JOURNAL OF NATURAL REMEDIES

DOI: 10.18311/jnr/2023/33991 REVIEW ARTICLE

Role of Phytoflavonoids in the Management of

Anxiety and Depression: An Overview
Avijit Mazumder*, Arbaz Khan and Jatin Saini
Noida Institute of Engineering and Technology (Pharmacy Institute)
19 Knowledge Park II, Greater Noida - 201306, Uttar Pradesh, India; avijitmazum@yahoo.com

Abstract
The main global health issue, anxiety, and depression have significant psychological, social, and financial repercussions.
It promotes an anticipatory and adaptable reaction to difficult or stressful situations. When anxiety is excessive, it
destabilizes the person, which leads to a dysfunctional state. In the absence of intense situations, it’s a pathological state.
It comprises posttraumatic stress disorder, general anxiety, aversion to social situations, obsessive-compulsive disorder,
and panic disorder. Some people think about using natural therapies as an alternative to anxiety drugs because they may
cause negative side effects. Due to their natural origins and lack of adverse effects, these medications and herbal medicine
are becoming more and more popular in both developed and developing nations. Minerals, organic matter, and medicinal
plants are the sources of many traditional remedies. Alkaloids, also saponins, glycosides, flavonoids, which, etc. are all
present. The goal of this summary is to provide in-depth knowledge about the many phytoconstituents that have the
potential to reduce anxiety and play a significant role in CNS activity.

Keywords: Anxiety, Depression, Flavonoids, Medicinal Plants, Phytoconstituents, Traditional Medicine

1. Introduction in psychiatric nosography, anxiety, and depression

may coexist and make coping more challenging8.
Over the past ten years, a growing body of evidence The therapy of anxiety disorders involves the use of
has emerged connecting abnormalities of the oxidative several herbs. Anxiety problems are treated with herbs
process to anxiety-related illnesses1, high levels of including lemon balm, Brahmi, ginseng, passionflower,
anxiety2, and sadness3. Depression and anxiety may and Valerian. In clinical use, current pharmacological
coexist; depression is characterized as an anti-depressive methods for managing anxiety have not yet produced
state in psychiatric nosography, which makes coping the desired effects9. Natural herbal blends are regarded
harder4. People in contemporary culture experience a as nature-based modern pharmaceuticals since they
variety of psychiatric problems, particularly sadness, work synergistically to give an effective treatment for
anxiety, and sleeplessness. Depressive disorders, one anxiety10.
of the most common types of mental disease, have a
significant impact on people and society. By the year
2. Herbal Psychopharmacological
20245, Major Depressive Disorder (MDD) would
rank as the second most common disease worldwide, Likely, controlling a single target may not exert the
according to the World Health Organization antipsychotic effect as effectively as targeting many
(WHO). Evidence linking abnormalities of oxidative systems due to the complexity of psychiatric diseases.
metabolism to anxiety disorders6, extreme anxiety, Herbal medicine is frequently used to treat mental
and depression has grown during the past ten years7. illnesses through a variety of processes that act on
In what is known as an anxious-depressive syndrome multiple systems. Considering that neurological factors

Article Received on: 06.06.2023 Revised on: 20.07.2023 Accepted on: 26.09.2023
1224 Role of Phytoflavonoids in the Management of Anxiety and Depression: An Overview

underlie mental disorders like depression, anxiety, and production15. The importance of neuroendocrinological
insomnia, which are frequently found in the same abnormalities, such as cortisol overabundance cytokine
patient, it is likely that the mechanisms of treatment for or steroid changes, modifications to neurotransmitters
these illnesses are intertwined. When certain factors act such and/or glutamatergic delivery, diminished natural
on one target, activity in a different area may manifest. opioid operation, and abnormal rhythms, has also
Of course, this could affect how other mental diseases received more attention in recent years16 (Figure 1).
that are connected are treated11.
6. Mechanism of Action Herbal
3. Medicinal Herbs are Used in Medicines
the Treatment of Anxiety and
Depression There are several biological effects on the reuptake and
receptor binding of different monoamines, frequently
One of the primary sources of medicine in traditional along with endocrine and psychoneuroimmunological
Chinese medicine is herbs. It is becoming increasingly regulation, which make the antidepressant modes of
important in the management of anxiety and action of herbal medications less well understood than
depression. Furthermore, numerous research studies those of synthetic drugs17. Certain herbal remedies
have demonstrated that using herbal medicines to treat with anti-depressant properties, like H. perforatum, the
depression leads to improvements in the condition. cultivar Crocus sativus (saffron) (C. sativus) and rose root
Recently, certain therapeutic herbs have demonstrated (R. rosea) (roseroot), offer favourable outcomes for the
effects similar to those of antidepressants. Some of medical management of mood disorders via referred to
the herbal medications that have been listed below psychopharmacological acts such as reducing amine re-
and can be used in the treatment of anxiety and uptake (noradrenaline, serotonin, and dopamine), the
depression share similar psychopharmacological activity of monoamine oxidase inhibition, stimulation,
effects to those of antidepressants in that they help to and enhancement of serotonin receptor binding, or
regulate the serotonin, dopamine, and noradrenaline neuroendocrine modulation17. GABAergic effects,
reuptake, where they also aid in MAO inhibition and morphine, cannabinoid system effects, and other effects
modulation of the neuroendocrine system along with have also been proposed18 (Figure 2).
the Hypothalamic-Pituitary-Adrenal (HPA) axis12.
7. Herbal Plants with Anxiolytics and
4. Pathogenesis of Anxiety Antidepressants Activity
In comparison to depression, anxiety’s aetiology is One of the primary sources of medicine in traditional
less well understood and remains anxiety. abolished. Chinese medicine is herbs. It is becoming increasingly
However, recent research suggests that anomalies
in noradrenergic, serotonergic, GABAergic, and
glutamatergic communication are part of the
pathophysiology of anxiety13. The effectiveness of
sedatives, selective serotonin reuptake inhibitors, and
selective serotonin and noradrenalin inhibitors of
reuptake in the management of depression reflects the
participation of this system14.

5. Pathogenesis of Depression
The pathophysiology of depression has recently
been centred on secondary messenger malfunction,
monoamine impairment, and decreased monoamine Figure 1. Pathogenesis of anxiety and depression.

