A Review of Antimycobacterial Natural Products
20
REVIEW ARTICLE A Review of Antimycobacterial Natural Products Sandra M. Newton, 1 * Clara Lau 1,2 and Colin W. Wright 1 1 The School of Pharmacy, University of Bradford, West Yorkshire, UK 2 Department of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Tuberculosis is a chronic infectious disease caused by several species of mycobacteria. Due to multi- drug resistant strains of mycobacteria and to a high prevalence of tuberculosis in patients who have acquired human immunodeficiency syndrome (AIDS), the number of patients infected with the disease is increasing worldwide. Thus there is an urgent need for new effective antimycobacterial agents to replace those currently in use. In this instance, the plant kingdom is undoubtedly a valuable source for new anti- tuberculosis agents. The present review article reports the findings from an extensive literature search of all plants that have been assessed for antimycobacterial/antitubercular activity over the past 20–30 years. An attempt has been made to summarize the information in order to highlight those promising plant species which are worthy of further investigation as leads for drug development. Over 350 plant species from a wide range of families and origins, containing various chemical classes of compounds, have been screened for such activity. A review of the relevant in vitro assays using different species of pathogenic and non-pathogenic mycobacteria is also included. Copyright # 2000 John Wiley & Sons, Ltd. Keywords: mycobacteria; tuberculosis; plants; antimycobacterial; natural products; traditional medicine. INTRODUCTION The infectious killer disease, tuberculosis (TB), is the leading cause of death worldwide from a single human pathogen, claiming more adult lives than diseases such as acquired immunodeficiency syndrome (AIDS), malaria, diarrhoea, leprosy and all other tropical diseases combined (Zumla and Grange, 1998). The organism usually responsible is the tubercle bacillus, Mycobacter- ium tuberculosis (MT), discovered by Robert Koch in 1882. However, M. bovis, which infects cattle may also infect man and M. africanum is a cause of TB in West Africa. Furthermore, a number of normally non- pathogenic mycobacteria, especially M. avium, M. intracellulare and M. scrofulaceum, cause opportunistic infectious disease in patients with AIDS (Horne, 1996). Pulmonary TB, the most common type of the disease, is usually acquired by inhalation of the bacillus from an infectious patient and causes irreversible lung destruc- tion. About one third of the world’s population is currently infected with M. tuberculosis; 10% of those infected will develop clinical disease, particularly those who also have the human immunodeficiency virus (HIV) infection (Zumla and Grange, 1998). With the discovery of effective antimycobacterial agents (including ethambutol, isoniazid, pyrazinamide, rifam- picin and streptomycin) and a reduction in poverty, there was a drastic decline in the number of TB cases, especially in developed nations. However, since the late 1980s, the number of cases of TB throughout the world has been increasing rapidly due partly to the emergence of multidrug resistant M. tuberculosis. According to the World Health Organization (WHO, 1993), it was expected that the annual death rate caused by TB will reach an overwhelming 3.5 million by the year 2000. Thus the TB problem requires urgent attention. Short course anti-TB regimens initially using at least three first- line drugs (including isoniazid, rifampicin and pyrazina- mide) are effective. The major problems faced in tuberculosis control are poor infrastructures for diagnosis and drug supply and failure of patients to complete their course of drugs. This is usually due to poor supervision and medical care and, as a result, drug resistance develops. Second-line drugs (e.g. capreomycin, kanamy- cin, cycloserine, ethionamide) which are often more toxic have to be used in this case. Furthermore, drugs with broader ranges of activity are also required to target emerging pathogens, such as those of the M. avium complex. Hence, there is a great need to search for and develop new, affordable, anti-TB agents. For as long as man can remember, plants particularly, have been used worldwide in traditional medicines for PHYTOTHERAPY RESEARCH Phytother. Res. 14, 303–322 (2000) Copyright # 2000 John Wiley & Sons, Ltd. * Correspondence to: Dr S. M. Newton, The School of Pharmacy, University of Bradford, West Yorkshire, BD7 1DP, UK.
