acid as major products in AQE and EAE, respectively. Indeed, this study showed that the aqueous and ethyl acetate extracts significantly inhibited the pancreatic α-amylase and intestinal α-glucosidase, in vitro. To confirm this result, the inhibitory effect of these plant extracts on the enzymes has been evaluated in vivo. Oral intake of the aqueous extract significantly attenuated.
... Therefore, effective prevention and treatment strategies are required to overcome depression. Several studies have shown that the antidepressant effects of polyphenols, especially dietary polyphenols, have the potential to be widely used in depression worldwide because their antidepressant effects can be cost-effective [9][10][11][12]. Most dietary polyphenols are associated with reduced symptoms of depression, and consumption of some polyphenols significantly reduces depressive symptoms [9]. ...
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Flavonoids and carotenoids are bioactive compounds that have protective effects against depressive symptoms. Flavonoids and carotenoids are the two main types of antioxidant phytochemicals. This study investigated the association between flavonoid and carotenoid intake and depressive symptoms in middle-aged Korean females. We analyzed the mechanism of these associations using an in silico method. Depressive symptoms were screened using the Beck Depression Inventory-II (BDI-II), and flavonoid and carotenoid intake were assessed using a semi-quantitative food frequency questionnaire. Using a multivariate logistic regression model, we found that flavones, anthocyanins, individual phenolic compounds, lycopene, and zeaxanthin were negatively associated with depressive symptoms. In silico analysis showed that most flavonoids have high docking scores for monoamine oxidase A (MAOA) and monoamine oxidase B (MAOB), which are two important drug targets in depression. The results of the docking of brain-derived neurotrophic factor (BDNF) and carotenoids suggested the possibility of allosteric activation of BDNF by carotenoids. These results suggest that dietary flavonoids and carotenoids can be utilized in the treatment of depressive symptoms.
... could be a good strategy for preventing anxiety and depression ( Figure 2) [18,39]. Furthermore, the anti-inflammatory effect of a high dTAC may explain its inverse association with mental disorders, in addition to antioxidant protection [25,40]. ...
Article
Background and aim: We aimed to systematically review observational studies that evaluated the potential association of the dietary total antioxidant capacity (dTAC) with common mental disorders (depression and anxiety) and sleep disorders. Methods: Studies with an observational design that evaluated the association between the dTAC and common mental disorders and sleep disorders were identified using the PubMed and Scopus databases. The meta-analysis guideline of observational studies in epidemiology and the preferred reporting items for systematic reviews and meta-analysis were used to conduct and report the data of this systematic review. Results: Of the 439 records, seven studies were included in this review. There was a sample variation of 41-3297 participants. We highlight that five of the studies analyzed were conducted in the Iranian population. Four studies analyzed only women, and three studies were conducted with postmenopausal or climacteric women. Four cross-sectional studies showed inverse associations between the dTAC and depression, anxiety, and sleep disorders in Iranians. Conclusion: The consumption of a diet rich in antioxidants, characterized by high dTAC scores, seems to be inversely associated with depression, anxiety, and sleep disorders. However, further studies with different populations and designs are necessary for a better understand this relationship. Relevance to patients: This review assesses the association of the dTAC with common mental disorders (depression and anxiety) with sleep disorders. This will help guide further studies on the relationship between diet and mental disorders and sleep disorders. Knowledge about these relationships is essential for the creation of non-pharmacological practices for the prevention of these disorders.
... Despite the fact that in vitro studies have highlighted the cytoprotective effect of dietary antioxidant constituents like polyphenols or carotenoids against oxidative stress or cell death, they can also display prooxidant activity, such as a number of polyphenols known by their antioxidant activity like catechin, epicatechin and quercetin, in a high concentration or in the presence of metal ions (70)(71)(72). The strong reducing power of antioxidants may affect the metal ions e.g., Cu 2+ , Fe 3+ , increasing their ability to form hydroxyl radicals in high concentrations through Fenton reaction from peroxides (73,74). ...