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 Avijit Mazumder, Arbaz Khan and Jatin Saini 1225

Figure 2. The mechanism of action of central nervous effects of medicinal plants.

important in the management of depression and cortex by inhibiting monoamine neurotransmitters

anxiety. Furthermore, numerous research has like a substance called (5-HT), noradrenaline, and
demonstrated that using herbal medicines to treat dopamine levels21. One of the main purposes of H.
depression led to improvements in the condition. perforatum is overexpression of the 5-HT receptors,
Recently, certain therapeutic herbs have demonstrated which has the effect of upregulating the neurons, it in
the same antidepressant-like properties. Some herbal turn results in a dopamine-related component lowering
medications are a few that are listed below and can the neurons’ background activity. This herb has effects
be utilized to treat depression. These medications similar to SSRIs in that it increases the element in
have the same psychopharmacological effects against 5-HTAA receptors. It also has effects similar to SSRIs in
the nervous system as antidepressants, and they that it blocks GABA3 binding, which affects the central
help in maintaining the serotonin, dopamine, and nervous system’s reduced memory. H. perforatum
noradrenaline reuptake, while additionally assisting in has an impact on N-methyl-D-aspartate receptors
the MAO limitation and shifting of the neuroendocrine (NMDARs), which are necessary for nootropics to
system’s functions along with Hypothalamic-Pituitary- work22.
Adrenal (HPA) axis19.
8.2 Lavender
Lavandula angustifolia is the scientific name for the
8. Flavonoids-Rich Plant with
herbaceous plant known as lavender. According to
Antianxiety and Antidepressant
recent research, lavender has outstanding hypnotic and
Properties
mild sedative effects when used in aromatherapy, and it
8.1 St. John’s Wort has helped postpartum depressive disorder in women
Another name for Hypericum perforatum is St. John’s who have given birth. Recent research has shown that
wort. According to the current research, St. John’s the active elements of lavender, linalool, and linalyl
wort’s medicinal form consists of a variety of leaves acetate quickly reach their plasma peak levels23.
and flowering tops that contain flavonoids, which Lavender flowers contain 1-3 % essential oil, coumarin
include phloroglucinols (hyperforin), xanthones, derivatives (umbelliferon, herniarin), flavonoids, traces
naphthodianthrones, and hypericin. Recent of sterols (cholesterol, campesterol, stigmasterol, and
studies have demonstrated that H. perforatum has -sitosterol), traces of triterpenes (micrometric acid,
similar antidepressant effects to those of tricyclic ursolic acid), up to 13% tannins, and phenol carboxylic
antidepressants and selective reuptake inhibitors of acids (such as rosmarinic acid, ferulic acid, is feral24.
serotonin20. H. perforatum has been shown to elevate Aromatherapy has been shown to make up most of
the level of different monoamines and 5HT in the lavender’s medicinal uses, and studies have shown
cerebellum, amygdala, hippocampus, and prefrontal that the herb’s effects on sleep-related breathing have

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1226 Role of Phytoflavonoids in the Management of Anxiety and Depression: An Overview

enhanced sleep quality by suppressing the cause of balm and variations in the Similar amounts of serotonin
sleeplessness. Studies have even found that an elevated (5-HT) present in the central nervous system. The
2nd phase of sleep has a substantial impact. Whereas antioxidant property tested targeted serotonin in the
there were no side effects recorded and sleep could CNS30.
be effectively induced along with an improvement
in mood, this indirectly improved depression by 8.5 Aegle marmelos
modifying the circadian rhythm25. In Aegle marmelos various studies have shown the
presence of flavonoids in phytochemical screening
8.3 Ginseng which are responsible for the anxiolytic effect through
Ginseng is commonly managed clinically under the benzodiazepine receptors. Therefore, flavonoids
botanical name Panax ginseng. It was once considered present in Aegle marmelos may be responsible for the
to be one of the greatest medicines, and recent studies anti–anxiety activity. Various studies on Aegle marmelos
have proved that ginseng’s component ginsenosides have shown the presence of phytoconstituents other
exhibits antidepressant-like effects in preclinical than flavonoids like tannic acid, phenols, marmesinin,
animal models. Numerous causes might cause ascorbic acid, eugenol, skimmianine, saponin etc.,
depression, such as glial cell aggregation and blocking which may possess anxiolytic properties. Aegle
neuronal cells, but current research has revealed that marmelos can be a safe and effective drug for the
glial cells also contain astrocytes, which are crucial to treatment of several anxiety disorders. The fruit
the pathology of depression26. Ginseng successfully contains ethanolic extracts. These are used to care for
controls the immune response reaction, and it also fatigue, anxiety, and depression. The fruit has steroids,
aids in the preservation of the body system. It has a coumarin, and alkaloids31.
variety of impacts in treating disorders that are like
depression in addition to psychiatric illnesses. Recent 8.6 Acoros calamus
research has demonstrated that ginseng is effective in Due to the presence of alpha- or beta-asarone, chewing
treating the HPA axis and managing the hormones that the rootstock of the Acorus calamus herbs might result
are necessary for the subsequent phase. The HPA axis, in hallucinations. In rats, the Acorus calamus exhibits
the brain’s control centre, is where cortisol is primarily neuroprotective properties against chemically induced
made and controlled. the sympathetic nervous system neurodegeneration and stroke. It protects against
also plays a vital role in this cycle27. neurotoxicity brought on by acrylamide. Acorus
calamus leaves and roots both exhibit antioxidant
8.4 Lemon balm qualities. Since ancient times, the Indian system of
Melissa officinalis, usually referred to as lemon balm, is conventional healing has recognized the roots and
an old remedy that has long been used for treatment. rhizomes of the Acorus calamus as rejuvenating agents
M. officinalis has a strong antioxidant property and for the brain and neurological system. Alpha and beta
a high phenolic content. Lemon balm has even been asarone, two compounds found in the rhizomes of the
shown to have immune-suppressant and antioxidant Acorus calamus, have a variety of pharmacological
characteristics, as well as the ability to oxidize linoleic properties, including sedative, CNS depressive,
acid via autoxidation and EDTA-mediated oxidation28. behaviour-modifying, epilepsy, acetylcholinesterase
Because of the rush of free radicals in the postsynaptic restricting, and memory-improving effects32.
junction and its well-known antioxidant action, lemon
balm has a major impact on the neurotransmitter. A 8.7 Viola odorata
recent study in Iranian diabetic patients revealed that Viola odorata, a species of the genus Viola that is native
the prevalence of depression and anxiety in diabetes to Europe and Asia, has also made its way to North
mellitus patients was estimated to be 24/4% and 64/5%, America and Tasman. It is also known by the names
respectively29. The appearance of depression in diabetic sweet violet, English violet, garden violet, and wood
patients is associated with poorer medication adherence. violet33. This flower’s pleasant aroma has been well-
Numerous pathways describe the applications of lemon liked throughout history, especially in the late Victoria