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Transcript of A Review of Antimycobacterial Natural Products
REVIEW ARTICLE
A Review of Antimycobacterial NaturalProducts
Sandra M. Newton,1* Clara Lau 1,2 and Colin W. Wright 1
1The School of Pharmacy, University of Bradford, West Yorkshire, UK2Department of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong
Tuberculosis is a chronic infectious disease caused by several species of mycobacteria. Due to multi-drug resistant strains of mycobacteria and to a high prevalence of tuberculosis in patients who haveacquired human immunodeficiency syndrome (AIDS), the number of patients infected with the disease isincreasing worldwide. Thus there is an urgent need for new effective antimycobacterial agents to replacethose currently in use. In this instance, the plant kingdom is undoubtedly a valuable source for new anti-tuberculosis agents. The present review article reports the findings from an extensive literature search ofall plants that have been assessed for antimycobacterial/antitubercular activity over the past 20–30 years.An attempt has been made to summarize the information in order to highlight those promising plantspecies which are worthy of further investigation as leads for drug development. Over 350 plantspecies from a wide range of families and origins, containing various chemical classes of compounds,have been screened for such activity. A review of the relevantin vitro assays using different speciesof pathogenic and non-pathogenic mycobacteria is also included. Copyright# 2000 John Wiley &Sons, Ltd.
Keywords:mycobacteria; tuberculosis; plants; antimycobacterial; natural products; traditional medicine.
INTRODUCTION
The infectious killer disease, tuberculosis (TB), is theleading cause of death worldwide from a single humanpathogen, claiming more adult lives than diseases such asacquired immunodeficiency syndrome (AIDS), malaria,diarrhoea, leprosy and all other tropical diseasescombined (Zumla and Grange, 1998). The organismusually responsible is the tubercle bacillus,Mycobacter-ium tuberculosis(MT), discovered by Robert Koch in1882. However,M. bovis, which infects cattle mayalso infect man andM. africanum is a cause of TB inWest Africa. Furthermore, a number of normally non-pathogenic mycobacteria, especiallyM. avium, M.intracellulare andM. scrofulaceum, cause opportunisticinfectious disease in patients with AIDS (Horne, 1996).Pulmonary TB, the most common type of the disease, isusually acquired by inhalation of the bacillus from aninfectious patient and causes irreversible lung destruc-tion.
About one third of the world’s population iscurrently infected withM. tuberculosis;10% of thoseinfected will develop clinical disease, particularlythose who also have the human immunodeficiency
virus (HIV) infection (Zumla and Grange, 1998). Withthe discovery of effective antimycobacterial agents(including ethambutol, isoniazid, pyrazinamide, rifam-picin and streptomycin) and a reduction in poverty,there was a drastic decline in the number of TB cases,especially in developed nations. However, since thelate 1980s, the number of cases of TB throughout theworld has been increasing rapidly due partly to theemergence of multidrug resistantM. tuberculosis.According to the World Health Organization (WHO,1993), it was expected that the annual death rate causedby TB will reach an overwhelming 3.5 million by theyear 2000.
Thus the TB problem requires urgent attention. Shortcourse anti-TB regimens initially using at least three first-line drugs (including isoniazid, rifampicin and pyrazina-mide) are effective. The major problems faced intuberculosis control are poor infrastructures for diagnosisand drug supply and failure of patients to complete theircourse of drugs. This is usually due to poor supervisionand medical care and, as a result, drug resistancedevelops. Second-line drugs (e.g. capreomycin, kanamy-cin, cycloserine, ethionamide) which are often more toxichave to be used in this case. Furthermore, drugs withbroader ranges of activity are also required to targetemerging pathogens, such as those of theM. aviumcomplex. Hence, there is a great need to search for anddevelop new, affordable, anti-TB agents.
