invited review plant drugs used to combat menace of anxiety
TRANSCRIPT
4 (c) Copyright 2011 EManuscript Publishing Services, India
Invited Review
Pharmacognosy Communications www.phcogcommn.org
Volume 1 | Issue 1 | Jul-Sep 2011
*Correspondence: [email protected]; [email protected].: +91-9872981142, +91-9815916142DOI: 10.5530/pc.2011.1.2
Plant Drugs Used to Combat Menace of Anxiety DisordersReecha Madaan*1, Suresh Kumar2, Gundeep Bansal2, Anupam Sharma3
1Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, India ([email protected]). 2Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala- 147 002, Punjab, India ([email protected]). 3Pharmacognosy Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh-160 014, India ([email protected])
INTRODUCTION
Anxiety Disorders: An OverviewGlobal scenario of persons afflicted by mental disorders is alarming.[1] About 500 million people suffer from neurotic, stress related and somatoform problems, 200 million from mood disorders, 83 million from mental retardation, 30 million from epilepsy, 22 million from dementia, and 16 million from schizophrenia. Anxiety disorders are serious medical illnesses that have affected 1/8th of total population worldwide irrespective of gender, age, religion, nationality and profession.[2] Anxiety Disorders Association of America (ADAA) described anxiety disorders as the most common mental illness in the US, that have affected 19.1 million (13.3%) of the adult (18-54 years) US population.[3] A study commissioned by ADAA on ‘The Economic Burden of Anxiety Disorders’ revealed that anxiety disorders cost the US more than $42 billion a year, almost one-third of the $148 billion total mental health bill for the US. In India, prevalence rate for all mental disorders is 65.4 per 1000 population, and that for anxiety neurosis is 18.5 per 1000 population.[4] The Global Research on Anxiety and Depression (GRAD) network, a consortium of world’s leading psychiatric epidemiologists and clinical researchers, during the 154th annual meeting of ‘American
Psychiatric Association’ (APA) has observed that, “a significant number of world’s population is plagued by chronic and excessive anxiety, also known as generalized anxiety disorder (GAD), which is more serious than those of lung disease, sleep disorders and major depression, and affects more than 5% of the world population”.[5] Following is the categories of anxiety disorders. [3,6]
1. Panic disorder (PD) is characterized by panic attacks, sudden feeling of terror that strike repeatedly and without warning. Physical symptoms include chest pain, heart palpitations, sweating, trembling, shortness of breath, dizziness, abdominal discomfort, fear of losing control, fear of dying, tingling sensations, and hot flushes. Panic disorders have affected 6 million (2.7%) adult US population. Women are twice more likely to be afflicted than men.
2. Obsessive–compulsive disorder (OCD) is characterized by uncontrollable obsessions (recurring thoughts or impulses that are intrusive or inappropriate and cause the sufferer anxiety) and compulsions (repetitive behaviours or rituals). It has affected 2.2 million (1%) adult US population. It is equally common among men and women.
3. Post-traumatic stress disorder (PTSD) is characterized by persistent symptoms (nightmares, flashbacks, numbing of emotions, depression, feeling angry and irritable) that occur after experiencing a traumatic event such as war, rape, child abuse and natural disaster. It has affected 7.7 million (3.5%) adult US population. Women are more likely to be afflicted by this disorder.
ABSTRACT: In present era, a sudden holocaust of mental disorders, and recognition of severe side effects and addiction liabilities associated with long term administration of widely prescribed synthetic drugs have aroused the attention of researchers towards natural resources. This review includes 351 references, and emphasizes pharmacological reports on anxiolytic plant products and formulations. Various chemical constituents (with structures), isolated from different plants, responsible for antianxiety activity, and their possible mechanism of actions have been incorporated in this review.The review has been compiled using references from major databases like Chemical Abstracts, Medicinal and Aromatic Plants Abstracts, PubMed, Scirus, Science Direct and Online Journals. It has been concluded that preliminary antianxiety activity studies have been carried out on crude extracts of most of traditonally used and clinically potential plants. Such plantsneed to be explored properly with a view to isolate anxiolytic constituents, and to evaluate their possible mode of actions.
KEY WORDS: Antianxiety activity, chemical constituents, mechanism of action, pharmacology
Invited Review
5
Madaan, et. al.: Plant Drugs Used to Combat Menace of Anxiety Disorders
Thought patternsNegative thoughts can actually create physical symptoms of anxiety.
Management of anxiety disordersSuch a horrid emergence of mental disorders has attracted the attention of researchers towards various pharmacotherapeutic approaches for the management of these ‘modernization borne diseases’.[10] Barbiturates, benzodiazepines (BZDs), azaspirones, norepinephrine and serotonin-reuptake inhibitors, monoamine oxidase inhibitors and phenothiazines are some of the commonly used psychotropic drugs.[10] Among these, BZDs are the most widely prescribed synthetic chemical drugs for the treatment of anxiety, insomnia, epilepsy, and stress. Regular use of BZDs causes deterioration of cognitive functioning, addiction, physical dependence and tolerance.[10-12] Abrupt cessation of chronic treatment with BZDs causes the appearance of withdrawal effects comprising re-bound anxiety, restlessness, epilepsy, and motor agitation.[13,14] In the light of adverse effects associated with the synthetic drugs, researchers have been exploring natural resources to find out safer and effective drugs. Investigating plants, based on their use in traditional systems of medicine, is a sound, viable and cost effective strategy to develop new drugs.[15] Plants like Valeriana officinalis, Nardostachys jatamansi, Withania somnifera and Panax ginseng have been used extensively in various traditional systems of therapy because of their adaptogenic and psychotropic properties. Inclusion of these well-established CNS affecting plants in the arsenal of modern therapeutics has revived the faith of researchers in the plants.[16]
Targets for Treatment of AnxietyWith anxiety, various brain neurotransmitters and hormones levels change immediately. In particular, monoamines, such as norepinephrine, serotonin and dopamine, are involved in mood, stress and other physical homeostasis.[17] Serotonin and norepinephrine mainly regulate stress and negative mood in the mammalian brain, and their dysfunctions cause various mood disorders, such as social anxiety disorder and depression.[18] Dopamine also regulates mood and emotion-related behaviors and has a motivation/reward function and conditional fear responses.[19,20] Various anxiolytics and antidepressants aim at monoamine neurocircuitry, such as their receptors and transporters.[21]
The 5-hydroxytryptamine 1A (5-HT1A) receptor is viewed as a relevant target for the treatment of psychiatric disorders, notably anxiety and depression.[22] 5-HT1A receptors are located at the presynaptic and postsynaptic sites.[23] The somatodendritic autoreceptor, when activated by systemic stimulation, is believed to exert anxiolytic-like effects and to reduce 5-HT release both in the cell body and in the terminal regions of the serotonergic neurons.[24] The other 5-HT1A receptor is localized postsynaptically to the serotonergic neurons in the hippocampus, septum, amygdala, and cortex, where it increases signal transfer, which leads to an inhibition of the firing activity.[25]
4. Social phobia or Social anxiety disorder (SAD) is characterized by an intense fear of situations where embarrassment may occur. Physical symptoms include palpitations, tremors, sweating, diarrhoea, confusion and blushing. It has affected 15 million (6.8%) US adult population. It is equally common among men and women.
5. Specific phobia (SP) is characterized by the excessive fear of an object or a situation, exposure to which causes an anxious response. Specific phobias affect an estimated 19 million (8.7%) US adult population and are twice as common in women as in men.
6. Generalized anxiety disorders (GAD) are characterized by chronic, exaggerated worry about everyday routine life events and activities, lasting at least six months. Physical symptoms include fatigue, trembling, muscle tension, headache or nausea. It has affected an estimated 6.8 million (3.1%) US adult population and is twice as common in women as in men. Though, GAD is the most frequent anxiety disorder, yet only 20% of patients receive proper treatment.[7] GAD results loss of 6 for every 30 work-impairment days.
Causes of Anxiety DisordersVarious factors causing anxiety disorders are described below. [8-9]
Heredity/Genetic factorsAnxiety disorders (PD and OCD) tend to run in families. Studies have shown that if one of the twins has an anxiety disorder, the second is more likely to have an anxiety disorder.
Brain chemistryThe symptoms of long term social anxiety disorder can be attributed to the improper chemical balance in the brain. Several neurotransmitters namely serotonin, norepinephrine, gamma-amino butyric acid (GABA), which are produced in the brain, directly affect one’s feelings about a given situation. Thus brain, too, appears to play a role in the onset of anxiety disorders because symptoms of anxiety disorders are often relieved by medications that alter the level of chemicals in the brain.
PersonalityPeople with low self-esteem and poor coping skills are more prone to anxiety disorders. Conversely, an anxiety disorder that begins in childhood may itself contribute to the development of low self-esteem.
Life experiencesLong term exposure to abuse, violence, poverty or stressful experiences (the early death of a parent, bad marital or family relationships, or traumatic experiences) may affect individual’s susceptibility to anxiety disorders.
Stress overload/Lifestyle factorsExcessive stress over time, and poor lifestyle habits such as overwork, lack of sleep, poor diet and lack of regular exercise promote anxiety.
6
Madaan, et. al.: Plant Drugs Used to Combat Menace of Anxiety Disorders
In brain, Nitric oxide synthase (NOS) has been localized in regions involved with anxiety, such as hypothalamus, amygdala and hippocampus.[36,37] Inhibition of NOS by nonselective or by relatively selective inhibitors of nNOS produced antianxiety-like effect. Neurosteroids can rapidly alter the excitability of central nervous system by modulating neurotransmitter-gated ion channels such as GABAA and N-methyl-D-aspartate receptors. [38] Anxiolytic, anticonvulsant and anaesthetic effects of neuroactive steroids are mediated by their capacity to positively modulate GABAA receptor. 5-alpha reductase, the enzyme that converts into 5-alpha-reduced metabolites like the GABAA positive neuroactive steroid 3-alpha-hydroxy-5-alpha-pregnan-20-one, thus, few drugs exhibits anxiolytic action via an indirect activation of the GABA-ergic system through neuroactive steroids.[39]
PLANTS HAVING ANTIANXIETY ACTIVITY
Antianxiety activity reports of various plants, and plant constituents and formulations have been presented in tables 1 and 2. Various patented formulations of anxiolytic plant drugs have been depicted in table 3. Various review articles published on anxiolytic plants are shown in table 4.
GABA is a major inhibitory transmitter in the central nervous system. The γ-aminobutyric acid type A (GABAA) receptor, the chloride ion channel complex and the central benzodiazepine receptors located on the neuronal membranes within this complex have been suggested to play an important role in the regulation of the stress and anxiety states.[26,27] The benzodiazepine binding site and GABAA receptor are structurally and functionally coupled. [28] Benzodiazepines (BZDs) have become the primary pharmacological treatment for generalized anxiety disorder. However, BZDs are often associated with tolerance development and withdrawal symptoms, which pose a risk of relapse upon discontinuation.[29,30]
Monoamine oxidase (MAO) catalyzes the oxidative deamination of a variety of monoamines such as dopamine, norepinephrine and serotonin. The MAO reaction yields aldehydes and hydrogen peroxide (H2O2), which induces apoptosis.[31] Increased endogenous MAO inhibitory activity (tribulin activity) is associated with conditions associated with stress and anxiety, both in animals and in man. [32] Rat brain tribulin activity is significantly augmented by anxiogenic agents like pentylenetetrazole, and this effect can be prevented by anxiolytic agents.[33] Inhibition of MAO and subsequent H2O2 generation effectively prevents depression and various oxidative stresses in the brain.[34] The presence of plant-derived MAO inhibitors suggests that such plant extracts could be useful as potential neuroprotectants in the treatment or prevention of depression.[35]
OH
O
(1)
O
OO
O
O
(2)
N
H
O R 1
R 2
R 1 R 2
(3) OH
(4) H
OH
H
O O
(5)
7
Madaan, et. al.: Plant Drugs Used to Combat Menace of Anxiety Disorders
OHO
OOH
OH
OH
(6)
O
OH
OH
HO
O
OH
OH
(7)
NHO
O
NH2
O
(8)
H
OH
HO
H
(9)
O
O OH
HO
(10)
CH3
OCH3
OH
OHOH
O
OCH2OH
OH
OHO
HO
HOH2C CH3
H3C
CHO
CH3
O
OCH2
OH OH
OH
(11)
CHO
CH2OOCCH2CH(CH3)2
(12)
8
Madaan, et. al.: Plant Drugs Used to Combat Menace of Anxiety Disorders
OR O
R
O
O
(13), R = β-Gentiobiosyl
O
(14)
OOH
HO
OH
OH
OH
(15)
HO
CH3
H3CO
(16)
OH
HO
O
OH
OCH3H3CO
(17)
O(18)
N
RO
R'
CH3O
CH3O
R R’(19) CH3 OH(20) H H(21) H OH
N
RO
H3CO
H3CO
R
(22) H
(23) CH3
N
N
N
N
O
NH2
OH
HO
HO
(24)
9
Madaan, et. al.: Plant Drugs Used to Combat Menace of Anxiety Disorders
O
R 3O
H H
O
OH
OR 2R 1
H3CO 2C
R1 R2 R3
(25)
(26)
H H H
H OH H
OOH
OH
(27)
O
O
O
O
OH
OO
OH O
R 1
R 2
H3C
C(CH 3)3
R 1 R 2
(28) H H
N
OCH3
OCH3
(29)
OOH
CH3HOR
O
OH
HO
OH OH
(30), R=CH3(31), R =CH2OH
O
OH
HO
O
OHO
HO
HOHO
CH2OH
(32)
O
OH
HO
O
OH
OH
R 1
R 2
R2
(33) -Glc
(34)
H
H -Glc
R1
O
O
O
O
O
HO
CH3O
(35)
β
β
10
Madaan, et. al.: Plant Drugs Used to Combat Menace of Anxiety Disorders
OH
OH
(36)
O
OH
CH2
H2C
OH
(37)
O
OH
HO
OH O
(38)
N
O
N
HHO
CH3
H3C
HOCH3
OCH3
OCH3
H3CO
(39)
O
OO
OH
HOH
OH
OH
OH
OH OH
OH
OH
OH
HO
HO
HOHO
HO
H
O
OO
O
O
H
H
H
H
(40)
11
Madaan, et. al.: Plant Drugs Used to Combat Menace of Anxiety Disorders
O O
HO
OH
OR
HO
OHHO
R
(41) D-glucose
(42) H
OHO
OOH
(43)
O
OH
HO
O
OH
OH
(44)
O
OOH
HO
O OH
OH
OH
(45)
CH COOH
OH
OH
CH
(46)
O2
3
45
6O
7
8
9
10
1
11
1213
14
OCH 3
R 1
R 2
R 3
R 4
R 5
R1 R2 R3 R4 R5 C5-C6
(47) H OCH 2OH H =
(48) H OCH 2OH H
(49) H H H H H H
(50) H H H H H =
(51) H H H H H = H
(52) H OCH 3 H H = HH
C7-C8
O
O O
N
O
O
(53)
12
Madaan, et. al.: Plant Drugs Used to Combat Menace of Anxiety Disorders
O2
3
45
6O
7
8
9
10
1
11
1213
14
OCH3
R1
R2
R3
R4
R5
R3
(54)(55)(56)(57)(58)(59)(60)
R1 R2 R4 R5 C5-C6 C7-C8
OCH2OOCH2OOCH2OOCH2OOCH2OOCH2O
H H H =H H =H H =H H H = =H H = =H H H = =
OCH3O CH3
OCH3
OCH3
OCH3
OCH3H H H =
H
H
H
HO
(61)
H
H
H
HO
(62)
OHO
OH
OH
OH
OH
HOOC
(63)
O
O
O
O
O
O
O
O
H H
H
(64)
O
O
(65)
OHO
OOH
OCH3
(66)
OH
H
OHH
OH
OH
HH
OO
COOH
HOOH O
(67)
13
Madaan, et. al.: Plant Drugs Used to Combat Menace of Anxiety Disorders
O
HOOH O
HO
(68)
HO
(69)
O
OH
HO
OH O
H3C
(70)
O OO O O
OHHO OOH
OH
OH
OHOHHO
H3C
OCH3
(71)
O
O
OH
HO
OO O
O
OH OH
OH
HO
HOH3C
OCH3
(72)
CH3
COOH
H
CH3
CH3
(73)
NH
O
HN NH
N
O O
O
CH3
CH3
(74)
O
(75)
14
Madaan, et. al.: Plant Drugs Used to Combat Menace of Anxiety Disorders
O
CH3
CH3
CH3
(76)
O
(77)
O
(78)
CH3
H2CHH
CH3
CH3
(79)
OH
(80)
OH
(81)
OH
(82)
N
N
O
O
O
H
H
H
(83)
CONCLUSION
In present era, a sudden holocaust of mental disorders, and recognition of severe side effects and addiction liabilities associated with long term administration of widely prescribed synthetic drugs have aroused the attention of researchers towards natural resources. Plants like Valeriana officinalis, Nardostachys jatamansi, Withania somnifera and Panax ginseng have been used extensively in various traditional systems of therapy because of their adaptogenic and psychotropic properties. Inclusion of these well-established CNS affecting plants in the arsenal of
modern therapeutics has revived the faith of researchers in the plants.
In present review article, amongst 143 plants reported to possess antianxiety activity (Table 1):
(a) only 07 plants have been tested clinically, (b) preliminary antianxiety activity screening on crude extracts
has been carried out on 90 plants. Such plants need to be explored with a view to isolate active constituents and their mode of actions,
15
Madaan, et. al.: Plant Drugs Used to Combat Menace of Anxiety DisordersTa
ble
1: L
ist
of
vari
ou
s p
lan
ts r
epo
rted
to
po
sses
s an
tian
xiet
y ac
tivi
ty.
S.
No
. B
iolo
gic
al s
ou
rce
Ext
ract
/Fra
ctio
n/Is
ola
teD
ose
An
imal
/ H
um
an b
ein
g
Exp
erim
enta
l mo
del
/ A
sses
smen
t o
f cl
inic
al
par
amet
ers
Mec
han
ism
o
f ac
tio
nA
ctiv
ity
Ref
.
01A
bies
pin
drow
Roy
le
(Pin
acea
e)
Talis
pat
ra, S
ilver
F
ir, P
ind
row
Fir
Eth
anol
ext
ract
of
leav
es50
and
100
m
g/kg
, ora
lly
once
dai
ly fo
r 3
days
Wis
tar
rats
Ele
vate
d pl
us m
aze
(EP
M),
Ope
n fie
ld te
st (
OF
T),
Ele
vate
d ze
ro m
aze
(EZ
M)
—A
nxio
lytic
[40]
02A
chill
ea m
illef
oliu
m
Linn
. (C
ompo
sita
e)
Yarr
ow
, Milf
oil
Aqu
eous
ext
ract
of
flow
ers
12 m
g/kg
, p.o
.Fe
mal
e W
ista
r ra
tsC
onfli
ct b
ehav
iour
—A
nxio
lytic
[41]
03A
coru
s ca
lam
us
Linn
. (A
race
ae)
Bac
h/B
acop
a m
onni
eri L
inn.
(S
crop
hula
riace
ae)
Bra
hm
i
Pow
der
of w
hole
pla
nt50
0 m
g T
DS
fo
r 6
wee
ks81
Pat
ient
s su
fferin
g fr
om
anxi
ety
diso
rder
Ele
ctro
phys
iolo
gica
l par
amet
ers
like
EE
G, E
CG
—Im
prov
emen
t in
ne
rvou
snes
s,
rest
less
ness
, ir
ritab
ility
, poo
r co
ncen
trat
ion,
sl
eep
and
loss
of
app
etite
[42]
04A
ctae
a sp
icat
a Li
nn.
