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Khanum and Razack Res Rev Biomed Biotech 1(2); 2010
www.rrbb.in 71
ISSN 2229–7154
Research and Reviews in Biomedicine and Biotechnology
Volume [1], Issue [2], 2010, 71-89
www.rrbb.in
Review article
Anxiety- Herbal Treatment: A Review Farhath Khanum
* and Sakina Razack
Biochemistry and Nutrition, Defence Food Research Laboratory, Mysore-570011, Karnataka,
India *Corresponding author email: [email protected]
Article received on 19.09.2010; Revised article accepted on 16.12.2010
Copyright: © 2010 rrbb.in
ABSTRACT
Stress has become a part of the modern world and lifestyles. Persistent stress leads to anxiety.
Anxiety is a general feeling of getting worried. In small quantities stress and anxiety are good
as they can motivate and help one be more productive but people with persistent stress feel
anxious quite often and anxiety interferes in their daily lives and is a matter of concern.
Evidences suggest anxiety to be caused by dysfunction of one or more neurotransmitters and
their receptors and has emerged to be a very important area of research. Plants have known to
possess enormous potential to cure ailments from time immemorial. This review lists most
widely used herbal anxiolytes and classifies them according their mechanisms of action.
Keywords: Anxiety, Gamma Amino Butyric Acid, Herbal Anxiolytes, Neuropeptides,
Serotonin.
INTRODUCTION:
Stress and anxiety are common psychiatric
manifestations of the modern world and
lifestyles. In small quantities, stress and
anxiety are good; they can motivate and
help one be more productive. However, too
much stress, or a strong response to stress, is
harmful. It can set up for general poor
health as well as specific physical or
psychological illnesses like infection, heart
disease, or depression. Persistent and
unrelenting stress often leads to anxiety and
unhealthy behaviours.
Anxiety is a Central Nervous System
disorder [1-2]
. Anxiety is a common
emotional phenomenon in humans [3].
Anxiety is an emotional state, unpleasant in
nature and is associated with uneasiness,
discomfort and concern or fear about some
defined or undefined future threat [4].
Anxiety is considered to be a normal
reaction to stress and is characterized by
heart palpitations, fatigue, nausea and
shortness of breath. Anxiety is the most
common mental illness affecting one eighth
of the total population and has become a
very important area of research in
psychopharmacology in the current decade [5].
Anxiety disorders are psychiatric disorders
affecting nearly 25% of the adult population
at some point in their life. The prevalence of
anxiety disorders is 30.5% and 19.2% in
women and men respectively. The
prevalence of anxiety disorders is
remarkably high in young people. Children
aged 7 to 11 years reported a 15.4%
prevalence rate of anxiety disorders. A
survey has also stated that less than 14% of
people with such psychiatric disorders
receive treatment [6]. Anxiety can aggravate
many physical and mental ailments and also
impede recovery from any other problems.
Khanum and Razack Res Rev Biomed Biotech 1(2); 2010
www.rrbb.in 72
Classically, anxiety is distinguished into the
‘state’ and the ‘trait’ anxiety. “State
anxiety” is anxiety a subject experiences at
a particular moment and is increased by the
presence of an anxiogenic stimulus. In
contrast, “trait anxiety” does not vary from
moment to moment and is considered to be
an “enduring” feature of an individual [7-9]
.
FORMS OF ANXIETY DISORDERS
Anxiety disorders comprise clinical
conditions of Generalized Anxiety Disorder,
Obsessive-compulsive Disorder, Panic
Disorder, Post-traumatic Stress Disorder,
Social Anxiety Disorder and Phobias.
• Generalized Anxiety Disorders :
Generalized Anxiety Disorder involves a
broad presentation of anxiety. It is
characterized by long-lasting anxiety (for
over 6 months) that is not focused on any
one object or situation. Those suffering
from this disorder experience non-specific
persistent fear and worry and become overly
concerned with everyday matters like
health, work, money or family and
experience these symptoms even when there
are no signs of trouble in their life [4,10]
.
• Obsessive-compulsive Disorder :
This is a particularly important form of
anxiety disorder which is characterized by
obsessions i.e. recurrent thoughts that may
not be about real-life problems and which
the person fails to ignore or suppress.
Compulsions are repetitive behaviours that
the person feels driven to perform in
response to an obsession. The compulsive
behaviours attempt to reduce the distress
from the obsessions.
• Panic Disorder :
In this type of a disorder the person suffers
from brief attacks of intense terror and
apprehension which is often characterized
by trembling, shaking, confusion, dizziness,
nausea, and difficulty in breathing, lasting
for a few minutes. The person also believes
that he or she is seriously ill or about to die
and this feeling can leave the person
depressed or shaken for quite a while
afterwards [4].
• Post-traumatic Stress Disorder:
Post-traumatic stress disorder is an anxiety
disorder which results from a traumatic
experience. The symptoms include
flashbacks or nightmares about what
happened, hyper vigilance, startling easily,
withdrawing from others, and avoiding
situations that remind the person of the
event. This disorder can continue for a
sustained period of time with marked
impairment in function.
