An overview on traditional uses and pharmacological profile of Acorus calamus Linn. (Sweet flag) and other Acorus species

Abstract

Acorus calamus (Sweet flag) has a long history of use and has numerous traditional and ethnomedicinal applications. Since ancient times, it has been used in various systems of medicines such as Ayurveda, Unani, Siddha, Chinese medicine, etc. for the treatment of various aliments like nervous disorders, appetite loss, bronchitis, chest pain, colic, cramps, diarrhea, digestive disorders, flatulence, gas, indigestion, rheumatism, sedative, cough, fever, bronchitis, inflammation, depression, tumors, hemorrhoids, skin diseases, numbness, general debility and vascular disorders. Various therapeutic potentials of this plant have been attributed to its rhizome. A number of active constituents from leaves, rhizomes and essential oils of A. calamus have been isolated and characterized. Of the constituents, alpha and beta-asarone are the predominant bioactive components. Various pharmacological activities of A. calamus rhizome such as sedative, CNS depressant, anticonvulsant, antispasmodic, cardiovascular, hypolipidemic, immunosuppressive, anti-inflammatory, cryoprotective, antioxidant, antidiarrheal, antimicrobial, anticancer and antidiabetic has been reported. Genotoxicity and mutagenecity of beta and alpha-asarone is reported, which limits their use at high dosage. Though A. calamus has been used since ancient times, many of its uses are yet to be scientifically validated. In the present review an attempt has been made to explore traditional uses and pharmacological properties of A. calamus.

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Phytomedicine
21
(2014)
268–276
Contents
lists
available
at
ScienceDirect
Phytomedicine
jou
rn
al
h
om
epage:
www.elsevier.de/phymed
Review
An
overview
on
traditional
uses
and
pharmacological
profile
of
Acorus
calamus
Linn.
(Sweet
flag)
and
other
Acorus
species
Sandeep
B.
Rajputa,
Madan
B.
Tongeb,
S.
Mohan
Karuppayila,∗
aDST-FIST
and
UGC-SAP
Sponsored
School
of
Life
Sciences,
SRTM
University,
Nanded
431-606,
MS,
India
bPrabhu
Ayurvedic
Clinic,
Nanded
431-606,
MS,
India
a
r
t
i
c
l
e
i
n
f
o
Article
history:
Received
10
June
2013
Received
in
revised
form
19
August
2013
Accepted
29
September
2013
Keywords:
Acorus
calamus
Sweet
flag
Pharmacological
properties
a
b
s
t
r
a
c
t
Acorus
calamus
(Sweet
flag)
has
a
long
history
of
use
and
has
numerous
traditional
and
ethnomedicinal
applications.
Since
ancient
times,
it
has
been
used
in
various
systems
of
medicines
such
as
Ayurveda,
Unani,
Siddha,
Chinese
medicine,
etc.
for
the
treatment
of
various
aliments
like
nervous
disorders,
appetite
loss,
bronchitis,
chest
pain,
colic,
cramps,
diarrhea,
digestive
disorders,
flatulence,
gas,
indi-
gestion,
rheumatism,
sedative,
cough,
fever,
bronchitis,
inflammation,
depression,
tumors,
hemorrhoids,
skin
diseases,
numbness,
general
debility
and
vascular
disorders.
Various
therapeutic
potentials
of
this
plant
have
been
attributed
to
its
rhizome.
A
number
of
active
constituents
from
leaves,
rhizomes
and
essential
oils
of
A.
calamus
have
been
isolated
and
characterized.
Of
the
constituents,
alpha
and
beta-
asarone
are
the
predominant
bioactive
components.
Various
pharmacological
activities
of
A.
calamus
rhizome
such
as
sedative,
CNS
depressant,
anticonvulsant,
antispasmodic,
cardiovascular,
hypolipidemic,
immunosuppressive,
anti-inflammatory,
cryoprotective,
antioxidant,
antidiarrheal,
antimicrobial,
anti-
cancer
and
antidiabetic
has
been
reported.
Genotoxicity
and
mutagenecity
of
beta
and
alpha-asarone
is
reported,
which
limits
their
use
at
high
dosage.
Though
A.
calamus
has
been
used
since
ancient
times,
many
of
its
uses
are
yet
to
be
scientifically
validated.
In
the
present
review
an
attempt
has
been
made
to
explore
traditional
uses
and
pharmacological
properties
of
A.
calamus.
©
2013
Elsevier
GmbH.
All
rights
reserved.
Contents
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Common
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269
Traditional
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269
Uses
in
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medicine
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269
Phytochemical
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Pharmacological
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bioactivity
studies
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Anti-inflammatory
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immunomodulatory
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Antioxidant
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272
Anti-diabetic
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Hypolipidemic
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Anticancer
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Antimicrobial
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273
Pesticidal
properties
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273
∗Corresponding
author.
Tel.:
+91
9028528438;
fax:
+91
2462
229245.
E-mail
address:
prof.karuppayil@gmail.com
(S.M.
Karuppayil).
0944-7113/$
–
see
front
matter
©
2013
Elsevier
GmbH.
All
rights
reserved.
http://dx.doi.org/10.1016/j.phymed.2013.09.020

Author's personal copy
S.B.
Rajput
et
al.
/
Phytomedicine
21
(2014)
268–276
269
Other
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273
Toxicity
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273
Acknowledgements
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References
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275
Introduction
Acorus
calamus
Linn.,
commonly
known
as
‘Sweet
flag’,
is
an
aro-
matic
medicinal
plant,
well
known
for
its
medicinal
values.
It
is
an
integral
part
of
the
traditional
Indian
and
Chinese
systems
of
medicine
and
has
a
long
history
of
use
(Wu
et
al.
2009;
Lee
et
al.
2011).
In
the
vedic
periods
it
was
used
as
a
‘rejuvenator’
of
the
brain
and
nervous
system.
Charaka
categorized
it
as
a
lekhaniya
(natural
substances
that
remove
fat
from
the
body),
trptighna
(anti-saturative),
asthapanopaga
(an
adjunct
to
decoction
enemas),
sitaprasamana
(relieves
cold
sensation
on
the
skin),
samjnastha-
pana
(restores
consciousness),
vayasthapana
(promotes
longevity),
arsoghna
(anti-hemorrhoidal)
and
sirovirecana
(cleansing
nasal
therapy)
(Sharma
2000).
It
is
widely
used
in
traditional
folk
medicine
of
America
and
Indonesia
for
gastrointestinal
disorders
such
as,
colic
pain,
diarrhea
and
in
the
therapy
of
diabetes
(Gilani
et
al.
2006;
Si
et
al.
2010).
It
is
also
used
in
the
treatment
of
cough,
fever,
bronchitis,
inflammation,
depression,
tumors,
hemorrhoids,
skin
diseases,
numbness,
general
debility,
as
antidotes
for
several
poisoning
(Nadkarni
1998;
Vaidyaratnam
1994).
This
plant
is
also
described
in
Siddha
medicine
for
its
pediatric
uses.
Paste
of
the
rhi-
zome
is
used
in
rural
areas
of
southern
India
to
improve
the
speech
and
to
memory
in
children
(Meena
et
al.
2010).
Habitat
and
habit
A.
calamus
is
a
native
of
central
Asia
and
eastern
Europe,
and
is
indigenous
to
the
marshes
of
the
mountains
of
India
(Gupta
1964).
It
is
cultivated
throughout
India,
ascending
to
an
altitude
of
about
2200
m.
It
is
found/cultivated
in
the
states
of
Jammu
Kash-
mir,
Himachal
Pradesh,
Manipur,
Naga
land,
Uttarakhand,
Uttar
Pradesh,
Tamil
Nadu,
Andhra
Pradesh,
Maharashtra
and
Karnataka
(Pawar
et
al.