(Api
acea
e)
Ban
eber
ry,
Gra
pew
ort
Fla
vono
idal
moi
ety
2 m
g/kg
, p.o
.La
ca m
ice
EP
M—
Anx
ioly
tic[4
3]
(a)
Met
hano
l ext
ract
(b
) P
olyp
heno
l fra
ctio
n(a
) 10
0 m
g/kg
, p.
o.
(b)
50 m
g/kg
, p.
o.
Laca
mic
eE
PM
—A
nxio
lytic
[44]
05A
dian
tum
te
trap
hyllu
m H
umb.
&
Bon
pl. e
x W
illd.
(A
dian
tace
ae)
Fo
url
eaf
mai
den
hai
r
Eth
anol
ext
ract
(95
%)
of
leav
es20
0 m
g/kg
, p.
o.M
ale
Spr
ague
Daw
ley
rats
OF
T, E
PM
, Aco
ustic
sta
rtle
re
spon
se te
st—
Anx
ioly
tic[4
5]
06A
ethu
sa c
ynap
ium
Li
nn. (
Api
acea
e)
Fo
ol’s
Par
sley
Fatty
aci
d: tr
idec
a-7,
9,11
-trie
noic
aci
d(1)
is
olat
ed fr
om m
etha
nol
extr
act o
f ae
rial p
arts
20 m
g/kg
, p.o
.S
wis
s al
bino
mic
e[1
-(3-
chlo
rphe
nyl)p
iper
azin
e]
indu
ced
hypo
loco
mot
ion
test
—A
nxio
lytic
[46]
07A
lbiz
zia
julib
rissi
n D
uraz
z. (
Faba
ceae
)S
ilktr
ee, M
imo
sa,
Nem
un
oki
Aqu
eous
ext
ract
of
stem
ba
rk10
0 an
d 20
0 m
g/kg
, p.o
.M
ale
SD
rat
sE
PM
Ser
oton
ergi
c sy
stem
Anx
ioly
tic[4
7]
Aqu
eous
ext
ract
of
bark
200
mg/
kg,
p.o.
for
seve
n da
ys
Mal
e S
D r
ats
EP
MIn
tera
ctio
n w
ith
5-H
T1A
rece
ptor
Anx
ioly
tic[4
8]
08A
lbiz
zia
lebb
eck
Ben
th. (
Faba
ceae
)S
iris
tre
e, A
lbiz
ia
Sap
onin
s ric
h n-
buta
nolic
frac
tion
of
petr
oleu
m e
ther
ext
ract
fr
om le
aves
25 o
r 50
mg/
kg, p
.o.
Alb
ino
Sw
iss
mic
eE
PM
Inhi
bitio
n of
G
AB
Aer
gic
tran
smis
sion
Anx
ioly
tic a
nd
noot
ropi
c[4
9]
16
Madaan, et. al.: Plant Drugs Used to Combat Menace of Anxiety Disorders
Tab
le 1
: Co
nti
nu
ed
S.
No
. B
iolo
gic
al s
ou
rce
Ext
ract
/Fra
ctio
n/Is
ola
teD
ose
An
imal
/ H
um
an b
ein
g
Exp
erim
enta
l mo
del
/ A
sses
smen
t o
f cl
inic
al
par
amet
ers
Mec
han
ism
o
f ac
tio
nA
ctiv
ity
Ref
.
09A
loys
ia p
olys
tach
ya
Gris
eb.
(Ver
bena
ceae
) B
urr
ito
Hyd
ro-a
lcoh
olic
ext
ract
(6
0% e
than
ol)
of le
aves
1.56
to 5
0 m
g/kg
, i.p
.Fe
mal
e S
prag
ue D
awle
y ra
tsE
PM
, For
ced
Sw
imm
ing
Test
(F
ST
)—
Anx
ioly
tic a
nd
antid
epre
ssan
t[5
0]
Eth
anol
ext
ract
of
aeria
l pa
rts
1.0,
10.0
and
10
0.0
mg/
kg,
p.o.
Sw
iss
albi
no m
ale
mic
eE
PM
Oth
er m
echa
nism
th
an B
ZD
-bs
mod
ulat
ion
at th
e G
AB
AA r
ecep
tors
Anx
ioly
tic
with
out
seda
tive
effe
cts
[51]
10A
lpin
ia
zeru
mbe
t(P
ers.
) B
urtt
& R
M
(Zin
gibe
race
ae)
Sh
ell f
low
er, P
ink
po
rcel
ain
lily
Ess
entia
l oil
from
leav
esIn
hala
tion
3.5
mg/
L ai
rM
ale
ICR
mic
eLi
ght/D
ark
mod
el (
LDM
) , O
FT,
E
PM
—A
nxio
lytic
[52]
11A
ngel
ica
Ess
entia
l oil
30.0
mg/
kg,
p.o.
Mal
e S
wis
s m
ice
EP
M, L
DM
—A
nxio
lytic
[53]
Ess
entia
l oil
21 m
g/kg
, p.o
.M
ale
Wis
tar
rats
Soc
ial i
nter
actio
n in
rat
s (S
I),
Hol
e B
oard
Tes
t (H
BT
)—
Anx
ioly
tic[5
4]
12A
ngel
ica
dahu
rica
(Fis
ch. e
x H
offm
.)
Ben
th. (
Api
acea
e)
Dah
uri
an a
ngel
ica
Fur
anoc
oum
arin
–
Phe
llopt
erin
(2)
isol
ated
fr
om m
etha
nol e
xtra
ct o
f ro
ots
IC50
= 0
.36
mic
roM
In v
itro
—B
ZD
rec
epto
rs
agon
ist
Anx
ioly
tic[5
5]
13A
niba
rip
aria
(N
ees)
M
ez (
Laur
acea
e)
Ro
sew
oo
d
Rip
arin
III(
3) is
olat
ed
from
unr
ipe
frui
ts25
and
50
mg/
kg, i
.p.
Mal
e S
wis
s m
ice
EP
M, F
ST
—A
nxio
lytic
, an
tidep
ress
ant
[56]
Rip
arin
I (4
) is
olat
ed
from
unr
ipe
frui
ts25
and
50
mg/
kg, i
.p.
Mal
e S
wis
s m
ice
EP
M, O
FT,
HB
T—
Anx
ioly
tic[5
7]
Rip
arin
- III
(3)
isol
ated
fr
om u
nrip
e fr
uits
25 a
nd 5
0 m
g/kg
, p.o
.M
ale
Sw
iss
mic
eO
FT,
EP
M, H
BT
—A
nxio
lytic
but
de
void
of
seda
tive
activ
ity
[58]
14A
nnon
a ch
erim
olia
M
ill. (
Ann
onac
eae)
C
her
imoy
a,
Cu
star
d a
pp
le
Hex
ane
extr
act o
f le
aves
6.25
, 12.
5,
25.0
and
50.
0 m
g/kg
, p.o
.
Alb
ino
mic
eM
ouse
avo
idan
ce e
xplo
rato
ry
beha
vior
, Mar
ble
bury
ing
test
(M
BT
)
GA
BA
/BZ
D
rece
ptor
com
plex
Anx
ioly
tic[5
9]
15A
nnon
a di
vers
ifolia
S
aff.
(Ann
onac
eae)
L
lam
a, A
no
na
bla
nca
Pal
mito
ne(5
) is
olat
ed
from
hex
ane
extr
act o
f le
aves
0.3,
1, 3
, 10
and
30 m
g/kg
i.p
.
Alb
ino
mic
eE
PM
—A
nxio
lytic
[60]
17
Madaan, et. al.: Plant Drugs Used to Combat Menace of Anxiety Disorders16
Apo
cynu
m v
enet
um
Linn
. (A
pocy
nace
ae)
Do
gb
ane
Eth
anol
ext
ract
of
leav
es30
and
125
m
g/kg
, p.o
.M
ale
C75
BL/
6 m
ice
EP
MIn
volv
emen
t of
GA
BA
ergi
c sy
stem
Anx
ioly
tic[6
1]
Kae
mpf
erol
(6)
isol
ated
fr
om h
ydro
-alc
ohol
ic
extr
act (
70%
eth
anol
) of
le
aves
>0.0
2 m
g/kg
, p.
o.M
ale
BL6
/C57
J m
ice
EP
MB
ZD
rec
epto
r in
tera
ctio
nA
nxio
lytic
[62]
17A
roni
a m
elan
ocar
pa
Mic
hx. (
Ros
acea
e)
Bla
ck c
ho
keb
erry
Frui
t jui
ce5
and
10 m
l/kg
, p.o
.W
ista
r ra
tsS
I, O
FT
—A
nxio
lytic
[63]
18A
zadi
rach
ta in
dica
A
. Jus
s. (
Mel
iace
ae)
Nee
m t
ree
Aqu
eous
ext
ract
from
le
aves
10, 2
0, 5
0, 1
00
and
200
mg/
kg, p
.o.
Wis
tar
rats
EP
M, O
FT
—A
nxio
lytic
[64]
Aqu
eous
ext
ract
from
le
aves
500
mg/
kg/
day
× 15
day
sM
ale
Cha
rles-
Fost
er a
lbin
o ra
tsO
FT
and
Mor
ris w
ater
maz
eIn
crea
se in
as
corb
ic a
cid
leve
l of
brai
n w
hich
falls
dur
ing
brai
n is
chem
ia
Anx
ioly
tic[6
5]
19B
aphi
a ni
tida
Lodd
. (F
abac
eae)
A
fric
an
san
dal
wo
od
, B
arw
oo
d
Eth
yl a
ceta
te e
xtra
ct o
f le
aves
100-
400
mg/
kg, p
.o.
Adu
lt al
bino
mic
e of
eith
er
sex
EP
M, Y
maz
e—
Anx
ioly
tic[6
6]
20B
yrso
carp
us
cocc
ineu
s S
chur
n.
and
Tho
nn.
(Con
nara
ceae
) K
imb
ar m
ahal
ba
Aqu
eous
ext
ract
of
leav
es20
0 an
d 40
0 m
g/kg
, p.o
.A
lbin
o m
ice
of e
ither
sex
Hex
obar
bito
ne in
duce
d sl
eepi
ng
time,
Y-m
aze,
EP
M, H
BT
—A
nxio
lytic
and
se
dativ
e[6
7]
21C
allu
na v
ulga
ris
Linn
. (H
ull)
(Eric
acea
e)
Hea
ther
Que
rcet
in(7
) is
olat
ed
from
met
hano
l ext
ract
of
aeria
l par
ts
41µg
/mg
—In
vitr
oIn
hibi
tion
of
MA
O-A
Anx
ioly
tic[6
8]
22C
alot
ropi
s gi
gant
ea
(L.)
Dry
and.
(A
pocy
nace
ae)
Gia
nt
Milk
wee
d,
Cro
wn
Flo
wer
, Aak
Alc
ohol
ic e
xtra
ct o
f pe
eled
roo
ts25
0 an
d 50
0 m
g/kg
, p.o
. A
lbin
o ra
ts o
f ei
ther
sex
EP
M, H
ot p
late
met
hod,
Ace
tic
acid
indu
ced
writ
hing
, A
sses
smen
t of
loco
mot
or
activ
ity, r
ota
rod
and
PT
Z-
indu
ced
conv
ulsi
ons
—A
nxio
lytic
, an
ticon
vuls
ant,
anal
gesi
c an
d se
dativ
e
[69]
23C
amel
lia s
inen
sis
(L.)
O. K
untz
e (T
heac
eae)
G
reen
tea
L-th
eani
ne(8
)10
mg/
kg, p
.o.
Spr
ague
Daw
ley
rats
EP
MIn
crea
se in
do
pam
ine
leve
ls b
ut n
ot
GA
BA
A r
ecep
tor
inte
ract
ion
Anx
ioly
tic[7
0]
18
Madaan, et. al.: Plant Drugs Used to Combat Menace of Anxiety Disorders
Tab
le 1
: Co
nti
nu
ed
S.
No
. B
iolo
gic
al s
ou
rce
Ext
ract
/Fra
ctio
n/Is
ola
teD
ose
An
imal
/ H
um
an b
ein
g
Exp
erim
enta
l mo
del
/ A
sses
smen
t o
f cl
inic
al
par
amet
ers
Mec
han
ism
o
f ac
tio
nA
ctiv
ity
Ref
.
24C
anna
bis
sativ
a Li
nn.
(Can
naba
ceae
) B
han
g
Can
nabi
diol
(9)
15, 3
0 an
d 60
nm
ol,
intr
a-dl
PAG
(D
orso
late
ral
peri
aque
duct
al
gray
)
Mal
e W
ista
r ra
tsE
PM
, Vog
el c
onfli
ct te
stC
anna
bidi
ol
inte
ract
ion
with
5H
T1A
rec
epto
rs
in d
IPA
G in
bra
in
Anx
ioly
tic[7
1]
Can
nabi
diol
(9)
15, 3
0 an
d 60
nm
ol,
intr
a-B
NS
T
bila
tera
l in
ject
ions
Mal
e W
ista
r ra
tsE
PM
, Vog
el c
onfli
ct te
stFa
cilit
ates
lo
cal 5
-HT
1A
rece
ptor
-m
edia
ted
neur
o-tr
ansm
issi
on
Anx
ioly
tic[7
2]
25C
asim
iroa
edul
is
Llav
e &
Lex
. (R
utac
eae)
W
hit
e S
apo
te,
Zap
ote
bla
nco
Aqu
eous
ext
ract
of
Leav
es25
and
35
mg/
kg, i
.p.
Wis
tar
rats
EP
M, O
FT
—A
nxio
lytic
[73]
Hyd
ro-a
lcoh
olic
(60
%
etha
nol)
extr
act o
f le
aves
40, 8
0, 1
60,
and
320
mg/
kg, p
.o. i
n m
ice,
or
1.56
, 3.
12,
6.25
,12.
5 an
d 50
mg/
kg,
i.p. i
n ra
ts
Mal
e an
d fe
mal
e S
prag
ue-
Daw
ley
rats
Spo
ntan
eous
mot
or a
ctiv
ity,
EP
M, F
ST,
HB
T, M
BT
—A
nxio
lytic
, an
tidep
ress
ant
and
seda
tive
[74]
26C
asim
iroa
prin
glei
(S
. Wat
son)
Eng
l. (R
utac
eae)
P
rin
gle
’s Z
apo
te
Ess
entia
l oil
from
leav
es79
5 an
d 10
00
mg/
kg, p
.o.
Wis
tar
rats
EP
M, O
FT,
HB
T
—A
nxio
lytic
and
se
dativ
e[7
5]
27C
assi
a si
amea
Lam
. (F
abac
eae)
K
aso
d, S
iam
ese
cass
ia
Bar
akol
(10
)10
mg/
kg, i
.p.
Mal
e w
ista
r ra
tsE
PM
—A
nxio
lytic
[76,
77
]
28C
ecro
pia
glaz
ioui
S
neth
(U
rtic
acea
e)
Em
bau
ba,
Yar
um
o
(a)
Aqu
eous
ext
ract
of
leav
es
(b)
But
anol
ic fr
actio
n of
aq
ueou
s ex
trac
t of
leav
es
(a)
0.5
and
1.0
g/kg
, p.o
. (b
) 25
-100
m
g/kg
, p.o
.
Mal
e ad
ult S
wis
s m
ice
EP
M—
Anx
ioly
tic[7
8]
29C
elas
trus
pa
nicu
latu
s W
illd.
(Cel
astr
acea
e)
Jyo
tish
mat
i, M
aak
kan
gn
i
Pet
role
um e
ther
ext
ract
of
see
ds3.
2 g/
kg/d
ay
for
5 da
ysA
lbin
o m
ice
Beh
avio
ural
dis
inhi
bitio
n m
odel
—A
nxio
lytic
[79]
Oil
of s
eeds
1 an
d 1.
5 g/
kg,
i.p.
Wis
tar
rats
OF
T, E
PM
, Thi
rsty
rat
con
flict
pa
radi
gmS
erot
oner
gic
mec
hani
smA
nxio
lytic
[80]
19
Madaan, et. al.: Plant Drugs Used to Combat Menace of Anxiety Disorders30
Cen
tella
asi
atic
a (L
.)
Urb
. (U
mbe
llife
rae)
G
otu
Ko
la
Pow
dere
d dr
ug12
g/d
ay, p
.o.
Dou
ble-
blin
d, p
lace
bo-
cont
rolle
d st
udy
in 2
0 su
bjec
ts
Sig
nific
antly
atte
nuat
ed th
e pe
ak o
f ac
oust
ic s
tart
le
resp
onse
am
plitu
de
—A
nxio
lytic
[81]
(a)
Mar
kete
d fo
rmul
atio
ns
(b)
Met
hano
l ext
ract
(c
) E
thyl
ace
tate
ext
ract
(d
) A
siat
icos
ide(
11)
(a)
500
mg/
kg,
p.o.
(b
) 30
47 m
g/kg
, p.o
. (c
) 11
1 m
g/kg
, p.
o.
(d)
3 m
g/kg
, p.
o.
Mal
e S
prag
ue-D
awle
y (S
D)
rats
EP
M, O
FT,
SI,
loco
mot
or a
ctiv
ity,
puni
shed
drin
king
, nov
el c
age
test
—A
nxio
lytic
[82]
31C
entr
anth
us r
uber
(L
.) D
C
(Val
eria
nace
ae)
Red
val
eria
n
Val
epot
riate
–
valtr
ate(
12)
5 m
g/kg
, p.o
.W
ista
r ra
tsIn
hibi
tion
of o
rient
atio
n re
flexe
s an
d m
otor
act
ivity
—A
nxio
lytic
[83]
32C
erat
onia
sili
qua
Linn
. (Fa
bace
ae)
Car
ob
tre
e
Met
hano
l ext
ract
of
leav
es a
nd p
ods
Pod
s -
12.1
7 ng
and
Lea
ves
- 18
.7 n
g di
azep
am
equi
vale
nt
In v
itro
—B
ZD
rec
epto
r in
tera
ctio
nA
nxio
lytic
[84]
33C
inna
mom
um
cass
ia B
lum
e.
(Lau
race
ae)
Cas
sia
Bar
k,
Ch
ines
e ci
nn
amo
n
50%
Eth
anol
ext
ract
fr
om s
tem
bar
ks75
0 m
g/kg
, p.
o.M
ale
ICR
mic
eE
PM
Reg
ulat
ion
of
5-H
T1A
and
GA
BA
re
cept
or s
yste
m
Anx
ioly
tic[8
5]
34C
issu
s si
cyoi
des
Linn
. (V
itace
ae)
Po
ssu
m g
rap
e vi
ne,
Pri
nce
ss v
ine
Hyd
ro-a
lcoh
olic
ext
ract
(7
0% e
than
ol)
of le
aves
300,
600
and
10
00 m
g/kg
, i.p
.
Mal
e an
d fe
mal
e S
wis
s al
bino
mic
e E
PM
, HB
T, M
BT,
Sod
ium
P
ento
barb
ital-i
nduc
ed s
leep
ing
time,
PT
Z-in
duce
d co
nvul
sion
—A
nxio
lytic
, an
ticon
vuls
ant
[86]
35C
itrus
aur
antiu
m
Linn
. (R
utac
eae)
B
itte
r O
ran
ge
Ess
entia
l oil
from
pee
l (E
OP
) of
leav
es1
g/kg
, p.o
.M
ale
Sw
iss
mic
eE
PM
, OF
T—
Anx
ioly
tic[8
7]
Ess
entia
l oil
from
frui
ts
0.5
and
1.0
g/kg
, p.o
.M
ale
Sw
iss
mic
eLD
M, M
BT
—A
nxio
lytic
[88]
36C
itrus
sin
esis
Lin
n.