For as long as man can remember, plants particularly,have been used worldwide in traditional medicines for
PHYTOTHERAPY RESEARCHPhytother. Res.14, 303–322 (2000)
Copyright# 2000 John Wiley & Sons, Ltd.
* Correspondence to: Dr S. M. Newton, The School of Pharmacy, Universityof Bradford, West Yorkshire, BD7 1DP, UK.
the treatmentof disease.It is estimatedthat eventodayapproximatelytwo-thirdsto three-quartersof theworld’spopulation rely on medicinal plants as their primarysourceof medicines(McChesney,1995).Today,manyofthe drugs currently used are derived from naturalproductsor have dependedupon a natural product fortheir developmentand the recent discoveriesof theantimalarialartemisininand the anticanceragenttaxolindicate the continuing importanceof plant speciesindrug discovery.However, only a small proportion ofplantspecieshavebeenthoroughlyinvestigatedfor theirmedicinalproperties(Frameet al., 1998) and undoubt-edly therearemanynovelbiologicallyactivecompoundsto be discovered.During the pasttwo decades,pharma-ceuticalcompaniesandresearchscientistshaveshownanincreasedinterest in phytomedicine. Currently largenumbersof speciesare being screenedfor pharmaco-logical activitiesespeciallythoseusedin traditional/folkmedicine.Althoughplantspecieshavenot sofar yieldedantibacterialcompoundsof comparablepotencyto theantibiotics produced by microorganisms,many plantextractshavebeentestedfor activity againstmicroorgan-ismsin theanticipationthathighly activecompoundswillbefound.With theurgentneedfor newanti-TBagents,itis particularly appropriateat this time to review theliterature for information on plant specieswhich havebeenassessedfor antimycobacterial activity. Thepresentreview attempts to identify those species,which areworthy of further investigation as leads for drugdevelopmentand to stimulate further work in thisimportantarea.
IN VITRO TESTS FOR ANTIMYCOBA CTERIALACTIVITY
Screeningplantextractsfor antimycobacterial activity isusually carried out using mycobacteria cultured invarious types of broth and agar based media. M.tuberculosishasthedisadvantagesof beingslowgrowingso that teststake severalweeksandcontainmentfacili-ties are neededas it is a dangerouspathogen.Manyinvestigators have therefore used non-pathogenicspeciesof mycobacteriasuchasM. avium,M. intracel-lulare and M. kansaii, which like M. tuberculosisareslow growing, andotherspeciesincluding M. chelonei,M. fortuitumandM. smegmatiswhich arefastergrowingallowing tests to be completedin a few days. Mostcommonly, the test methods employed are the discdiffusion and the broth dilution methods.In the discdiffusion method, paper discs impregnatedwith theextract under test are placed on a semi-solid (agarbased)mediumwhich hasbeeninoculatedwith myco-bacteria.After incubation,zonesof inhibition of bacterialgrowth around the discs are measured.The maindisadvantageswith this method are that non-polarcompoundsmay not diffuse into the agarso that activecompoundsmay be missedandthat it is not possibletoobtain reliable quantitative results for comparativepurposes.In the broth dilution method, the minimumconcentrationrequiredto inhibit bacterialgrowth (mini-muminhibitory concentration,MIC) is determinedusinga seriesof tubescontainingserialdilutionsof theextractin inoculatedbroth;howeversolubilizationof theextracts
under test may be a problem (Satim and Washington,1991).