2011;
Malabadi
et
al.
2007;
Rao
and
Sreeramulu
1985).
A.
calamus
is
a
semi-evergreen
perennial
hairless
herb
that
can
grow
to
two
meters
high.
It
has
a
creeping
rhizome.
It
is
extensively
branched
and
up
to
three
centimeter
in
diameter.
The
rhizome
is
pale
yellow
to
pinkish-brown
on
the
outside
and
whitish
but
some-
times
slightly
pinkish
on
the
inside.
The
upper
surface
is
marked
with
large
V-shaped
leaf-scars
and
longitudinally
furrowed.
The
surface
beneath
has
circular
pitted
scars
of
rootlets
arranged
in
irregular
lines.
Rhizome
sections
exhibit
a
large
stele
separated
by
a
yellowish
line,
the
endodermis
from
a
thick
cortex;
numer-
ous
small,
oval,
vascular
bundles
are
scattered
throughout
the
section.
Leaves
are
bright
green
having
sword-shaped,
based
equi-
tant,
thickened
in
middle
and
wavy
margins.
Flowers
of
A.
calamus
have
both
male
and
female
organs
(Hermaphrodite),
pollinated
by
insects
(Prajapati
et
al.
2003;
Nadkarni
1998;
Wallis
1997).
Common
names
English-Sweet
Flag.;
Chinese-Shi
chang
pu;
Arabic-vash,
vaj;
French-acore
calame;
German-Kalmus;
Italian-calamo
aromatic;
Dutch-kalmoeswortel;
Hindi-Bajai,
Gora-bach,
Vasa
Bach;
Marathi-Vekhand;
Tamil-Vashambu;
Telugu-Vadaja,
Vasa;
Kannada-Baje;
Malayalam-Vayambu;
Sanskrit-
Bhutanashini,
Jatila.
Vacha
(Seidmann,
2005).
In
sanskrit,
the
language
in
which
ayurveda
is
rendered,
a
num-
ber
of
synonyms
are
given
to
A.
calamus
(Table
1).
The
synonyms
give
clue
about
the
properties
of
this
drug.
Table
1
Synonyms
of
A.
calamus
in
Ayurveda.
Sanskrit
name
Meaning
Ugragandha
Aggressive
odor
Shadgrandha
Having
multiple
nodes
Golomi
Having
hairs
(as
on
a
cow)
Shatvarvika
Having
six
nodes
Lomasha
Having
hairs
on
nodes
Aruna
Reddish
brown
rhizomes
Ikshuparni
Leaves
resembles
sugarcane
leaves
Jatila
Hairy
rhizome
Taxonomy
(Seidemann,
2005)
Kingdom:
Plantae
Subkingdom:
Tracheobionta
(Vascular
plant)
Superdivision:
Spermatophyta
(Seed
plants)
Division:
Magnoliophyta
(Flowering
plants)
Class:
Liliopsida
(Monocotyledons)
Subclass:
Arecidae
Order:
Arales
Family:
Acoraceae
Genus:
Acorus
L.
Species:
calamus
Synonyms:
Acorus
asiaticus
Nakai;
Acorus
terrestris
Spreng.
The
genus
name,
Acorus
is
derived
from
Acoron
(coreon
=
the
pupil
of
the
eye)
and
the
species
calamus
is
derived
from
the
Greek
word,
Calamos
(a
reed).
The
family
Acoraceae
comprises
about
110
genera
and
more
than
1800
species.
The
members
of
the
family
are
rhizomatous
or
tuberous
herbs.
The
genus
Acorus
comprises
about
40
species,
however,
only
few
species
like
A.
calamus
(Linn.),
A.
christophii,
A.
tatarinowii
(Schott.)
and
A.
gramineus
(Solandin
Ait.)
have
been
investigated
for
their
chemical
composition
and
bioac-
tivities.
A.
calamus
is
extensively
studied
due
to
its
medicinal
and
pharmacological
significance
(Ganjewala
and
Srivastava
2011).
Traditional
uses
Uses
in
traditional
medicine
A.
calamus
rhizome
has
a
long
history
of
usage
in
many
countries:
at
least
2000
years
in
China
and
India.
Many
native
American
tribes
were
familiar
with
calamus
and
it
was
used
as
an
anesthetic
for
toothache
and
headaches.
The
ancient
Chinese
used
it
to
lessen
swelling
and
for
constipation.
The
rhizome
was
also
used
by
the
ancient
Greeks
and
included
in
the
traditional
remedies
of
many
other
European
cultures.
A.
calamus
is
used
for
the
treatment
of
various
ailments
like
appetite
loss,
bronchitis,
chest
pain,
colic,
cramps,
diarrhea,
digestive
disorders,
flatulence,
gas,
indigestion,
nervous
disor-
ders,
rheumatism,
sedative,
and
vascular
disorders
(Kirtikar
and
Basu
1987).
In
the
Ayurvedic
system
of
medicine,
the
rhizomes
of
A.
calamus
are
considered
to
possess
aromatic,
stimulant,
bit-
ter
tonic,
emetic,
expectorant,
emmenagogue,
aphrodisiac,
laxative,
diuretic,
antispasmodic,
carminative,
and
anthelmintic
properties.
It
is
found
to
be
effective
in
various
disorders
like
chronic
diarrhea,
dysentery,
bronchial
catarrh,
intermittent
fevers,
tympanitis,
colic,
otitis
media,
cough,
asthma,
and
glandular
and
abdominal
tumors
(Anonymous
2001).
In
Western
herbal
medicine
the
herb
is
chiefly
employed
for
digestive
problems
such
as
gas,
bloating,
colic,
and
poor
digestive
function.
Calamus
helps
distended
and
uncomfortable
stomachs

Author's personal copy
270
S.B.
Rajput
et
al.
/
Phytomedicine
21
(2014)
268–276
and
headaches
associated
with
weak
digestion.
Small
amounts
are
thought
to
reduce
stomach
acidity,
while
larger
doses
increase
deficient
acid
production.
They
are
also
employed
for
kidney
and
liver
troubles,
rheumatism,
and
eczema.
In
acidity,
it
is
taken
with
honey
and
jaggary.
In
indigestion,
vacha
is
taken
with
salt
and
water
leads
to
emesis
(Bangasen
1984).
In
Vamana
therapy,
it
is
used
as
emetic
(Vantikrut)
while
in
dyspepsia,
it
is
employed
as
an
appetizer
(Vanhikrut)
(Chunekar
and
Pandey
1998).
It
is
widely
used
as
a
carminative
(Vibandhanhara,
Adhmanahara)
in
distension.
It
exerts
antispasmodic
(Shulaghni)
effect
by
relieving
abdominal
pain.
It
removes
stools
(i.e.
Shukrut
Vishodhini)
from
body
as
well
as
improves
its
quality.
It
is
also
employed
as
mild
diuretic
(Mutravishodhini)
which
improves
quality
of
urine.
Vacha
in
combination
with
milk
and
water
is
useful
in
obstructive
uri-
nary
disorders
particularly
in
distended
urinary
bladder
(Bangasen
1984).
The
decoction
or
powder
of
rhizome
has
been
given
in
var-
ious
pediatric
aliments
like
cough,
fever,
abdominal
pain,
epilepsy
etc.
(Ignacimuthu
et
al.
2006;
Chellaiah
et
al.
2006).
A.
calamus
rhizomes
are
used
for
the
treatment
of
host
dis-
eases
such
as
mental
ailments
like
schizophrenia,
psychoneurosis,
insomnia,
hysteria,
epilepsy
and
loss
of
memory
in
the
Indian
ayurvedic
system
of
medicine
(Prajapati
et
al.