(Rut
acea
e)
Sw
eet
Ora
ng
e,
Blo
od
Ora
ng
e
Ess
entia
l oil
100,
200
and
40
0 µl
Wis
tar
mal
e ra
tsE
PM
, LD
M—
Anx
ioly
tic[8
9]
37C
litor
ia te
rnat
ea
Linn
. (P
apili
onac
eae)
B
utt
erfly
pea
Met
hano
l ext
ract
of
root
s10
0-40
0 m
g/kg
, p.o
.M
ale
Sw
iss
albi
no m
ice
and
Wis
tar
rats
EP
M, L
DM
—A
nxio
lytic
[90]
38C
onvu
lvul
us
plur
icau
lis C
hois
y. (C
onvo
lvul
acea
e)
Sh
ankh
pu
spi
Eth
yl a
ceta
te fr
actio
n of
et
hano
l ext
ract
of
the
aeria
l par
ts
100
mg/
kg, p
.o.
Spr
ague
-Daw
ley
rats
and
S
wis
s al
bino
mic
eE
PM
, OF
T a
nd r
otar
od
perf
orm
ance
—
Anx
ioly
tic
[91]
39C
opai
fera
ret
icul
ata
Duc
ke
(Leg
umin
osae
) B
razi
lian
co
pai
ba
Ess
entia
l oil
100,
400
and
80
0 m
g/kg
, i.p
.W
ista
r ra
tsE
PM
—A
nxio
lytic
[92]
20
Madaan, et. al.: Plant Drugs Used to Combat Menace of Anxiety Disorders
Tab
le 1
: Co
nti
nu
ed
S.
No
. B
iolo
gic
al s
ou
rce
Ext
ract
/Fra
ctio
n/Is
ola
teD
ose
An
imal
/ H
um
an b
ein
g
Exp
erim
enta
l mo
del
/ A
sses
smen
t o
f cl
inic
al
par
amet
ers
Mec
han
ism
o
f ac
tio
nA
ctiv
ity
Ref
.
40C
oria
ndru
m s
ativ
um
Linn
. (U
mbe
llife
rae)
C
ori
and
er, D
han
iya
Aqu
eous
ext
ract
of
seed
s10
0 m
g/kg
, p.
o.M
ale
albi
no m
ice
EP
M—
Anx
ioly
tic[9
3]
41C
rocu
s sa
tivus
Lin
n.
(Lili
acea
e)
Saf
fro
n, A
utu
mn
cr
ocu
s
Cro
cin(
13)
isol
ated
from
aq
ueou
s ex
trac
t of
red
drie
d st
igm
as
50 m
g/kg
, i.p
. W
ista
r ra
tsLD
M—
Anx
ioly
tic[9
4]
(a)
Aqu
eous
ext
ract
of
stig
mas
(b
) C
roci
n(13
)(c
) S
afra
nal (
14)
(a)
56, 8
0, 3
20
and
560
mg/
kg, i
.p.
(b)
50, 2
00
and
600
mg/
kg, i
.p.
(c)
0.05
, 0.1
5 an
d 0.
35 m
l/kg
, i.p
.
Raz
i mal
e m
ice
EP
M, O
FT,
Pen
toba
rbita
l sl
eepi
ng ti
me,
Rot
arod
test
—A
nxio
lytic
(A
t lo
wer
dos
e),
hypn
otic
(A
t hi
gher
dos
e)
[95]
42C
roto
n ce
ltidi
foliu
s B
aill.
(E
upho
rbia
ceae
) S
ang
ue-
de-
adav
e
Pro
anth
ocya
nidi
n(15
) ric
h fr
actio
n is
olat
ed
from
aqu
eous
ext
ract
of
bark
3 m
g/kg
, i.p
.W
ista
r ra
tsE
PM
—A
nxio
lytic
[96]
43C
roto
n ze
hntn
eri
Pax
& H
offm
an
(Eup
horb
iace
ae)
Can
ela
de
Cu
nh
a
Met
hyl e
ugen
ol(1
6) fr
om
esse
ntia
l oil
1, 3
and
10
µl/1
00 g
, p.o
.M
ale
Wis
tar
rats
OF
T, S
I, E
PM
, HB
T, F
ST
—
Ant
idep
ress
ant
and
mild
an
xiol
ytic
[97]
44C
urcu
ma
long
a Li
nn.
(Zin
gibe
race
ae)
Cu
rcu
ma,
Tu
rmer
ic
Cur
cum
in(1
7)20
mg/
kg, i
.p.
Sw
iss
albi
no m
ice
EP
M, O
FT,
LD
M, S
IIn
volv
emen
t of
indu
cibl
e N
OS
Anx
ioly
tic[9
8]
45C
ymbo
pogo
n ci
trat
us (
DC
.) S
tapf
(P
oace
ae)
Lem
on
gra
ss,
Gin
ger
gra
ss
Citr
al (
18)
or te
a ab
afad
o20
0 m
g/kg
, i.p
.M
ale
albi
no S
wis
s m
ice
OF
T, R
ota-
rod
test
, Spo
ntan
eous
m
otor
act
ivity
, Bar
bitu
rate
sl
eepi
ng-t
ime,
Tra
nsco
rnea
l el
ectr
osho
ck, P
TZ
-indu
ced
conv
ulsi
ons,
Pun
ishe
d re
spon
se
test
—C
entr
al
Ner
vous
de
pres
sant
[99]
Ess
entia
l oil
0.5
and
1.0
g/kg
, i.p
.S
wis
s m
ale
mic
eE
PM
, LD
M—
Anx
ioly
tic[1
00]
46D
avill
a ru
gosa
P
oire
t (D
illen
iace
ae)
Cip
o-C
abo
clo
, Fir
e vi
ne
Hyd
ro-a
lcoh
olic
ext
ract
(7
0% e
than
ol)
of s
tem
s 15
mg/
kg, p
.o.
Mal
e W
ista
r ra
tsE
PM
, OF
T—
Anx
ioly
tic[1
01]
47D
rym
aria
cor
data
(L
.) W
illd.
ex
Roe
m.
& S
chul
t. (C
aryo
phyl
lace
ae)
Tro
pic
al c
hic
kwee
d
Hyd
ro-a
lcoh
olic
ext
ract
(5
0% e
than
ol)
of le
aves
100
mg/
kg,
p.o.
Sw
iss
albi
no m
ice
EP
M, L
DM
, OF
T, H
BT
—A
nxio
lytic
[102
]
21
Madaan, et. al.: Plant Drugs Used to Combat Menace of Anxiety Disorders48
Duc
rosi
a an
ethi
folia
B
oiss
. (A
piac
eae)
H
azza
, Haz
zaz
Ess
entia
l oil
25, 5
0, 1
00,
200
and
400
mg/
kg, p
.o.
Sw
iss
albi
no m
ice
EP
M, S
pont
aneo
us m
otor
ac
tivity
, Ket
amin
e-in
duce
d sl
eep
time
—A
nxio
lytic
but
no
t sed
ativ
e[1
03]
49E
chin
acea
pur
pure
a (L
.) M
oenc
h.
(Ast
erac
eae)
C
on
e fl
ow
er
(a)
E. p
urpu
rea
root
ex
trac
t (et
hano
l 4%
v/v
; E
chin
acos
ide
4%)
(b)
E. p
urpu
rea
herb
ex
trac
t (et
hano
l 60%
m
/m; t
otal
phe
nols
4%
) (c
) E
. ang
ustif
olia
roo
t ex
trac
t (et
hano
l 85%
v/v
; E
chin
acos
ide
4%)
(d)
E. p
urpu
rea
root
ex
trac
t (et
hano
l 70%
v/v
)
3-7
mg/
kg, p
.o.
Mal
e W
ista
r ra
tsE
PM
, SI,
shoc
k in
duce
d so
cial
av
oida
nce
test
, OF
T—
Onl
y ex
trac
t (d
) sh
owed
an
xiol
ytic
ac
tivity
[104
]
50E
chiu
m a
moe
num
F
isch
. Et M
ey.
(Bor
agin
acea
e)
Vip
er’s
bu
glo
ss,
Red
fea
ther
s
Aqu
eous
ext
ract
of
flow
ers
5, 1
0, 3
0, 6
2.5,
80
and
125
m
g/kg
, i.p
.
Mal
e N
MR
I alb
ino
mic
eE
PM
—A
nxio
lytic
[105
]
Hyd
ro-e
than
ol e
xtra
ct
(80%
) of
the
plan
t flo
wer
s
50 m
g/kg
, i.p
.M
ale
TO m
ice
EP
M—
Anx
ioly
tic[1
06]
51E
clip
ta a
lba
Linn
. (A
ster
acea
e)
Bh
rin
gar
aj, F
alse
d
aisy
(a)
Aqu
eous
, hyd
ro-
alco
holic
ext
ract
s (b
) H
ydro
lyze
d fr
actio
n ob
tain
ed fr
om w
hole
pl
ant
(a)
150
and
300
mg/
kg,
p.o.
(b
) 30
mg/
kg,
p.o.
Wis
tar
rats
Lo
com
otor
act
ivity
, EP
M, H
BT,
C
old
rest
rain
t ind
uced
gas
tric
ul
cer
and
whi
te b
lood
cel
l cou
nt
in th
e m
ilk in
duce
d le
ukoc
ytos
is
chal
leng
e
Noo
trop
ic,
seda
tive,
an
xiol
ytic
and
an
tistr
ess
[107
]
52E
ryth
rina
mul
ungu
M
art.
(Pap
ilion
acea
e)
Mu
lun
gu
, C
ort
icei
ra
Hyd
ro-a
lcoh
olic
ext
ract
(7
0% e
than
ol)
from
the
inflo
resc
ence
Acu
te (
200
mg/
kg, p
.o.)
ch
roni
c (5
0 m
g/kg
, p.o
. for
7
days
)
Mal
e W
ista
r ra
tsE
leva
ted
T m
aze
(ET
M),
LDM
, C
at o
dor
test
—A
nxio
lytic
[108
, 10
9]
Wat
er :
Alc
ohol
(7:
3)
extr
act o
f in
flore
scen
ceA
cute
stu
dy
200
and
400
mg/
kg, p
.o.
and
chro
nic
stud
y fo
r 21
da
ys, 5
0 an
d 20
0 m
g/kg
, p.
o.
Mal
e W
ista
r ra
tsE
TM
—A
nxio
lytic
[110
]
Ery
thrin
ian
alka
loid
s i.e
(+
)-α–
hydr
oxye
rsot
rine(
19),
eryt
hrav
ine(
20)
and
(+)-
11-α
–hyd
roxy
er
ythr
avin
e(21
) is
olat
ed
from
hyd
ro-a
lcoh
olic
ex
trac
t of
flow
ers
3 an
d 10
mg/
kg, p
.o.
Mal
e S
wis
s M
ice
EP
M, L
DM
—A
nxio
lytic
[111
]
22
Madaan, et. al.: Plant Drugs Used to Combat Menace of Anxiety Disorders
Tab
le 1
: Co
nti
nu
ed
S.
No
. B
iolo
gic
al s
ou
rce
Ext
ract
/Fra
ctio
n/Is
ola
teD
ose
An
imal
/ H
um
an b
ein
g
Exp
erim
enta
l mo
del
/ A
sses
smen
t o
f cl
inic
al
par
amet
ers
Mec
han
ism
o
f ac
tio
nA
ctiv
ity
Ref
.
Cru
de e
xtra
ct (
CE
), E
ryth
rinia
n al
kalo
ids:
(+
)-α–
hydr
oxye
rsot
rine(
19),
eryt
hrav
ine(
20)
and
(+)-
11-α
–hyd
roxy
er
ythr
avin
e(21
) is
olat
ed
from
hyd
ro-a
lcoh
olic
ex
trac
t of
flow
ers
3-10
mg/
kg,
p.o.
C
E (
50, 1
00,
200
and
400
mg/
kg, p
.o.)
Mal
e S
wis
s m
ice
T-m
aze,
Loc
omot
or a
ctiv
ity te
st—
Anx
ioly
tic[1
12]
53E
ryth
rina
sube
rosa
R
oxb.
(Fa
bace
ae)
Co
ral t
ree
Alk
aloi
ds –
E
ryso
dine
(22)
and
er
ysot
hrin
e(23
) is
olat
ed
from
hyd
ro-a
lcoh
olic
ex
trac
t of
flow
ers
3 an
d 10
mg/
kg, p
.o.
Mal
e al
bino
mic
eE
PM
, LD
M—
Anx
ioly
tic[1
13]
54E
ryth
rina
velu
tina
Will
d. (
Faba
ceae
) B
ico
-De-
Pap
agai
o
Wat
er :
Alc
ohol
(7:
3)
extr
act o
f st
em b
ark
Acu
te s
tudy
-
200
and
400
mg/
kg, p
.o.,
and
chro
nic
stud
y -
50 a
nd
200
mg/
kg,
p.o.
Mal
e W
ista
r ra
tsE
TM
—A
nxio
lytic
[110
]
Hyd
ro-e
than
ol e
xtra
ct o
f st
em b
ark
50 a
nd 1
00
mg/
kg, p
.o. f
or
23-2
6 da
ys
Adu
lt m
ale
Sw
iss
albi
no
mic
eE
PM
—A
nxio
lytic
[114
]
55E
schs
chol
zia
calif
orni
ca C
ham
. (P
apav
erac
eae)
C
alifo
rnia
po
pp
y,
Go
ld p
op
py
Hyd
ro-a
lcoh
olic
ext
ract
(6
0% e
than
ol)
of a
eria
l pa
rts
25 m
g/kg
, i.p
.M
ale
Sw
iss
mic
eLD
MB
ZD
rec
epto
r in
tera
ctio
nA
nxio
lytic
[115
]
70%
eth
anol
ext
ract
of
aeria
l par
ts10
0 to
300
m
g/kg
, i.p
.M
ale
Wis
tar
rats
CC
l 4 in
duce
d ne
urop
athi
c pa
in,
hot p
late
and
car
rage
enan
in
duce
d pa
in
—A
nxio
lytic
and
an
ti-
neur
opat
hic
pain
[116
]
56E
upho
rbia
hir
ta
Linn
. (E
upho
rbia
ceae
) A
sth
ma
wee
d
Aqu
eous
ext
ract
of
who
le p
lant
12.5
and
25
mg/
kg, i
.p.
Sw
iss
albi
no m
ice
Sta
ir ca
se te
st, L
DM
—A
nxio
lytic
[117
]
57E
upho
ria lo
ngan
a La
mar
ck
(Sap
inda
ceae
) L
on
gan
Ari
llus
(a)
Met
hano
l ext
ract
(b
) ad
enos
ine(
24)
isol
ated
from
pul
p or
fle
sh
(a)
2 g/
kg, s
.c.
(b)
30 m
g/kg
, s.
c.
Mal
e dd
Y m
ice
Vog
el ty
pe a
nti-c
onfli
ct m
etho
d—
Anx
ioly
tic[1
18]
58E
upho
rbia
ner
rifol
ia
Linn
. (E
upho
rbia
ceae
) In
dia
n s
pu
rge
tree
, O
lean
der
sp
urg
e
Hyd
ro-a
lcoh
olic
(50
%
etha
nol)
extr
act o
f le
aves
400
mg/
kg,
p.o.
Sw
iss
albi
no m
ice
EP
M—
Anx
ioly
tic[1
19]
23
Madaan, et. al.: Plant Drugs Used to Combat Menace of Anxiety Disorders59
Eur
ycom
a lo
ngifo
lia
Jack
(S
imar
ouba
ceae
) To
ng
kat
ali,
Pen
awar
bia
s
Chl
orof
orm
, n-b
utyl
al
coho
l and
wat
er
frac
tions
obt
aine
d fr
om
met
hano
l ext
ract
of
root
s
0.3
g/kg
, p.o
. fo
r 5
days
tw
ice
daily
Alb
ino
mic
eE
PM
, OF
T, F
oot s
hock
indu
ced
fligh
ting
beha
viou
r—
Anx
ioly
tic[1
20]
60E
volv
ulus
als
inoi
des
Linn
. (C
onvo
lvul
acea
e)
Sh
ankh
pu
shp
i
Eth
yl a
ceta
te fr
actio
n of
et
hano
l ext
ract
of
the
aeria
l par
ts
100
mg/
kg, p
.o.
Spr
ague
-Daw
ley
rats
and
S
wis
s al
bino
mic
eE
PM
, OF
T a
nd r
otar
od
perf
orm
ance
—
Anx
ioly
tic,
neur
omus
cula
r co
ordi
natio
n an
d an
tioxi
dant
[91]
61G
alph
imia
gla
uca
Cav
. (M
alpi
ghia
ceae
) C
ald
ero
na
amar
illa
Gal
phim
ine
B(2
5),
galp
him
ine
A(2
6) a
nd
galp
him
ine
rich
frac
tions
(G
RF
s) o
btai
ned
from
m
etha
nol e
xtra
ct o
f ae
rial p
arts
15 m
g/kg
, i.p
.M
ale
ICR
mic
eE
PM
—A
nxio
lytic
[121
]
Met
hano
l ext
ract
of
aeria
l par
ts12
5, 2
50, 5
00,
1000
and
20
00 m
g/kg
, p.
o.
ICR
alb
ino
mic
eE
PM
, LD
M, F
ST
—A
nxio
lytic
and
an
tidep
ress
ant
[122
]
Cap
sule
s co
ntai
ning
310
m
g of
aqu
eous
ext
ract
of
aer
ial p
arts
310
mg
twic
e da
ily fo
r 4
wee
ks
A c
ontr
olle
d ra
ndom
ized
do
uble
blin
d cl
inic
al tr
ial
HA
MA
sca
le, t
he c
linic
al g
loba
l im
pres
sion
sca
le a
nd p
atie
nt
glob
al e
valu
atio
n
—A
nxio
lytic
[123
]
62G
arde
nia
jasm
inoi
des
Elli
s (R
ubia
ceae
) C
ape
jasm
ine
Kam
isho
yosa
n50
-200
mg/
kg,
p.o.
M
ale
ddY
mic
eS
I—
Anx
ioly
tic[1
24]
63G
astr
odia
ela
ta
Blu
me
(Orc
hida
ceae
) T
ian
ma
(Ch
ina)
; G
astr
od
ia
Tub
er(E
ng
lish
n
ame)
(a)
Aqu
eous
ext
ract
of
rhiz
omes
(b
) Phe
nolic
con
stitu
ents
: 4-
hydr
oxyl
-ben
zyl
alco
hol,
and
benz
alde
hyde
and
its
phen
olic
con
stitu
ents
(a)
400
mg/
kg,
p.o.
(b
) 50
and
100
m
g/kg
, i.p
.
Mal
e IC
R m
ice
EP
MIn
tera
ctio
n w
ith
5-H
T(1
A) r
ecep
tor
Anx
ioly
tic[1
25]
64G
else
miu
m
sem
perv
irens
(L.
) A
it. (
Loga
niac
eae)
C
aro
lina
yello
w
Jasm
ine
Met
hano
l ext
ract
of
root
s an
d rh
izom
es15
0 m
g/kg
, p.
o.S
wis
s al
bino
mic
e E
PM
—A
nxio
lytic
[126
]
Cen
tesi
mal
dilu
tions
of
hydr
o-al
coho
lic e
xtra
ct
of p
lant
as
in
hom
eopa
thic
sys
tem
5C, 9
C a
nd
30C
dilu
tions
ICR
-CD
1 m
ale
mic
eLD
M, O
FT
—A
nxio
lytic
[127
]
24
Madaan, et. al.: Plant Drugs Used to Combat Menace of Anxiety Disorders
Tab
le 1
: Co
nti
nu
ed
S.