For high-throughputscreening,rapid methodswhichcanbe automatedareneeded;thesehavebeenreviewedby Gordon et al. (1996). The first rapid methodsdevelopedinvolved measuringthe evolution of 14CO2from M. tuberculosiscultured in medium containing14C-palmiticacidandformedthebasisfor theBACTECsystem(Becton-Dickinson,Oxford, UK). This is usedfor the susceptibilitytestingof clinical isolatesandcanprovide resultsin an averageof 5 dayscomparedwith3–4 weeks for conventional methods. However, theBACTEC system is not suitable for high-throughputscreeningdue to the technical difficulties involved inmeasuring14CO2. Chung et al. (1995) developedanassaybasedon measuringthe uptake of radiolabelleduracil into M. aurum, a fastgrowingandnon-pathogenicspecieswhich appearsto be a good model for M.tuberculosisas it hasa similar profile of sensitivity toanti-TB drugs.The latter methodmay be usedfor high-throughputscreeningand doesnot requirecontainmentfacilities but the separationof incorporatedfrom unin-corporateduracil is labour intensive. The major dis-advantageof the above is the need for radiolabelledsubstratesbut this hasbeenovercomewith the develop-ment of assaysin which mycobacterial viability isdeterminedusing either bacterial or firefly luciferase.The bacterialenzymeusesreducedflavin (producedbyviable mycobacteria) to oxidize an added aldehydesubstrate (decanal) which is accompanied by theproduction of light at 490nm. Firefly luciferase isdependentuponATP generatedby the mycobacteriatodecarboxylateluciferin, resulting in the production oflight at 562nm. Light production may be measuredeasilyusinga luminometerin high-throughputsystems.Severalspeciesof mycobacteria,including M. tubercu-losis, have beengenetically modified by inserting thegenesfor the production of bacterial luciferase; onlyviablebacilli emit light whendecanalis addedandthereis no requirementfor growthsothatsusceptibilitytestingmaybecarriedout rapidly.Similarly, thegenefor fireflyluciferase has been incorporated into a number ofmycobacteriaspeciesincluding M. aurum (Chung etal., 1995).
Colorimetric methodsare very suitable for use inmicrotitre platesand the resultsmay be easilyobtainedusing a spectrophotometer.Gomez-Floreset al. (1995)reported an assay for testing against the M. aviumcomplexwhich dependson theability of viable bacteriato reducedimethylthiazoldiphenyltetrazolium(MTT) toformazan.Anothersimilar methodutilizestheredoxdyeAlamar blue which changescolour from blue to pink inthe presenceof viable M. tuberculosis(Yajko et al.,1995).Theseassayshavetheadvantagesof beingsimpleand do not require radioactive substratesbut requireseveraldaysfor growthof the bacteriaso that they maynotbeasrapidasthebioluminescencemethodsdescribedabove.
While simple antimycobacterial testsare convenientfor screeningcrude plant extracts and isolated com-pounds,it mustnot be forgottenthat M. tuberculosisisprimarily an intracellularpathogenresidingin theacidicvacuolesof macrophagecells. This environmentmayaffect the actionof anti-TB drugssuchasstreptomycin(activity reduced)andpyrazinamide(activity increased)and it may be valuableto evaluatethe ability of plant
304 S. M. NEWTON ET AL.
Copyright# 2000JohnWiley & Sons,Ltd. Phytother.Res.14, 303–322(2000)
Tab
le1.