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 Avijit Mazumder, Arbaz Khan and Jatin Saini 1227

era, and as a result, it is utilized to make numerous the chemical chlorogenic acid significantly decreased
medical perfumes and perfumes33. It has been used anxiety in mice without impairing their ability to
in the conventional system to treat anxiety34, and move37. The curve of dose-response for chlorogenic
sleeplessness, and to reduce blood pressure35. Violet acid appeared to have a reverse U-shape in the light/
is mostly utilized as a natural treatment for a variety dark choice test: 20 mg/kg were productive, while
of respiratory conditions. Treatment of sore throat, 3, 13, and 65 mg/kg were not37. The hypothesis that
coughing, and congestion can all benefit greatly from the medication acts on multiple organs (stimulant,
it. Recent research has revealed that Common Violet depressive), each of having distinct criteria for
leaves contain salicylic acid glycoside, which explains sensitivity, is commonly used to explain the distribution
why they are effective in treating headaches and of doses in psychopharmacology. We established the
other bodily ailments. Common violet flower syrup active chlorogenic acid dosage’s anxiolytic-like effects
possesses expectorant, laxative, anti-inflammatory, and in the elevated plus maze37. The anti-anxiety effects
antiseptic qualities. In addition to treating headaches, of chlorogenic acid were abolished when flumazenil,
sleeplessness, vertigo, and tiredness, it can be beneficial a benzodiazepine receptor antagonist, was combined
in cases of certain respiratory disorders, Alkaloids, with it (20 mg/kg, intraperitoneal injection). This
glycosides, saponins, methyl salicylate, mucilage, finding indicated that chlorogenic acid acts as a
and vitamins E and C are all present in the viola36. benzodiazepine receptor agonist to reduce anxiety in
Along with other therapeutic effects, the plant has mice38. This outcome appears to refute our initial theory
been claimed to have anti-inflammatory and diuretic that chlorogenic acid’s ability to act as an antioxidant
properties, but no research has been identified on its accounts for its ability to reduce anxiety. Nevertheless,
ability to decrease cholesterol or blood pressure36. we concluded that chlorogenic acid has two favourable
effects that may help worried subjects: cytoprotective
and anxiolytic effects39. Chlorogenic acid is proven
9. Polyphenols: Antianxiety and
to be digested in the small intestine without causing
Antidepressant Activities
any structural changes40. This raises the polyphenol’s
Because oxidative stress and anxiety have been nutritional value and implies that fruit consumption,
connected, we undertook a study to investigate the including that of apples, plums, cherries, and other
effect of an antioxidant on mental strain37,38. We fruits, should be encouraged. Our results support those
choose chlorine dioxide as the antioxidant model since who showed that polyphenols might interact with the
it is one of many common polyphenols consumed by GABAA transmitter40. These researchers discovered
humans and may be in large quantities in fruits such as that the neuroprotective compound EGCG (Table 1),
apples, plums, and berries (Table 1). We discovered that a polyphenol present in green tea, can be utilized to

Table 1. Dietary polyphenols: anxiolytic-like effects, antidepressant-like effects, side effects and dietary sources
Polyphenols CNS Activity Adverse event Dietary Source
Chlorogenic acid Sedative effects42 Fruits and vegetables of many varieties
(apples, plums, cherries, etc.)43,44.
Rosmarinic acid Anxiolytic-like and Peel of apples81.
antidepressant-like actions45
Caffeic acid Antidepressant-like effects45 Several different kinds of vegetables and
fruits (apples, plums, cherries, kiwi fruit
etc.)43,44.
Quercetin Anxiolytic-like effects47 Sedative effect48. Different types of natural products (apples,
plums, onions, broccoli, tea)43,44.
Rutin Antidepressant-like effects46 Different types of natural products (apples,
plums, cherries, onions, tomato, etc)43,44.
Apigenin Anxiolytic-like effects48 Slight sedative effect48 Parsley and celery48

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1228 Role of Phytoflavonoids in the Management of Anxiety and Depression: An Overview

lessen anxiety41. Additionally, some naturally occurring in healthy volunteers. It has been demonstrated that
flavonoids, such as apigenin (Table 1), have a specific L-theanine sympathetically reduces nerve responses50.
and comparatively low activity for benzodiazepine Numerous investigations have demonstrated that
receptors. The pharmacological profile of these prefrontal cortisol function, which has a dominant
compounds points to a limited agonistic action that impact on cognitive impairment and processes related
might induce the anxiolytic-like benefits of polyphenols to memory impairment, has an impact on both sites
without the negative side effects. Apigenin causes and -waves of electroencephalogram51.
no depression or myorelaxant effects in mice when
administered at 3 mg/kg. However, a tenfold rise in 11.2 Carvacrol
the flavonoid dosage led to very little sedative effects41. Oregano and thyme are combined to produce the
Rosmarinic acid is another example of a polyphenol fragrant herb carvacrol. Essential oils and aromatic
that lessens anxiety at lower levels (Table 1). plants both contain a significant amount of carvacrol.
It has proven to have a variety of cognitive benefits
10. P
 hytoflavonoids and the and a considerable effect on depression. Even though
Monoaminergic System the safety index has not been determined, it has been
established that the substance is a chemical flavonoid.
According to the monoamine theory of depression, Because carvacrol only affects depression in females
a drop in the levels of the catecholamine NE and during the oestrous cycle and because it has been
the indoleamine 5-HT in the synaptic cleft is demonstrated to affect the serotonin and metabolites
related to anxiety and depression. These substances’ tissue composition of the prefrontal cortex, cerebellum,
serotonergic properties provide them with anxiolytic and nucleus acumens, it has been the subject of
and antidepressant effects. Metabolic abnormalities of numerous clinical studies52. The monoterpenoid
monoamine neurotransmitters implicated in NE, 5-HT, phenol carvacrol significantly affects the V3 and A1
and DA signalling are the primary molecular causes potential, which is what causes the warmth. Carvacrol
of depression. Additionally, it was discovered that the modulates human ion channels and transient receptor
HPA axis’s ability to function properly was impaired in prospective in turn. Carvacrol has the important
many depressive patients. Numerous flavonoids have feature of inhibiting the depression caused by
been found to have anti-inflammatory, antioxidant, cyclooxygenase-2 and functioning on the peroxisome
and antidepressant properties in animal studies49. proliferator-activated receptor53,54. Administration of
carvacrol has been shown to affect dopaminergic brain
11. Phytochemicals are used Against circuits, increase levels of 5-HT and dopamine, and
Anxiety and Depression stimulate the prefrontal cortex55.

11.1 L-theanine 11.3 Curcumin

The plant C. sinensis, also known as green tea, is the source Curcumin comes from turmeric, also called Curcuma
of the amino acid L-theanine. In contrast, L-theanine longa. These phytoconstituents have shown that the
has the amazing ability to cross the blood-brain barrier levels of neurotransmitters in the brain are enhanced
and has been demonstrated to increase brain volume where it has an antidepressant action and is prevented
in a dose-dependent manner. Numerous preclinical by MAO B and A. The depressing characteristics
research on rats studied the loss of hippocampal of curcumin have been proven to represent the
CA1 over time following stimulation to the stressful cytokine explanation and the monoamine hypothesis,
suppression of recall of recognition. L-theanine and its which together make up the primary hypothesis of
antidepressant abilities were found to be more helpful depression56. Whereas curcumin has demonstrated
in treating cognitive impairment in mice. L-theanine an elevation similar to that of tricyclic antidepressants
exhibits agonist action when combined with NMDARs in the amount of monoamine that can attach to the
to treat depression. L-theanine has demonstrated binding site57. Curcumin has been shown to exhibit
superior efficacy in the treatment of stress and phobia anti-inflammatory activity, which supports the cytokine