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Objective: To unveil the role of reactive oxygen species (ROS) and antioxidants in signaling and involvement in cancer progression and therapy. Background: Cancer is considered one of the main causes of mortality in developed countries and expected to be more in developing countries as well. Although some cancers may develop at young age, yet almost all types of cancers are an accumulation of genetic and epigenetic cell damages. Cancer is considered a diverse collection of diseases on a cellular level rather than a single disease; and each disease has a different cause as well. ROS have been seen as harmful toxic molecules; however, they are recognized for cellular signaling capabilities. Elevated levels of ROS have protumorigenic activities; they induce cancer cell proliferation, and adaptation to hypoxia in addition to other effects like DNA damage and genetic instability. They are produced excessively by cancer cells to hyperactivate cellular transformation meanwhile increasing antioxidant capacity to avoid cell death. Methods: We discussed peer reviewed published research work from 1987 to 2021. In this paper, we review the role of antioxidants as defensive barrier against excessive ROS levels for maintaining oxidation-reduction (redox) balance; however, antioxidant can also strive in tumor cells with their scavenging capacities and maintain protumorigenic signaling and resist the cancer cell oxidative stress and apoptosis. High doses of antioxidant compounds could be toxic to cells as they are capable of reacting with the physiological concentrations of ROS present for normal cellular processes and signaling. Conclusions: Maintaining cellular redox homeostasis is vital for healthy biological system. Therefore, therapeutic modalities for cancer including antioxidants and ROS management should be used at certain doses to target specific redox pathways involved in cancer progression without disrupting the overall redox balance in normal cells.
... All those facts combined have stepped up the hunt for other safe and affordable alternative therapies [21]. Several reviews of herbal extracts and secondary metabolites are used in conventional medicine owing to their anxiolytic and antidepressant properties [22,23]. Clinical and pre-clinical trials have reported successful use of medications for certain plant metabolites, such as alkaloids, terpenes, flavonoids, and sterols and others [24,25]. ...
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Mental disorders are psychological symptoms that impact multiple areas of an individual’s life. Depression and anxiety are chronic illnesses described as the most prevalent stress-related mood disorders that cause injury and early death. In Morocco, Anise “Pimpinella anisum L.” is one of the most traditionally used condiment plants, which has long been used to cure various illnesses and in phytotherapy. The present study was designed to investigate the antidepressant, anxiolytic, and memory impact of the total extract of Pimpinella anisum (PATE) at the doses of 100 and 200 mg/kg, using the Forced Swimming Test (FST), Tail Suspension Test (TST), Open Field Test (OFT), and Light–Dark Box Test (LDBT) as an experimental paradigm of anxiety and depression, and Novel Object Recognition Test (NORT) and the Morris Water Maze Test (MWMT) as memory tests on Swiss albino mice. The tests were carried out on the 1st, 7th, 14th, and the 21st days of the study, and the extract groups were compared with normal controls and positive controls (receiving bromazepam and paroxetine at the doses of 1 mg/kg and 11.5 mg/kg for anxiety and depression, respectively). The daily oral gavage of the mice by the PATE induced a significant anxiolytic and antidepressant-like effect by shortening immobility time and decreasing downtime in the different tests. PATE at both doses was shown to have no impact on memory following the NORT and MWM tests. Different compounds, such as gallic acid, catechin, chlorogenic acid, caffeic acid, oleuropein, p-coumaric acid, trans-4-hydroxy-3-methoxycinnamic acid, myricetin, and quercetin, were identified during the phytochemical analysis carried out using HPLC analysis. This research supports and promotes the extract’s traditional use, suggesting its use as a phytomedicine against depression and anxiety, and calls for further research to clarify its mode of action.
... This event eventually leads to cell death (7,8). The use of natural antioxidants can reduce the rate of food oxidation and if used properly and applied can increase the life of food products during consumption (9). ...
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Fat peroxidation is one of the problems in food processing, cooking, and storage. Oxidative changes cause pathological effects in biological systems and reduce the taste and quality and ultimately spoil food. The use of aromatic plants and vegetables with antioxidant properties can play an important role in preventing these adverse effects. The antioxidant effects of Mentha longifolia have been considered in recent years. The aim of this study was to investigate the antioxidant activity of the peppermint plants and determine its protective effect on lipid oxidation of high consumption meat products in Tabriz. For this purpose, aqueous-alcoholic extract of mint leaves and twigs with concentrations of 0.1%, 1%, 5% with homogeneous mixtures of 10%, 90% meat hamburger products, and 45% sausages were exposed. Lipid oxidation was measured by measuring malondialdehyde by the TBARS method on day 0 and after 42 days of exposure to peppermint extract at 0-4 ° C and was compared with the control group. The results show that increasing the shelf life of meat mixtures significantly increases fat peroxidation (P 0.0 0.05). Also, increasing the concentration of peppermint extract in meat solution samples will reduce the amount of malondialdehyde significantly (P 0.0 0.05). The results show the antioxidant activity of peppermint during the storage time of meat products and its benefits can be used in the food industry.