2003;
Nadkarni
1998).
Vacha
taken
with
milk
for
one
month
improves
‘pragnya’
and
‘shrutidharana’
i.e.
intellectual,
grasping
and
memory
(Shah
2005).
Traditionally
the
new
born
child
is
given
vasambu
(rhizome
paste)
with
honey
and
gold
for
proper
brain
development,
speech
ability,
better
visual
power,
increased
seminal
power.
It
stimulates
ner-
vous
system
(i.e.
vatanadi
sasthana)
to
get
relief
from
depression.
It
is
useful
in
improving
speech
in
stammering
and
other
disorders.
After
birth
its
paste
is
applied
on
tongue
with
ghee,
gold
and
water
to
improve
memory
and
grasping
qualities
(Jadhav
1994).
It
is
a
good
sedative
so
that
the
extract
is
used
for
epilepsy,
insanity
and
as
a
tranquillizer
along
with
Valeriana
jatamansi
and
Nardostacys
gran-
diflora.
It
is
an
ingredient
of
the
ayurvedic
preparation
“Brahmi
Bati”
(Budhivardhar)
which
is
indicated
in
epilepsy,
coma,
and
hysteria
and
in
cases
of
mental
retardation;
the
same
uses
are
prescribed
for
an
Acorus
containing
Unani
drug
“Ma’jun
Baladur”.
In
headache,
drowsiness,
sinusitis,
more
sleepy
feelings
the
‘Pradhaman
nasya’
i.e.
its
dry
powder
is
inhaled
in
nostrils
(Jadhav
1994).
A.
calamus
rhizomes
are
found
to
be
very
useful
as
a
topical
agent
in
skin
related
problems.
The
rhizomes
are
used
in
the
form
of
pow-
der,
balms,
enemas,
and
pills
and
also
in
ghee
preparations
(Kirtikar
and
Basu
1987;
Anonymous
2001).
A
tub
bath
in
the
decoction
of
vacha,
kustha
(Savccera
lappa)
and
vidanga
(Embelina
ribes)
is
use-
ful
in
eczema
and
other
skin
diseases.
It
acts
as
‘sagnyasthapaka’
i.e.
it
restores
sensation
useful
in
various
comatose
conditions.
Its
pow-
der
is
sprinkled
on
infective
and
wounds
with
maggots.
On
baby’s
head
it
is
applied
in
powder
form
after
bath
for
protecting
from
cold.
After
bath
its
powder
is
applied
to
body
like
talcum
powder
(Kirtikar
and
Basu
1987).
The
skin
of
the
rhizomes
is
said
to
be
haemostatic.
In
hemor-
rhoids,
its
fumes
are
given
to
pile
masses
to
reduce
swelling
and
pain.
In
the
treatment
of
hemorrhoids,
non-bleeding
hemorrhoids
are
fomented
with
Poltice
(Lukeworm)
of
vacha
and
Antheum
sowa
(Shatapushpa).
Its
application
with
mustard
seeds
paste
is
use-
ful
in
hydrocele.
In
earache
and
tinnitus,
vacha
swarasa
(juice)
is
poured
in
ear.
Vacha
is
prescribed
as
‘Vedanasthapalea’
(analgesic)
in
arthritis,
rheumatoid
arthritis,
inflammatory
conditions
as
exter-
nal
application
in
the
form
of
paste
(Lepa)
(Shastri
and
Pandey
1997).
In
Ayurveda,
A.
calamus
is
described
as
‘Lekhana’
(lipid
lowering
action)
(Table
2).
The
decoction
of
Vacha
and
Nimba
(Azadirecta
indica)
is
given
for
emesis
in
cardiac
disease.
It
has
lipid
scavenging
property
that
removes
excessive
fats
from
the
body.
Sometimes
it
is
also
prescribed
along
with
honey,
hot
water
and
ava
(Barley)
in
cardiac
diseases
(Bangasen
1984).
Table
2
Ayurvedic
terms
indicating
properties
of
Acorus
calamus.
Ayurvedic
term
Use/properties
Vantikrut
Induces
vomiting
in
Vamana
therapy
(a
therapy
where
the
patient
is
made
to
vomit)
Vanhikrut
Used
as
appetizer
in
dyspepsia
Vibandhhara
or
Adhanahara
Carminative
Shulaghni
Antispasmodic
(relieves
abdominal
pain)
Shakrut
vishodhini
Removes
stool
from
body
Mathrushodihni
Act
as
a
diuretic
Bhodhaneeya
Arousing
consciousness
Karshini
Reduces
body
weight
Rokshoghni
Checks
or
destroys
the
organisms
Bhutaharet/Jantuharet
Antimicrobial
or
antihelminthic
properties
Anilhara
or
Vatanasaka
Anti-inflammatory,
analgesic,
pain
reducing
Vednasthapaka
Analgesic,
anti-inflammatory,
arthritis
Lekhana
Lipid
lowering
Swaralu
Improving
speech
or
voice
Smarani
Memory
promoter
Shleshmaghni
Pacifies
kapha
Vijaya
Victory
over
diseases
Mangalya
Helps
to
keep
healthy
Phytochemical
studies
A
wide
variety
of
chemical
constituents
have
been
reported
from
the
rhizomes,
leaves
and
essential
oil
of
Acorus
calamus
(Namba
1993;
Wang
et
al.
1998).
The
content
and
composition
of
chem-
ical
constituents
in
plant
parts
vary
with
geographical
condition,
plant
age,
climate
and
ploidy
of
the
plant
(Venakutonis
and
Dagilyte
2003).
According
to
Ogra
et
al.
(2009)
and
Zhang
(2005)
the
dif-
ferent
Acorus
species
appear
to
follow
a
geographical
pattern
of
distribution
with
respect
to
ploidy
level.
A
total
of
fifty
three
organic
volatile
compounds
of
rhizomes
of
Nepalese
Acorus
calamus
L
were
isolated
and
identified,
which
belongs
to
alcohol
(11),
aldehyde
(14),
ester
(3),
furan
(1),
hydro-
carbon
(19),
ketone
(4),
N-containing
miscellaneous
(1).
␤-Asarone
(46.78%)
was
found
to
be
a
major
bioactive
compound
(Gyawali
and
Kim
2009).
At
least
one
hundred
and
eighty
five
compounds
in
the
oil
of
the
triploid
European
A.
calamus
var.
calamus,
and
ninety-three
com-
pounds
in
the
oil
of
the
tetraploid
Indian
A.
calamus
var.
angustatus
with
f-asarone
as
the
major
constituent
is
reported.
Sixty-seven
hydrocarbons,
fifty
three
carbonyl
compounds,
fifty
six
alcohols,
eight
phenols,
two
furans
and
four
oxido
compounds
were
detected
in
an
alcohol
extract
of
A.
calamus
var.
calamus
(Motley
et
al.,
1994).
The
content
of
␤-asarone
in
essential
oil
of
Acorus
spp.
varies
with
the
grade
of
polyploidy
of
the
various
Acorus
cytotypes,
sub
varieties
and/or
species.
␤-Asarone
(90–96%)
is
abundantly
found
in
tetraploid
variety.
In
A.
calamus
var,
angustata
ENGER
(tetraploid),
about
80%
␤-asarone
is
reported.
In
triploid
plants
(e.g.
A.
calamus
var.
calamus
L.),
5%
␤-asarone
was
present
in
the
oil,
while
diploid
plants
such
as
A.
calamus
var.
americanus
WULFF
lacked
␤-asarone,
but
it
has
high
amount
of
geranyl
acetate
(Wagner
et
al.
2011).