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 Avijit Mazumder, Arbaz Khan and Jatin Saini 1229

hypothesis that these molecules play a vital part in the dismutase, and catalase enzymes, proanthocyanidin is a
emergence of the main depressive problem, according protective substance that functions as an antioxidant and
to the mechanism. Additionally, curcumin has shown aids in the reduction of glutathione in the liver66. Where
a significant inhibitory effect on the anti-inflammatory proanthocyanidin maintains ROS scavenging activity and
cytokines nuclear factor kappa A, NLRP2 inflammatory has a natural antioxidant function. In comparison to the
mediators, and interleukin-2A. Trials with curcumin antioxidant vitamins C and vitamin E, proanthocyanidin
from a long time ago coupled with conventional therapy has demonstrated improved hydroxyl radical scavenging67.
have shown it to be neuroprotective58. Furthermore,
behavioural modifications in the Brain-Attached 11.6 Resveratrol
Neurotrophic Function (BDNF) and HPA axis have Red wine and grapes both contain the natural phenol
been demonstrated in laboratory investigations. It was known as resveratrol. Resveratrol exhibits exceptional
discovered that treating synthetic medicine alongside neuroprotective qualities68. By reducing the excitability
a natural plant or phytochemical was an innovative of the HPA axis, resveratrol has a substantial impact on
approach to the medical profession59. The investigation the control of the anxiolytics effect. Resveratrol is also
employed a lot of the drug curcumin, and the action implicated in the breakdown of adrenaline and dopamine
was discovered to be synergistic. The HPA axis and the and functions as a further anxiolytic function. The most
disrupted monoaminergic pathways may be brought common method of demonstrating resveratrol’s impact
into balance by large-scale sequential therapy options is by the control of BDNF in the brain. Resveratrol
for depression60. has been demonstrated to have a predominant role
in functioning as a neuroprotective ingredient with a
11.4 Ferulic Acid significant capacity to increase neurogenesis, alongside
The organic substance ferulic acid is mostly present many other brain problems. The finest sleep inducer
in plant cell walls, seeds, and leaves. According to having anti-ageing characteristics has also been
reports, ferulic acid has a variety of neurotherapeutic demonstrated to be resveratrol69. The hypothalamic-
actions that include reducing apoptosis, high pituitary-thyroid centre and the HPA axis are both
levels of Reactive Oxygen Species (ROS), and affected by depression, which is also associated with
glutamate excitotoxicity61. The aberrant increase in monoaminergic and molecular markers. Resveratrol
indoleamine 2,3-dioxygenase activity in the brain has been shown in numerous studies to operate on
is what leads to the abnormal switch in tryptophan 5-HT and adrenaline to regain the monoaminergic
metabolism away from serotonin. Where ferulic acid system’s normal function and to induce an anxiolytic
has proven to have antidepressant properties, the fall effect through BDNF-work transcription in the body70.
in cerebral levels explains the efficiency of medicines
and must be boosted62. The main study discovered 12. Other Essential Flavonoids Act
that depressive persons typically exhibited the as Anti-anxietic Agents and
effects of reduced and hyperactivated NMDAR, Antidepressant Actions
which causes cell death, and excess glucocorticoid
synthesis, which is involved in antioxidant defence.
The majority of therapies for treating depression will 12.1 Apigenin
be monoaminergic systems63. Fruits and vegetables include an antioxidant called
apigenin, a 4´, 5, 7-trihydroxy flavone. Numerous
11.5 Proanthocyanidin medical effects have been documented, including
Apple, cocoa, beans, grapes, tea, and other plants also antineoplastic, analgesic, and antioxidant properties.
contain proanthocyanidin, an oligomeric and molecular Apigenin has been shown to have anxiolytic properties
flavan-3-ol64. Proanthocyanidin can counteract the in several pre-clinical investigations. Nakazawa
increased levels of mediators of inflammation in the evaluated the antianxiety effects of apigenin via a
prefrontal cortex of the brain and amygdala, according forced swim experiment on rodents and found that it
to research65. Together with peroxidase, superoxide enhanced resistance-like behavior in animals, which

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1230 Role of Phytoflavonoids in the Management of Anxiety and Depression: An Overview

was supported by the cholinergic pathway71. In a

different investigation, mice treated with an unexpected
chronic mouse model were used to evaluate whether
apigenin had an antidepressant effect. The analysis of
the researcher suggests that two increases in the level
of expression of the Peroxisome Proliferator-Activated
Receptor (PPAR), which blocked the production of
NLRP2 and ILL, may be the source of the action72.
Apigenin’s ability to increase hippocampal BDNF levels Figure 4. Baicalein.
and block the mono-amino oxidase enzyme is more
evidence of its antidepressant effects, because it can anti-cancer, and anti-depressant effects77. In a study, it
decrease inflammation73 (Figure 3). was found that myricetin inhibited the FST-predicted
depressive behaviour in stressed-out mice. Myricetin’s
12.2 Baicalein anti-depressant potential was increased by research
Baicalein is a trihydroxyflavone flavonoid that contains showing that this flavonol reduced blood levels of
hydroxyl molecules at positions 5, 6, and 7. Baicalensis corticosterone, elevated BNF levels, and increased
has been shown to contain the most active flavonoid. oxygen species reactive enzyme production in the
According to multiple reports74, baicalein is a powerful brain78 (Figure 5).
chemical with properties like many others, including
antioxidant and free radical scavenging action. This 12.4 Quercetin
flavone passes the blood-brain barrier and notably Quercetin, also known as pentahydroxy flavone, is
exhibits relaxing and CNS depressive effects, according often found in pineapple, garlic, ginger, and red wine79.
to published research75. Additional studies have shown Numerous flavonoids exhibit strong anti-free radical
that baicalein, which was isolated from the root of capabilities that can be used to treat a range of diseases
the Scutellaria plant using ethanolic extraction, could and conditions79. In a few animal models, the anxiolytic
inhibit the brain, contribute to a drop in prostaglandin function was also proven, and it was found that MAO
E2 amounts in the brain, act as a strong antioxidant, inhibitors raised the levels of 5HT and nor-epinephrine
and stop the emergence of depressive behaviour in mice in clefts of synapses. According to research showing
models. Six out of 48 rodent brains were reported to quercetin’s antidepressant effects in diabetic animals,
have lower prostaglandin E2 levels. Additionally acting it may be utilized as a preventative measure to reduce
as a strong antioxidant, this chemical helps to manage stress in diabetes conditions80 (Figure 6).
mice’s chronic stress behavior76 (Figure 4).
12.5 Rutin
12.3 Myricetin Citrus bioflavonoids like rutin (tetrahydroxy flavone),
Myricetin, a hexahydroxy flavone, has hydroxyl groups also known as sophorin, quercetin, and rutosine, are also
replaced at positions 3, 3´, 4´, 5, 5´, and 7. Vegetables, known by these names. This is a glycoside composed
dry fruits, rum, tea, and other substances are all of the flavonoid myricetin and the saccharide, with
widely available. It has been proven to have analgesic,

Figure 3. Apigenin. Figure 5. Myrecetin.