• Social Anxiety Disorder :
Is a marked and persistent fear of social or
performance situations [4].
• Phobias :
A phobia is an unrealistic or exaggerated
fear of a specific stimulus, such as heights,
enclosed places or other situations. The
phobic individual may experience full panic
attacks when exposed to such stimuli.
Phobias tend to be the most common form
of anxiety disorder whereas panic disorders
are fairly rare in the general population [11]
.
PHYSIOLOGY OF ANXIETY
The human brain is the centre of human
nervous system and is a highly complex
organ. The part of the brain that triggers a
response to danger is the Locus ceruleus and
the area of the brain responsible for the
acquisition and expression of fear
conditioning is the Amygdala [12]
.
Once the neurotransmitters pick up over
activity/hyperactivity in the locus ceruleus,
the amygdala senses danger and instructs us
to run from danger. Hence, once the
amygdala gets activated it sends an alarm to
the heart to beat faster, breathing to become
rapid and in turn activates all the biological
components of fight/flight response.
The symptoms experienced during an
anxiety attack include:
• Rapid heartbeat and rapid breathing
• Twitching or trembling
• Muscle tension
• Headaches
• Sweating
• Dry mouth and difficulty in
swallowing and
• Abdominal pain
Khanum and Razack Res Rev Biomed Biotech 1(2); 2010
www.rrbb.in 73
Sometimes other symptoms accompany
anxiety, such as:
• Blurred vision and Dizziness
• Diarrhoea or frequent need to urinate
• Irritability, including loss of temper
• Sleeping difficulties and nightmares
• Decreased concentration and
• Sexual problems.
All these physical symptoms are felt when
one is anxious or having a panic attack and
are part of a system that is designed to keep
one safe and do not cause any harm. They
cause a problem only when they occur in
response to situations where one is not
physically threatened.
ANXIETY - MECHANISM OF ACTION Anxiety is recognised as one of the most
important emotional processes with firm
neurobiological roots. The neurochemistry
of anxiety although not well understood has
emerged to be a major area of research
leading to new approaches in the treatment
of anxiety.
Anxiety is caused due to too many or too
few neurotransmitters in the brain. Brain
synthesizes several neurotransmitters such
as acetylcholine, adrenaline, dopamine,
endorphins, serotonin, gamma amino
butyric acid, glutamate etc. Most
information has come from studying the
action of anxiety-reducing or anxiolytic
drugs. The evidences suggest anxiety to be
caused by dysfunction of one or more
neurotransmitters and their receptors.
The major thrusts of current work dealing
with anxiety disorders have centered around
the gamma amino butyric acid mechanisms,
the serotonergic system, noradrenergic
mechanisms and neuropeptides [10]
. New
evidences suggest a role for adenosine and
cholecystokinin in the development of
anxiety; drugs interactions with these
neurotransmitters also may have anxiolytic
effects.
Gamma amino butyric acid (GABA) is one
among the chief inhibitory neurotransmitters
in the mammalian brain and an increasing
wealth of information suggests that
GABAergic mechanisms have a special role
in the neurophysiology of anxiety [13]
.
GABA works to regulate the neuronal
excitability and thereby serves as a ‘brake’
on the neuronal circuitry during stress and is
the brain’s natural stress reliever [14]
.
Khanum and Razack Res Rev Biomed Biotech 1(2); 2010
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GABA is formed by the decarboxylation of
L-glutamate. Brain has three different types
of GABA receptors GABAA, GABAB,
GABAC. GABAA receptors are ligand-gated
ion channels (ionotropic receptors) and
GABAB receptors are the seven
transmembrane spanning G-protein coupled
receptors (metabotropic receptors). The
physiologic role of GABAC receptors is yet
to be described.
Schematic representation of GABA receptor
Khanum and Razack Res Rev Biomed Biotech 1(2); 2010
www.rrbb.in 75
The GABAA receptors mediate fast
inhibitory synaptic transmissions and
regulate the neuronal excitability and are
responsible for rapid mood changes (e.g.
anxiety, panic and stress response). GABAA
receptors are targets of sedating drugs such
as benzodiazepines, barbiturates,
neurosteroids and ethanol. Alteration of the
influx of chloride ions within this receptor
complex is associated with development of
anxiety. All of the most commonly used
anti-anxiety drugs (benzodiazepines, the
barbiturates, and ethanol) selectively
enhance only GABA mediated
transmission[13]
, thereby elevating GABA
levels.
The GABAB receptors mediate slow
inhibitory potentials and are known to play
an important role in memory, depressed
mood and pain. The GABAB receptor
ligand/agonists include baclofen, phenibut
etc among others.
Thus, these GABA agonists/analogues
elevate GABA levels thereby exerting anti-
anxiety, relaxing and anti-convulsant
effects.
Serotonin has long been viewed as a
neurotransmitter involved in regulating
emotional states. Of the 14 or so
mammalian serotonin receptor subtypes that
have been described, at least four have been
implicated in anxiety in various animal
models [15]
.