In
the
rhizomes
of
some
Chinese
Acorus
tatarinowii
samples,
formerly
known
as
Acorus
gramineus,
an
uncommonly
high
amount
of
␤-asarone
(up
to
80%)
were
detected
(Wagner
and
Urlich-Merzenich
2013).
The
percentage
of
chemical
components
varies
depending
on
the
part
of
the
plant
from
which
the
oil
is
extracted
(Motley
1994).
␤-Asarone
[(Z)-asarone]
is
the
major
constituent
in
the
leaves
(27.4–45.5%),
whereas
acorenone
is
dominant
in
the
rhizomes
(20.86%)
followed
by
isocalamen-
diol
(12.75%).
Monoterpene
hydrocarbons,
sequestrine
ketones,
(trans-
or
Alpha)
Asarone
(2,4,5-trimethoxy-1-propenylbenzene),
and
beta-asarone
(cis-isomer)
and
eugenol
were
also
identified
(Balakumbahan
et
al.
2010;
Raja
et
al.
2009).
Other
constituents

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271
such
as
alkaloids,
flavanoids,
gums,
lectins
mucilage,
phenols,
qui-
nine,
saponins,
sugars,
tannins
and
triterpenes
are
also
recorded
from
this
plant.
Various
sugars
such
as
maltose
(0.2%),
glucose
(20.7%)
and
fructose
(79.1%)
are
reported
(Balakumbahan
et
al.
2010).
Calamenone
(a
tricyclic
sesquiterpene)
as
well
as
calamen-
diol
and
isocalamendiol
(both
sesquiterpenes)
occur
in
the
roots.
The
volatile
oil
also
contains
terpenoids
like
calamine,
calamenol,
calamenone,
eugenol,
camphene,
pinene
and
asaronaldehyde.
Aco-
rafuran
is
a
sesquiterpenoid
found
in
Calamus
oil
(Pandy
et
al.
2009).
␤-Asarone,
geranylacetate,
methyleugenol,
cis-
methylisoeugenol,
␤-farnesene,
shyobunone,
epishyobunone
and
isoshyobunone
are
abundantly
present
in
the
essential
oil.
The
other
chemical
components
include
␣-
and
␥-asarone,
calamenene,
asaronaldehyde,
acorenone,
calamenone,
n-heptanic
acid,
calamendiol,
numerous
sesquiterpenes,
tannins,
starches,
mucin,
soft
gums
and
resins
(Motley
et
al.,
1994).
Other
compounds
identified
in
A.
calamus
were
4-terpineol,
2-allyl-5-ethoxy-4-methoxyphenol,
epieudesmin,
lysidine,
spathulenol,
borneol,
furylethyl
ketone,
nonanoic
acid,
2,2,5,5-
tetramethyl-3-hexanol,
bornyl
acetate,
galgravin,
retusin,
(9E,12E,15E)-9,12,15-octadecatrien-1-ol,
butyl
butanoate,
geranyl
acetate,
sakuranin,
acetic
acid,
camphor,
isoelemicin,
a-ursolic
acid,
acetophenone,
dehydroabietic
acid,
isoeugenol
methylether,
apigenin
4,7-dimethyl
ether,
dehydrodiisoeugenol,
linalool,
elemicin,
linolenic
acid
(Balakumbahan
et
al.
2010).
Pharmacological
and
bioactivity
studies
Rhizomes
and
its
essential
oils
possess
important
bioactivi-
ties
such
as
immunomodulatory
and
anticellular
(Jayaraman
et
al.
2010;
Mehrotra
et
al.
2003;
Kim
et
al.
2009;
Lad
et
al.
2010),
antidi-
abetic
(Wu
et
al.
2009;
Lee
et
al.
2011;
Lee
et
al.
2010;
Si
et
al.
2010),
antitumor/anticancer
(Gaidhani
et
al.
2009;
Chaitali
et
al.
2010)
and
antimicrobial
properties
(MacGaw
et
al.
2002;
Phongpaichit
et
al.
2005;
Devi
and
Ganjewala
2009).
Anti-inflammatory
and
immunomodulatory
activity
Several
studies
have
recognized
the
anti-inflammatory
poten-
tial
of
A.
calamus.
The
anti-inflammatory
activity
of
A.
calamus
in
rats
using
acute
and
chronic
experimental
models
is
evaluated.
The
oral
administration
of
the
extract
showed
inhibition
of
the
carragenin-induced
paw
edema,
inhibition
of
cotton
pellet
gran-
uloma
formation,
and
inhibition
of
croton
oil
granuloma
pouch
inflammatory
response.
The
rhizomes
extract
showed
significant
anti-inflammatory
effect
in
acute,
chronic,
and
immunologic
mod-
els
of
inflammation
(Varde
et
al.
1988;
Vohra
et
al.
1989).
In
another
study
anti-inflammatory
activity
of
A.
calamus
leaf
extract
have
been
elucidated
using
human
keratinocyte
HaCaT
cells.
The
extract
inhibited
production
of
pro-inflammatory
cytokines
through
mul-
tiple
mechanisms
(Kim
et
al.
2009).
Acetone
extract
of
A.
calamus
displayed
anti-inflammatory
response
in
albino
rat,
where,
inflam-
matory
effect
was
completely
diminished
and
the
normal
status
of
paw
was
achieved
when
25–75%
acetone
extract
was
tested
against
inflammation
within
30
min
(Lad
et
al.
2010).
Mehrotra
et
al.
(2003)
demonstrated
immunomodulatory
prop-
erties
of
ethanolic
extract
of
A.
calamus
rhizome.
The
extract
inhibited
proliferation
of
mitogen
(phytohaemagglutinin;
PHA)
and
antigen
(purified
protein
derivative;
PPD)-stimulated
human
peripheral
blood
mononuclear
cells
(PBMCs),
nitric
oxide
and
interleukins-2
production.
Antioxidant
and
protective
effects
Several
researchers
have
evaluated
antioxidant
potential
of
Acorus
spp.
and
validated
its
protective
roles
in
free
radical
and
reactive
oxygen
species
(ROS)
generated
disorders.
The
ethyl
acetate
extract
of
A.
calamus
exhibited
strong
antioxidant
effect
by
inhibiting
1,1-diphenyl-2-picrylhydrazyl
(DPPH)
free
radical
(Acuna
et
al.
2002).
In
another
in
vitro
experiment,
maximum
DPPH
scavenging
activity
of
86.43%
was
recorded
at
0.2
g/ml
of
extract
(Govindarajan
et
al.
2003).
The
free
radical
scavenging
activity
of
A.
calamus
has
been
found
to
be
useful
to
overcome
excess
produc-
tion
of
ROS
generated
due
to
continuous
exposure
to
loud
noise
(Manikandan
and
Devi
2005).
The
ethyl
acetate
and
methanolic
extracts
of
A.
calamus
have
protected
most
of
the
changes
induced
by
noise
stress
in
the
rat
brain.
These
changes
were
evaluated
by
measurement
of
the
activities
of
superoxide
dismutase,
cata-
lase,
glutathione
peroxidase,
levels
of
reduced
glutathione,
level
of
vitamin
C,
E,
protein
thiols
and
lipid
peroxidation.
␤-Asarone
is
believed
to
be
involved
in
reducing
the
stress
(Manikandan
and
Devi
2005).
In
another
study,
the
antioxidant
property
of
␣-asarone
was
demonstrated
against
noise-stress-induced
changes
in
the
rat
brain.
In
this
study,
a-asarone
was
administered
intra-peritoneally
one-half
hour
before
the
animals
were
exposed
to
noise-stress
for
30
days.