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 Avijit Mazumder, Arbaz Khan and Jatin Saini 1231

(CNS). Given the effects benzodiazepines, which are full

agonists, have adverse effects like reliance, polyphenols
with partial agonistic characteristics at the receptor site
may be attractive anxiolytic medicines. It may be possible
to successfully reduce the active dose while also facilitating
the passage of polyphenols over the blood-brain barrier by
administering them intranasally in the form of liposomes.
Certain polyphenols can be used to treat depressive
Figure 6. Baicalein. people by regulating their emotions because they have
been shown to have similar advantages to traditional
the sugar groups rhamnose and glucose substituting antidepressants at lower doses. The emergence of anxiety,
for the -OH group of the quercetin at position C3. depression, and other diseases linked to oxidative stress
Citrus-containing foods, plants, and beverages have may be prevented (or delayed) with a varied diet rich in
all been discovered to contain, including figs, wheat, naturally occurring polyphenols.
tea made from green tea, and others81,82. It facilitates
collagen synthesis and vitamin C absorption by the 14. Acknowledgement
body. Numerous activities of rutin, including neural
protection, antioxidant properties, analgesic effects, The authors extend their gratitude to the Director
and anti-tumour characteristics, have been reported76. and management of Noida Institute of Engineering
Through the methanolic extract of Schinus moll L. and and Technology (Pharmacy Institute) for continuous
its aerial parts, a substance separates that exhibit CNS support and for providing all kinds of facilities to
suppressive effects in TST. Increases in the level of rutin complete this research.
anti-depressant substances were evidence for their
effectiveness of 5HT and noradrenaline83 (Figure 7). 15. References
1. Kuloglu M, Atmaca M, Tezcan E, Ustundag B, Bulut S.
13. Conclusion Antioxidant enzyme and malondialdehyde levels in patients
with panic disorder. Neuropsychobiology. 2002; 46(4):186-
Potent naturally occurring antioxidant compounds 9. https://doi.org/10.1159/000067810 PMid:12566935
known as polyphenols have been shown to have 2. Bouayed J, Rammal H, Younos C, Soulimani R. Positive
pharmacological effects on the Central Nervous System correlation between peripheral blood granulocyte
oxidative status and level of anxiety in mice. Eur J
Pharmacol. 2007; 564(1-3):146-9. https://doi.org/10.1016/j.
ejphar.2007.02.055 PMid:17395178
3. Bilici M, Efe H, Köroğlu MA, Uydu HA, Bekaroğlu M, Değer
O. Antioxidative enzyme activities and lipid peroxidation in
major depression: alterations by antidepressant treatments.
J Affect Disord. 2001; 64(1):43-51. https://doi.org/10.1016/
S0165-0327(00)00199-3 PMid: 11292519
4. Guelfi JD. Comorbidity of anxiety-depression and its
treatment. Encéphale. 1993; 19(2):397-404. PMID 7904238.
5. Ferrari AJ, Charlson FJ, Norman RE, Patten SB, Freedman
G, Murray CJ, et al. The burden of depressive disorders by
country, sex, age, and year: findings from the global burden
of disease study 2010. PLOS Med. 2013; 10(11):e1001547.
ht t p s : / / d o i . o r g / 1 0 . 1 3 7 1 / j o u r n a l . p m e d . 1 0 0 1 5 4 7
PMid:24223526 PMCid: PMC3818162
6. Kuloglu M, Atmaca M, Tezcan E, Ustundag B, Bulut S.
Antioxidant enzyme and malondialdehyde levels in patients
Figure 7. Rutin.

Journal of Natural Remedies | ISSN: 2320-3358 http://www.informaticsjournals.com/index.php/jnr | Vol 23 (4) | October 2023
1232 Role of Phytoflavonoids in the Management of Anxiety and Depression: An Overview