No
. B
iolo
gic
al s
ou
rce
Ext
ract
/Fra
ctio
n/Is
ola
teD
ose
An
imal
/ H
um
an b
ein
g
Exp
erim
enta
l mo
del
/ A
sses
smen
t o
f cl
inic
al
par
amet
ers
Mec
han
ism
o
f ac
tio
nA
ctiv
ity
Ref
.
65G
inkg
o bi
loba
Lin
n.
(Gin
kgoa
ceae
) G
inkg
o,
Mai
den
hai
r tr
ee
Aqu
eous
and
eth
anol
ex
trac
ts o
f le
aves
5
and
10 m
g eq
uiva
lent
In v
itro
usin
g ra
t bra
in
mito
cond
rial e
xtra
ct—
Inhi
bitio
n of
m
onoa
min
e ox
idas
e (M
AO
A
and
B)
Anx
ioly
tic[1
28]
Gin
kgo
bilo
ba e
xtra
ct
(EG
b-76
1)8-
16 m
g/kg
, i.p
.W
ista
r A
F r
ats
SI
GA
BA
/ BZ
D/
Cl-
chan
nel
rece
ptor
in
tera
ctio
n
Anx
ioly
tic[1
29]
Gin
kgol
ic a
cid(
27)
conj
ugat
es (
GA
C)
isol
ated
from
chl
orof
orm
: m
etha
nol e
xtra
ct (
2:1)
of
the
leav
es
0.6
mg/
kg, p
.o.
Cha
rles
Fost
er r
ats
EP
M, O
FT,
nov
elty
-indu
ced
feed
ing
late
ncy
and
SI
—A
nxio
lytic
[130
]
G. b
iloba
ext
ract
(G
BE
), st
anda
rdiz
ed to
con
tain
24
% g
inkg
o-fla
vogl
ycos
ides
and
6%
gi
nkgo
-ter
peno
id
lact
ones
or
gink
golid
e A
(28)
0.5
and
1.0
g/kg
, p.o
. for
7
days
; 1
and
2 m
g/kg
, p.
o. fo
r fiv
e da
ys
Mal
e dd
Y m
ice
EP
MO
ther
mec
hani
sm
but n
ot th
roug
h G
AB
A/ B
ZD
/C
l- ch
anne
l re
cept
or
inte
ract
ion
Anx
ioly
tic[1
31]
66G
lycy
rrhi
za g
labr
a Li
nn. (
Legu
min
osae
) L
ico
rice
, Mu
leth
i
Hyd
ro-a
lcoh
olic
ext
ract
of
roo
ts a
nd r
hizo
mes
10-3
00 m
g/kg
, i.p
.S
wis
s al
bino
mic
eE
PM
, foo
t sho
ck in
duce
d ag
gres
sion
—A
nxio
lytic
[132
]
67H
edyo
smum
br
asili
ense
Mar
t. (C
hlor
anth
acea
e)
Ch
a d
e bu
gre
Eth
anol
ext
ract
of
aeria
l pa
rts
100
mg/
kg, i
.p.
Mal
e S
wis
s al
bino
mic
eE
PM
, OF
T, B
arbi
tura
te-in
duce
d sl
eepi
ng ti
me
test
—A
nxio
lytic
and
se
dativ
e[1
33]
68H
eter
opte
rys
glab
ra
Hoo
k. &
Arn
. (M
alpi
ghia
cae)
R
edw
ing
Eth
anol
ext
ract
of
frui
ts35
0 m
g/kg
, p.
o.D
BA
/2J
mic
eS
leep
wak
eful
ness
cyc
le,
elec
troe
ncep
halo
gram
(E
EG
) an
d vi
sual
evo
ked
pote
ntia
ls
(VE
P)
—A
nxio
lytic
and
se
dativ
e[1
34]
69H
ibis
cus
sabd
ariff
a Li
nn. (
Mal
vace
ae)
Jam
aica
so
rrel
, R
ed s
orr
el
Aqu
eous
, hyd
ro-
alco
holic
, and
eth
anol
ex
trac
t of
caly
xes
of
plan
t
300
mg/
kg,
p.o.
Wis
tar
rats
EP
M, k
etam
ine-
indu
ced
slee
p—
Anx
ioly
tic a
nd
seda
tive
(at
mul
tiple
do
ses)
[135
]
70H
ippe
astr
um
vitta
tum
(L’
Her
it)
Her
bert
(A
mar
yllid
acea
e)
Am
aryl
lis
Isoq
uino
line
alka
loid
: M
onta
nine
(29)
isol
ated
fr
om e
than
ol e
xtra
ct o
f bu
lbs
Anx
ioly
tic a
nd
seda
tive
(1-1
0 m
g/kg
, i.p
.),
antic
onvu
lsan
t (3
0 an
d 60
, m
g/kg
, i.p
.)
Sw
iss
albi
no m
ice
EP
M, S
odiu
m p
ento
barb
ital-
indu
ced
slee
p, P
TZ
-pro
voke
d co
nvul
sion
s, F
ST
—A
nxio
lytic
, mild
se
dativ
e an
d an
ticon
vuls
ant
but n
ot
antid
epre
ssan
t
[136
]
25
Madaan, et. al.: Plant Drugs Used to Combat Menace of Anxiety Disorders71
Hyp
eric
um
perfo
ratu
m L
inn.
(G
uttif
erae
) S
t Jo
hn
’s w
ort
H. p
erfo
ratu
m e
xtra
ct
LI60
—In
vitr
o—
β re
cept
or
activ
atio
nA
nxio
lytic
[137
]
Sta
ndar
dize
d ex
trac
t of
the
who
le p
lant
, co
ntai
ning
0.5
4% to
tal
hype
ricin
s [0
.11%
hy
peric
in(3
0) a
nd 0
.43%
ps
eudo
hype
ricin
(31)
]and
0.
09%
pro
tofo
rms
2778
and
18
52 m
g/kg
, p.
o.
Mal
e S
prag
ue–D
awle
y ra
tsO
FT,
LD
MIn
hibi
tory
in
fluen
ce o
n gl
utam
ater
gic
tran
smis
sion
m
edia
ted
by
NM
DA
rec
epto
rs
Anx
ioly
tic[1
38]
Lyop
hiliz
ed a
queo
us
extr
act
5 m
g/kg
, p.o
.M
ale
albi
no S
wis
s m
ice
EP
M—
Anx
ioly
tic[1
39]
Hyd
ro-a
lcoh
olic
ext
ract
of
who
le p
lant
100
or 2
00
mg/
kg, p
.o. O
D
for
3 da
ys
Wis
tar
rats
EP
M, O
FT,
EZ
M, n
ovel
ty-in
duce
d su
ppre
ssed
feed
ing
late
ncy,
SI
Affe
ct
mon
oam
ines
co
ncen
trat
ion
in
rats
’ bra
in
Anx
ioly
tic[1
40]
H. p
erfo
ratu
m e
xtra
ct L
I 16
0 30
0 m
g/kg
, p.
o. fo
r 21
da
ys
Mal
e al
bino
Sw
iss
mic
eM
ouse
def
ense
test
bat
tery
—A
nxio
lytic
[141
]
H. p
erfo
ratu
m e
xtra
ct L
I 16
030
0 m
g/kg
, p.o
Mal
e al
bino
Sw
iss
mic
eE
TM
—A
nxio
lytic
[142
]
H. p
erfo
ratu
m e
xtra
ct L
I 16
038
0 m
g/kg
/da
y ch
roni
c ad
min
istr
atio
n
C57
BL/
6J M
ice
OF
T, L
DM
, FS
T—
Anx
ioly
tic a
nd
antid
epre
ssan
t[1
43]
H. p
erfo
ratu
m e
xtra
ct L
I 16
015
0 an
d 30
0 m
g/kg
, p.o
.S
wis
s al
bino
mic
eM
BT,
FS
T—
Anx
ioly
tic a
nd
antid
epre
ssan
t[1
44]
Hyd
ro-a
lcoh
olic
ext
ract
of
who
le p
lant
200-
400
mg/
kg, p
.o.
Mal
e La
ca m
ice
Mir
rore
d ch
ambe
r, E
PM
, EZ
M—
Anx
ioly
tic[1
45]
72Ja
trop
ha c
iliat
a M
. A
rg.
(Eup
horb
iace
ae)
Hu
anar
po
Vite
xin(
32),
iso-
orie
ntin
(33)
and
or
ient
in(3
4) fr
om
met
hano
l ext
ract
of
Ste
ms
40 m
g/kg
, s.c
. M
ale
ddY
mic
eV
ogel
type
Ant
icon
flict
effe
ct in
m
ice
—A
nxio
lytic
[146
]
73K
ielm
eyer
a co
riace
a M
art.
(Clu
siac
eae)
P
áu s
anto
Eth
anol
ext
ract
of
leav
es12
0 m
g/kg
/da
y, p.
o.M
ale
Wis
tar
rats
EP
M—
Anx
ioly
tic[1
47]
26
Madaan, et. al.: Plant Drugs Used to Combat Menace of Anxiety Disorders
Tab
le 1
: Co
nti
nu
ed
S.
No
. B
iolo
gic
al s
ou
rce
Ext
ract
/Fra
ctio
n/Is
ola
teD
ose
An
imal
/ H
um
an b
ein
g
Exp
erim
enta
l mo
del
/ A
sses
smen
t o
f cl
inic
al
par
amet
ers
Mec
han
ism
o
f ac
tio
nA
ctiv
ity
Ref
.
74La
vand
ula
angu
stifo
lia M
iller
(L
amia
ceae
) E
ng
lish
Lav
end
er
Ess
entia
l oil
from
leav
esIn
hala
tion
0.1-
1.0
ml
Adu
lt m
ale
Spr
ague
-D
awle
y al
bino
rat
sO
pen
field
beh
avio
r te
stLa
vend
er o
il po
tent
iate
s th
e re
spon
ses
of
GA
BA
rec
epto
rs
at lo
w
conc
entr
atio
ns
and
inhi
bits
re
spon
ses
of
GA
BA
rec
epto
rs
at h
igh
conc
entr
atio
ns in
vi
tro
Anx
ioly
tic[1
48,
149]
Lave
nder
oil
I ml/1
00 g
, i.p
.M
ale
ICR
Mic
eG
alle
r ty
pe c
onfli
ct te
st—
Anx
ioly
tic[1
50]
Lave
nder
odo
ur—
Mat
ure
mal
e an
d fe
mal
e ge
rbils
EP
M—
Anx
ioly
tic[1
51]
75Le
ptos
perm
um
scop
ariu
m J
.R. e
t G.
Fors
t. (M
yrta
ceae
) M
anu
ka o
r Tea
tre
e
(a)
Hyd
ro-a
lcoh
olic
ex
trac
t (70
% e
than
ol)
(b)
5,7-
dim
etho
xyfla
vone
(1
), 5,
7-di
met
hoxy
-6-
met
hylfl
avon
e (2
), 5-
hydr
oxy-
7-m
etho
xy-6
-m
ethy
lflav
one
(3)
and
5-hy
drox
y-7-
met
hoxy
-6,
8-di
met
hylfl
avon
e (4
)
(a)
250
mg/
kg,
p.o.
(b
) IC
50-
valu
es o
f 2.
1 m
icro
M (
1), 4
5 m
icro
M (
2),
3.3
mic
roM
(3)
an
d 40
m
icro
M (
4)
(a)
Rat
s (b
) In
vitr
o ra
dio
rece
ptor
as
say
with
[3H
] Flu
nitr
aze-
pam
Loco
mot
ion
stud
yIn
tera
ctio
n w
ith
GA
BA
A/B
ZD
re
cept
or
Anx
ioly
tic[1
52,
153]
76Li
ppia
alb
a (M
ill.)
N
.E. B
row
n (V
erbe
nace
ae)
Cid
reir
a, B
ush
y m
atg
rass
Thr
ee c
hem
otyp
es o
f es
sent
ial o
il (E
O1,
EO
2,
EO
3) fr
om le
aves
EO
1 an
d E
O3
(100
mg/
kg,
i.p.)
and
EO
2 (2
5 m
g/kg
, i.p
.)
Mal
e S
wis
s M
ice
EP
M, O
FT
and
rot
arod
—A
nxio
lytic
and
m
yore
laxa
nt[1
54]
77Lo
esel
ia m
exic
ana
Bra
nd
(Pol
emon
iace
ae)
Mex
ican
fal
se
calic
o, E
spin
osi
lla
Dap
hnor
etin
(35)
isol
ated
fr
om h
ydro
-alc
ohol
ic
extr
act (
60%
eth
anol
) of
w
hole
pla
nt
1.8,
3.7
, 7.5
an
d 15
.0 m
g/kg
, i.p
.
Mal
e IC
R m
ice
OF
T, E
PM
—A
nxio
lytic
[155
]
78M
agno
lia d
ealb
ata
Zuc
c.
(Mag
nolia
ceae
) E
loxo
chit
i
Eth
anol
ext
ract
of
leav
es10
0 an
d 30
0 m
g/kg
, p.o
.M
ale
Sw
iss
albi
no m
ice
EP
M, H
BT,
exp
lora
tory
rea
rings
, S
odiu
m p
ento
barb
ital-i
nduc
ed
hypn
osis
, PT
Z-in
duce
d se
izur
es
—A
nxio
lytic
, se
dativ
e an
d an
ticon
vuls
ant
[156
]
27
Madaan, et. al.: Plant Drugs Used to Combat Menace of Anxiety Disorders
79M
agno
lia O
bava
ta
Thu
nb.
(Mag
nolia
ceae
) Ja
pan
ese
big
leaf
m
agn
olia
Hon
okio
l (36
)0.
2-1
mg/
kg,
p.o.
for
seve
n da
ys
Mal
e m
ice
of th
e dd
Y
stra
inE
PM
—A
nxio
lytic
[157
]
Hon
okio
l (36
)0.
2 m
g/kg
, se
ven
days
, p.
o.
Mal
e m
ice
of th
e dd
Y
stra
inE
PM
—A
nxio
lytic
[158
]
Obo
vato
l (37
)isol
ated
fr
om le
aves
0.2,
0.5
and
1.
0 m
g/kg
, p.o
.IC
R m
ale
mic
eE
PM
, HB
TG
AB
A-B
ZD
- re
cept
ors
/ C
l- cha
nnel
ac
tivat
ion
Anx
ioly
tic[1
59]
80M
artic
aria
ch
amom
ila L
inn.
or
Mat
ricar
ia r
ecut
ita
(Ast
erac
eae)
G
erm
an
cham
om
ile,
Am
eral
e
Api
geni
n(38
) is
olat
ed
from
aqu
eous
ext
ract
of
bran
chle
ts w
ith fl
ower
s
3 m
g/kg
, i.p
.M
ale
C F
l mic
eE
PM
, HB
T, L
ocom
otor
act
ivity
te
st, H
oriz
onta
l-wire
test
, S
eizu
re te
stin
g
Inte
ract
ion
with
G
AB
AA/B
ZD
re
cept
or
Anx
ioly
tic a
nd
mild
sed
ativ
e at
10
times
do
se
[160
]
Api
geni
n(38
)30
mM
In v
itro,
Rat
s—
Inte
ract
ion
with
G
AB
AA/B
ZD
re
cept
or
Anx
ioly
tic[1
61-
163]
81M
elis
sa o
ffici
nalis
Li
nn. (
Lam
iace
ae)
Lem
on
bal
m,
Co
mm
on
bal
m
Cyr
acos
: hy
dro-
alco
holic
(3
0% e
than
ol)
extr
act o
f ae
rial p
arts
120,
240
and
36
0 m
g/kg
, p.
o. fo
r 15
da
ys
C57
Bl/6
Jico
mic
eE
PM
In
hibi
ts G
AB
A-T
(t
rans
amin
ase)
ac
tivity
and
in
crea
se G
AB
A
leve
l in
brai
n
Anx
ioly
tic[1
64]
82M
itrag
yna
parv
ifolia
R
oxb.
(R
ubia
ceae
) K
aim
, Gu
likad
am
Met
hano
l, et
hyl a
ceta
te
and
alka
loid
ric
h fr
actio
n of
ste
m b
ark
200
and
400
mg/
kg, p
.o.
Sw
iss
albi
no m
ice
EP
M, M
BT
Inte
ract
ion
with
G
AB
A r
ecep
tors
Anx
ioly
tic[1
65]
83M
orin
da c
itrifo
lia
Linn
. (R
ubia
ceae
) N
on
i, In
dia
n
mu
lber
ry
(a)
Met
hano
l ext
ract
of
frui
ts
(b)
But
anol
ic fr
actio
n
(a)
IC50
– 2
2.8
µg/m
l (b
) IC
50 –
27.
2 µg
/ml
In v
itro
—G
AB
AA a
goni
stA
nxio
lytic
[166
]
84N
aucl
ea la
tifol
ia
J.E
.Sm
ith
(Rub
iace
ae)
Neg
ro p
each
, A
fric
an p
each
Dec
octio
n fr
om b
ark
of
the
root
s 80
and
160
m
g/kg
, i.p
.A
dult
Sw
iss
mal
e m
ice
EP
M, D
iaze
pam
-indu
ced
slee
p,
ME
S-,
Str
ychn
ine-
, PT
Z-in
duce
d co
nvul
sion
s te
st, O
FT
—A
nxio
lytic
[167
]
85N
elum
bo n
ucife
ra
Gae
rtne
r (N
ymph
yaea
ceae
) S
acre
d w
ater
lilly
, P
ink
lotu
s
Nef
erin
e(39
) is
olat
ed
from
met
hano
l ext
ract
of
embr
yos
of th
e se
eds
100
mg/
kg, i
.p.
Mal
e IC
R m
ice
EP
M—
Anx
ioly
tic[1
68]
86N
epet
a pe
rsic
a B
oiss
. (La
mia
ceae
) C
atm
int
Hyd
ro-a
lcoh
olic
ext
ract
(8
0% e
than
ol)
of a
eria
l pa
rts
50 m
g/kg
, i.p
.M
ale
NM
RI m
ice
EP
M—
Anx
ioly
tic[1
69]
87O
cim
um
grat
issi
mum
Lin
n.
(Lam
iace
ae)
Van
a Tu
lsi
Met
hano
l ext
ract
of
leav
es
200
and
400
mg/
kg, p
.o.
Sw
iss
albi
no m
ice
OF
T, P
TZ
-indu
ced
seiz
ure
test
—A
nxio
lytic
and
an
ticon
vuls
ant
[170
]
28
Madaan, et. al.: Plant Drugs Used to Combat Menace of Anxiety Disorders
Tab
le 1
: Co
nti
nu
ed
S.
No
. B
iolo
gic
al s
ou
rce
Ext
ract
/Fra
ctio
n/Is
ola
teD
ose
An
imal
/ H
um
an b
ein
g
Exp
erim
enta
l mo
del
/ A
sses
smen
t o
f cl
inic
al
par
amet
ers
Mec
han
ism
o
f ac
tio
nA
ctiv
ity
Ref
.
88O
cim
um s
anct
um
Linn
. (La
mia
ceae
) Tu
lsi,
Ho
ly b
asil
Aqu
eous
ext
ract
of
who
le p
lant
200
mg/
kg,
p.o.