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Depression is a prevalent neuropsychiatric disease with a high recurrence rate, affecting over 350 million people worldwide. Intestinal flora disorders and gut-brain-axis (GBA) dysfunction may cause mental disorders. Alterations in the intestinal flora composition could increase the permeability of the gut barrier, activate systemic inflammation and immune responses, regulate the release and efficacy of monoamine neurotransmitters, alter the activity and function of the hypothalamic-pituitary-adrenal (HPA) axis, and modify the abundance of the brain-derived neurotrophic factor (BDNF); all of these showed a close correlation with the occurrence of depression. In addition, the disturbance of the intestinal flora is related to circadian rhythm disorders, which aggravate the symptoms of depression. Tea polyphenols (TPs) have been found to have antidepressant effects. Therefore, the close reciprocity between the intestinal flora and circadian rhythm provides a new opportunity for TPs to regulate depression relying on the intestinal flora. In this review, we discussed the relationship between intestinal flora dysbiosis and the pathogenesis of depression and the mechanism of TPs relieving depression via the GBA.
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Dioxygen is an element essential to our survival, our life, our development, our capacity of adaptation. Nevertheless, dioxygen is also at the origin of toxicity, acidity, deterioration, degeneration. Indeed, when the metabolism of dioxygen is altered, as in the respiratory diseases, an “oxidative stress” can appeared and induced metabolic anomalies associated with important consequences. Oxidative stress is defined as an imbalance between pro-oxidant (reactive oxygen species) and antioxidant factors, in favour of the former. The genomic, metabolic and functional modifications induced by oxidative stress were implied in the development of various degenerative diseases. Antioxidant treatments, in a nutritional or pharmacological way, appeared consequently as new potent therapies. In this review, the role of dioxygen in the cellular metabolism, and in the production of the reactive oxygen species is discussed. The negative effects of the oxidative stress on the organism are reported. Finally, the results of the studies on the nutritional antioxidant treatment firstly in the degenerative diseases, secondly in a chronic respiratory disease, the chronic obstructive pulmonary disease, are discussed in a last part.
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A prior national survey documented the high prevalence and costs of alternative medicine use in the United States in 1990. To document trends in alternative medicine use in the United States between 1990 and 1997. Nationally representative random household telephone surveys using comparable key questions were conducted in 1991 and 1997 measuring utilization in 1990 and 1997, respectively. A total of 1539 adults in 1991 and 2055 in 1997. Prevalence, estimated costs, and disclosure of alternative therapies to physicians. Use of at least 1 of 16 alternative therapies during the previous year increased from 33.8% in 1990 to 42.1% in 1997 (P < or = .001). The therapies increasing the most included herbal medicine, massage, megavitamins, self-help groups, folk remedies, energy healing, and homeopathy. The probability of users visiting an alternative medicine practitioner increased from 36.3% to 46.3% (P = .002). In both surveys alternative therapies were used most frequently for chronic conditions, including back problems, anxiety, depression, and headaches. There was no significant change in disclosure rates between the 2 survey years; 39.8% of alternative therapies were disclosed to physicians in 1990 vs 38.5% in 1997. The percentage of users paying entirely out-of-pocket for services provided by alternative medicine practitioners did not change significantly between 1990 (64.0%) and 1997 (58.3%) (P=.36). Extrapolations to the US population suggest a 47.3% increase in total visits to alternative medicine practitioners, from 427 million in 1990 to 629 million in 1997, thereby exceeding total visits to all US primary care physicians. An estimated 15 million adults in 1997 took prescription medications concurrently with herbal remedies and/or high-dose vitamins (18.4% of all prescription users). Estimated expenditures for alternative medicine professional services increased 45.2% between 1990 and 1997 and were conservatively estimated at $21.2 billion in 1997, with at least $12.2 billion paid out-of-pocket. This exceeds the 1997 out-of-pocket expenditures for all US hospitalizations. Total 1997 out-of-pocket expenditures relating to alternative therapies were conservatively estimated at $27.0 billion, which is comparable with the projected 1997 out-of-pocket expenditures for all US physician services. Alternative medicine use and expenditures increased substantially between 1990 and 1997, attributable primarily to an increase in the proportion of the population seeking alternative therapies, rather than increased visits per patient.