with panic disorder. Neuropsychobiology. 2002; 46(4):186- 20. Ng QX, Venkatanarayanan N, Ho CY. Clinical use of
9. https://doi.org/10.1159/000067810 PMid:12566935 Hypericum perforatum (St. John’s Wort) in depression: A
7. Bouayed J, Rammal H, Younos C, Soulimani R. Positive meta-analysis. J Affect Disord. 2017; 210:211-21. https://
correlation between peripheral blood granulocyte doi.org/10.1016/j.jad.2016.12.048 PMid:28064110
oxidative status and level of anxiety in mice. Eur J 21. Canenguez Benitez JS, Hernandez TE, Sundararajan R,
Pharmacol. 2007; 564(1-3):146-9. https://doi.org/10.1016/j. Sarwar S, Arriaga AJ, Khan AT, et al. Advantages and
ejphar.2007.02.055 PMid:17395178 disadvantages of using St. John’s Wort as a treatment
8. Rammal H, Bouayed J, Younos C, Soulimani R. Evidence for depression. Cureus. 2022; 14(9):e29468. https://doi.
that oxidative stress is linked to anxiety-related behaviour org/10.7759/cureus.29468
in mice. Brain Behav Immun. 2008; 22(8):1156-9. https:// 22. Dell’Aica I, Garbisa S, Caniato R. The renaissance of
doi.org/10.1016/j.bbi.2008.06.005 PMid:18620042 Hypericum perforatum: biomedical research catches up
9. Patel KP, Chandel SS. Pharmacological models to with folk medicine. Curr Bioact Compd. 2007; 3(2):109-19.
appraisement of antianxiety activity in experimental https://doi.org/10.2174/157340707780809644
animals. Int J Green Pharm. 2018; 12(3):1-10. 23. Chen SL, Chen CH. Effects of lavender tea on fatigue,
10. Adwas AA, Jbireal JM. Anxiety: insights into signs, depression, and maternal-infant attachment in sleep-
symptoms, aetiology, pathophysiology, and treatment. East disturbed postnatal women. Worldviews Evid-Based Nurs.
Afr Scholars J Med Sci. 2019; 2:580-91. 2015; 12(6):370-9. https://doi.org/10.1111/wvn.12122
11. Liu L, Liu C, Wang Y, Wang P, Li Y, Li B. Herbal PMid:26523950
medicine for anxiety, depression and insomnia. Curr 24. Montemurro N, Ricciardi L, Scerrati A, Castorina A,
Neuropharmacol. 2015; 13(4):481-93. https://doi.org/10.2 Nawrot J, Gornowicz-Porowska J, et al. Medicinal herbs in
174/1570159X1304150831122734 PMid:26412068 PMCid: the relief of neurological, cardiovascular, and respiratory
PMC4790408 symptoms after covid-19 infection a literature review. Cells
12. Gurib-Fakim A. Medicinal plants: traditions of yesterday 2022, 11, 1897. Pharmacol Ther. 2019; 204:107402. https://
and drugs of tomorrow. Mol Aspects Med. 2006; 27(1):1-93. doi.org/10.3390/cells11121897 PMid:35741026 PMCid:
https://doi.org/10.1016/j.mam.2005.07.008 PMid:16105678 PMC9220793
13. Antonijevic IA. Depressive disorders-is it time to endorse 25. Effati-Daryani F, Mohammad-Alizadeh-Charandabi S,
different pathophysiologies? Psychoneuroendocrinology. Mirghafourvand M, Taghizadeh M, Mohammadi A. Effect
2006; 31(1):1-15. https://doi.org/10.1016/j. of lavender cream with or without footbath on anxiety,
psyneuen.2005.04.004 PMid:15950391 stress and depression in pregnancy: A randomized placebo-
14. Sarris J, Kavanagh DJ. Kava and St. John’s wort: current controlled trial. J Caring Sci. 2015; 4(1):63-73.
evidence for use in mood and anxiety disorders. J Altern 26. López V, Nielsen B, Solas M, Ramírez MJ, Jäger AK.
Complement Med. 2009; 15(8):827-36. https://doi. Exploring pharmacological mechanisms of lavender
org/10.1089/acm.2009.0066 PMid:19614563 (Lavandula angustifolia) essential oil on central nervous
15. Hindmarch I. Expanding the horizons of depression: beyond system targets. Front Pharmacol. 2017; 8:280. https://doi.
the monoamine hypothesis. Hum Psychopharmacol. org/10.3389/fphar.2017.00280 PMid:28579958 PMCid:
2001; 16(3):203-18. https://doi.org/10.1002/hup.288 PMC5437114
PMid:12404573 27. Chen L, Wang X, Lin ZX, Dai JG, Huang YF, Zhao YN.
16. Young SN, Leyton M. The role of serotonin in human mood Preventive effects of ginseng total saponins on chronic
and social interaction. Insight from altered tryptophan levels. corticosterone-induced impairment in astrocyte structural
Pharmacol Biochem Behav. 2002; 71(4):857-65. https://doi. plasticity and hippocampal atrophy. Phytother Res.
org/10.1016/S0091-3057(01)00670-0 PMid:11888576 2017; 31(9):1341-8. https://doi.org/10.1002/ptr.5859
17. Sarris J, Kavanagh DJ. Kava and St. John’s wort: current PMid:28656606
evidence for use in mood and anxiety disorders. J Altern 28. Safari M, Asadi A, Aryaeian N, Huseini HF, Jazayeri S, Malek
Complement Med. 2009; 15(8):827-36. https://doi. M, et al. The effects of Melissa officinalis on depression
org/10.1089/acm.2009.0066 PMid:19614563 and anxiety in type 2 diabetes patients with depression: a
18. Nutt DJ, Ballenger JC, Sheehan D, Wittchen HU. randomized double-blinded placebo-controlled clinical
Generalized anxiety disorder; comorbidity, comparative trial. BMC Complement Med Ther. 2023; 23(1):1-0. https://
biology, and treatment int J Neuropsychopharmacol. Int doi.org/10.1186/s12906-023-03978-x PMid:37131158
J Neuropsychopharmacol. 2002; 5(4):315-25. https://doi. PMCid: PMC10152712
org/10.1017/S1461145702003048 PMid:12466031 29. Dahchour A. Anxiolytic and antidepressive potentials
19. Spinella M. The psychopharmacology of herbal medicine: of rosmarinic acid: a review with a focus on antioxidant
plant drugs that alter the mind. Brain Behav. 2001. and anti-inflammatory effects. Pharmacol Res. 2022;

Journal of Natural Remedies | ISSN: 2320-3358 http://www.informaticsjournals.com/index.php/jnr | Vol 23 (4) | October 2023
 Avijit Mazumder, Arbaz Khan and Jatin Saini 1233

184:106421. https://doi.org/10.1016/j.phrs.2022.106421 42. Bouayed J, Rammal H, Dicko A, Younos C, Soulimani R.

