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Khanum and Razack Res Rev Biomed Biotech 1(2); 2010

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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.

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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

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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]

.

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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

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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]

.

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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

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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

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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

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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.

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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

www.rrbb.in 82

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