The
antioxidant
activity
was
measured
by
assessing
the
activity
of
superoxide
dismutase
(SOD),
catalase
(CAT),
glutathione
peroxidase
(GPx),
levels
of
reduced
glutathione
(GSH),
vitamin
C,
vitamin
E,
protein
thiols
and
lipid
peroxidation
(LPO)
in
different
regions
of
the
rat
brain.
␣-Asarone
exhibited
protective
effect
by
normalizing
the
increased
SOD
and
LPO,
and
decreasing
CAT,
GPx,
GSH,
vitamins
C
and
E,
and
protein
thiols
(Manikandan
and
Devi
2005).
Palani
et
al.
(2010)
studied
the
antioxidant
activities
of
etha-
nolic
extract
of
A.
calamus
on
acetaminophen
induced
toxicity
in
male
albino
rats.
Acetaminophen
increased
the
level
of
hemoglobin,
total
leukocyte
count,
packed
cell
volume,
differential
leukocyte
count
(DLC),
mean
corpuscular
volume,
granulocytes,
raised
body
weight,
uric
acid
and
platelet
concentration.
A.
calamus
extract
sig-
nificantly
increased
activities
of
the
renal
superoxide
dismutase,
glutathione
peroxidase,
catalase
and
decreased
the
level
of
monodi-
aldehyde
content
of
acetaminophen-treated
rats.
A.
calamus
extract
inhibited
hemolysis
caused
by
acetaminophen.
Histopathologi-
cal
studies
showed
the
protective
nature
of
the
ethanolic
extract
against
acetaminophen
induced
necrosis
and
renal
damage
in
rats
(Palani
et
al.
2010).
A.
calamus
rhizome
and
leaves
are
traditionally
used
for
the
treatment
of
various
neurological
disorders
due
to
its
neuro-
protective
properties.
Hydro-alcoholic
extract
of
A.
calamus
has
demonstrated
neuroprotective
effects
in
the
middle
cerebral
artery
occlusion-induced
ischemia
in
rats
(Shukla
et
al.
2006).
␣
and
␤-
Asarone
inhibited
N-Methyl-d-Aspartate
(NMDA)
and
glutamate
induced
excitotoxicity
in
primary
cortical
cultures
(Cho
et
al.
2002).
Studies
by
Sandeep
and
Nair
(2010)
have
demonstrated
in
vitro
radio-protective
effects
of
A.
calamus.
The
protective
effects
were
evaluated
by
measuring
the
degree
of
lipid
peroxidation.
In
vitro
DNA
damage
was
measured
by
assessing
the
radiation
induced
relaxation
of
supercoiled
plasmid
DNA
(pBR322)
and
alkaline
sin-
gle
cell
gel
electrophoresis
or
comet
assay
was
used
to
analyze
any
damage
to
cellular
DNA.
The
free
radical
scavenging
property
of
A.
calamus
safeguarded
DNA
and
membrane
damage
caused
due
to
␥-
radiations
in
murine
cells
and
human
peripheral
blood
leukocytes.
Anticonvulsant
and
antispasmodic
activity
The
anticonvulsant
effect
against
the
pain
models
in
mice
was
observed
when
methanol
extract
of
A.
calamus
was
administered
orally
at
the
doses
of
the
100
and
200
mg/kg.
The
anticonvulsant

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effect
was
studied
through
the
Pentylenetetrazol-induced
seizures
method.
This
study
suggested
that
the
anticonvulsant
effects
might
be
potentiated
by
the
activity
of
gamma
aminobutyric
acid
(GABA)
(Jayaraman
et
al.
2010).
Calamus
oil
has
also
been
reported
for
its
antiepileptic
property
in
adult
albino
mice,
where
it
successfully
prevented
seizures
in
maximal
electroshock
seizure
test
(Khare
and
Sharma
1982).
␣-Asarone
has
shown
a
tendency
to
protect
against
metrazole
mediated
convulsions
(Sharma
et
al.
1961).
In
another
study,
A.
calamus
crude
extract
was
found
to
display
anti-spasmodic
activity.
In
the
isolated
rabbit
jejunum
preparation,
the
crude
extract
of
A.
calamus
caused
inhibition
of
spontaneous
and
high
K+(80
mM)-induced
contractions,
with
EC50 values
of
0.42
and
0.13
mg/ml
respectively,
resulting
in
spasmolytic
activity
which
is
mediated
through
the
calcium
channel
blockade
(CCB).
Results
of
the
study
suggest
that
the
spasmolytic
effect
of
the
plant
extract
is
mediated
through
the
presence
of
CCB-like
constituent(s),
which
is
concentrated
in
the
n-hexane
fraction,
and
this
study
provides
a
strong
mechanistic
base
for
its
traditional
use
in
gastrointesti-
nal
disorders
such
as
colic
pain
and
diarrhea.
Additionally,
the
methanolic
extract
of
A.
calamus
exhibited
anti-diarrheal
poten-
tial
against
castor
oil-induced
diarrhea.
The
extract
significantly
reduced
induction
time
of
diarrhea
and
total
weight
of
the
feces
(Shoba
and
Thomas
2001).
The
essential
oil
was
found
to
be
more
antispasmodic
than
the
alcohol
and
aqueous
extracts
(Bose
et
al.
1960).
Further,
it
was
observed
that
␣-asarone
is
more
active
than
that
of
essential
oil
(Das
et
al.
1962).
Actions
on
cardiovascular
system
(CVS)
A.
calamus
extract
has
been
reported
for
its
properties
of
low-
ering
blood
pressure
and
vascular
modulation
(Shaha
and
Gilani
2010).
The
essential
oil
was
found
to
combat
auricular
fibrilla-
tion,
auricular
flutter,
and
ventricular
arrhythmias
after
two-stage
coronary
ligation
in
dogs.
It
prolonged
the
conduction
time
and
refractory
period
in
isolated
rabbit
auricles
(Madan
et
al.
1960).
The
alcoholic
extract
of
A.
calamus
exhibited
a
dose
dependant
hypoten-
sive
action
on
blood
pressure
of
dog
(Moholkar
et
al.
1975).
In
a
clinical
study
on
forty-five
patients
of
ischemic
heart
disease,
the
health
of
A.
calamus-treated
group
was
found
to
be
significantly
improved.
A.
calamus
was
effective
in
the
improvement
of
chest
pain,
dyspnea
of
effort,
reduction
of
body
weight
index,
improving
ECG,
decreasing
serum
cholesterol
and
serum
low-density
lipopro-
tein
(SLDL),
and
increasing
serum
high-density
lipoproteins
(SHDL)
(Mamgain
and
Singh
1994).
Actions
on
respiratory
system
A.
calamus
has
been
found
to
be
a
famous
remedy
for
the
respi-
ratory
disorders
due
to
the
unique
combination
of
airways
relaxant
constituents
that
were
found
in
the
crude
extract
of
A.
calamus
such
as
papaverine-like
dual
inhibitor
of
calcium
channels
and
phospho-
diesterase
in
the
hexane
fraction
and
anticholinergic,
rolipram-like
phosphodiesterase-4
inhibitor
in
the
ethyl
acetate
fraction.
The
associated
cardiac
depressant
effect
has
provided
a
pharmacolog-
ical
basis
for
the
traditional
use
of
A.
calamus
in
the
treatment
of
the
disorders
of
airways
such
as
asthma
(Jabbar
and
Hassan
2010;
Shaha
and
Gilani
2010).
In
a
clinical
trial
of
patients
with
moderate
to
severe
bronchial
asthma,
the
fresh
rhizome
of
A.
calamus
was
administered
by
a
chewing
method
for
2–4
weeks.
The
A.
calamus
was
found
to
have
antiasthmatic
potential
without
any
side
effects
(Rajasekharan
and
Srivastava
1977).