Sw
iss
Mic
eE
PM
, Pas
sive
avo
idan
ce
para
digm
, Sco
pola
min
e an
d di
azep
am in
duce
d am
nesi
a
—A
nxio
lytic
and
no
otro
pic
effe
cts
[171
]
Aqu
eous
ext
ract
of
who
le p
lant
500
mg/
caps
ule
twic
e da
ily a
fter
mea
l
35 m
ale
and
fem
ale
hum
an b
eing
sH
amilt
on’s
brie
f ps
ychi
atric
ra
ting
scal
e (B
PR
S)
—A
nxio
lytic
[172
]
89P
achy
rhiz
us e
rosu
s Li
nn. (
Legu
min
osae
) B
ang
kwan
g,
Jica
ma
Eth
anol
ext
ract
of
seed
s15
0 m
g/kg
, p.
o.S
wis
s al
bino
mic
eS
tairc
ase
test
, EP
M, a
ggre
ssiv
e be
havi
or, P
ento
barb
itone
in
duce
d sl
eepi
ng ti
me,
lo
com
otor
act
ivity
, rot
orod
test
—S
edat
ive,
an
tianx
iety
m
uscl
e re
laxa
nt a
nd
antia
ggre
ssiv
e ac
tivity
[173
]
90P
anax
gin
seng
C
.A.M
eyer
(A
ralia
ceae
) C
hin
ese,
Ja
pan
ese,
Ko
rean
g
inse
ng
, Nin
jin
Gin
seng
ext
ract
G-1
1510
0 m
g/kg
, p.
o.W
ista
r ra
tsV
ogel
con
flict
pro
cedu
re—
Anx
ioly
tic[1
74]
Aqu
eous
ext
ract
of
whi
te
and
red
root
s po
wde
r20
and
50
mg/
kg, p
.o. t
wic
e da
ily fo
r 5
days
Mal
e W
ista
r st
rain
alb
ino
rats
and
alb
ino
mic
eE
PM
, OF
T, c
onfli
ct b
ehav
ior
in
thirs
ty r
ats,
foot
sho
ck in
duce
d fig
htin
g in
pai
red
mic
e
Dec
reas
e M
AO
ac
tivity
in b
rain
Anx
ioly
tic[1
75]
But
anol
frac
tions
of
root
s of
red
(R
G)
and
sun
gins
eng
(SG
)
RG
(10
0 m
g/kg
, p.o
.) a
nd
SG
(25
and
50
mg/
kg, p
.o.)
Alb
ino
mic
eE
PM
—A
nxio
lytic
[176
]
(a)
Gin
seng
roo
t pow
der
(b)
Cru
de s
apon
in
gins
eng
frac
tion
(c)
Gin
seno
side
Rb1
(40)
(a)
300,
600
an
d 12
00 m
g/kg
, p.o
(b
) 50
, 100
, an
d 20
0 m
g/kg
, p.o
(c
) 2.
5, 5
and
10
mg/
kg, i
.p
Mal
e IC
R a
lbin
o m
ice
EP
M—
Anx
ioly
tic[1
77]
(a)
Gin
seng
aqu
eous
ex
trac
t (b
) G
inse
nosi
des
Rg3
(41)
and
Rh2
(42)
fr
om r
oots
(a)
50 a
nd 1
00
mg/
kg, p
.o.
(b)
5, 1
0 an
d 25
mg/
kg, p
.o.
once
dai
ly fo
r 3
days
Mal
e IC
R m
ice
EP
MIn
tera
ctio
n w
ith
GA
BA
/BZ
D
rece
ptor
s
Anx
ioly
tic[1
78]
91P
anax
qui
nque
foliu
s Li
nn. (
Ara
liace
ae)
Am
eric
an g
inse
ng
Sap
onin
s50
and
100
m
g/kg
, p.o
.M
ale
Sw
iss
albi
no m
ice
EP
M, L
DM
, HB
T—
Anx
ioly
tic[1
79]
29
Madaan, et. al.: Plant Drugs Used to Combat Menace of Anxiety Disorders92
Pas
siflo
ra a
ctin
ia
Hoo
ker
(Pas
siflo
race
ae)
Wild
bel
l ap
ple
, m
arac
ujá
-do
-mat
o
Hyd
ro-e
than
ol (
HE
) an
d M
etha
nol (
ME
) E
xtra
ct fr
om le
aves
HE
(30
0 an
d 60
0 m
g/kg
, p.
o.)
ME
(10
0 an
d 30
0 m
g/kg
, p.
o.)
Mal
e al
bino
-Sw
iss
mic
eE
PM
G
AB
AA r
ecep
tor
inte
ract
ion
Anx
ioly
tic[1
80]
93P
assi
flora
ala
ta
Dry
ande
r (P
assi
flora
ceae
) W
ing
ed-s
tem
P
assi
on
flo
wer
Hyd
ro-a
lcoh
olic
ext
ract
(4
0% e
than
ol)
of le
aves
50,1
00 o
r 15
0 m
g/kg
, i.p
.A
dult
fem
ale
Wis
tar
rats
EP
M—
Anx
ioly
tic[1
81]
Spr
ay d
ried
pow
der
of
aque
ous
extr
act o
f le
aves
400
and
800
mg/
kg,
p.o
.A
dult
mal
e W
ista
r ra
tsE
PM
—A
nxio
lytic
[182
]
Aqu
eous
ext
ract
of
leav
es50
and
100
m
g/kg
, i.p
.W
ista
r ra
tsE
PM
—A
nxio
lytic
[183
, 18
4]
94P
assi
flora
coe
rule
a Li
nn.
(Pas
siflo
race
ae)
Blu
e P
assi
on
fl
ow
er
Chr
ysin
(43
)1
mg/
kg, i
.p.
Mal
e C
F1
mic
eE
PM
, HB
TIn
tera
ctio
n w
ith
BZ
D r
ecep
tors
Anx
ioly
tic[1
85,
186]
95P
assi
flora
edu
lis
Sim
s (P
assi
flora
ceae
) B
at-L
eave
d
Pas
sio
n f
low
er
Hyd
ro-a
lcoh
olic
ext
ract
(4
0% e
than
ol)
of le
aves
50, 1
00 a
nd
150
mg/
kg, i
.p.
Adu
lt fe
mal
e W
ista
r ra
tsE
PM
—A
nxio
lytic
[181
]
(a)
Aqu
eous
ext
ract
(b
) Tot
al fl
avon
oid
frac
tion
(c)
Lute
olin
-7-O
-(2-
rh
amno
syl g
luco
side
)(4
4) fr
om to
tal f
lavo
noid
fr
actio
n of
aqu
eous
ex
trac
t of
leav
es
(a)
230
mg/
kg,
p.o.
(b
) 10
0 m
g/kg
, p.
o.
(c)
30 m
g/kg
, p.
o.
Adu
lt m
ale
Sw
iss
mic
eE
PM
, MB
T—
Anx
ioly
tic[1
87]
Spr
ay d
ried
pow
der
of
aque
ous
extr
act o
f le
aves
400
and
800
mg/
kg,
p.o
.A
dult
mal
e W
ista
r ra
tsE
PM
—A
nxio
lytic
[182
]
Aqu
eous
ext
ract
50
, 100
and
15
0 m
g/kg
, i.p
.W
ista
r ra
tsE
PM
—A
nxio
lytic
[183
, 18
4]
Aqu
eous
ext
ract
of
mat
ure
frui
ts a
nd it
s bu
tano
lic fr
actio
n
100
and
300
mg/
kg, p
.o.
Adu
lt m
ale
Sw
iss
mic
eLD
M, E
thyl
eth
er–i
nduc
ed
hypn
osis
, PT
Z-in
duce
d co
nvul
sion
s
—A
nxio
lytic
and
se
dativ
e bu
t no
t an
ticon
vuls
ant
[188
]
96P
assi
flora
inca
rnat
a Li
nn.
(Pas
siflo
race
ae)
Pas
sio
n f
low
er,
May
po
p
Aqu
eous
ext
ract
(P
assi
payT
M, I
ran
Dar
ouk)
45 d
rops
/day
fo
r 4
wee
ksA
dou
ble
blin
d ra
ndom
ized
tr
ial o
n 36
pat
ient
with
G
AD
HA
MA
sco
res
—A
nxio
lytic
[189
]
Met
hano
l ext
ract
of
aeria
l par
ts12
5 m
g/kg
, p.
o.S
wis
s A
lbin
o m
ice
EP
M—
Anx
ioly
tic[1
90-
193]
Hom
oeop
athi
c fo
rmul
atio
ns10
0 m
g/kg
, p.
o.S
wis
s A
lbin
o m
ice
EP
M—
Anx
ioly
tic[1
94]
Ben
zofla
vone
nuc
leus
as
basi
c m
oiet
y co
mpo
und
from
met
hano
l ext
ract
10 m
g/kg
, p.o
.S
wis
s A
lbin
o m
ice
EP
M
—A
nxio
lytic
[195
]
30
Madaan, et. al.: Plant Drugs Used to Combat Menace of Anxiety Disorders
Tab
le 1
: Co
nti
nu
ed
S.
No
. B
iolo
gic
al s
ou
rce
Ext
ract
/Fra
ctio
n/Is
ola
teD
ose
An
imal
/ H
um
an b
ein
g
Exp
erim
enta
l mo
del
/ A
sses
smen
t o
f cl
inic
al
par
amet
ers
Mec
han
ism
o
f ac
tio
nA
ctiv
ity
Ref
.
Met
hano
l ext
ract
of
aeria
l par
ts a
nd C
hrys
in
2 m
g/kg
, i.p
.M
ale
Spr
ague
-Daw
ley
rats
EP
MIn
tera
ctio
n w
ith
GA
BA
/BZ
D-
rece
ptor
s
Anx
ioly
tic[1
96,
197]
Tabl
et c
onta
inin
g 1.
01
mg
benz
ofla
vone
(B
ZF
) 50
0 m
g, p
.o.
A d
oubl
e bl
ind
plac
ebo-
cont
rolle
d st
udy
on 6
0 pa
tient
s w
ith a
nxie
ty
Num
eric
al r
atin
g sc
ale,
Trie
ger
dot t
est a
nd th
e di
git-
sym
bol
subs
titut
ion
test
—A
nxio
lytic
[198
]
Hyd
ro-e
than
ol e
xtra
ct
(50%
eth
anol
) of
aer
ial
part
s
375
mg/
kg,
p.o.
Mal
e B
L6/C
57 J
mic
eE
PM
Inte
ract
ion
with
G
AB
A r
ecep
tors
Anx
ioly
tic[1
99,
200]
(a)
Hyd
ro-a
lcoh
olic
ex
trac
t (50
% e
than
ol)
of
aeria
l par
ts
(b)
But
anol
frac
tion
(c)
Chl
orof
orm
ext
ract
(a)
150
and
300
mg/
kg,
p.o.
(b
) 2.
1 an
d 4.
2 m
g/kg
, p.o
. (c
) 0.
17 a
nd
0.34
mg/
kg,
p.o.
Mal
e C
57B
L/6J
mic
eE
PM
—A
nxio
lytic
[201
]
97P
assi
flora
qu
adra
ngul
aris
Lin
n.
(Pas
siflo
race
ae)
Gia
nt
gra
nad
illa
Aqu
eous
and
eth
anol
ex
trac
t of
leav
es25
0 an
d 50
0 m
g/kg
, p.o
.A
dult
mal
e W
ista
r ra
ts a
nd
Sw
iss
mic
eE
PM
, OF
T, H
BT
—A
nxio
lytic
[202
]
98P
erill
a fr
utes
cens
(L
.) B
ritto
n (L
amia
ceae
) P
urp
le P
erill
a, W
ild
red
bas
il
Ros
mar
inic
aci
d (4
5)an
d ca
ffeic
aci
d(46
) is
olat
ed
from
hyd
ro-a
lcoh
olic
ex
trac
t of
leav
es
10 m
g/kg
, p.o
.A
lbin
o m
ice
FS
T
Mod
ulat
ion
of th
e α 1A
- ad
reno
cept
or-
med
iate
d si
gnal
tr
ansd
uctio
ns a
nd
also
atte
nuat
es
the
dow
n re
gula
tion
of
BD
NF
tr
ansc
riptio
n
Anx
ioly
tic[2
03]
99P
etiv
eria
alli
acea
Li
nn.
(Phy
tola
ccac
eae)
G
uin
ea h
en w
eed
Hex
ane,
hyd
ro-a
lcoh
olic
, an
d pr
ecip
itate
d hy
dro-
alco
holic
ext
ract
(5
0%)
of r
oots
100
and
200
mg/
kg, i
.p. a
nd
p.o.
Fem
ale
Sw
iss
mic
eE
PM
, OF
T—
Anx
ioly
tic[2
04]
Who
le p
lant
ext
ract
300
and
900
mg/
kg, p
.o.
Mal
e al
bino
Sw
iss
mic
eE
PM
, OF
T—
Anx
ioly
tic[2
05]
31
Madaan, et. al.: Plant Drugs Used to Combat Menace of Anxiety Disorders10
0P
iper
met
hyst
icum
Fo
rst.
(Pip
erac
eae)
K
ava,
Kaw
a
WS
149
0 ex
trac
t 50
mg,
p.o
.25
-wee
k m
ultic
ente
r ra
ndom
ized
pla
cebo
-co
ntro
lled
doub
le-b
lind
tria
l on
121
out
patie
nts
suffe
ring
from
anx
iety
of
non-
psyc
hotic
orig
in
HA
MA
, som
atic
and
psy
chic
an
xiet
y, C
linic
al G
loba
l Im
pres
sion
(C
GI)
, Sel
f-R
epor
t S
ympt
om In
vent
ory-
90 It
ems
revi
sed,
and
Adj
ectiv
e M
ood
Sca
le
—A
nxio
lytic
[206
]
Kav
a ex
trac
t LI 1
503
tabl
ets
daily
eq
uiva
lent
to
135
mg
kava
py
rone
s da
ily
for
12 w
eeks
Con
trol
led
clin
ical
tria
l on
a 37
-yea
r-ol
d fe
mal
e ou
tpat
ient
with
GA
D, S
P
and
SA
D
CG
I sca
le, A
MD
P –
mod
ule,
H
AM
A, H
amilt
on d
epre
ssio
n sc
ale,
Bec
k an
xiet
y in
vent
ory,
Spe
ilber
ger
trai
t anx
iety
in
vent
ory
—A
nxio
lytic
[207
]
Kav
a ex
trac
t st
anda
rdiz
ed to
30%
ka
vala
cton
es
280
mg/
day
for
4 w
eeks
Pat
ient
s su
fferin
g w
ith
GA
DB
aror
efle
x co
ntro
l of
hear
t rat
e (B
RC
) an
d re
spira
tory
sin
us
arrh
ythm
ia (
RS
A)
—A
nxio
lytic
[208
]
Kav
a-K
ava
spec
ial
extr
act W
S 1
490
50 m
g/da
y fo
r 4
wee
ksA
ran
dom
ized
dou
ble-
blin
d pl
aceb
o-co
ntro
lled
clin
ical
tr
ial o
n 37
pat
ient
with
D
SM
-IV
GA
D
HA
MA
Sca
le, H
ospi
tal A
nxie
ty
and
Dep
ress
ion
Sca
le (
HA
DS
), S
elf-
Ass
essm
ent o
f R
esili
ence
an
d A
nxie
ty (
SA
RA
)
—A
nxio
lytic
[209
]
Hyd
ro-a
lcoh
olic
ext
ract
of
roo
ts12
0-24
0 m
g/kg
, p.o
.W
ista
r ra
tsE
PM
—A
nxio
lytic
[210
]
Kav
a K
ava
LI15
0 ex
trac
t40
0 m
g/da
yA
ran
dom
ized
dou
ble-
blin
d pl
aceb
o-co
ntro
lled
clin
ical
tr
ial o
n 12
9 pa
tient
s su
fferin
g fr
om G
AD
HA
MA
Sca
le a
nd B
oern
er
Anx
iety
Sca
le (
BoE
AS
), C
GI,
a sl
eep
ques
tionn
aire
(sf
-13)
, and
a
qual
ity o
f lif
e qu
estio
nnai
re
—A
nxio
lytic
[211
]
Sam
ples
con
tain
ing
12.8
-100
% to
tal
kava
lact
ones
, and
fr
actio
ns c
onta
inin
g ka
vala
cton
es 1
-6(4
7-52
) in
var
ying
con
cent
ratio
n (0
.1-6
7.5%
)
Coc
kere
ls
(Gal
lus
gallu
s;
stra
in W
36)
i.p. i
njec
tions
of
diffe
rent
co
ncen
trat
ions
Chi
ck s
ocia
l sep
arat
ion
proc
edur
e —
Anx
ioly
tic[2
12]
Eth
anol
ext
ract
of
the
aeria
l par
ts12
5 m
g/kg
an
d 88
mg/
kg,
i.p.
Sw
iss
albi
no m
ice
Mir
rore
d ch
ambe
r av
oida
nce
assa
y an
d E
PM
—
Anx
ioly
tic[2
13]
Kav
a-K
ava
spec
ial
extr
act W
S 1
490
50 m
g/da
y fo
r 4
wee
ksA
ran
dom
ized
dou
ble-
blin
d pl
aceb
o-co
ntro
lled
clin
ical
tr
ial o
n 14
1 pa
tient
s su
fferin
g fr
om n
euro
tic
anxi
ety
The
tota
l sco
re o
f th
e A
nxie
ty
Sta
tus
Inve
ntor
y (A
SI)
obs
erve
r ra
ting
scal
e, s
truc
ture
d w
ell-b
eing
sel
f-ra
ting
scal
e (B
f-S
) an
d C
GI
—A
nxio
lytic
[214
]
Kav
a-K
ava
spec
ial
extr
act W
S 1
490
50-3
00 m
g/da
y fo
r 4
wee
ks
A r
ando
miz
ed d
oubl
e-bl
ind
plac
ebo-
cont
rolle
d cl
inic
al
tria
l on
230
patie
nts
suffe
ring
from
neu
rotic
an
xiet
y
HA
MA
Sca
le, s
ubje
ctiv
e w
ell-
bein
g sc
ale
(Bf-
s), E
rlang
er
Anx
iety
, Ten
sion
, Agg
ress
ion
Sca
le (
EA
AS
), C
GI,
The
Brie
f P
erso
nalit
y S
truc
ture
Sca
le a
nd
The
Adj
ectiv
e C
heck
list
—A
nxio
lytic
[215
, 21
6]
101
Pip
er s
olm
sian
um C
. D
C. (
Pip
erac
eae)
P
arip
aro
ba
Em
ulsi
on o
f th
e es
sent
ial o
il fr
om a
eria
l pa
rts
5 or
10%
v/v
Sw
iss
mal
e m
ice
EP
M—
Anx
ioly
tic[2
17]
32
Madaan, et. al.: Plant Drugs Used to Combat Menace of Anxiety Disorders
Tab
le 1
: Co
nti
nu
ed
S.
No
. B
iolo
gic
al s
ou
rce
Ext
ract
/Fra
ctio
n/Is
ola
teD
ose
An
imal
/ H
um
an b
ein
g
Exp
erim
enta
l mo
del
/ A
sses
smen
t o
f cl
inic
al
par
amet
ers
Mec
han
ism
o
f ac
tio
nA
ctiv
ity
Ref
.
102
Pip
er tu
berc
ulat
um
Jacq
. (P
iper
acea
e)
Pim
enta
dar
ta a
nd
P
imen
ta L
on
ga
Pip
lart
ine
(53)
am
ide
alka
loid
isol
ated
from
ro
ots
50 a
nd 1
00
mg/
kg, i
.pS
wis
s m
ale
mic
e E
PM
, OF
T—
Anx
ioly
tic[2
18]
103
Pol
ygal
a sa
bulo
sa
A.W
. Ben
nett
(Pol
ygal
acea
e)
Tim
utu
-pin
hei
rin
ho
Thr
ee d
ihyd
rost
yryl
-2-
pyro
nes
I-III
(54
-56)
and
fo
ur s
tyry
l-2-p
yron
es I-
IV
(57-
60)
isol
ated
from
et
hyl a
ceta
te fr
actio
n of
hy
dro-
etha
nol (
HE
) ex
trac
t of
who
le p
lant
HE
, fra
ctio
ns
(250
, 500
and
10
00 m
g/kg
), p.
o.,
Dih
ydro
styr
yl-
2-py
rone
s an
d st
yryl
-2-
pyro
nes
(0.3
fm
ol–2
5 pm
ol,
i.c.v
.)