Khanum and Razack Res Rev Biomed Biotech 1(2); 2010
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Serotonin is synthesised from the
conversion of L-tryptophan to 5-
hydroxytryptophan which then crosses the
blood-brain barrier and is then broken down
to 5-hydroxytryptamine (5-HT) commonly
known as serotonin. It has been reported
that reduced levels of serotonin can produce
anxiolytic effects [16]
. The brain serotonin
receptors have been divided into a wide
range of subtypes based on their
pharmacological specificities, anatomical
distribution and function [10]
.
One of the receptor subtypes implicated in
anxiety is the serotonin 1A receptor subtype
(5-HT1A), an autoreceptor located
presynaptically on serotonin neurons. When
stimulated, this receptor inhibits the
synthesis and secretion of serotonin [10]
.
The 5-HT1A receptor agonist buspirone
exhibits anxiolytic effects in animals and is
useful in the treatment of generalized
anxiety disorder but not in panic disorder. In
contrast to benzodiazepines, buspirone has a
delayed onset of action and must be
administered for up to several weeks before
a significant reduction in anxiety is
observed and has no sedative, anti-
convulsant or muscle-relaxant activity and
no significant addiction liability [17, 10]
.
Other serotonin receptors potentially
involved in anxiety include the 5-HT2A, 5-
HT2C and 5-HT3 receptors. Antagonists for
5-HT2A receptor like ritanserin exhibit
anxiolytic effects in some animal models [18-
19]. Likewise, blockage of the 5-HT2C
receptor produces anxiolytic effect in
animals [20]
. In humans 5-HT2A receptor
agonist m-chlorophenyl piperazine (m CPP)
has been shown to generate anxiety in
control subjects and in patients with a wide
variety of anxiety disorders [10]
.
The 5-HT3 receptor antagonist ondansetron
has been reported to be anxiolytic in some
animal models [21]
.
The selective serotonin reuptake inhibitors
(SSRIs) have proven useful for panic and
obsessive-compulsive disorder. Thus, the
finding that a number of drugs that are
useful in panic disorder are not useful in
generalized anxiety disorder and vice versa
suggests that the fundamental mechanism of
these processes are different [10]
.
Norepinephrine – Elevated levels of
norepineprine are helpful in situations of
emergencies or in fight/flight response.
However, continuously elevated levels even
when not in situations of danger put the
person in states of anxiety, fear, irritability
etc. Thus, the role of catecholamines in
anxiety is being studied using adrenergic
receptor agonists and antagonists [10]
.
Neuropeptides - Neuropeptides have been
implicated in the regulation of complex
behaviour including anxiety related
behaviours and psychopathology.[22-23]
There is increasing evidence suggesting that
neuropeptides including substance P,
corticotropin-releasing factor, neuropeptides
Y, vasopressin, oxytocin, somatostatin,
cholecystokinin, galanin have relevance in
anxiety [24-25]
. Behavioural effects of these
peptides also have been studied using
molecular biology techniques, including the
central administration of antisense
sequences that block translation of peptides
or peptide receptor proteins, over expression
of peptides in intact animals and generation
of knockout mice lacking particular peptides
or peptide receptors [10]
.
MANAGEMENT OF ANXIETY
Management of anxiety disorders varies and
depends on the nature of the disorder and
individual patient characteristics [26]
. The
treatment involves:
1. Medications
2. Psychological treatment
3. Alternative therapy
Medication:
includes Selective Serotonin Reuptake
Inhibitors (SSRIs) which may be the first
choice of medication for generalised social
phobia. These drugs elevate the level of
neurotransmitter serotonin, among other
effects. Ex. Fluoxetine, sertraline,
paroxetine, citalopram etc.
Other medications commonly prescribed for
anxiety disorders include Benzodiazepines
Khanum and Razack Res Rev Biomed Biotech 1(2); 2010
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(ex: diazepam, chlordiazepoxide etc.) which
facilitate inhibitory GABA transmission.
Monoamine Oxidase Inhibitors (MAOIs)
(Phenelzine, Moclobemide) that prevent the
breakdown of serotonin and noradrenalin.
Beta-blockers like propranolol, atenolol
which reduce the ability to produce
adrenaline.
The common limitations of anxiety
medications or drug therapy include co-
morbid psychiatric disorders and increase in
dose leading to unbearable side-effects [27-
28], such as allergic reactions, drowsiness,
coordination problems, fatigue, mental
confusion, nausea and addiction liability
among others.
Psychological treatment:
Cognitive-Behavioural therapy and
Exposure therapy are effectively used to
treat anxiety disorders. Cognitive therapy
focuses on changing patterns of thinking
and beliefs that are associated with, and
trigger, anxiety. The most important
component of behaviour therapy is
exposure. Exposure therapy includes
confronting your fears to desensitise
yourself to such dangers/fears that can
trigger anxiety.
Alternative treatments:
Meditation – beneficial to patients with
phobias and panic disorders.