PMid:36096427 Chlorogenic acid, a polyphenol from Prunus domestica
30. Haybar H, Javid AZ, Haghighizadeh MH, Valizadeh E, (Mirabelle), with coupled anxiolytic and antioxidant effects.
Mohaghegh SM, Mohammadzadeh A. The effects of Melissa J Neurol Sci. 2007; 262(1-2):77-84. https://doi.org/10.1016/j.
officinalis supplementation on depression, anxiety, stress, jns.2007.06.028 PMid:17698084
and sleep disorder in patients with chronic stable angina. 43. Manach C, Scalbert A, Morand C, Rémésy C, Jiménez L.
Clin Nutr ESPEN. 2018; 26:47-52. https://doi.org/10.1016/j. Polyphenols: food sources and bioavailability. Am J Clin Nutr.
clnesp.2018.04.015 PMid:29908682 2004; 79(5):727-47. https://doi.org/10.1093/ajcn/79.5.727
31. Machado DG, Bettio LE, Cunha MP, Capra JC, Dalmarco PMid:15113710
JB, Pizzolatti MG, et al. Antidepressant-like effect of the 44. Bouayed J, Rammal H, Dicko A, Younos C, Soulimani
extract of Rosmarinus officinalis in mice; involvement of the R. The antioxidant effect of plums and polyphenolic
monoaminergic system. Prog Neuropsychopharmacol Biol compounds against H2O2-induced oxidative stress in mice
Psychiatry. 2009; 33(4):642-50. https://doi.org/10.1016/j. blood granulocytes. J Med Food. 2009; 12(4):861-8. https://
pnpbp.2009.03.004 PMid:19286446 doi.org/10.1089/jmf.2008.0165 PMid:19735188
32. Jinna P. Acorus calamus Linn. A herbal tonic for the central 45. Takeda H, Tsuji M, Inazu M, Egashira T, Matsumiya T.
nervous system. J Sci Innov Res. 2013; 2(5):950-4. Rosmarinic acid and caffeic acid produce an antidepressive-
33. Arctander S. Perfume and flavour materials of natural like effect in the forced swimming test in mice. Eur J
origin. Perfume Flavor Mater Nat Orig. 1960. Pharmacol. 2002; 449(3):261-7. https://doi.org/10.1016/
34. Moghari M, Sadat Z, Mirbagher N. Effects of aromatherapy S0014-2999(02)02037-X PMid:12167468
using sour lemon on anxiety in patients undergoing 46. Amzad Hossain M, Salehuddin SM, Kabir MJ, Rahman
chemotherapy: a clinical trial study. J Clin Care Skills. 2023; SMM, Rupasinghe HPV. Sinensetin, rutin, 3´-hydroxy-5,
4(1):0-. 6, 7, 4´- tetramethoxyflavone and rosmarinic acid contents
35. Vishal A, et al. Diuretic, laxative and toxicity Studies of Viola and antioxidative effect of the skin of apple fruit. Food
odorata aerial parts. Pharmacol Online. 2009; 1:739-48. Chem. 2009; 113(1):185-90. https://doi.org/10.1016/j.
36. Anderson RA. Roussel AM. 2008 Cinnamon, glucose and foodchem.2008.07.085
insulin sensitivity. Nutraceuticals, glycemic health and type. 47. Priprem A, Watanatorn J, Sutthiparinyanont S, Phachonpai
2:127-40. https://doi.org/10.1002/9780813804149.ch8 W, Muchimapura S. Anxiety and cognitive effects of
37. Bouayed J, Rammal H, Younos C, Soulimani R. Positive quercetin liposomes in rats. Nanomedicine. 2008;
correlation between peripheral blood granulocyte 4(1):70-8. https://doi.org/10.1016/j.nano.2007.12.001
oxidative status and level of anxiety in mice. Eur J PMid:18249157
Pharmacol. 2007; 564(1-3):146-9. https://doi.org/10.1016/j. 48. Medina JH, Viola H, Wolfman C, Marder M, Wasowski
ejphar.2007.02.055 PMid:17395178 C, Calvo D, et al. Overview—flavonoids: a new family of
38. Bouayed J, Rammal H, Dicko A, Younos C, Soulimani R. benzodiazepine receptor ligands. Neurochem Res. 1997;
Chlorogenic acid, a polyphenol from Prunus domestica 22(4):419-25. https://doi.org/10.1023/A:1027303609517
(Mirabelle), with coupled anxiolytic and antioxidant effects. PMid:9130252
J Neurol Sci. 2007; 262(1-2):77-84. https://doi.org/10.1016/j. 49. Grosso C, Valentão P, Andrade PB. Depressive disorders:
jns.2007.06.028 PMid:17698084 prevalence, costs, and theories. In: Grosso C, editor. Herbal
39. Pereira P, Tysca D, Oliveira P, da Silva Brum LF, Picada medicine in depression: traditionalmedicine to
JN, Ardenghi P. Neurobehavioral and genotoxic aspects innovativedrugdelivery. Cham: Springer International
of rosmarinic acid. Pharmacol Res. 2005; 52(3):199-203. Publishing. 2016. p. 1-41. https://doi.org/10.1007/978-3-
https://doi.org/10.1016/j.phrs.2005.03.003 PMid:16026713 319-14021-6_1
40. Shamabadi A, Kafi F, Arab Bafrani M, Asadigandomani H, 50. Salmani H, Hakimi Z, Arab Z, Marefati N, Mahdinezhad
A Basti F, Akhondzadeh S. l-theanine adjunct to sertraline MR, Rezaei Golestan A, et al. Carvacrol attenuated
for major depressive disorder: A randomized, double- neuroinflammation, oxidative stress and depression and
blind, placebo-controlled clinical trial. J Affect Disord. anxiety-like behaviours in lipopolysaccharide-challenged
2023; 333:38-43. https://doi.org/10.1016/j.jad.2023.04.029 rats. Avicenna J Phytomed. 2022;12(5):514-26.
PMid:37084960 51. Shen M, Yang Y, Wu Y, Zhang B, Wu H, Wang L, et al.
41. Azuma K, Ippoushi K, Nakayama M, Ito H, Higashio H, L-theanine ameliorate depressive-like behaviour in a
Terao J. Absorption of chlorogenic acid and caffeic acid chronic unpredictable mild stress rat model via modulating
in rats after oral administration. J Agric Food Chem. the monoamine levels in limbic-corticalstriatal-pallidal-
2000; 48(11):5496-500. https://doi.org/10.1021/jf000483q circuit related brain regions. PhytotherRes. 2019; 33(2):412-
PMid:11087508 21. https://doi.org/10.1002/ptr.6237 PMid:30474152

Journal of Natural Remedies | ISSN: 2320-3358 http://www.informaticsjournals.com/index.php/jnr | Vol 23 (4) | October 2023
1234 Role of Phytoflavonoids in the Management of Anxiety and Depression: An Overview

52. Ogawa S, Ota M, Ogura J, Kato K, Kunugi H. Effects of 125:131-6. https://doi.org/10.1016/j.steroids.2017.07.006

L-theanine on anxiety-like behaviour, cerebrospinal fluid PMid:28733038
amino acid profile, and hippocampal activity in Wistar Kyoto 63 .Liu YM, Shen JD, Xu LP, Li HB, Li YC, Yi LT. Ferulic acid
rats. Psychopharmacol (Berl). 2018; 235(1):37-45. https:// inhibits neuro-inflammation in mice exposed to chronic
doi.org/10.1007/s00213-017-4743-1 PMid:28971241 unpredictable mild stress. Int Immunopharmacol. 2017;
53. Lopresti AL. Potential role of curcumin for the treatment of 45:128-34. https://doi.org/10.1016/j.intimp.2017.02.007
major depressive disorder. CNS Drugs. 2022;36(2):123-41. PMid:28213267
https://doi.org/10.1007/s40263-022-00901-9 PMid:35129813 64. Jiang X, Liu J, Lin Q, Mao K, Tian F, Jing C, et al.
PMCid: PMC8863697 Proanthocyanidin prevents lipopolysaccharide-induced
54. Trabace L, Zotti M, Morgese MG, Tucci P, Colaianna depressive-like behaviour in mice via the neuroinflammatory
M, Schiavone S, et al. The oestrous cycle affects the pathway. Brain Res Bull. 2017; 135:40-6. https://doi.
neurochemical and neurobehavioral profile of carvacrol- org/10.1016/j.brainresbull.2017.09.010 PMid:28941603
treated female rats. Toxicol Appl Pharmacol. 2011; 65. Abhijit S, Subramanyam MVV, Devi SA. Grape seed
255(2):169-75. https://doi.org/10.1016/j.taap.2011.06.011 proanthocyanidin and swimming exercise protect
PMid:21723308 against cognitive decline: A study on M1 acetylcholine
55. Amiresmaeili A, Roohollahi S, Mostafavi A, Askari N. receptors in ageing male rat brain. Neurochem Res. 2017;
Effects of oregano essential oil on brain TLR4 and TLR2 42(12):3573-86. https://doi.org/10.1007/s11064-017-2406-
gene expression and depressive-like behaviour in a rat 6 PMid:28993969
model. Res Pharm Sci. 2018; 13(2):130-41. https://doi. 66. Xu Y, Wang Z, You W, Zhang X, Li S, Barish PA, et
org/10.4103/1735-5362.223795 PMid:29606967 PMCid: al. Antidepressant-like effect of trans-resveratrol:
PMC5842484 involvement of serotonin and noradrenaline system.
56. Ng QX, Koh SSH, Chan HW, Ho CYX. Clinical use of curcumin EurNeuropsychopharmacol. 2010; 20(6):405-13. https://
in depression: A meta-analysis. J Am Med Dir Assoc. 2017; doi.org/10.1016/j.euroneuro.2010.02.013 PMid:20353885
18(6):503-8. https://doi.org/10.1016/j.jamda.2016.12.071 67. El-Shitany NA, Eid B. Proanthocyanidin protects against
PMid: 28236605 cisplatin-induced oxidative liver damage through
57. Lopresti AL, Drummond PD. Efficacy of curcumin, and inhibition of inflammation and NF-κβ/TLR-4 pathway.
a saffron/curcumin combination for the treatment of Environ Toxicol. 2017;32(7):1952-63. https://doi.org/10.1002/
major depression: A randomised, double-blind, placebo- tox.22418 PMid:28371137
controlled study. J Affect Disord. 2017; 207:188-96. https:// 68. Moore A, Beidler J, Hong MY. Resveratrol and depression
doi.org/10.1016/j.jad.2016.09.047 PMid:27723543 in animal models: A systematic review of the biological
58. He X, Yang L, Wang M, Zhuang X, Huang R, Zhu R, et mechanisms. Molecules. 2018; 23(9):e2197. https://doi.
al. Targeting the endocannabinoid/CB1 receptor system org/10.3390/molecules23092197 PMid:30200269 PMCid:
for treating major depression through antidepressant PMC6225181
activities of curcumin and dronabinol-loaded solid lipid 69. Ali SH, Madhana RM, Athira KV, Kasala ER, Bodduluru
nanoparticles. Cell Physiol Biochem. 2017; 42(6):2281-94. LN, Pitta S, et al. Resveratrol ameliorates depressive-like
https://doi.org/10.1159/000480001PMid:28848078 behaviour in repeated corticosterone-induced depression
59. Lopresti AL. Curcumin for neuropsychiatric disorders: in mice. Steroids. 2015; 101:37-42. https://doi.org/10.1016/j.
A review of in vitro, animal and human studies. J steroids.2015.05.010 PMid:26048446
Psychopharmacol. 2017; 31(3):287-302. https://doi. 70. Dasgupta B, Milbrandt J. Resveratrol stimulates AMP
org/10.1177/0269881116686883 PMid:28135888 kinase activity in neurons. Proc Natl Acad Sci U S A. 2007;
60. Dong X, Huang R. Ferulic acid: An extraordinarily 104(17):7217-22. https://doi.org/10.1073/pnas.0610068104
neuroprotective phenolic acid with anti-depressive PMid:17438283 PMCid: PMC1855377
properties. Phytomedicine. 2022; 105:154355. https://doi. 71. Nakazawa T, Yasuda T, Ueda J, Ohsawa K. Antidepressant-like
org/10.1016/j.phymed.2022.154355 PMid:35908520 effects of apigenin and 2,4,5-trimethoxycinnamic acid from
61 Singh T, Kaur T, Goel RK. Ferulic acid supplementation Perilla frutescens in the forced swimming test. Biol Pharm
for the management of depression in epilepsy. 2017; Bull.2003;26(4):474-80. https://doi.org/10.1248/bpb.26.474
42(10):2940-8:28608235. https://doi.org/10.1007/s11064- PMid:12673028
017-2325-6 PMid:28608235 72. Li R, Wang X, Qin T, Qu R, Ma S. Apigenin ameliorates
62. Zeni ALB, Camargo A, Dalmagro AP. Ferulic acid reverses chronic mild stress-induced depressive behaviour
depression-like behaviour and oxidative stress induced by by inhibiting interleukin-1β production and NLRP3
chronic corticosterone treatment in mice. Steroids. 2017; inflammasome activation in the rat brain. Behav Brain Res.