Mal
e ad
ult S
wis
s m
ice
EP
M, P
ento
barb
ital-a
nd e
thyl
et
her-
indu
ced
hypn
osis
, P
TZ
-indu
ced
conv
ulsi
ons,
R
ota-
rod
test
—H
ypno
tic,
antic
onvu
lsan
t an
d an
xiol
ytic
[219
]
Dih
ydro
styr
yl-2
-py
rone
s(54
-56)
and
st
yryl
-2-
pyro
nes(
57-6
0)is
olat
ed fr
om e
thyl
ac
etat
e fr
actio
n of
hy
dro-
etha
nol (
HE
) ex
trac
t of
who
le p
lant
0.3
fmol
–25
pmol
, i.c
.v.
Mal
e ad
ult S
wis
s m
ice
EP
MB
ZD
rec
epto
r in
tera
ctio
nA
nxio
lytic
[220
]
104
Pol
ygal
a te
nuifo
lia
Will
d.
(Pol
ygal
acea
e)
Yuan
Zh
i
Pol
ygal
a sa
poni
ns
40, 8
0 an
d 16
0 m
g/kg
, p.
o.
Mal
e ad
ult S
wis
s m
ice
EP
M, O
FT,
HB
T—
Anx
ioly
tic[2
21]
105
Pro
tium
he
ptap
hyllu
m (
Aub
l.)
Mar
ch.
(Bur
sera
ceae
) B
rasi
l res
intr
ee
α an
d β
amyr
in (
61-6
2)
pent
acyc
lic tr
iterp
enes
is
olat
ed fr
om s
tem
bar
k re
sin
10, 2
5 an
d 50
m
g/kg
i.p.
or
p.o.
Mal
e S
wis
s m
ice
EP
M, O
FT
BZ
D r
ecep
tor
inte
ract
ion
Anx
ioly
tic[2
22]
106
Pru
nus
dom
estic
a Li
nn.
(Ple
uron
ectid
ae)
Mir
abel
le, P
lum
, A
lu b
ukh
ara
Chl
orog
enic
aci
d(63
)is
olat
ed fr
om fr
uits
20
mg/
kg, i
.p.
Sw
iss
albi
no m
ale
mic
eE
PM
, LD
M, f
ree
expl
orat
ory
test
—A
nxio
lytic
[223
]
107
Pul
satil
la n
igric
ans
Sto
erck
(R
anun
cula
ceae
) P
asq
uef
low
er,
Win
dfl
ow
er,
Mea
do
w a
nem
on
e
Met
hano
l ext
ract
of
aeria
l par
ts20
0 m
g/kg
, p.
o.La
ca m
ice
EP
M—
Anx
ioly
tic[2
24]
33
Madaan, et. al.: Plant Drugs Used to Combat Menace of Anxiety Disorders10
8P
unic
a gr
anat
um
Linn
. (P
unic
acea
e)
Po
meg
ran
ate,
G
ran
ada
Eth
anol
ext
ract
of
seed
s10
0, 2
50, a
nd
500
mg/
kg,
p.o.
Youn
g an
d ol
d m
ale
Sw
iss
albi
no m
ice
EP
M, P
ento
barb
ital-i
nduc
ed
slee
ping
tim
e, F
ST,
tail
flick
and
ho
t pla
te te
st
—A
nxio
lytic
, an
tidep
ress
ant
and
anti-
noce
cept
ive
[225
]
109
Rho
diol
a ro
sea
Linn
.(R
hizo
phor
acea
e)
Arc
tic
roo
t, G
old
en
roo
t, R
ose
roo
t
Hyd
ro-a
lcoh
olic
ext
ract
(c
onta
ins
3% r
osav
in
and
1% s
alid
rosi
de)
15 m
g/kg
, p.o
.M
ale
CD
1 m
ice
LDM
—A
nxio
lytic
[226
]
110
Rol
linia
muc
osa
(Jac
q.)
Bai
ll.
(Ann
onac
eae)
W
ild s
ug
ar a
pp
le
Hex
ane
extr
act o
f le
aves
1.62
to 6
.25
mg/
kg, p
.o.
Alb
ino
mic
eA
void
ance
exp
lora
tory
beh
avio
r pa
radi
gmG
AB
A/B
ZD
re
cept
ors
inte
ract
ion
Anx
ioly
tic[2
27]
111
Rub
us b
rasi
liens
is
Mar
tius
(Ros
acea
e)
Am
ora
bra
nca
Eth
anol
ext
ract
of
leav
es15
0 m
g/kg
, pe
r ga
vage
Mal
e W
ista
r ra
ts a
nd S
wis
s m
ice
EP
MIn
tera
ctio
n w
ith
GA
BA
A r
ecep
tor
Anx
ioly
tic[2
28,
229]
112
Rut
a ch
alep
ensi
s Li
nn. (
Rut
acea
e)
Fri
ng
ed r
ue,
h
erb
-of-
gra
ce
Eth
anol
ext
ract
of
aeria
l pa
rts
300
mg/
kg,
p.o.
Mal
e S
wis
s al
bino
mic
eP
TZ
-indu
ced
seiz
ures
, sod
ium
pe
ntob
arbi
tal-i
nduc
ed h
ypno
sis,
ex
plor
ator
y ac
tivity
, anx
iety
by
unfa
mili
ar e
nviro
nmen
t and
no
cice
ptio
n
—A
nxio
lytic
, an
ticon
vuls
ant,
seda
tive,
an
tinoc
icep
tive
[230
]
113
Sal
ix a
egyp
tiaca
Li
nn. (
Sal
icac
eae)
E
gyp
tian
m
usk
will
ow
Aqu
eous
ext
ract
of
flow
ers
100
mg/
kg, i
.p.
Mal
e N
MR
I mic
eE
PM
—A
nxio
lytic
[231
]
114
Sal
via
cinn
abar
ina
M.M
arte
ns &
G
aleo
tti (L
amia
ceae
) S
age,
Wild
Ku
s
A d
iterp
enoi
d C
MP
I10
mg/
kg, p
.o.
Alb
ino
mic
eE
PM
, FS
T—
Anx
ioly
tic[2
32]
115
Sal
via
divi
noru
m
Epl
ing
& J
átiv
a (L
amia
ceae
) D
ivin
er’s
sag
e
Sal
vino
rin-A
(64)
0.00
1-10
00
µg/k
g, s
.c.
Adu
lt m
ale
Spr
ague
-Daw
ley
rats
EP
M, F
ST,
Spo
ntan
eous
mot
or
activ
ity in
mic
e, T
ail s
uspe
nsio
n te
st
k-op
ioid
and
en
doca
nnab
inoi
d sy
stem
s
Anx
ioly
tic,
antid
epre
ssan
t[2
33]
116
Sal
via
eleg
ans
Vah
l. (L
amia
ceae
) S
carl
et p
inea
pp
le
Hyd
ro-a
lcoh
olic
(60
%
etha
nol)
extr
act o
f le
aves
and
flow
er
125,
250
, 500
, 10
00 a
nd
2000
mg/
kg,
p.o.
Mal
e IC
R m
ice
EP
M, L
DM
, OF
T—
Anx
ioly
tic[2
34]
60%
eth
anol
ext
ract
of
leav
es12
.5 m
g/kg
, i.p
.S
prag
ue D
awle
y ra
tsE
PM
, FS
T—
Psy
chot
ropi
c[2
35]
117
Sal
via
milt
iorr
hiza
B
ge. (
Lam
iace
ae)
Red
sag
e
Dite
rpen
e qu
inin
e –
Milt
irone
(65)
isol
ated
fr
om e
ther
eal e
xtra
ct o
f ro
ots
10-6
0 m
g/kg
, p.
o.A
lbin
o m
ice
Four
pla
te te
stB
ZD
rec
epto
r in
tera
ctio
nA
nxio
lytic
[236
]
118
Sal
via
reut
eran
a B
oiss
. (La
mia
ceae
) S
age
Hyd
ro-a
lcoh
olic
ext
ract
(8
0% e
than
ol)
of a
eria
l pa
rts
100
mg/
kg,
i.p
.M
ale
Syr
ian
mic
eE
PM
, Spo
ntan
eous
loco
mot
or
activ
ity—
Anx
ioly
tic[2
37]
34
Madaan, et. al.: Plant Drugs Used to Combat Menace of Anxiety DisordersTa
ble
1: C
on
tin
ued
S.
No
. B
iolo
gic
al s
ou
rce
Ext
ract
/Fra
ctio
n/Is
ola
teD
ose
An
imal
/ H
um
an b
ein
g
Exp
erim
enta
l mo
del
/ A
sses
smen
t o
f cl
inic
al
par
amet
ers
Mec
han
ism
o
f ac
tio
nA
ctiv
ity
Ref
.
119
Sap
indu
s m
ukor
ossi
G
aert
n.
(Sap
inda
ceae
) S
oap
ber
ry,R
ith
a
Met
hano
l ext
ract
of
seed
s an
d fr
uits
200
and
400
mg/
kg, p
.o.
Alb
ino
mic
eE
PM
, Y-m
aze,
HB
T, A
ctop
hoto
-m
eter
, MB
TG
AB
Aer
gic
tran
smis
sion
Anx
ioly
tic[2
38]
120
Sau
ssur
ea la
ppa
C.B
. Cla
rke
(Ast
erac
eae)
K
uth
, Ku
sth
a
Ess
entia
l oil
Inha
latio
nA
nxie
ty in
a w
oman
in
labo
urB
ehav
iour
al r
espo
nses
—A
nxio
lytic
[239
]
121
Scu
tella
ria
baic
alen
sis
Geo
rgi
(Lab
iata
e)
Hu
ang
qin
A m
onof
lavo
noid
W
ogon
in(6
6), i
sola
ted
from
dic
hlor
omet
hane
ex
trac
t of
root
s
7.5,
15
and
30
mg/
kg, p
.o.
Mal
e IC
R m
ice
EP
MIn
tera
ctio
n w
ith
GA
BA
/ BZ
D
rece
ptor
Anx
ioly
tic[2
40]
Onl
y 2’
-OH
flav
ones
is
olat
ed fr
om
dich
loro
met
hane
, wat
er
extr
acts
of
root
s
IC50
val
ues
0.00
8 to
100
µM
In v
itro,
For
ebra
ins
of
Spr
ague
-Daw
ley
rats
R
adio
rec
epto
r B
ZD
-S a
ssay
Inte
ract
ion
with
G
AB
AA
/ B
ZD
re
cept
or
Anx
ioly
tic[2
41]
(a)
5,7,
2’-t
rihyd
roxy
-6,8
-di
met
hoxy
flav
ones
(b
) 5,
7-di
hydr
oxy-
6-m
etho
xyfla
vone
isol
ated
fr
om d
ichl
orom
etha
ne
extr
act o
f ro
ots
6.05
mM
In v
itro
Rad
io r
ecep
tor
BZ
D-S
ass
ay(a
) In
tera
ctio
n w
ith G
AB
AA
/ B
ZD
re
cept
or (
agon
ist)
(b
) In
tera
ctio
n w
ith G
AB
AA
/ B
ZD
re
cept
or
(sel
ectiv
e an
tago
nist
)
Anx
ioly
tic[2
42,
243]
Fla
vono
id b
aica
lin(6
7)
and
its a
glyc
one
baic
alei
n(68
)
Bai
cale
in (
10
mg/
kg, i
.p.)
an
d ba
ical
in
(20
mg/
kg, i
.p.)
Mal
e IC
R m
ice
Vog
el s
hock
con
flict
test
Inte
ract
ion
with
B
ZD
bin
ding
site
of
GA
BA
A
rece
ptor
s
Anx
ioly
tic[2
44]
122
Scu
tella
ria la
terif
lora
Li
nn. (
Labi
atae
) B
lue
sku
llcap
, H
oo
dw
ort
Aqu
eous
ext
ract
of
root
s10
0 m
g/m
l, or
ally
Mal
e S
prag
ue-D
awle
y ra
tsE
PM
Inte
ract
ion
with
G
AB
AA
/ B
ZD
re
cept
or
Anx
ioly
tic[2
45]
(a)
Fla
vono
id
baic
alin
(67)
in e
than
ol
extr
act o
f ro
ots
(b)
baic
alei
n(68
) in
et
hano
l ext
ract
of
root
s (c
) E
than
ol e
xtra
ct o
f ro
ots
(d)
glut
amin
e in
wat
er
extr
act o
f ro
ots
(a)
40 m
g/g,
p.
o.
(b)
33 m
g/g,
p.
o.
(c)
1.6
mg/
g,
p.o.
(d
) 31
mg/
g,
p.o.
Adu
lt m
ale
Spr
ague
-D
awle
y ra
tsE
PM
, SI
Inte
ract
ion
with
G
AB
AA
/ B
ZD
re
cept
or
Anx
ioly
tic[2
45]
123
Sec
urid
aca
long
eped
uncu
lata
Fr
esen
(P
olyg
alac
eae)
V
iole
t tr
ee
Aqu
eous
roo
ts e
xtra
ct10
0-40
0 m
g/kg
, p.o
.A
lbin
o m
ice
of e
ither
sex
EP
M, Y
-maz
e, S
tryc
hnin
e- a
nd
Pic
roto
xin-
indu
ced
seiz
ure,
H
exob
arbi
tone
- in
duce
d sl
eep
test
, Exp
lora
tory
act
ivity
—A
nxio
lytic
, an
ticon
vuls
ant,
seda
tive
[246
]
35
Madaan, et. al.: Plant Drugs Used to Combat Menace of Anxiety Disorders12
4S
esba
nia
gran
diflo
ra
(L.)
Poi
r. (F
abac
eae)
A
gat
i
Ben
zene
:eth
yl a
ceta
te
(BE
) fr
actio
n of
the
acet
one
solu
ble
part
of
petr
oleu
m e
ther
ext
ract
of
leav
es
100
and
200
mg/
kg, p
.o.
Mal
e S
prag
ue-D
awle
y ra
ts
and
mal
e m
ice
(NIN
str
ain)
EP
M, M
ES
-, P
TZ
-, S
tryc
hnin
e-,
Lith
ium
-pilo
carp
ine-
and
elec
tric
ally
indu
ced
seiz
ures
, P
ento
barb
ital-i
nduc
ed s
leep
, A
mph
etam
ine
anta
goni
sm
Incr
ease
in th
e br
ain
cont
ent o
f G
AB
A a
nd 5
-HT
Anx
ioly
tic a
nd
antic
onvu
lsan
t[2
47]
125
Son
chus
ole
race
us
Linn
. (A
ster
acea
e)
So
w t
his
tle,
Milk
y ta
ssel
Hyd
ro-a
lcoh
olic
(5
0% e
than
ol)
and
dich
loro
met
hane
ext
ract
fr
om a
eria
l par
ts
30-3
00 m
g/kg
, p.
o.A
dult
mal
e S
wis
s m
ice
EP
M—
Anx
ioly
tic[2
48]
126
Sph
aera
nthu
s in
dicu
s Li
nn.
(Ast
erac
eae)
M
un
di
Pet
role
um e
ther
ext
ract
(P
E),
90%
eth
anol
ex
trac
t (E
E),
Wat
er
extr
act (
WE
) of
flow
ers
PE
(10
mg/
kg,
i.p.)
, EE
(10
m
g/kg
, i.p
.),
WE
(30
mg/
kg,
i.p.)
Sw
iss
albi
no m
ale
mic
eE
PM
, OF
T, F
oot s
hock
indu
ced
aggr
essi
on
—A
nxio
lytic
[249
]
Hyd
ro-a
lcoh
olic
E
xtra
ct (
50%
eth
anol
)fr
om fu
lly g
row
n flo
wer
ing
herb
100
mg/
kg,
p.o.
Alb
ino
Wis
tar
mic
e an
d ra
ts o
f ei
ther
sex
EP
M—
Anx
ioly
tic[2
50]
127
Spo
ndia
s m
ombi
n Li
nn.
(Ana
card
iace
ae)
Ho
g p
lum
, Jo
bo
, Ye
llow
mo
mb
in
Eth
anol
ext
ract
of
leav
es12
.5 to
100
m
g/kg
, i.p
.A
lbin
o w
ista
r ra
ts a
nd
Sw
iss
mic
eM
uric
idal
act
ion
of r
ats,
Por
solt’
s F
ST
GA
BA
A r
ecep
tor
Anx
ioly
tic a
nd
antid
epre
ssan
t[2
51]
128
Sta
chys
la
vand
ulifo
lia V
ahl.
(Lam
iace
ae)
Lav
end
elb
laet
rig
e an
d W
oo
d b
eto
ny
Hyd
ro-a
lcoh
olic
ext
ract
(8
0% e
than
ol)
and
esse
ntia
l oil
of a
eria
l pa
rts
100
mg/
kg, i
.p.
Mal
e TO
mic
eE
PM
—A
nxio
lytic
[252
]
Pet
role
uum
eth
er (
PF
), et
hyl a
ceta
te (
EF
) an
d w
ater
(A
F)
frac
tions
of
hydr
o-al
coho
lic e
xtra
ct
(80%
eth
anol
) of
aer
ial
part
s
PF
(25
and
50
mg/
kg, i
.p.)
E
F (
25 a
nd 5
0 m
g/kg
, i.p
.)
AF
(50
mg/
kg,
i.p.)
Mal
e S
yria
n m
ice
EP
M—
Anx
ioly
tic[2
53]
129
The
obro
ma
caca
o Li
nn. (
Ste
rcul
iace
ae)
Cac
ao, C
ho
cola
te
tree
, Kak
ao
Mas
s or
cak
e10
0 m
g/10
0g,
o.s.
Mal
e W
ista
r st
rain
rat
sE
TM
Con
ditio
nal f
ear
rela
ting
beha
viou
r, bu
t did
not
affe
ct
the
conc
entr
atio
n of
bra
in
mon
oam
ines
su
ch a
s no
r-ep
inep
hrin
e,
sero
toni
n an
d do
pam
ine
Anx
ioly
tic[2
54]
36
Madaan, et. al.: Plant Drugs Used to Combat Menace of Anxiety Disorders
Tab
le 1
: Co
nti
nu
ed
S.
No
. B
iolo
gic
al s
ou
rce
Ext
ract
/Fra
ctio
n/Is
ola
teD
ose
An
imal
/ H
um
an b
ein
g
Exp
erim
enta
l mo
del
/ A
sses
smen
t o
f cl
inic
al
par
amet
ers
Mec
han
ism
o
f ac
tio
nA
ctiv
ity
Ref
.
130
Tili
a am
eric
ana
Linn
.var
. mex
ican
a (M
alva
ceae
) A
mer
ican
b
assw
oo
d,
Am
eric
an li
nd
en
β-si
tost
erol
(69)
isol
ated
fr
om h
exan
e ex
trac
t of
inflo
resc
ence
s
1 to
10
mg/
kg,
i.p.
Mal
e S
wis
s al
bino
mic
eE
PM
, HB
T, s
odiu
m
pent
obar
bita
l-ind
uced
hyp
nosi
s an
d am
bula
tory
act
ivity
—A
nxio
lytic
and
S
edat
ive
at
high
er d
ose
(30
mg/
kg, i
.p.)