Hydrotherapy – promotes general relaxation
of the nervous system.
Exercise – a natural stress buster and
anxiety reliever.
Relaxation techniques (Yoga) – include
progressive muscle relaxation and
controlled breathing which when practised
regularly attenuate anxiety.
Biofeedback – an effective method that uses
sensors that measure physiological functions
like heart rate, breathing and muscle tension
and help to recognise the body’s anxiety
response and learn how to control them
using relaxation techniques.
Hypnotherapy – is sometimes used in
combination with cognitive-behavioural
therapy. The hypnotherapist applies
different therapeutic approaches to help you
confront your fears while in a state of deep
relaxation.
Acupuncture – used in traditional Chinese
medicine, helps alleviate anxiety [4].
ANIMAL MODELS OF ANXIETY
Serotonin receptor 1A Knock-out mice:
Low levels of serotonin 1A (5-HT1A) have
been repeated found in mood and anxiety
disorders. Mice lacking in serotonin
receptor 1A (5-HT1A KO) have been
developed by three independent research
groups in three different genetic background
mice (C57BL/6J, 129/SV and Swiss-
Webster; [29-31]
. It was found that all mice
independent of the genetic background
showed an ‘anxious’ phenotype compared
to their corresponding wild-type mice. The
autonomic changes associated with anxiety
have also been found pronounced in these
KO mice. Thus, indicating that the 5-HT1A
receptor knock-out mice represent a genetic
animal model for anxiety. However, strain-
dependent variability within the core
phenotype restricts the use of these KO
mice.
Apart from the receptor KO mice, there are
groups of researchers who have selectively
bred high anxiety breeds (HAB) and low
anxiety breeds (LAB) of mice [32]
.
A number of psychogenetically selected rat
models such as Maudsley reactive and non-
reactive strain, Ronan high and low
avoidance rat lines, Tsukuba strains and
high/low anxiety-related behaviour
(HAB/LAB) rat lines have been developed [32, 3, 33]
.
Co-transmission:
Different neurotransmitters can be released
from a single nerve terminal, including
neuropeptides and small molecule
neurotransmitters. Neuropeptides, acting as
neurotransmitters can also act as co-
transmitters and as co-transmitters they are
known to activate specific pre or post-
synaptic receptors that can alter the
responsiveness of the neuronal membrane to
the action of other neurotransmitters like
noradrenaline, serotonin etc.
Neurotransmitters like serotonin,
noradrenaline and dopamine are known to
Khanum and Razack Res Rev Biomed Biotech 1(2); 2010
www.rrbb.in 78
control many of our mental states
sometimes acting on their own or at other
times together. These and other
neurotransmitters have been implicated to
play a major role in mental illnesses and
diseases related to the brain.
Oxidative stress and anxiety:
Oxidative stress has been implicated in the
aetiology of many pathological conditions
including anxiety [34-35]
. Brain is prone to
oxidative stress due to high consumption of
oxygen, its lipid rich constitution and
modest antioxidant defences [36-37]
.
Hovatta et al.[146]
in 2005 identified that the
expression of glutathione reductase 1 and
glyoxalase 1 (genes involved in
antioxidative metabolism) is correlated to
anxiety-related phenotypes. They also found
that the activity of these enzymes is highest
in the most anxious mice and lowest in the
least anxious strains. Genetic manipulation
studies using lentivirus-mediated gene
transfer showed that local overexpression of
glutathione reductase 1 and glyoxalase 1 in
the cingulated cortex of murine brain results
in an increase of anxiety-like behaviour,
whereas inhibition of glyoxalase 1
expression produces low-anxiety mice.
Thus, it was hypothesised that glyoxalase1
and glutathione reductase 1 regulate anxiety
in mice. Another group of researchers
generated HAB-M (high anxiety-related
behaviour mouse) and LAB-M (low
anxiety-related behaviour mouse) CD1
mouse lines as models of extremes in trait
anxiety and used comparative proteomics to
identify anxiety related protein markers and
also reported differences in expression of
glyoxalase 1 between HAB-M and LAB-M
animals[38]
.
TEST FOR ANXIETY-
Studies related to the Central Nervous
System and brain is accomplished using
animals as experimental models. Animal
models form the backbone of preclinical
research on the neurobiology of psychiatric
disorders, and are employed as screening
tools in the search for novel therapeutic
agents.[39]
Rodents especially mice have
proven to be helpful in research as mice and
humans share more than 90% of their genes
in common. Furthermore, animal models are
particularly helpful in situations when the
impact of stress cannot be studied in
humans because of ethical and other reasons [40]
. A variety of tests for anxiety have been
developed of which the commonly used
ones include Elevated plus maze, Elevated
zero maze, Light/Dark test, Vogel’s conflict
test etc.
Elevated plus Maze (EPM)–
The Elevated plus maze is a simple method
for assessing anxiety responses of rodents.
The EPM has four arms (two open and two
enclosed) that are arranged to form a plus
shape and elevated 40-70 cm from the floor.