Med
icin
alpl
ants
/nat
ural
prod
ucts
whi
chha
vebe
enas
sess
edfo
ran
timyc
obac
teria
lact
ivity
Pla
nt/
Na
tura
lp
rod
uct
Ori
gin
Pa
rtu
sed
Mo
de
lu
sed
/R
ou
teo
fa
dm
inis
tra
tio
nA
ctiv
eC
on
stit
ue
nt(
s)/
ex
tra
ct(s
)A
ctiv
ity
Sid
ee
ffe
cts/
tox
icit
yR
em
ark
sR
efe
ren
ce
Acta
ea
sp
ica
ta(R
an
un
cu
lace
ae
)±
±M
TE
tha
no
le
xtr
act
Inh
ibit
ory
dilu
tio
n(n
og
row
tho
rle
ssth
an
5co
lon
ies)
=1
:32
0±
Hig
ha
ctiv
ity
Gra
ng
ea
nd
Da
ve
y,
19
90
Ad
ha
tod
av
asic
a(A
ca
nth
ace
ae
)In
dia
Le
af
BC
GM
TB
rom
he
xin
eA
mb
rox
ol
(se
mi-
syn
the
tic
de
riv
ati
ve
so
fa
lka
loid
va
sici
ne
)
Av
era
ge
MIC
for
5cl
inic
al
iso
late
so
fM
Tw
ith
am
bro
xo
lw
as
64
mg
/mL
Av
era
ge
MIC
for
bro
mh
ex
ine
wa
s1
28
mg
/mL
for
3cl
inic
al
iso
late
so
fM
TW
he
na
ge
nt
dis
solv
ed
inD
MS
O,
MIC
of
bro
mh
ex
ine
wa
slo
we
red
±B
oth
com
po
un
ds
ha
ve
inv
itro
inh
ibit
ory
eff
ect
sa
ga
inst
MT
Pre
pa
rati
on
so
fth
e¯
ow
ers
,le
av
es
an
dro
ots
ha
ve
be
en
wid
ely
use
din
Ind
iafo
rth
etr
ea
tme
nt
of
tub
erc
ulo
sis,
ast
hm
aa
nd
als
oa
se
xp
ect
ora
nts
(Dy
mo
cke
ta
l.,
18
93
).C
om
po
un
ds
are
wid
ely
use
da
sm
uco
lyti
ca
ge
nts
.A
mb
rox
ol
ha
sb
ee
nsh
ow
nto
be
we
llto
lera
ted
clin
ica
lly
wh
en
giv
en
ora
lly
inu
pto
50
0m
gd
ose
stw
ice
da
ily
(Oo
ste
rhu
ise
ta
l.,
19
93
).
Gra
ng
ea
nd
Sn
ell,
19
96
Aila
nth
us
alt
issim
a(S
ima
rou
ba
ce
ae
)±
±M
T(Q
ua
ssin
oid
s)
Sh
inju
lact
on
e-K
Aila
nth
on
eS
hin
jud
ila
cto
ne
Pe
rce
nta
ge
inh
ibit
ion
sa
t1
2.5
mg
/mL
are
:1
9%
17
%1
5%
±A
ctiv
itie
so
fa
llq
ua
ssin
oid
ssc
ree
ne
dw
ere
ve
rylo
w.<
19
%in
hib
itio
na
t1
2.5
mg
/mL
.R
ifa
mp
icin
wa
su
sed
as
the
po
siti
ve
dru
gco
ntr
ol
Ra
hm
an
et
al.,
19
97
Alliu
msa
tiv
um
(Lilia
ce
ae
)±
Bu
lbM
TD
ieth
yl
eth
er
ex
tra
ctG
uin
ea
-pig
sIn
hib
ito
rye
ffe
cta
t0
.5m
g/m
La
nd
1.0
mg
/mL
±In
hib
ito
rye
ffe
cto
fth
etw
oh
igh
er
con
cen
tra
tio
ns
of
ga
rlic
ex
tra
ctÐ
0.5
an
d1
.0m
g/m
L.
Gu
ine
a-p
igs,
wh
ich
we
rein
ocu
late
dw
ith
MT
an
dg
ive
ng
arl
ice
xtr
act
,p
rod
uce
dfe
we
rm
ark
ed
lesi
on
sin
the
vis
cera
.P
osi
tiv
ed
rug
con
tro
lsin
clu
de
d,
iso
nia
zid
,p
ara
-a
min
salicy
lic
aci
da
nd
stre
pto
my
cin
Ja
in,
19
98
±B
ulb
MT
an
d1
6o
the
rsp
eci
es
of
my
cob
act
eri
a
Allic
in(d
ially
lth
iols
ul®
na
te)
iso
late
dfr
om
wa
ter
ex
tra
ctM
ea
nM
IC(n
=6
)is
1.6
7m
g/m
Lfo
rM
T±
All
17
spe
cie
so
fM
Tw
ere
inh
ibit
ed
by
va
rio
us
con
cen
tra
tio
ns
of
ex
tra
ct.