In
another
study,
small
pieces
of
the
rhizome
were
administered
to
asthmatic
patients
by
a
chewing
method,
and
sig-
nificant
effect
in
relieving
of
bronchospasm
was
observed
without
any
side
effects
(Chandra
1980).
Actions
on
nervous
system
The
in
vitro
acetyl
cholinesterase
(AChE)
inhibitory
potential
of
the
hydroalcoholic
extract
and
of
the
essential
oil
from
A.
calamus
rhizomes
and
that
of
its
major
constituents
was
eval-
uated
based
on
Ellman’s
method
in
96-well
microplates
using
bovine
erythrocytes.
The
IC50 values
obtained
for
the
hydroal-
coholic
extract,
the
essential
oil,
beta-asarone
and
alpha-asarone
were
182.31
±
16.78
␮g/ml,
10.67
±
0.81
␮g/ml,
3.33
±
0.02
␮M
and
46.38
±
2.69
␮M,
respectively.
The
A.
calamus
essential
oil
and
its
constituents
exhibited
significant
AChE
inhibitory
potential.
␤-
Asarone
showed
the
maximum
inhibitory
potential
(Mukherjee
et
al.
2007).
Methanolic
extract
of
A.
calamus
displayed
signifi-
cant
AChE
inhibition
at
a
concentration
200
␮g/ml
(Oh
et
al.
2004).
Because
cognitive
performance
and
memory
are
related
to
acetyl
choline
levels,
the
AChE-inhibitory
effect
of
the
plant
may
account
for
its
traditional
use.
A.
calamus
is
well-known
traditionally
for
its
sedative
proper-
ties.
The
volatile
fraction
of
the
petroleum
ether
extract
potentiated
the
sedative
activity
with
pentobarbital,
hexobarbital,
and
ethanol
in
mice
(Dandiya
and
Cullumbine
1959).
The
essential
oil
showed
sedative-tranquilizing
action
in
rats,
mice,
dogs,
and
enhanced
motor
activities
in
mice.
It
was
observed
that
a
high
dose
of
oil
inhibited
monoamine
oxidase
activity
(Dhalla
and
Bhattacharya
1968).
Anti-diabetic
properties
A.
calamus
extract
has
the
potential
to
be
used
in
the
treatment
of
diabetes
(Wu
et
al.
2009).
Ethanol
extract
of
A.
calamus
has
been
reported
to
enhance
differentiation
in
adipocytes
which
is
very
use-
ful
in
the
treatment
of
type
2
diabetes.
However,
␤-asarone
from
essential
oil
of
A.
calamus
has
shown
inhibitory
effect
on
adipo-
genesis
in
3T3-L1
cells.
It
has
been
suggested
that
␤-asarone
might
have
suppressed
the
expression
of
adipogenic
transcription
fac-
tors
(Lee
et
al.
2011).
In
earlier
study,
the
same
group
has
reported
that
asarones
inhibit
adipogenesis
and
may
reduce
intracellular
triglyceride
levels
by
stimulating
the
phosphorylation
of
hormone
sensitive
lipase
which
triggers
lipolysis
in
3T3-L1
adipocytes
(Lee
et
al.
2010).
A.
calamus
extract
has
also
been
reported
to
cause
suppression
of
blood
glucose
level
in
the
normal
mice.
A.
calamus
extract
had
hypoglycemic
effects
and
alpha
glucosidase
inhibition
and
improved
the
postprandial
hyperglycemia
and
cardiovascular
complications
(Si
et
al.
2010).
Hypolipidemic
properties
A.
calamus
extract
demonstrated
its
cholesterol-reducing
effect
by
decreasing
cholesterol
biosynthesis
in
the
liver
(D’Souza
et
al.
2007).
The
alcoholic
extract
of
A.
calamus
containing
saponins,
prevent
the
cholesterol
absorption
and
interferes
with
its
entero-
hepatic
circulation
and
also
increase
its
fecal
excretion
(Parab
and
Mengi
2002).
The
hypolipidemic
mechanism
of
action
of
␣-asarone
has
been
established
in
a
rat
model
where
it
is
shown
to
inhibit
hepatic
HMG-CoA
reductase
(Rodriguez-Paez
et
al.
2003).
In
silico
studies
have
revealed
that
␣-asarone
binds
to
the
active
site
of
HMG-CoA
reductase.
The
methoxy
groups
play
a
key
role
in
the
binding
and
probably
also
in
its
biological
activity,
as
shown
by
extensive
SAR
studies
reported
for
analogs
of
␣-asarone
(Medina-Franco
et
al.
2005).
Anticancer
properties
A.
calamus
rhizomes
have
been
reported
to
have
promising
antiproliferative
activities
(Gaidhani
et
al.
2009;
Chaitali
et
al.

Author's personal copy
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al.
/
Phytomedicine
21
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273
2010).
Lectins
derived
from
A.
calamus
rhizomes
shows
potent
antimitogenic
activity
toward
mouse
splenocytes
and
human
lym-
phocytes.
These
lectins
also
significantly
inhibited
the
growth
of
J774,
a
murine
macrophage
cancer
cell
line
and,
to
a
lesser
extent,
WEHI-279,
a
B-cell
lymphoma
cell
line
(Bains
et
al.
2005).
The
eth-
anolic
extract
of
A.
calamus
exhibited
in
vitro
anticellular
property
by
inhibiting
production
of
nitric
oxide,
interleukin-2,
and
tumor
necrosis
factor-␣
(Mehrotra
et
al.
2003).
Epieudesmin
and
galgravin
from
methanolic
extracts
of
A.
cala-
mus
leaves
have
been
identified
as
anticancer
agents.
Epieudesmin
have
antineoplastic
activity
against
the
murine
P388
lymphocytic
leukemia
cell
line
and
several
human
cancer
cell
lines
(BXPC-3,
MCF-7,
SF268,
NCI-H460,
KM20L2,
and
DU-145).
Galgravin
pre-
vented
neuronal
death
and
stimulating
neurite
growth.
Studies
have
also
suggested
that
the
anticancer
activity
of
calamus
oil
may
be
attributed
to
␤-asarone
(Palani
et
al.
2010).
Antimicrobial
properties
Phongpaichit
et
al.
(2005)
reports
promising
antifungal
activity
of
A.
calamus
extracts
against
Trichophyton
rubrum,
Microsporum
gypseum
and
Penicillium
marneffei
with
IC50 values
of
0.2,
0.2
and
0.4
mg/ml,
respectively.
However,
it
showed
moderate
activ-
ity
against
yeasts:
Candida
albicans,
Cryptococcus
neoformans
and
Saccharomyces
cerevisiae
(MIC
0.1–1
mg/ml).
Scanning
electron
microscopic
studies
revealed
that
hyphae
and
conidia
treated
with
extract
were
shrunken
and
collapsed
due
to
cell
fluid
leakage
(Phongpaichit
et
al.
2005).
The
minimum
inhibitory
concentration
(MIC)
of
the
rhizome
and
leaf
extracts
for
fungi,
Aspergillus
niger,
A.
flavus
and
Microsporum
canis
was
achieved
at
2–4
mg/ml
whereas,
against
yeasts
Cryptococcus
gastricus
and
C.
albicans
it
was
relatively
higher
i.e.
4–8
mg/ml.
In
addition,
authentic
␣-
and
␤-asarones
were
also
tested
for
their
antimicrobial
potential.
Both
␣-
and
␤-
asarones
exhibited
very
strong
antimicrobial
activities
against
the
fungi
and
yeasts
than
those
of
rhizome
and
leaf
extracts.