The model is based on rodent’s aversion of
open spaces. The assessment of anxiety
behavior of rodents is done by using the
ratio of time spent on the open arms to the
time spent on the enclosed arms. The
elevated plus maze relies upon rodents
proclivity towards dark (enclosed spaces)
and an unconditioned fear of heights (open
spaces).
Elevated zero maze –
Elevated zero maze, a modification of the
EPM comprises an elevated annular
platform with two enclosed and two open
quadrants, mounted on a base that raises the
maze above the floor. The Elevated Zero
Maze does not have a centre compartment
thereby allowing uninterrupted exploration
of the open and enclosed spaces and
eliminating any ambiguity in interpretation
of the time spent in a centre compartment.
Light/Dark test –
The light/dark test in mice is based on the
innate aversion to brightly illuminated areas
and the spontaneous exploratory activity of
mice. The apparatus comprises of a light
(brightly lit) and a dark compartment
separated with a partition. The distance
traveled in each chamber, the total number
of transitions, the time spent in each
chamber and the latency to enter the light
chamber are noted. The anxiolytic
compounds are known to increase the total
duration of time spent in the light
Khanum and Razack Res Rev Biomed Biotech 1(2); 2010
www.rrbb.in 79
compartment whereas the anxiogenic
compounds work in the opposite way.
Vogel’s conflict test –
The Vogel conflict test is based on the
principle that the water deprived animal is
placed in the test cage with a special
conductive floor grid and a drinking bottle
with an electrically conductive nipple. The
animal licks are recorded and monitored by
very low electrical currents applied to the
nipple that are below the animal's perception
level. After a specified number of licks an
electric shock is applied to the nipple and
the animal can escape the shock by
withdrawing from the drinking tube/nipple.
The number of shocks received after
treatment with the anxiolytic drug is
compared with the untreated animals. The
anxiolytic drugs significantly increase the
number of licks and therefore the number of
shocks applied.
Open field test –
It is generally used paradigm to
assess/evaluate the locomotor, exploratory
and anxiety-like behaviour in laboratory
animals. The open field area/arena usually
consists of brightly lit square or round area
enclosed by walls with the animal usually
being placed in the centre and its behaviour
being recorded for a known period of time
(3-15 minutes). It relies on the fact that the
rodent when anxious stays close to the
enclosed walls and measures the degree to
which the rodent avoids the central area.
Hole-board test –
A generally used paradigm to measure the
exploratory behaviour of rodents and the
potentiality of anxiolytics. The apparatus
usually consists of a wooden chamber with
16 holes measuring about 3cm in diameter
present on the floor which is elevated from
the ground ensuring that the rats could peep
through the holes and each rat is placed
individually and the latency to the first head
dip, the number of head dips, the total time
spent with the head dips, the number of
rearings and the total number of defecations
are noted.
State-Trait Anxiety Inventory (STAI)-
STAI [9] is one of the most widely used self-
report measures of anxiety. A means for
appraisal of anxiety in research & clinical
settings with questionnaires. The scores
obtained are directly related with anxiety i.e.
higher the score (20-80) greater the anxiety.
It helps practitioners differentiate between
anxiety and depression. The STAI occurs in
three forms. The STAI Form X is the first
version of the STAI, the STAI Form Y
differentiates between temporary or
emotional state anxiety versus long standing
personality trait anxiety in adults, and the
third form is the STAI for children [41]
.
HERBAL ANXIOLYTES:
Plants are known to have enormous
potential to cure ailments from time
immemorial. Ayurveda and Unani are such
inherited traditional systems of health and
longevity that are based on herbal
medicines. The ‘World Health
Organization’ has approved that traditional
health and folk medicine systems have
proved to be more effective in health
problems worldwide [42]
. Traditional
medicines are used by about 60% of the
world populations in rural areas in the
developing countries and is gaining
acceptance in the developed countries where
modern medicines predominates [4].
However, the major hurdle in the
uninhibited exploitation of herbal medicines
into the regular practice of prescription is
the lack of sufficient scientific data and
better understanding of efficacy and safety
of the herbal products [43]
.
A number of plants have been scrutinised
for their anxiolytic effects. Table 1 gives a
list of some of the widely studied plants for
anxiolytic effects.
Khanum and Razack Res Rev Biomed Biotech 1(2); 2010
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Table 1: List of plants with anxiolytic properties Plant name Family Active constituents Reference
Abies pindrow Royle Pinaceae
The fresh leaves yield 0.25% oil which contains α-pinene (14.7%), l-
limonene (10.6%), ∆3-carene (11.8%), dipentene (8.4%), l-bornyl
acetate (15.7%) and l-codinene (9.9%).[44]
[45]
Achillea millefolium. L. Asteraceae
The herb contains an alkaloid achilleine, isovaleric acid, salicylic acid,
asparagines, sterols, flavonoids, tannins, choline and trigonelline and
coumarins.[46] Flowers yield an essential oil azulene.[47] Presence of
choline has been shown to impart hypotensive effect.[51]
[48-50]
Aloysia polystachya
Griseb & Moldenke Verbenaceae [52-53]
Albizzia lebbeck. (L).