Ho
we
ve
r,th
em
ea
nM
ICd
em
on
stra
ted
ve
rylo
wa
ctiv
ity
Ga
rlic
ha
sb
ee
nu
sed
intr
ad
itio
na
lC
hin
ese
an
dE
gy
pti
an
me
dic
ine
for
ma
ny
cen
turi
es
(Bo
lto
ne
ta
l.,
19
82
;Y
ua
ng
,1
95
4)
De
lah
aa
nd
Ga
rag
usi
,1
98
5
Alliu
msa
tiv
um
(Lilia
ce
ae
)±
Bu
lb1
MT
2M
AC
3M
K
Allic
in(d
ially
lth
iosu
l®n
ate
)M
IC(m
ea
n)
11
.72
mg
/mL
22
.29
mg
/mL
31
.96
mg
/mL
±S
ign
i®ca
nt
act
ivit
y.
Po
siti
ve
con
tro
lsin
clu
de
dis
on
iazi
d,
stre
pto
my
cin
,e
tha
mb
uto
l,ri
fam
pic
in.
Ab
bru
zze
see
ta
l.,
19
87
±L
ea
fM
TA
qu
eo
us
ex
tra
ctM
IC(c
om
ple
tein
hib
itio
n)
=1
:64
0d
ilu
tio
n±
Sig
ni®
can
tly
act
ive
Fit
zpa
tric
k,1
95
4A
lnu
sru
bra
Bo
ng
.(B
etu
lace
ae
)B
rC
Ba
rkC
atk
inM
TM
AM
eth
an
ol
ex
tra
ctB
oth
pa
rts
of
the
pla
nt
com
ple
tely
inh
ibit
ed
gro
wth
of
MT
an
dM
Aa
t5
0m
ge
xtr
act
/dis
c
±S
ign
i®ca
nt
act
ivit
y.
Iso
nia
zid
wa
su
sed
as
po
siti
ve
con
tro
l.P
rev
iou
sly
use
din
tra
dit
ion
al
me
dic
ine
by
Fir
stN
ati
on
'sp
eo
ple
McC
utc
he
on
et
al.
,1
99
7
Alo
ech
ine
nsis
(Lilia
ce
ae
)±
Le
af
MT
Eth
an
ol
ex
tra
ctA
ctiv
e.
(Co
nce
ntr
ati
on
no
tst
ate
d)
±A
ctiv
ity
ag
ain
stM
T.
Act
ivit
yp
rese
nt
wh
en
scre
en
ed
ag
ain
stS
Aa
nd
EC
Go
ttsh
all
et
al.,
19
49
Alo
esu
cco
trin
a(L
ilia
ce
ae
)±
Le
af
MT
Eth
an
ol
ex
tra
ctA
ctiv
e.
(Co
nce
ntr
ati
on
no
tst
ate
d)
±A
ctiv
ity
ag
ain
stM
T.
No
act
ivit
yw
he
nsc
ree
ne
da
ga
inst
SA
an
dE
CG
ott
sha
lle
ta
l.,
19
49
Alp
inia
Ku
ma
tak
eM
ak
.(Z
ing
ibe
race
ae
)
Ch
ina
±M
TA
lco
ho
le
xtr
act
No
inh
ibit
ion
of
MT
usi
ng
a1
:50
dilu
tio
n±
No
sig
ni®
can
ta
ctiv
ity
Wa
ng
,1
95
0
ANTIMYCOBACTERIAL NATURAL PRODUCTS 305
Copyright# 2000JohnWiley & Sons,Ltd. Phytother.Res.14, 303–322(2000)
Tab
le1.
Con
tinue
d.