The
study
clearly
suggested
that
A.
calamus
rhizomes
and
leaves
must
possess
active
principle
␣-
and
␤-asarones
which
is
believed
to
be
respon-
sible
for
their
antimicrobial
activities,
further
it
was
established
that
␤-asarone
has
high
antimicrobial
activity
as
compared
to
the
␣-asarone
(Devi
and
Ganjewala
2009).
Rajput
and
Karuppayil
(2013)
demonstrated
anticandida
prop-
erties
of
A.
calamus
rhizome
(ethyl
acetate)
extract
and
its
active
principle,
␤-asarone.
␤-Asarone
exhibited
promising
growth
inhibitory
activity
at
0.5
mg/ml
and
it
was
fungicidal
at
8
mg/ml.
Minimum
fungicidal
concentration
(MFC)
of
␤-asarone
was
highly
toxic
to
C.
albicans,
killing
99.9%
inoculum
within
120
min
of
expo-
sure.
␤-Asarone
inhibited
C.
albicans
morphogenesis
and
biofilm
development
at
sub-inhibitory
concentrations.
␤-Asarone
was
non-toxic
to
human
RBCs,
even
at
concentrations
approaching
minimum
inhibitory
concentration
(MIC)
value.
Dose
depen-
dant
reduction
in
ergosterol
content
was
observed
in
␤-asarone
treated
cells
where
complete
inhibition
was
achieved
at
growth
inhibitory
concentration,
indicating
the
growth
inhibitory
effect
of
␤-asarone
through
inhibition
of
ergosterol
biosynthesis
(Rajput
and
Karuppayil
2013).
A.
calamus
leaves
extract
show
peroxi-
dase
activity.
The
enzyme
was
purified
and
evaluated
through
the
chromatography
and
peak
giving
fractions
were
tested
for
the
anti-
fungal
activity
by
gel
filtration
using
Superose
1210/300
GL
column
(Ghosh
2006).
The
leaf
and
rhizome
part
of
A.
calamus
is
found
to
possess
the
antibacterial
activity.
A.
calamus
rhizomes
exhibit
strong
antibac-
terial
activity
against
P.
aeruginosa,
S.
aureus,
B.
subtilis
showing
MIC
at
0.25
(Sabitha
et
al.
2003).
Mycobacterium
spp.
and
B.
sub-
tilis
were
susceptible
to
calamus
oil
(Radusiene
et
al.
2006).
Devi
and
Ganjewala
(2009),
demonstrated
that
the
rhizome
and
leaf
ethyl
acetate
extract
did
not
inhibit
Gram
+ve
and
–ve
bacteria
except
E.
coli
strains.
Similar
activity
was
observed
with
authen-
tic
␣
and
␤-asarone
(Devi
and
Ganjewala
2009).
Various
studies
suggest
that
the
antibacterial
activity
may
be
attributed
to
␣
and
␤-asarone
(Bhuvaneswari
and
Balasundaram
2006;
Devi
and
Ganjewala
2009).
Badam
(1995)
reported
that
the
alcohol
extract
of
the
rhi-
zome
showed
potent
antiviral
activity
against
Herpes
Simplex
Virus
HSV-1
and
HSV-2
at
a
concentration
well
below
the
cytotoxic
con-
centration.
Pretreatment
of
vero
cells
with
the
extract
did
not
inhibit
viral
replication
of
HSV-1
and
HSV-2.
It
shows
that
host
cells
were
not
affected
by
the
extract.
␤-Asarone
possesses
strong
inhibitory
activity
against
the
replication
of
both
virus
types.
The
crude
alcohol
extract
and
b-asarone
showed
toxicity
to
the
host
cells
(Badam
1995).
Pesticidal
properties
The
essential
oils
of
the
Pakistanian
A.
calamus
exhibit
poten-
tial
pesticidal
activity
and
also
found
to
be
effective
on
the
cuts
and
wounds
(Tariq
et
al.
2010).
Essential
oil
was
toxic
against
late
3rd
instar
larvae
of
Dengue
fever
virus
vector
mosquito,
the
Aedes
aegypti.
The
LC50 was
found
to
be
1250
(Tariq
et
al.
2009).
Asarones
(2,4,5-trimethoxypropenyl-benzenes)
isolated
from
the
essential
oil
of
A.
calamus
L.
rhizomes,
exhibited
growth
inhibitory
and
anti-feedant
effect
to
the
variegated
cutworm
(Balakumbahan
et
al.
2010).
The
repellent
effect
of
petroleum
ether
extract
of
A.
calamus
has
been
investigated
against
Tribolium
castaneum.
2,4,5-
Trimethoxybenzaldehyde
was
identified
as
bioactive
compound
by
1H
NMR, 13C
NMR,
H–H
Cozy
and
HMBC
spectra
analyses
(Hossain
et
al.
2008).
The
pharmacological
properties
of
A.
calamus
and
its
active
con-
stituents
are
shown
in
their
entirety
in
Table
3.
Other
bioactivities
A.
calamus
extract
prevented
the
development
the
FeCl3induced
epileptogenesis
by
modulating
antioxidant
enzymes
(Pradhan
et
al.
2007).
Anti-mutagenic
effect
of
A.
calamus
has
been
studied
using
Salmonella
typhimurium
tester
strains,
where
it
showed
decrease
in
revertants
colonies
against
NaN3induced
mutagenecity
(Aqil
et
al.
2008).
Toxicity
studies
It
is
demonstrated
that
␤-asarone
is
potentially
toxic
and
car-
cinogenic
(Keller
and
Stahl
1983;
Taylor
et
al.
1967).
In
this
study,
rats
were
fed
with
diets
containing
various
concentrations
of
␤-asarone
for
two
years.
The
tumors
were
identified
as
leiomyosar-
comas
of
the
small
intestine
and
were
found
in
800
ppm
(0.08%)
and
2000
ppm
(0.2%).
Also
thrombosis
within
the
chambers
of
the
heart
was
observed
in
the
800
and
2000
ppm
(0.08
and
0.27%)
(Taylor
et
al.
1967).
␤-Asarone
has
an
oral
LD50 of
1010
mg/kg
bw
in
rats
and
an
i.p.
LD50
of
184
mg/kg
bw
in
mice
(JECFA
1981).
The
oral
LD50 of
calamus
oil
in
rats
is
reported
to
be
8880
mg/kg
bw
(Opdyke
1977).
Jenner
et
al.
(1964)
reported
an
oral
LD50 in
rats
of
777
mg/kg
bw
for
Jammu
calamus
oil
(containing
approximately
75%
␤-asarone).
It
was
found
that
␤-asarone
at
a
dose
of
5000
ppm
(0.5%)
showed
mutagenicity
in
Salmonella
typhimurium
while
␣-asarone
was
inac-
tive
at
5000
ppm
(Hsia
et
al.
1979).
However,
there
are
no
reports
on
in
vivo
genotoxicity
of
␤-asarone.
A
study
by
Chamarro
et
al.
(1998)
demonstrated
that
␣-asarone
has
hepatocarcinogenic
and
mutagenic
activity
in
mice.
In
this
study
a
dominant
lethal
muta-
tion
as
well
as
direct
␣-asarone
toxicity
to
spermatozoa
has
been
observed.
In
acute
and
chronic
toxicity
experiments,
ethanolic
extract
of
A.
calamus
did
not
cause
significant
changes
in
Winstar
rats.
This

Author's personal copy
274
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/
Phytomedicine
21
(2014)
268–276
Table
3
Pharmacological
properties
of
Acorus
calamus
and
its
active
constituents.
Activity
Active
compound
or
extract
Reference
Antifungal
Candida
albicans,
Cryptococcus
neoformans
Epidermophyton
floccosum,
Microsporum
gypseum
Trichophyton
mentagrophytes
and
T.
rubrum
Essential
oil,
␤-asarone
Rajput
and
Karuppayil
(2013),
Thirach
et
al.