Benth. Fabaceae
The leaves have been shown to contain caffeic acid, alkaloids,
kaempferol and quercetin.[44] [54-55]
Albizzia
julibrissin Durazz Fabaceae Two flavonol glycosides quercitrin and isoquercitrin. [56]
Angelica sinensis Oliv.
Diels. Apiaceae
The essential oil contains lingustilide.
[57]
Aniba riparia Nees Mez. Lauraceae Riparins (methyl ether of N-benzoyl tyramine) exert antianxiety effects.
[58]
Annona cherimola Mill. Annonaceae β-cariophyllene, β-selinene, α-cubebene, and linalool [59]
Apocynum venetum. L. Apocynaceae
The chemical constituents of the leaves and flowers include ionone
glucosides named apocynoside I and II, several compounds have been
isolated and include kaempferol, kaempferol 3-0-beta-D-glucoside,
vanillic acid, baimaside, daucosterol.
[60]
Azadirachta indica. A.
Juss
Meliaceae
The chemical compounds isolated from Neem oil include nimbin,
nimbinin, and nimbidin. The seeds contain a complex secondary
metabolite azadirachtin.
[61]
Bacopa monnieri. L
Pennell
Scrophularia-
ceae
Major chemical constituents found in B.monnieri are saponins,
triterpenes & dammoranes such as bacosides A, B & C, bacosaponines
D, E & F.[63-64]
[62]
Caesalpinia Bonducella
(Roxb).
Fabaceae
The chemical constituents include diterpenes, fattyacids, isoflavones,
lipids and phenolic compounds.
[65]
Casimiroa edulis Llave
& Lex. Rutaceae [66]
Cannabis sativa L. Cannabaceae Cannabidiol an cannabinoid exerts anti-anxiety effects [67]
Cecropia glazioui. Sneth. Moraceae [68]
Centella asiatica. (L)
Urban Apiaceae
The essential oil includes triterpeniod saponins such as asiaticoside (got
from fresh leaves, a glucoside), brahmoside and thankuniside, alkaloids
(hydrocotyline, isolated from the dried plant) an some bitter
principles.[69]
[70]
Citrus aurantium. Linn.
Rutaceae
The chemical constituents include 4-methulacetophenone, carotenoids,
and essential oil containing monoterpenes sesquiterpenes, coumarins,
caffeinel isoquinoline, alkaloids, flavonoids, triterpenoids and
steroids.[51]
[71]
Citrus sinensis L. Osbeck
Rutaceae
The chemical constituents include monoterpenes, sesquiterpenes,
flavonoids, caretenoids, alkaloids, coumarins and vitamin c.[51]
Clitoria ternatea. L. Fabaceae The active constituents include tannins, resins, starch and the roots
contain taraxerol and taraxerone. [72]
Coriandrum sativum L.
Apiaceae
The phytoconstituents include linalool, linalyl acetate, thymol, β-
caryphyllene, α-pinene, borneol, limonene, β-phellandrene, citranellol,
1, 8-cineole and geranyl acetate.[51]
[73]
Coptis chinensis Franch Ranunculaceae Berberine, atrorrhizine, palmatine, epiberberine, coptisine, and
jatrorrhizine. [74]
Crinum giganteum
Andrews. Amaryllidaceae [75]
Crocus sativus L.
(Saffron/kesar) Iridaceae
Saffron contains more than 150 volatile and aroma yielding
compounds. Among the non-volatile active compounds include
carotenoids like zeaxanthine, lycopene and various α and β-carotenes.
α-crocin (a digentiobiose ester of carotenoid crocetin) imparts the
golden yellow-orange colour. Safranal and picrocrocin give saffron
much of its distinctive aroma.
[76]
Khanum and Razack Res Rev Biomed Biotech 1(2); 2010
www.rrbb.in 81
Davilla rugosa Poiret Dilleniaceae [77]
Echium amoenum Boraginaceae The chemical constituents include flavonoids, saponins, unsaturated
terpeniods and sterols.[78] [79-80]
Erythrina velutina Willd. Fabaceae Erythrina plants produce alkaloids, flavonoids and terpenes.[81-81] [83]
Erythrina variegata L
Fabaceae
The chemical constituents include alkaloids, flavonoids and terpenes.
The leaves and stems contain the alkaloid erythrinaline. The seeds yield
the alkaloid hypaphorine and a saponin-migarrhin.[51]
[84]
Erythrina mulungu
Mart.ex.Benth. Fabaceae
Tetrahydroisoquinoline alkaloids erythravine and (+)-11α-hydroxy-
erythravine.[85] [86]
Eschscholzia californica
cham. Papaveraceae The chemical constituents include alkaloids and flavone glycosides. [87]
Euphoria longana Lamk. Sapindaceae The active principle is adenosine. [88]
Euphorbia hirta L. Euphorbiaceae The chemical constituents include flavonoids, polyphenols, tannins,
alkanes, triterpenes and phytosterols.[89] [90]
Eurycoma longifolia
Jack. Simaroubaceae [91]
Euphorbia neriifolia
Linn. Euphorbiaceae
The phytochemical constituents include a variety of triterpenes like
nerifolione, euphol, euphorbol and others from latex, bark, root, whole
plant and leaf. Anthocyanins like delphin and tulipanin and diterpenes
were isolated from the bark and roots.[92]
The phytochemical study showed the presence of steroidal saponins,
reducing sugar, tannins, flavonoids in the crude leaf extract.[93]
[93]
Galphimia glauca Cav. Malpighiaceae [94]
Gastrodia elata Blume.