[255
, 25
6]
Met
hano
l ext
ract
from
br
acts
and
flow
ers
[Tili
rosi
de(7
0) m
ain
cons
titue
nt]
25-1
00 m
g/kg
, p.
o.A
lbin
o IC
R m
ice
EP
M—
Anx
ioly
tic[2
57]
Aqu
eous
ext
ract
of
inflo
resc
ence
s [Q
uerc
etin
(7)
and
kaem
pfer
ol(6
) m
ay b
e ac
tive
cons
titue
nts]
10-3
00 m
g/kg
, p.
o.M
ale
Sw
iss
albi
no m
ice
EP
M, H
BT,
sod
ium
pen
toba
rbita
l (S
P)-
indu
ced
hypn
osis
po
tent
iatio
n, a
mbu
lato
ry
Act
ivity
—A
nxio
lytic
and
se
dativ
e[2
58]
131
Tili
a to
men
tosa
M
oenc
h (M
alva
ceae
) S
ilver
Lim
e
Hyd
ro-a
lcoh
olic
ext
ract
(7
0% e
than
ol)
of
Inflo
resc
ence
s an
d bu
tano
l fra
ctio
n
Dos
e eq
uiva
lent
to 1
g
of p
lant
m
ater
ial
Sw
iss
albi
no M
ice
EP
M, H
BT
Inte
ract
ion
with
B
ZD
rec
epto
rs
Anx
ioly
tic[2
59]
132
Trifo
lium
pra
tens
e Li
nn. (
Faba
ceae
) R
ed c
love
r
Isof
avon
es (
MF
11R
CE
) 80
mg
Wom
en w
ith p
ostm
eno-
paus
al a
nxie
tyH
AD
S,
Zun
g’s
self-
rat
ing
depr
essi
on
scal
e
—A
nxio
lytic
and
an
tidep
ress
ant
[260
]
133
Turn
era
aphr
odis
iaca
War
d (T
urne
race
ae)
Dam
ian
a
Met
hano
l ext
ract
of
aeria
l par
ts25
mg/
kg, p
.o.
Laca
mic
eE
PM
—A
nxio
lytic
[261
]
Hom
oeop
athi
c fo
rmul
atio
ns50
mg/
kg, p
.o.
Laca
mic
eE
PM
—A
nxio
lytic
[262
]
Api
geni
n(38
) is
olat
ed
from
met
hano
l ext
ract
of
aeria
l par
ts
2 m
g/kg
, p.o
.La
ca m
ice
EP
M—
Anx
ioly
tic[2
63]
134
Unc
aria
rh
ynch
ophy
lla (
Miq
.)
Jack
s (R
ubia
ceae
) C
at’s
Cla
w h
erb
Aqu
eous
ext
ract
of
root
s20
0 m
g/kg
/da
y p.
o fo
r 7
days
Mal
e S
D r
ats
and
mal
e IC
R m
ice
EP
M, H
BT
Ser
oton
ergi
c ne
rvou
s sy
stem
Anx
ioly
tic[2
64]
135
Vac
cini
um a
shei
R
eade
(E
ricac
eae)
B
lueb
erry
Ant
hocy
anin
frac
tion
from
96%
eth
anol
ext
ract
of
ber
ries
0.6–
1.0
and
2.6–
3.2
mg/
kg/d
ay, p
.o.
Adu
lt m
ale
Sw
iss
mic
e (a
ged
3 m
onth
s)E
PM
, OF
T, In
hibi
tory
avo
idan
ce—
Mem
ory-
enha
ncin
g,
anxi
olyt
ic a
nd
loco
mot
ion
incr
easi
ng
effe
cts
[265
]
136
Val
eria
na e
dulis
ssp.
P
roce
ra N
utt.
ex T
orr.
(Val
eria
nace
ae)
Tob
acco
ro
ot
Hyd
ro-a
lcoh
olic
(70
%
etha
nol)
extr
act o
f ro
ots
100,
300
and
10
00 m
g/kg
, p.
o.
Mal
e IC
R m
ice
PT
Z-in
duce
d se
izur
es,
Exp
lora
tory
rea
ring,
Rot
arod
—A
nxio
lytic
, an
ticon
vuls
ant
and
myo
rela
xant
[266
]
37
Madaan, et. al.: Plant Drugs Used to Combat Menace of Anxiety Disorders13
7V
aler
iana
gl
echo
mifo
lia M
eyer
(V
aler
iana
ceae
) V
aler
ian
Val
epot
riate
frac
tion
10 m
g/kg
, p.o
.M
ale
albi
no S
wis
s m
ice
EP
M, O
FT
—A
nxio
lytic
[267
]
138
Val
eria
na o
ffici
nalis
Li
nn.
(Val
eria
nace
ae)
Val
eria
n
Hyd
ro-a
lcoh
olic
ext
ract
ca
lled
vald
an d
rops
Val
dan
drop
s o.
s. d
aily
for
15 d
ays
Fem
ale
albi
no m
ice
Beh
avio
ural
stu
dies
in
loco
mot
ion
test
and
FS
T—
Anx
ioly
tic[2
68]
Val
epot
riate
s83
.1 m
g pe
r da
y36
pat
ient
s w
ith G
AD
DS
M
III-R
Psy
chic
fact
or o
f H
AM
AS
igni
fican
t re
duct
ion
in th
e ps
ychi
c fa
ctor
of
HA
MA
Anx
ioly
tic[2
69]
6-m
ethy
lapi
geni
n (7
0)an
d he
sper
idin
(71)
, is
olat
ed fr
om r
oots
and
rh
izom
es
Hes
perid
in (
4 m
g/kg
, i.p
.),
6-m
ethy
l-ap
igen
in (
1 m
g/kg
, i.p
.)
Adu
lt m
ale
Wis
tar
rats
EP
M ,
HB
TIn
tera
ctio
n w
ith
GA
BA
A /
BZ
D
rece
ptor
Anx
ioly
tic[2
70,
271]
Fla
vono
id li
narin
(72)
4 an
d 7
mg/
kg,
i.p.
Alb
ino
mic
eH
BT
—A
nxio
lytic
[272
]
Dic
hlor
omet
hane
ext
ract
of
roo
ts0.
2 g/
kg, p
.o.
Mal
e W
ista
r ra
tsE
PM
—A
nxio
lytic
[273
]
Val
eren
ic a
cid(
73)
isol
ated
from
hyd
ro-
alco
holic
ext
ract
of
root
s
3 m
g/kg
, i.p
.Fe
mal
e ho
oded
rat
sE
PM
GA
BA
(A)
–erg
ic
syst
emA
nxio
lytic
[274
, 27
5]
139
Vite
x ne
gund
u Li
nn.
(Ver
bena
ceae
) F
ive-
leav
ed c
has
te
tree
Eth
anol
ext
ract
of
root
s10
0 an
d 20
0 m
g/kg
, p.o
.S
wis
s al
bino
mic
eE
PM
, LD
M—
Anx
ioly
tic[2
76]
140
With
ania
som
nife
ra
(Lin
n.)
Dun
al
(Sol
anac
eae)
A
shw
agan
dh
a
Gly
cow
ithan
olid
es
isol
ated
from
the
root
s20
and
50
mg/
kg, p
.o. f
or 5
da
ys
Wis
tar
rats
SI,
Nov
elty
-indu
ced
supp
ress
ed
feed
ing
late
ncy,
EP
M
—A
nxio
lytic
[277
]
Aqu
eous
ext
ract
of
root
s50
, 200
and
50
0 m
g/kg
Wis
tar
rats
EP
M—
Anx
ioly
tic[2
78]
141
Zin
gibe
r of
ficin
ale
Linn
. (Z
ingi
bera
ceae
) G
ing
er
Ben
zene
frac
tion
of
acet
one
solu
ble
part
of
petr
oleu
m e
ther
ext
ract
of
drie
d rh
izom
es
15 a
nd 3
0 m
g/kg
, i.p
.M
ale
Spr
ague
-Daw
ley
rats
EP
M—
Anx
ioly
tic[2
79]
142
Ziz
iphu
s ju
juba
M
iller
(R
ham
nace
ae)
Des
i Ber
Eth
anol
ext
ract
of
seed
s0.
5 g/
kg, p
.o.
Mal
e IC
R m
ice
Bla
ck/w
hite
test
, EP
M a
nd
ambu
lato
ry b
ehav
iour
test
—A
nxio
lytic
[280
]
Alc
ohol
ic e
xtra
ct o
f se
eds
320
mg/
kg,
p.o.
thyr
oid
tabl
et fo
r ni
ne
days
Yin
def
icie
ncy
mic
eE
PM
, LD
MIn
crea
se th
e G
AB
A a
nd
expr
essi
on o
f G
AB
AA
Anx
ioly
tic[2
81]
San
join
ine-
A(7
4) fr
om
alka
loid
al fr
actio
n of
se
eds
2.0
mg/
kg, p
.o.
Mal
e IC
R m
ice
EP
M, O
FT,
HB
TG
AB
Aer
gic
tran
smis
sion
Anx
ioly
tic[2
82]
38
Madaan, et. al.: Plant Drugs Used to Combat Menace of Anxiety Disorders
Tab
le 2
: Lis
t o
f va
rio
us
anxi
oly
tic
form
ula
tio
ns
and
co
mp
ou
nd
s.
S.
No
. F
orm
ula
tio
n/E
xtra
ct/F
ract
ion
/Iso
late
Do
seA
nim
al/H
um
an
bei
ng
sE
xper
imen
tal m
od
el/C
linic
al
stu
die
s p
aram
eter
sM
ech
anis
m o
f ac
tio
nA
ctiv
ity
Ref
.
01O
ils o
f ro
se, y
lang
-yla
ng, a
nd C
ham
omile
ex
trac
ted
from
flow
ers
of R
osa
sp.,
Can
anga
od
orat
a, a
nd A
nthe
nis
nobi
lis (
or M
atric
aria
ch
amom
illa)
, res
pect
ivel
y. or
ange
oil
extr
acte
d fr
om th
e rin
d of
Citr
us s
p..
200–
1600
mg/
kg,
i.p.
Mal
e IC
R m
ice
Gel
ler
conf
lict t
est a
nd V
ogel
’s
conf
lict t
est
Oth
er m
echa
nism
bu
t not
thro
ugh
GA
BA
/BZ
D
Onl
y ro
se o
il ex
hibi
ted
anxi
olyt
ic
activ
ity
[283
]
Lave
nder
oil
1600
mg/
kg, i
.p.
Mal
e IC
R m
ice
Gel
ler
type
con
flict
test
—A
nxio
lytic
[284
]
Ess
entia
l oils
:
(a)
Lave
nder
oil
– 2-
phen
ethy
l alc
ohol
, ci
tron
ella
l(75)
(b)
Ros
e oi
l – 1
,8 c
ineo
le(7
6), m
enth
one(
77),
pule
gone
(78)
, met
hyl a
lcoh
ol,
cary
ophy
llene
(79)
(c)
Pep
perm
int -
men
thol
(80)
1 m
l/100
g, i
.p.
Mal
e IC
R m
ice
(a)
Ant
icon
flict
(b
) In
crea
sed
ambu
lato
ry e
ffect
(c
) In
crea
sed
ambu
lato
ry e
ffect
Dop
amin
e re
cept
or
invo
lvem
ent
Anx
ioly
tic[2
85]
Ros
e oi
l1
ml/1
00 g
, i.p
.M
ale
ICR
mic
eG
elle
r co
nflic
t tes
t and
Vog
el’s
co
nflic
t tes
t—
Anx
ioly
tic[2
86]
Ros
e oi
lIn
hala
tion
(1.0
, 2.
5 or
5.0
% w
/w)
Adu
lt W
ista
r m
ale
rats
EP
M—
Anx
ioly
tic[2
87]
Lem
on o
ilIn
hala
tion
1 m
lIC
R s
trai
n m
ice
EP
M, F
ST,
OF
T5-
HT
nerg
ic
path
way
and
the
supp
ress
ion
of D
A
activ
ity r
elat
ed to
en
hanc
ed
5-H
Tne
rgic
ne
uron
s
Anx
ioly
tic a
nd
antid
epre
ssan
t[2
88]
Ner
oli e
ssen
tial o
ilIn
hala
tion
100
µlG
erbi
lsLo
com
otor
act
ivity
, FS
T—
Anx
ioly
tic[2
89]
02M
onot
erpe
nic
phen
ol –
Car
vacr
ol(8
1) fr
om
esse
ntia
l oil
frac
tion
of O
rega
no a
nd T
hym
e12
.5, 2
5, 5
0 m
g/kg
, p.o
.M
ale
Sw
iss
mic
eE
PM
GA
BA
ergi
c tr
ansm
issi
onA
nxio
lytic
[290
]
03M
onot
erpe
ne a
lcoh
ol –
Isop
uleg
one(
82)
25, 5
0 m
g/kg
, i.p
.M
ale
Sw
iss
mic
eO
FT,
EP
M, H
BT,
Tai
l sus
pens
ion
and
FS
T—
Anx
ioly
tic a
nd
antid
epre
ssan
t[2
91]
04In
dole
alk
aloi
d al
ston
ine(
83)
1 m
g/kg
, i.p
.M
ale
Sw
iss
mic
eLD
M—
Anx
ioly
tic
[292
]
05A
swal
100-
250
mg/
l, i.p
.G
uine
a pi
gs a
nd
Long
-Eva
ns r
ats
Ext
race
llula
r an
d w
hole
cel
l pa
tch
clam
p re
cord
ings
on
CA
1 py
ram
idal
neu
rons
Het
ero-
gene
ous
with
cal
cium
an
tago
nism
Anx
ioly
tic a
nd
antie
pile
ptic
[293
]
06Ir
idol
con
tain
ing
com
poun
ds ir
idoi
ds10
mg/
kg, p
.o.
Mal
e ra
ts a
nd
patie
nts
with
ar
teria
l hy
pert
ensi
on I
- II
degr
ee,
acco
mpa
nied
by
psyc
ho-e
mot
iona
l di
stur
banc
es
Beh
avio
ural
par
amet
ers
Anx
ioly
tic[2
94]
39
Madaan, et. al.: Plant Drugs Used to Combat Menace of Anxiety Disorders07
Kav
ospo
ral f
orte
(S
tand
ardi
zed
extr
act o
f K
ava)
150
mg
for
a w
eek
Clin
ical
tria
l (20
pa
tient
s w
ith
situ
atio
nally
in
duce
d an
xiet
y)
Two
self-
rate
d sc
ale
and
one
obse
rver
rat
ed s
cale
—A
mel
iora
tion
of
anxi
ety
aris
es in
co
nnec
tion
with
m
amm
ary
biop
sy
[295
]
08S
tand
ardi
zed
prod
uct c
onta
inin
g M
elis
sa
offic
inal
is a
nd V
aler
iana
offi
cina
lis60
0 m
gD
oubl
e bl
ind,
pl
aceb
o co
ntro
lled,
ra
ndom
ized
cro
ss
over
, 24
heal
thy
volu
ntee
rs
Def
ined
Inte
nsity
Str
esso
r S
imul
atio
n (D
ISS
) an
d C
ogni
tive
perf
orm
ance
—A
mel
iora
ted
the
nega
tive
effe
cts
of
the
DIS
S o
n ra
tings
of
anxi
ety
[296
]
09Z
ingi
com
b, a
pre
para
tion
cons
istin
g of
Z
. offi
cina
le a
nd G
. bilo
ba e
xtra
cts
0.5,
1, 1
0 or
100
m
g/kg
, in
trag
astr
ical
ly
Mal
e W
ista
r ra
tsO
ne-t
rial s
tep-
thro
ugh
avoi
danc
e ta
sk—
Anx
ioly
tic[2
97]
10P
olyh
erba
l for
mul
atio
n50
, 100
, 300
mg/
kg, p
.o.
Mal
e S
wis
s m
ice
EP
M a
nd F
ST
—A
ntia
nxie
ty a
nd
antid
epre
ssan
t[2
98]
11S
uanz
aore
ntan
g, C
hine
se m
edic
ine
(Sem
en
Ziz
iphi
Spi
nosa
e, R
hizo
ma
Chu
anxi
ong,
P
oria
, Rhi
zom
a A
nem
arrh
enae
, Rad
ix e
t R
hizo
ma
Gly
cyrr
hiza
e)
5 g
Hum
an b
eing
s—
Dec
reas
e se
roto
nerg
ic
activ
ity
Anx
ioly
tic[2
99,
300]
12S
ho-ju
-sen
(S
K),
a Ja
pane
se h
erba
l m
edic
ine,
con
tain
s a
wat
er e
xtra
ct o
f S
asa
kurin
ensi
s M
akin
o et
Sib
ata
(Kum
azas
a;
Poa
ceae
) le
aves
(S
S),
etha
nol e
xtra
ct o
f P
inus
den
siflo
ra S
iebo
ld e
t Zuc
earin
i (J
apan
ese
red
pine
; Pin
acea
e) (
PN
) an
d P
anax
gin
seng
C.A
. Mey
er (
Gin
seng
; A
ralia
ceae
) (P
X)
in th
e ra
tio o
f 8:
1:1
SK
(10
%
solu
tions
for
7 da
ys)
Mal
e m
ice
of th
e dd
Y s
trai
nE
PM
—A
nxio
lytic
[301
]
13K
ami-S
hoya
-San
(T
J-24
) is
one
of
the
trad
ition
al C
hine
se h
erba
l med
icin
e:
Bup
leur
um s
corz
oner
aefo
llium
Will
d.
(Bup
leur
i Rad
ix; B
uple
urac
eae)
, Pae
onia
la
ctifl
ora
Pal
las
(Pae
onia
e R
adix
; P
aeon
acea
e), A
trac
tylo
des
lanc
era
(Thu
nb.)
D
C. (
Act
ract
ylod
is L
ance
ae R
hizo
ma;
C
ompo
sita
e), A
rcha
ngel
ica
offic
inal
is H
offm
. (A
ngel
icae
Rad
ix; U
mbe
llife
rae)
, Por
ia c
ocos
(S
chw
.) W
olf
(Hoe
len;
Pol
ypor
acea
e),
Gar
deni
a ja
smin
oide
s E
llis
(Gar
deni
ae
Fruc
tus;
Rub
iace
ae),
Pae
onia
suf
frut
icos
a A
ndr.
(Mou
tan
Cor
tex;
Pae
onac
eae)
, G
. gla
bra
(Gly
cyrr
hiza
e R
adix
; Le
gum
inos
ae),
Z. o
ffici
nale
(Z
ingi
beris
R
hizo
ma;
Zin
gibe
race
ae),
Men
tha
arve
nsis
M
alin
vaud
(M
enth
ae H
erba
; Lab
iata
e)
25-1
00 m
g/kg
, p.
o.A
lbin
o m
ice
SI
5α-r
educ
tase
in
hibi
tor,
invo
lvem
ent o
f ne
uros
tero
id
synt
hesi
s fo
llow
ed
by G
AB
A r
ecep
tor
stim
ulat
ion
Anx
ioly
tic[3
02]
40
Madaan, et. al.: Plant Drugs Used to Combat Menace of Anxiety DisordersTa
ble
2: C
on
tin
ued
S.
No
. F
orm
ula
tio
n/E
xtra
ct/F
ract
ion
/Iso
late
Do
seA
nim
al/H
um
an
bei
ng
sE
xper
imen
tal m
od
el/C
linic
al
stu
die
s p
aram
eter
sM
ech
anis
m o
f ac
tio
nA
ctiv
ity
Ref
.
14B
otan
ical
ext
ract
s
(a)
Aqu
eous
ext
ract
of
the
Rut
acea
e fa
mily
(b
) hy
dro-
alco
holic
ext
ract
of
Alc
hem
illa
eryt
hrop
oda
Juz.
(La
dies
Man
tle; R
osac
eae)
(a)
28 a
nd 5
6 m
g/kg
, i.p
. (b
) 12
.5 a
nd 2
5 m
g/kg
, i.p
.
Chi
ckC
hick
soc
ial s
epar
atio
n-st
ress
pr
oced
ure
—A
nxio
lytic
[303
]
(a)
Aq.