Pla
nt/
Na
tura
lp
rod
uct
Ori
gin
Pa
rtu
sed
Mo
de
lu
sed
/R
ou
teo
fa
dm
inis
tra
tio
nA
ctiv
eC
on
stit
ue
nt(
s)/e
xtr
act
(s)
Act
ivit
yS
ide
eff
ect
s/to
xic
ity
Re
ma
rks
Re
fere
nce
Am
yri
se
lem
ife
raL
.(R
uta
ce
ae
)G
ua
d±
MT
MA
MK
Ta
xa
lin
(Ox
azo
le)
MIC
(in
hib
ite
dm
ore
tha
n9
9%
of
the
ba
cte
ria
lp
op
ula
tio
n)
(mg
/mL
)M
eth
od
1(B
AC
TE
C)
=2
5,
25
,2
5M
eth
od
2(a
ga
rd
ilu
tio
n)
=2
5,
50
,5
0F
or
MT
,M
A,
MK
resp
ect
ive
lyd
ep
en
din
go
nth
em
eth
od
use
d
±T
ex
alin
sig
ni®
can
tly
act
ive
Ra
sto
gi
et
al.,
19
98
An
tirr
hin
um
ma
jus
(Scro
ph
ula
ria
ce
ae
)±
Ca
lyx
MT
an
do
the
rb
act
eri
al
spe
cie
sE
tha
no
le
xtr
act
MIC
(MT
)=
1:8
0d
ilu
tio
n±
Sig
ni®
can
ta
ctiv
ity
Lu
cas
et
al.
,1
95
1A
rnic
am
on
tan
a(A
ste
race
ae
)±
±M
TE
tha
no
le
xtr
act
Inh
ibit
ory
dilu
tio
n(N
og
row
tho
rle
ssth
an
5co
lon
ies)
=1
:16
0T
oo
tox
icin
hig
hd
ose
sto
be
clin
ica
lly
use
ful
(Wre
n,
19
88
)
Use
din
ho
me
op
ath
icp
ract
ice
for
relie
fo
fp
ain
an
din
¯a
mm
ati
on
(Wre
n,
19
88
)G
ran
ge
an
dD
av
ey
,1
99
0
Aza
dir
ach
tain
dic
aA
.J
uss.
(Me
lia
ce
ae
)
Ea
stA
fric
a(K
en
ya
)
Ste
m/
Ba
rk/
Le
af
MT
MA
MC
MI
an
db
act
eri
al
stra
ins
Me
tha
no
le
xtr
act
Co
nce
ntr
ati
on
of
2m
g/m
La
llo
we
dth
eg
row
tho
fm
ore
tha
n1
0%
of
the
ino
culu
mo
fth
e5
my
cob
act
eri
al
stra
ins.
Ag
ain
stth
efa
stg
row
ing
ba
cte
ria
MIC
=8
mg
/mL
±N
osi
gn
i®ca
nt
act
ivit
yto
wa
rds
the
my
cob
act
eri
um
an
dv
ery
low
an
tib
act
eri
al
act
ivit
y.
Gro
wth
con
tro
lsu
sin
gL
ow
en
ste
in-J
en
sen
me
diu
mw
ere
carr
ied
ou
t
Fa
bry
et
al.
,1
99
8
Azo
rella
ma
dre
po
rica
Clo
s(A
pia
ce
ae
)C
hile
Ae
ria
lM
TP
etr
ole
um
eth
er
ex
tra
ctM
IC(c
om
ple
teg
row
thin
hib
itio
n)
of
AC
=2
0m
g/m
LIC
50
vs
Ve
roce
lls
wa
s1
84
mg
/mL
Sig
ni®
can
ta
ctiv
ity
/mo
de
rate
tox
icit
yW
ach
ter
et
al.,
19
98
AC
=M
ulin
an
eD
ite
rpe
no
idA
nti
tub
erc
ula
ra
ctiv
ity
als
od
em
on
stra
ted
ine
xtr
act
so
bta
ine
dfr
om
sev
en
oth
er
Azo
rella
pla
nts
(A.
com
pa
cta
,A
.m
on
an
tho
s,A
.p
ata
go
nic
a,
A.