Orchidaceae
The phytochemical studies have revealed the presence of several
phenolic compounds, including 4-hydroxybenzyl alcohol, 4-
hydroxybenzaldehyde, vanillin, vanillyl alcohol, β-sitosterol and
gastrodin.[95]
[5]
Ginkgo biloba L.
Ginkgoaceae
The phytoconstituents include flavonoids, glycosides and terpenoids
(ginkgolides, bilobalides). [96]
Hypericum perforatum L. Hyperiaceae The phytochemical constituents include hypericin and other
dianthrones, flavonoids, xanthones and hyperforin. [97]
Ipomoea stans Cav. Convulvulaceae [98]
Justicia hyssopifolia
Linn. Acanthaceae
The active constituent of the plant Elenoside, a lignin (β-D-glucoside)
got from the leaves. [99]
Kielmeyera coriacea
Mart. ex Saddi. Clusiacea
Xanthones, triterpenes and their biphenyl derivatives.[100-101]
[102]
Magnolia dealbata Zucc. Magnoliaceae [103]
Matricaria chamomilla
L. Asteraceae
The flowers possess 1-2% volatile oils containing alpha-bisabolol,
alpha-bisabolol oxides A & B, and matricin (usually converted to
chamazulene). Other active constituents include the bioflavonoids
apigenin, luteolin, and quercetin. These active constituents contribute
to the myriad health benefits of the plant.
[104]
Melissa officinalis L.
Lamiaceae
It contains rosmarinic acid, phenolic acids, triterpenes, monoterpene
glycosides, flavonoids and the essential oil contains citronellal, citral,
germacrene and caryophyllene.
[105]
Momordica charantia
Linn. Cucurbitaceae
The phytoconstituents include alkaloids, steroids, triterpeniods, amino
acids, and flavonoids, reducing sugar, tannins and saponins.[106] [106]
Morus alba L.
Moraceae
The phytoconstituents include flavonoids, tannins, triterpenes,
anthocyanins, anthroquinones, phytosterols, sitosterols, benzofuran
derivatives, morusimic acid, oleanolic acid, alkaloids, steroids,
saponins and phenolic compounds.[107-108]
[109]
Mitragyna speciosa
Korth Rubiaceae
The active constituents are mitragynine, mitraphylline, and 7-
hydroxymitragynine. The chemical 7-hydroxymitragynine is effective
as a pain reliever. Mitragynine is also a pain reliever, but it is not as
powerful as 7-hydroxymitragynine.
Nardostachys jatamansi
DC. Valerianaceae
Chemically, N. jatamansi contains sesquiterpinenoids like jatamansone,
spirojatamol, patchouli alcohol, norseychelanone, jatamol A and B,
lignins and neolignins, jatmansic acid, terpenic caumarins like oroselol and jatamansin.
[110]
Nepeta persica Boiss. Lamiaceae Reports on Nepeta species show that the main constituents of the oil
are diastereomeric nepetalactones.
[111]
Khanum and Razack Res Rev Biomed Biotech 1(2); 2010
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Nepeta cataria L.
Lamiaceae
The principal constituents of the oil are nepetalactone and nepetalic
acid, nepetalic anhydride, β-caryophyllene and an ether and ester.
Pachyrrhizus erosus L.
Leguminosae
The phytoconstituents of the seed include rotinoids, flavonoids and phenylfuranocoumarin derivatives.
[112-113]
Paeonia mountan Sims. Paeoniaceae The phytoconstituents include paeonolide, paeonol, paeonoside and
paeoniflorin. [114]
Panax ginseng C. A.
Meyer Araliaceae.
Ginsenosides
[115-119]
Passiflora incarnata
Linn. Passifloraceae
It constitutes an array of phytoconstituents some of which include beta-
carboline harmala alkaloids, coumarins, flavonoids and their
glycosides, organic acids, phenolic compounds. Chrysin, a flavone is
known to render the anxiolytic properties.
[120]
Passiflora foetida L Passifloraceae [51, 13]
Passiflora edulis Sims. Passifloraceae [121]
Piper methysticum G.
Forster. Piperaceae The active compounds include kava-lactones/kava-pyrones. [122-125]
Rauvolfia serpentina (L.)
Benth. ex Kurz. Apocynaceae.
It contains a variety of bioactive compounds including reserpine (the most important alkaloid present in the root, stem & leaves of the plant),
ajmaline, deserpidine, rescinnamine, reserpinine, sarpagine,
serpentinine.