(2003)
Ascosphaera
apis
Essential
oil
Jatisatiener
and
Jatisatiener
(1999)
Aspergillus
oryzae,
A.
nidulans,
A.
fumigates,
Penicillum
aculactum,
Phomopsis
destuctum
Essential
oil
Chantawannakul
et
al.
(2005)
Curvularia
lunata,
Alternaria
alternata
Macrophomina
phaseolina
Fusarium
moniliforme,
Trichosporium
vesiculosum
Essential
oil
Alankararao
and
Prasad
(1981)
Essential
oil Begum
et
al.
(2004)
Essential
oil
Ghosh
(2006)
Helminthosporium
oryzae
Essential
oil
Saxena
et
al.
(1990)
Antibacterial
Aeromonas
hydrophila
Essential
oil,
␣-asarone,
␤-asarone
Bhuvaneswari
and
Balasundaram
(2006)
Bacillus
cereus,
B.
subtilis,
Shigella
dysenteriae,
Shigella
flexneri,
Vibrio
cholera,
Salmonella
paratyphi,
Pseudomonas
pseudoalcaligenes.
Essential
oil
Chowdhury
et
al.
(1993)
B.
proteus,
Aerobic
spore
bearers,
Staphylococcus
pyogens,
Shigella
shiga
Essential
oil
Alankararao
and
Prasad
(1981)
Staphylococcus
aureus,
Escherichia
coli,
Pseudomonas
aeruginosa,
Klebsiella
pneumoniae
Essential
oil
Chowdhury
et
al.
(1993),
Parekh
et
al.
(2006),
Rajendhran
et
al.
(1998)
Anti-inflammatory/immunomodulatory
Anti-inflammatory
effect
in
human
HaCaT
cells
Leaf
extract
Kim
et
al.
(2009)
immunomodulatory
activity
in
human
PBMCs
Ethanolic
extract
Mehrotra
et
al.
(2003)
Anti-inflammatory
activity
in
albino
rats
Acetone
extract
Lad
et
al.
(2010)
Anti-inflammatory
activity
in
rat
models
Rhizome
extract
Varde
et
al.
(1988)
Anti-inflammatory
activity
in
human
keratinocytes Leaf
extract
Kim
et
al.
(2009)
Antioxidative/protective
effect
Antioxidant
and
nephroprotective
effect
in
male
albino
rats
Ethanolic
extract
Palani
et
al.
(2010)
Antioxidant
activity
in
rats
brain
␣-Asarone,
ethyl
acetate
and
methanolic
extract
Manikandan
and
Devi
(2005),
Manikandan
et
al.
(2005)
Antioxidant
activity
Neuroprotective
effect
in
ischemic
rats
Ethyl
acetate
extract
Acuna
et
al.
(2002)
Hydroalcoholic
extract,
␣-
and
␤-asarone
Shukla
et
al.
(2006)
Anticonvulsant/antispasmodic
Anticonvulsant
activity
in
mice
models
Methanolic
extract,
␣-asarone
Jayaraman
et
al.
(2010),
Sharma
et
al.
(1961)
Antiepileptic
activity
in
adult
albino
mice
Calamus
oil
Khare
and
Sharma
(1982)
Antispasmolytic
activity
in
rabbit Crude
extract Shoba
and
Thomas
(2001)
Prevents
convulsions
and
electroshock
seizures
in
rats
Asarones
Dandiya
and
Sharma
(1962),
Dandiya
and
Menon
(1963)
Anticonvulsant
action
in
amygdale
kindled
rats
Ethanolic
extract
Hazra
et
al.
(2005)
Anticancer
Anti-carcinogenic
activity
in
human
carcinoma
cells
␣-Asarone
Hu
and
Ji
(1986)
Anti-proliferative
activity
in
mice Rhizome
extract Gaidhani
et
al.
(2009),
Chaitali
et
al.
(2010)
Anti-cancer
activity
against
human
cancer
cells
Epieudesmin
and
galgravin
from
methanolic
extract
Balakumbahan
et
al.
(2010)
Anticancer
activity
in
human
cancer
cells
␤-Asarone
from
calamus
oil
Palani
et
al.
(2010)
Antimitogenic
activity
in
mouse
and
human
cancer
lines
Lectins
from
rhizome
Bains
et
al.
(2005)
Anticellular
activity
in
human
cancer
cells
Ethanolic
extract
Mehrotra
et
al.
(2003)
Hypolipidemic
Decreased
cholesterol
and
triglyceride
levels
in
rats
Saponins
from
hydro-alcoholic
extract
Parab
and
Mengi
(2002)
Inhibited
cholesterol
synthesis
in
rat
liver
Rhizome
extract
D’Souza
et
al.
(2007)
Inhibited
hepatic
HMG-CoA
reductase
in
rats
␣-Asarone
Rodriguez-Paez
et
al.
(2003)
Antidiabetic
Exhibited
antidiabetic
effect
by
enhancing
differentiation
in
adipocytes
of
mouse
Ethanolic
extract
Wu
et
al.
(2009)
Suppress
blood
glucose
levels
in
normal
mice
Calamus
extract
Si
et
al.
(2010)
Cardiovascular
related
activity
Lowers
blood
pressure
in
cats,
dogs
and
rabbits
Essential
oil
Shaha
and
Gilani
(2010),
Dandiya
and
Cullumbine
(1959)
Hypotensive
activity
in
dogs
Alcoholic
extract
Moholkar
et
al.
(1975)
Cardiac
depressant/antiasthmatic
Airways
relaxant
activity
Crude
extract
Jabbar
and
Hassan
(2010),
Shaha
and
Gilani
(2010)
Antiasthmatic
activity
Rhizome
extract
Rajasekharan
and
Srivastava
(1977),
Chandra
(1980)
CNS
depressant/AChE-inhibitory
Calming
effect
in
monkeys
Asarones
Chak
and
Sharma
(1965)
AChE
inhibitory
activity
in
bovine
erythrocytes
Hydroalcoholic
and
methanolic
extract,
␣-
and
␤-asarone
Mukherjee
et
al.
(2007),
Oh
et
al.
(2004)
Sedative
effect
in
mice,
dogs
and
rats
Volatile
fraction
of
petroleum
ether
extract,
essential
oil
Dandiya
and
Cullumbine
(1959),
Dhalla
and
Bhattacharya
(1968)
Hypnosis
potentiating
activity
Volatile
oil
Malhotra
et
al.
(1962)

Author's personal copy
S.B.
Rajput
et
al.
/
Phytomedicine
21
(2014)
268–276
275
study
concluded
that
the
ethanolic
extract
of
A.
calamus
does
not
have
toxicity
on
acute
and
chronic
administration
in
Winstar
rats
(Shah
et
al.
2012).
There
was
no
significant
toxicity
in
rodents
when
orally
administered
with
hydroalcholic
extract
of
A.
calamus
(Muthuraman
and
Singh
2012).
Moreover,
the
rhizome
(but
not
the
isolated
essential
oil)
has
been
used
in
India
for
thousands
of
years
without
reports
of
cancer
which
suggests
that
using
the
whole
herb
may
be
safe,
though
more
research
is
needed
(Chevallier
1996).
Acknowledgements
SBR
is
thankful
to
DST,
New
Delhi,
for
providing
DST-INSPIRE
fellowship,
Ref
No.
DST/INSPIRE
FELLOWSHIP/2010/(290).
We
are
thankful
to
Prof.
S.B.
Nimse,
Hon’ble
Vice
Chancellor,
SRTM
Univer-
sity,
for
his
kind
support.
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