Ext
ract
of
Mel
issa
offi
cina
lis(b
) A
q. e
xtra
cts
of C
ente
lla a
siat
ica
and
Val
eria
na o
ffici
nalis
(c
) A
q. e
xtra
cts
of M
aric
aria
rec
utita
and
H
umul
us lu
pulu
s
(a)
IC50
– 0
.35
mg/
ml
(b)
1 m
g/m
l (c
) 0.
11-0
.65
mg/
ml
In v
itro
(a)
inhi
bit G
AB
A
tran
sam
inas
e (b
) st
imul
ate
glut
amic
aci
d de
carb
oxyl
ase
(c)
inhi
bit g
luta
mic
ac
id d
ecar
boxy
lase
Anx
ioly
tic[3
04]
15D
ieta
ry p
rodu
cts:
Die
tary
soy
ph
ytoe
stro
gens
Phy
to-
estr
ogen
rich
Phy
to-6
00 d
iet
Long
–Eva
ns
mal
es a
nd
fem
ales
rat
s
EP
M—
Anx
ioly
tic[3
05]
Tab
le 3
: Lis
t o
f an
xio
lyti
c p
aten
ted
form
ula
tio
ns.
S. N
o.
Co
mp
osi
tio
n o
f fo
rmu
lati
on
Act
ivit
yR
ef.
01L-
tryp
toph
an, l
inse
ed o
il, th
yme
oil,
aque
ous
extr
acts
of
St-
John
’s w
ort,
Are
naria
bl
osso
m, V
aler
ian,
Ele
cam
pane
Man
agem
ent o
f st
ress
incl
udin
g sl
eep
dist
urba
nces
, agg
resi
vene
ss,
inst
abili
ty o
f te
mpe
r an
d st
ate
of a
nxie
ty[3
06]
02T
hean
ine,
gre
en te
a, r
ed g
inse
ng, S
asam
orph
a pu
rpur
asce
ns e
xtra
cts
Man
agem
ent o
f an
xiet
y an
d st
ress
[307
]03
Wat
er, a
q.-a
lcoh
olic
and
CO
2 ex
trac
t of
Forg
et-m
e-no
t (M
yoso
tis)
Anx
ioly
tic, n
ootr
opic
, ant
icon
vuls
ant a
nd c
ereb
ropr
otec
tive
activ
ity[3
08]
04Ta
blet
, pill
or
gran
ule
com
pris
ing
Bup
leur
i Rad
ix, R
hizo
ma
Ane
mar
rhen
ae, s
apon
in
com
pone
nt is
olat
ed fr
om S
emen
Ziz
iphi
spi
nosa
eTr
eatm
ent o
f ac
ute
anxi
ety
(Pan
ic a
nxie
ty)
and
chro
nic
anxi
ety
(Gen
eral
ized
an
xiet
y)[3
09]
05E
xtra
cts
of p
lant
s co
ntai
ning
bet
ulin
ic a
cid
and
its d
eriv
ativ
esA
nxio
lytic
[310
]06
Cas
sia
tora
aq.
Ext
ract
Anx
ioly
tic[3
11]
07R
osam
arin
ic a
cid
isol
ated
from
Per
illa
extr
act
Ant
ianx
iety
and
ant
idep
ress
ant
[312
]08
Hyd
ro-a
lcoh
olic
ext
ract
of
Pip
er m
ethy
stic
um le
aves
Anx
ioly
tic, a
ntic
onvu
lsan
t, m
uscl
e re
laxa
nt, a
nalg
esic
, sle
ep in
duci
ng,
antii
nfla
mm
ator
y an
d ne
urop
rote
ctiv
e[3
13]
09H
omoe
opat
hic
com
plex
com
pris
ing
Aco
nite
, Ave
na s
ativ
a, P
assi
flora
inca
rnat
a,
Scu
tella
ria la
terif
olia
, Str
amon
ium
and
Val
eria
naA
ntia
nxie
ty[3
14]
10Ta
blet
, gra
nule
, cap
sule
s or
ora
l liq
uid
of m
etha
nol e
xtra
ct o
f R
umex
mad
aio
Ant
ianx
iety
[315
]11
Loze
nges
con
tain
ing
Citr
us p
ectin
, tris
odiu
m c
itrat
e, r
aw s
ugar
, wat
er, g
luco
se fr
ucto
se
syru
p, a
nd m
ixtu
re o
f la
vend
er o
il, e
xtra
cts
of M
elis
sa, h
op a
nd o
atA
ntia
nxie
ty[3
16]
12P
heno
lic c
ompo
unds
hav
ing
phen
olic
mol
ecul
e co
vale
ntly
link
ed a
n ox
ygen
con
tain
ing
grou
p, a
nito
gen
or a
noth
er o
xyge
n co
ntai
ng g
roup
and
C1-
C4
alko
xy g
roup
obt
aine
d fr
om m
onoc
otyl
edon
pla
nts
like
corn
Ant
ianx
iety
[317
]
41
Madaan, et. al.: Plant Drugs Used to Combat Menace of Anxiety DisordersTa
ble
4: L
ist
of
revi
ew a
rtic
les
pu
blis
hed
on
an
xio
lyti
c p
lan
ts, a
nd
th
eir
con
stit
uen
ts a
nd
form
ula
tio
ns.
S. N
o.
Info
rmat
ion
ava
ilab
leP
lan
t d
rug
sP
hyto
con
stit
uen
ts
rep
ort
edT
her
apeu
tic
acti
vity
re
po
rted
Mo
de
of
acti
on
rep
ort
edR
ef.
01P
harm
acol
ogic
al r
epor
tsV
aler
iana
offi
cina
lis, M
elis
sa
offic
inal
is, P
assi
flora
inca
rnat
a,
Hum
ulus
lupu
lus,
Lav
endu
la
offic
inal
is, P
iper
met
hyst
icum
, Tili
a pl
atyp
hyllo
s, L
eonu
rus
cord
iaca
, H
yper
icum
per
fora
tum
—A
nti-a
nxie
ty a
nd
antid
epre
ssan
t—
[318
]
02Tr
aditi
onal
use
s, c
hem
ical
co
nstit
uent
s, p
harm
acol
ogic
al r
epor
tsC
atha
edu
lis, C
ola
spec
ies,
Dat
ura
spec
ies,
Pau
siny
stal
ia y
ohim
be,
Tabe
rnan
the
ibog
a
—P
sych
oact
ive
—[3
19]
03P
harm
acol
ogic
al r
epor
ts(a
) E
phed
ra s
peci
es, P
aulli
nia
spec
ies,
Cat
ha e
dulis
(b)
Can
nabi
s sa
tiva,
Tab
erna
nthe
ib
oga,
Psy
chot
ria v
iridi
s,
Ban
iste
riops
is
(c)
Pas
siflo
ra in
carn
ata,
Val
eria
na,
Pip
er m
ethy
stic
um
—(a
) A
dapt
ogen
(b
) H
allu
cino
geni
c (c
) A
nalg
esic
and
an
xiol
yitc
—[3
20]
04C
linic
al r
epor
tsP
iper
met
hyst
icum
, Gin
kgo
bilo
ba,
Gal
phim
ia g
lauc
a, M
atric
aria
re
cutit
a, P
assi
flora
inca
rnat
a,
Val
eria
na o
ffici
nalis
—A
nxio
lytic
, Gen
eral
ized
an
xiet
y di
sord
ers
—[3
21]
05P
harm
acol
ogic
al r
epor
ts, M
ode
of
actio
nG
inkg
o bi
loba
, Hyp
eric
um
perfo
ratu
m, V
aler
iana
offi
cina
lis,
Pan
ax g
inse
ng
—A
nxio
lytic
Inte
ract
ion
with
rec
epto
rs o
f C
NS
(γ-
amin
obut
yric
aci
d,
glut
amat
e, d
opam
ine,
m
usca
rinic
and
ade
nosi
ne
rece
ptor
s)
[322
]
06P
harm
acol
ogic
al r
epor
tsK
ava,
Sku
llcap
, Lem
on b
alm
(M
elis
sa
offic
inal
is),
Val
eria
na o
ffici
nalis
, P
assi
flora
, Die
tary
sup
plem
ents
—A
nxio
lytic
—[3
23]
Pha
rmac
olog
ical
rep
orts
and
Clin
ical
re
port
sH
awth
orn
and
Cal
iforn
ia P
oppy
, Im
mat
ure
Oat
See
d, P
assi
onflo
wer
, Le
mon
balm
, Ver
vain
, Lav
ende
r an
d Li
nden
—N
ervi
ne, a
nxio
lytic
—[3
24]
07C
linic
al r
epor
tsP
iper
met
hyst
icum
, Bac
opa
mon
nier
a, K
ava
—A
nxio
lytic
—[3
25]
08P
hyto
cons
titue
nts,
Pha
rmac
olog
ical
re
port
s an
d M
echa
nism
of
actio
nH
erba
l dru
gs /
Her
bal c
onst
ituen
ts—
Psy
chia
tric
dis
orde
rs—
[326
]
09P
hyto
chem
ical
rep
orts
, P
harm
acol
ogic
al r
epor
tsB
razi
lian
plan
ts (
39-a
nxio
lytic
and
28
- hy
pnot
ic)
Fla
vono
ids,
ess
entia
l oi
ls, p
heno
lic a
cids
, al
kalo
ids
Anx
ioly
tic a
nd h
ypno
tic—
[327
]
10P
harm
acol
ogic
al r
epor
tsFo
ods
Anx
ioly
tic a
nd
antid
epre
ssan
t—
[328
]
42
Madaan, et. al.: Plant Drugs Used to Combat Menace of Anxiety DisordersTa
ble
4: C
on
tin
ued
S. N
o.
Info
rmat
ion
ava
ilab
leP
lan
t d
rug
sP
hyto
con
stit
uen
ts
rep
ort
edT
her
apeu
tic
acti
vity
re
po
rted
Mo
de
of
acti
on
rep
ort
edR
ef.
11P
hyto
chem
ical
rep
orts
, P
harm
acol
ogic
al r
epor
tsB
razi
lian
plan
ts(a
) F
lavo
noid
s (b
) A
lkal
oids
(c
) E
ssen
tial o
il (d
) Li
gnan
s (e
) Tan
nins
(f
) Trit
erpe
ne a
nd
sapo
nins
(a)
Ana
lges
ic, a
ntip
yret
ic,
antia
nxie
ty, h
ypno
tic
(b)
Hal
luci
noge
n,
stim
ulan
t (c
) A
ntip
yret
ic, a
ntia
nxie
ty
(d)
Hal
luci
noge
n (e
) A
ntia
nxie
ty
(f)
Hyp
notic
—[3
29]
12P
harm
acol
ogic
al r
epor
tsE
ight
y fiv
e he
rbal
dru
gs—
Anx
ioly
tic, a
ntid
epre
ssan
t, ne
urol
eptic
, ant
idem
entia
—[3
30]
13P
harm
acol
ogic
al r
epor
ts, M
ode
of
actio
nM
etha
nol e
xtra
cts
of tr
aditi
onal
pl
ants
—P
sych
othe
rape
utic
ac
tivity
In v
itro
radi
olig
and
rece
ptor
bi
ndin
g an
d en
zym
e as
says
su
ch a
s ac
etyl
chol
ine
este
rase
, cho
line
acet
yl
tran
sfer
ase,
mon
oam
ine
oxid
ase
A a
nd B
.
Sel
ectiv
ely
on G
AB
AA, N
MD
A
and
MA
O r
ecep
tors
[331
]
14P
harm
acol
ogic
al r
epor
ts, M
ode
of
actio
nE
than
ol e
xtra
cts
of 3
1 tr
aditi
onal
pl
ants
—A
nxio
lytic
and
an
tiepi
lept
icG
AB
AA –
BZ
D r
ecep
tor,
Inhi
bitio
n of
GA
BA
tr
ansa
min
ase
[332
]
15C
linic
al r
epor
tsN
atur
al r
emed
ies
such
as
St J
ohn’
s W
art,
Kav
a K
ava,
Pas
sion
flow
er,
Inos
itol,
Val
eria
n ro
ot, M
elat
onin
, O
meg
a-3-
fatty
aci
ds, s
-ade
nosy
l-L-
met
hion
ine
—A
nxio
lytic
—[3
33]
16P
harm
acol
ogic
al r
epor
ts(a
) K
ava
kava
roo
ts
(b)
Gin
kgo
extr
act
—(a
) A
nxio
lytic
(b
) N
ootr
opic
—[3
34]
17P
harm
acol
ogic
al r
epor
ts, C
linic
al
repo
rts
Hyp
eric
um p
erfo
ratu
m—
Ant
idep
ress
ant,
anxi
olyt
ic, n
ootr
opic
, se
dativ
e, a
nalg
esic
, an
ticon
vuls
ant,
antis
chiz
ophr
enic
, al
coho
l, ni
cotin
e an
d ca
ffein
e de
addi
ctio
n
—[3
35]
18E
ffic
acy,
Saf
ety
Pro
file,
P
harm
acol
ogic
al r
epor
tsK
ava
—A
nxio
lytic
—[3
36]
19S
afet
y pr
ofile
Kav
a—
Anx
ioly
tic—
[337
]
20C
linic
al r
epor
tsK
ava
—A
nxio
lytic
—[3
38-
341]
21P
harm
acol
ogic
al r
epor
ts, S
ide
effe
cts,
M
ode
of a
ctio
nK
ava
lact
ones
—(a
) A
nalg
esic
, ane
sthe
tic
(b)
Anx
ioly
tic
Sid
e ef
fect
s- S
kin
rash
an
d ka
va d
erm
opat
hy
(a)
Non
-opi
ate
path
way
(b
) G
AB
A r
ecep
tor
bind
ing
[342
]
43
Madaan, et. al.: Plant Drugs Used to Combat Menace of Anxiety Disorders22
Phy
toch
emic
al r
epor
ts,
Pha
rmac
olog
ical
rep
orts
Mat
ricar
ia r
ecut
itaF
lavo
noid
s, p
heno
lic
com
poun
ds, e
ssen
tial o
ilA
ntio
xida
nt, a
ntim
icro
bial
, an
tipla
tele
t, an
tiinf
lam
mat
ory,
antim
utag
enic
, an
tispa
smod
ic, a
nxio
lytic
, ch
oles
tero
l low
erin
g
—[3
43]
23P
harm
acol
ogic
al r
epor
tsZ
izyp
hus
juju
ba—
Anx
ioly
tic, s
edat
ive,
hy
pnot
ic, a
phro
disi
ac,
antic
ance
r, hy
pote
nsiv
e,
antii
nfla
mm
ator
y
—[3
44]
24P
hyto
cons
titue
nts,
Pha
rmac
olog
ical
re
port
s—
Alk
aloi
ds in
Sce
letiu
m
and
Mes
embr
yant
ham
acea
e
Nar
cotic
-anx
ioly
tic,
hallu
cino
geni
c—
[345
]
25P
hyto
cons
titue
nts,
Pha
rmac
olog
ical
re
port
s—
Can
nabi
noid
s, δ
9 -te
trah
ydro
cann
abin
ol,
cann
abid
iol
Sed
ativ
e, h
ypno
tic,
anxi
olyt
ic, a
ntid
epre
ssan
t, an
tipsy
chot
ic,
antic
onvu
lsan
t
—[3
46]
26P
hyto
cons
titue
nts,
Pha
rmac
olog
ical
re
port
s—
Fla
vono
ids
– ch
rysi
n,
apig
enin
and
se
mis
ynth
etic
de
rivat
ives
of
flavo
ne
Anx
ioly
tic—
[347
]
27P
hyto
cons
titue
nts,
Pha
rmac
olog
ical
re
port
s, M
ode
of a
ctio
n—
Fla
vono
ids
Anx
ioly
ticB
ZD
site
on
GA
BA
A[3
48]
28P
hyto
cons
titue
nts,
Pha
rmac
olog
ical
re
port
s—
Food
pro
tein
s –
δ-op
ioid
pe
ptid
es, g
lute
n,
exor
phin
s, r
ubis
colin
s
Ant
inoc
icep
tive,
mem
ory
enha
ncin
g, a
nxio
lytic
—[3
49]
29P
hyto
cons
titue
nts,
Pha
rmac
olog
ical
re
port
s, M
ode
of a
ctio
n—
Terp
enoi
ds:
Mon
oter
peno
ids
(lina
lool
, α-t
hujo
ne,
born
eol,
vale
potr
iate
s);
Ses
quite
rpen
oids
(v
aler
enic
aci
d,
arte
mis
inin
); D
iterp
enoi
ds
(gin
kgol
ides
, for
skol
in,
salv
inor
ine
A);
Trite
rpen
oids
(g
inse
nosi
des)
; M
erot
erpe
noid
s (c
anna
bino
ids)
Sed
ativ
e, a
nxio
lytic
, an
tinoc
icep
tive,
an
ticon
vuls
ant,
hallu
cino
geni
c
—[3
50]
30P
hyto
cons
titue
nts,
Pha
rmac
olog
ical
re
port
s, M
ode
of a
ctio
n—
Wog
onin
(F
lavo
noid
)A
nxio
lytic
B
ZD
bin
ding
site
of
GA
BA
A
and
mod
ulat
ion
of r
ecep
tor
activ
ity
[351
]
44
Madaan, et. al.: Plant Drugs Used to Combat Menace of Anxiety Disorders
(c) chemical constituents responsible for antianxiety activity have been reported in 53 plants and
(d) possible mechanism of action has been reported in 41 plants.
Seven formulations of plant drugs, 02 well known classes of phytoconstitunts and 03 pure constituents present in various plants, and nutraceuticals reported to possess antianxiety activity in battery of experimental models of anxiety have been compiled in present work (Table 2). Twelve anxiolytic formulations containing plants have been patented (Table 3). A survey of literature revealed that 30 review articles have been published on anxiolytic plant formulations and specific plant covering broad aspects as phytochemistry, pharmacology, clinical studies, toxicology and safety profiles (Table 4).
This review article would of immense help to natural product researchers to select traditionally used and clinically potential plants for their future research work.
AKNOWLEDGEMENT
Authors are grateful to Mr Rakesh Chawla, Lecturer, S.D. College of Pharmacy, Barnala for providing necessary full research articles for compilation of this review.
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46
Madaan, et. al.: Plant Drugs Used to Combat Menace of Anxiety Disorders
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ABBREVIATIONS
ADAA American Psychiatric AssociationAPA Anxiety Disorders Association of AmericaASI Anxiety Status InventoryBRC Baroreflex control of heart rateBZD BenzodiazepinesBoEAS Boerner Anxiety ScaleCNS Central nervous systemCGI Clinical Global ImpressiondlPAG Dorsolateral peri aqueductalECG ElectrocardiogramEEG ElectroencephalographicEPM Elevated plus mazeEZM Elevated zero mazeEAAS Erlanger Anxiety, Tension, Aggression ScaleFRA Federal Regulatory AuthoritiesFST Forced swimming testGABA Gamma-amino butyric acidGAD Generalized anxiety disorderGRAD Global Research on Anxiety and DepressionHAMA Hamilton Anxiety Scale
HBT Hole board testHADS Hospital Anxiety and Depression Scale5-HT1A 5-hydroxytryptamine 1Ai.p. IntraperitoneallyLDM Light / Dark modelMBT Marble burying testMAO Monoamine oxidaseNOS Nitric oxide synthaseOCD Obsessive–compulsive disorderOFT Open field testPD Panic disorderPTZ Pentylenetetrazolep.o. Per oralPTSD Post-traumatic stress disorderSARA Self Assessment of Resilience and AnxietySI Social interactionSAD Social phobia or Social anxiety disorderSP Specific phobias.c. SubcutaneouslyTDS Thrice daily