Rhodiola rosea L.
Crassulaceae
R.rosea contains a variety compounds including phenylpropanoids like
rosavin, rosin, rosarin, phenylethanol derivatives like salidroside,
tyrosol, flavonoids like rodiolin, rodionin, monoterpenes like rosiridol,
triterpenes like daucosterol and phenolic acids like chlorogenic acids.
Ruta chalepensis L. Rutaceae [126]
Rubus brasiliensis
Martius. Rosaceae [127]
Santalum album Santalaceae The phytoconstituents include sesquiterpenes like santalene, farnesene
and alcohols like santalol.
Salvia officinalis L. Lamiaceae The active constituents are present in the essential oil, which contains
cineole, borneol, and thujone. [128]
Scutellaria baicalensis
Georgi Lamiaceae Wogonin-a monoflavanoid exerts anti-anxiety efffects. [129]
Scutellaria lateriflora L. Lamiaceae Flavonoids baicalin and its aglycone baicalein show anti-anxiety
effects [130]
Stachys lavundulifolia
Vahl. [131]
Sceletium tortuosum (L.)
N.E. Brown Aizoaceae.
The major alkaloids include mesembrine, mesembrenone,
mesembrenol and tortuosamine.
Sesbania grandiflora (L.)
Poiret. Fabaceae Triterpenes show anti-anxiety effects [132]
Sphaeranthus indicus
Linn. Asteraceae
Methyl chavicol, α-ionone, d-cadinene, p-methoxy cinnamaldehyde
have been identified as the major constituents. [133]
Tragia involucrata Linn. Euphorbiaceae [134]
Turnera aphrodisiaca
Ward. Turneraceae
The leaves contain volatile oil, tannins, flavonoids, beta-sitosterol,
damianin and glycosides. [135]
Tilia Americana L.
Malvaceae
The active constituents include flavonoids, volatile oils, mucilaginous
constituents and tannins. [136]
Uncaria rhynchophylla
(Miq.) Jacks Rubiaceae. [137]
Valeriana edulis ssp.
procera Meyer Valerianaceae [138]
Valeriana officinalis L.
Valerianaceae
The chemical constituents include alkaloids, lignans, glycosides,
volatile & non-volatile constituents, aminoacids, caffeic acid,
chlorogenic acid, beta-sitosterol, methyl 2-pyrrolketone, choline,
tannins, gum and a resin.
[139-140]
Vitex negundo Linn. Verbenaceae [141]
Withania somnifera (L.)
Dunal
Solanaceae.
The main constituents are alkaloids and steroidal lactones. Among the
various alkaloids withanine is the main constituent. The steroidal
lactones are commonly called withanolides and are the most important
bio-active components present in roots that account for the multiple
medicinal properties of the herb. Two acyl steryl glucoside namely sitoindoside VII and sitoindoside VIII have been isolated from root.
The glycowithanolides exhibited significant anxiolytic activity
[142]
Khanum and Razack Res Rev Biomed Biotech 1(2); 2010
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Zingiber officinale
Roscoe. Zingiberaceae
Sesquiterpenoids, monoterpenoids and nonvolatile phenylpropanoid-
derived compounds. [143]
Ziziphus jujuba Mill. Rhamnaceae
[144]
Table 2: Lists the plants influencing GABAergic system Plant name Common name Reference
Annona cherimola Mill. Cherimoya/Cherimolia/Custard apple [59]
Apocynum venetum. L [60]
Gastrodia elata Blume. [5]
Ipomoea stans Cav. Tumbavaqueros [98]
Melissa officinalis L. [105]
Pachyrrhizus erosus L. [113]
Rauvolfia serpentina (L.) Benth. ex Kurz Indian snakeroot or sarpagandha [145]
Rubus brasiliensis Martius. [127]
Scutellaria baicalensis Georgi Baikal skullcap [129]
Scutellaria lateriflora L. Skullcap [130]
Sesbania grandiflora (L.) Poiret. Agati [132]
Tragia involucrata Linn. [134]
Table 3: Lists the plants influencing the serotonergic system Plant name Common name Reference
Albizzia julibrissin Durazz. Persian silk tree or pink siris [56]
Gastrodia elata Blume. [5]
Sesbania grandiflora (L.) Poiret. Agati [132]
Uncaria rhynchophylla (Miq.) Jacks [137]
CONCLUSION
Thus, natural herbs/herbal mixtures that act
synergistically promise to provide an
effective remedy for anxiety. However, only
very few among these have been proved to
be effective anxiolytes with trials carried out
on humans. Synthetic drugs and medications
possess enormous side effects, so these
herbs with a wide therapeutic applicability
promise to alleviate anxiety with very few
adverse effects.
ACKNOWLEDGEMENT
The work has been carried out for a project
funded by Defense Research and
Development Organization, India. Authors
kindly acknowledge constant
encouragement given by Director, DFRL.
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Sources of support: DRDO, India
Conflict of interest: None declared