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A GC–MS method was developed for the separation and quantifiation of three flavones: sinensetin (SEN), rutin (RU) and 3′-hydroxy-5, 6, 7, 4′-tetramethoxyflavone (TMF) and rosmarinic acid (RA), a caffeic acid derivative, in the skin of apple fruit collected from different local markets of Bangladesh. The results showed significant variation in the amount of these markers in methanolic extracts of skin samples from different markets of Bangladesh, even though the values were almost identical for most of the cases. A variation in antioxidant activities, ranging from 62.82 to 92.34%, and variations in total phenolics, ranging from 6.69 to 10.20 mg caffeic acid/g dry weight of the methanol extracts, were observed. Antioxidative potency of the methanolic extracts was comparable to that of pure quercetin and the synthetic antioxidant butylated hydroxylanisole (BHA).
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Benzodiazepines (BDZs) are the most widely prescribed class of psychoactive drugs in current therapeutic use, despite the important unwanted side-effects that they produce such as sedation, myorelaxation, ataxia, amnesia, ethanol and barbiturate potentiation and tolerance. Searching for safer BDZ-receptor (BDZ-R) ligands we have recently demonstrated the existence of a new family of ligands which have a flavonoid structure. First isolated from plants used as tranquilizers in folkloric medicine, some natural flavonoids have shown to possess a selective and relatively mild affinity for BDZ-Rs and a pharmacological profile compatible with a partial agonistic action. In a logical extension of this discovery various synthetic derivatives of those compounds, such as 6,3′-dinitroflavone were found to have a very potent anxiolytic effect not associated with myorelaxant, amnestic or sedative actions. This dinitro compound, in particular, exhibits a high affinity for the BDZ-Rs (Ki = 12–30 nM). Due to their selective pharmacological profile and low intrinsic efficacy at the BDZ-Rs, flavonoid derivatives, such as those described, could represent an improved therapeutic tool in the treatment of anxiety. In addition, several flavone derivatives may provide important leads for the development of potent and selective BDZ-Rs ligands.
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Medicinal plants are a source for a wide variety of natural antioxidants. In the study reported here, we have conducted a comparative study between five medicinal plants having the same geographic origin: the Hamadan region in the west of Iran and growing in the same natural conditions. The amount of total phenolics and total flavonoids for parts of these plants used in Iranian popular medicine were evaluated. Furthermore, antioxidant activities for these parts using vitamin C equivalent antioxidant capacity (VCEAC) test were also evaluated. The results show that the antioxidant activities varied greatly among the different plant parts used in this study and some plants are rich in natural antioxidants especially leaves of Lavandula officinalis and of Melissa officinalis. A positive correlation between total phenolic or flavonoid contents and VCEAC was found with a correlation coefficient of R2=0.961 and R2=0.817, respectively. These findings show that phenolics in these plants provide substantial antioxidant activity.
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(-)-Epigallocatechin gallate (EGCG) has a sedative effect acting through γ-aminobutyric acid (GABA)A receptors in the brain, but it is unclear what structural components of the molecule are necessary for its action. To investigate the necessity of the galloyl group on the sedation induced by EGCG, the effect of EGCG was compared with (-)-epigallocatechin (EGC) in which the galloyl group is removed from EGCG. Intracerebroventricular (i.c.v.) injection of EGC, as well as EGCG, induced, and the effect of EGC were blocked by the GABAA receptor antagonist picrotoxin. It is concluded that catechins have a sedative effect acting through GABAA receptors under an acute stress condition irrespective of the presence of the galloyl group.
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Oxidative stress in central and peripheral systems is involved in many diseases, including cancer, cardiovascular diseases, neurodegenerative diseases and several psychiatric disorders. In the present study, the brain and peripheral oxidative status of non-anxious and anxious mice was evaluated using 2′,7′-dichlorofluorescin diacetate (DCFH-DA), a sensor of reactive oxygen species (ROS). Here we report that anxiety levels are linked to the oxidative status in both neuronal and glial cells in the cerebellum and hippocampus, in neurons of the cerebral cortex and in peripheral leucocytes (monocytes, granulocytes and lymphocytes), revealing the presence of oxidative stress in the central and peripheral systems of anxious mice. These findings suggest the redox system in anxious mice may play a role in neuroinflammation and neurodegeneration, predisposing them to recurrent infections and chronic inflammation.