Journal of Natural Remedies | ISSN: 2320-3358 http://www.informaticsjournals.com/index.php/jnr | Vol 23 (4) | October 2023
 Avijit Mazumder, Arbaz Khan and Jatin Saini 1235

2016; 296:318-25. https://doi.org/10.1016/j.bbr.2015.09.031 org/10.1186/s12906-020-03033-z PMid:32738903 PMCid:

PMid:26416673 PMC7395214
73. Li RP, Zhao D, Qu R, Fu Q, Ma SP. The effects of apigenin 78. Ma Z, Wang G, Cui L, Wang Q. Myricetin attenuates depressant-
on lipopolysaccharide-induced depressive-like behaviour like behaviour in mice subjected to repeated restraint stress.
in mice. Neurosci Lett. 2015; 594:17-22. https://doi. Int J Mol Sci. 2015; 16(12):28377-85. https://doi.org/10.3390/
org/10.1016/j.neulet.2015.03.040 PMid:25800110 ijms161226102 PMid:26633366 PMCid: PMC4691049
74. Liu C, Wu J, Gu J, Xiong Z, Wang F, Wang J, et al. 79. Li Y, Yao J, Han C, Yang J, Chaudhry MT, Wang S, et al.
Baicalein improves cognitive deficits induced by chronic Quercetin, inflammation, and immunity. Nutrients.
cerebral hypoperfusion in rats. Pharmacol Biochem 2016; 8(3):167. https://doi.org/10.3390/nu8030167 PMid:
Behav.2007; 86(3):423-30. https://doi.org/10.1016/j. 26999194 PMCid: PMC4808895
pbb.2006.11.005PMid:17289131 80. Demir EA, Gergerlioglu HS, Oz M. Antidepressant-like
75. Lee B, Sur B, Park J, Kim SH, Kwon S, Yeom M, et al. effects of quercetin in diabetic rats are independent of the
Chronic administration of baicalein decreases depression- hypothalamic-pituitary-adrenal axis. Acta Neuropsychiatr.
like behaviour induced by repeated restraint stress in rats. 2016; 28(1):23-30. https://doi.org/10.1017/neu.2015.45
Korean J Physiol Pharmacol. 2013; 17(5):393-403. https:// PMid:26234153
doi.org/10.4196/kjpp.2013.17.5.393 PMid:24227939 PMCid: 81. Ganeshpurkar A, Saluja AK. The pharmacological potential
PMC3823951 of Rutin. Saudi Pharm J. 2017; 25(2):149-64. https://doi.
76. Li YC, Shen JD, Li J, Wang R, Jiao S, Yi LT. Chronic treatment org/10.1016/j.jsps.2016.04.025 PMid:28344465 PMCid:
with baicalin prevents the chronic mild stress-induced PMC5355559
depressive-like behaviour: involving the inhibition of 82. Al-Dhabi NA, Arasu MV, Park CH, Park SU. An up-to-
cyclooxygenase-2 in rat brain. Prog Neuropsychopharmacol date review of rutin and its biological and pharmacological
Biol Psychiatry. 2013; 40:138-43. https://doi.org/10.1016/j. activities. Excli J. 2015; 14:59-63.
pnpbp.2012.09.007PMid:23022674 83. Gullón B, Lú-Chau TA, Moreira MT, Lema JM, Eibes
77. Taheri Y, Suleria HAR, Martins N, Sytar O, Beyatli A, G. Rutin: A review on extraction, identification and
Yeskaliyeva B, et al. Myricetin bioactive effects: moving purification methods, biological activities, and approaches
from preclinical evidence to potential clinical applications. to enhance its bioavailability. Trends Food Sci Technol.
BMC Complement Med Ther. 2020; 20(1):241. https://doi. 2017; 67:220-35. https://doi.org/10.1016/j.tifs.2017.07.008

Journal of Natural Remedies | ISSN: 2320-3358 http://www.informaticsjournals.com/index.php/jnr | Vol 23 (4) | October 2023