®la
me
nto
sa,
A.
trif
urc
ata
,A
.cr
ass
ipe
s,A
.cr
yp
tan
tha
)M
yro
xy
lon
ba
lsa
mu
mv
ar.
pe
reir
ae
(Le
gu
min
ose
ae
)
±±
MT
Eth
an
ol
ex
tra
ctM
IC(n
og
row
tho
rle
ssth
an
5co
lon
ies)
=1
:64
0d
ilu
tio
n.
±H
igh
act
ivit
yG
ran
ge
an
dD
av
ey
,1
99
0
Ba
lso
am
orh
iza
sa
git
tata
Pu
rsh
Nu
tt.
(Aste
race
ae
)
Br
CR
oo
tM
TM
AM
eth
an
ol
ex
tra
ctC
om
ple
tely
inh
ibit
ed
gro
wth
of
MT
at
50
mg
ex
tra
ct/d
isc
±S
ign
i®ca
nt
act
ivit
yN
oin
hib
itio
no
fM
Aw
ith
50
mg
ex
tra
ct/d
isc.
Po
siti
ve
con
tro
l-
iso
nia
zid
McC
utc
he
on
et
al.
,1
99
7
Ba
rba
rea
vu
lga
ris
(Cru
cif
era
e)
±F
low
er
MT
an
do
the
rb
act
eri
al
spe
cie
sE
tha
no
le
xtr
act
MIC
(MT
)=
1:8
0d
ilu
tio
n±
Sig
ni®
can
tly
act
ive
Lu
cas
et
al.
,1
95
1B
ide
ns
pilo
sa
L.
(Aste
race
ae
)R
wa
nd
aL
ea
fM
TM
AC
MS
iS
LM
Eth
an
ol
ex
tra
ctA
ctiv
ea
ga
inst
MT
at
10
0m
g/m
LN
oa
ctiv
ity
ag
ain
stM
AC
,M
Si
an
dS
LM
at
10
00
mg
/mL
±W
ea
ka
ctiv
ity
.U
sed
inR
wa
nd
ese
tra
dit
ion
al
me
dic
ine
(Va
nP
uy
ve
lde
et
al.
,1
97
5,
19
77
,1
98
2)
Co
ntr
ols
usi
ng
con
ve
nti
on
al
an
titu
be
rcu
losi
sd
rug
s
Va
nP
uy
ve
lde
et
al.
,1
99
4
Bo
rric
hia
fru
tesce
ns
L.
(Se
aD
ais
y)
(Aste
race
ae
)
US
AF
low
er
Le
af
Ste
m
MT
1(2
4R
)-2
4,2
5-
ep
ox
ycy
clo
art
an
e2
(3aH
,2
4R
)-2
4,2
5-
ep
ox
ycy
clo
art
an
e3
(23
R)-
3-o
xo
lan
ost
a-8
,24
-d
ien
-23
-ol
All
iso
late
dfr
om
dic
hlo
rom
eth
an
ee
xtr
act
MIC
18
mg
/mL
28
mg
/mL
31
28
mg
/mL
IC5
0v
s.V
ero
cells
=1
71
.8m
g/m
L2
39
.8m
g/m
L3
10
3.6
mg
/mL
Sig
ni®
can
ta
ctiv
ity
of
bo
thco
mp
ou
nd
s1
an
d2
Hig
he
stle
ve
lo
fa
nti
-my
cob
act
eri
al
act
ivit
yfo
un
din
¯o
we
re
xtr
act
Ca
ntr
ell
et
al.
,1
99
6
Bo
rric
hia
fru
tesce
ns
L.
(Aste
race
ae
)U
SA
Flo
we
rM
TM
AD
ich
loro
me
tha
ne
ex
tra
ct1
00
%in
hib
itio
na
ga
inst
MT
at
0.1
mg
/mL
.9
9%
inh
ibit
ion
ag
ain
stM
Aa
t1
mg
/mL
.
±S
ign
i®ca
nt
act
ivit
yP
osi
tiv
eco
ntr
ols
incl
ud
eri
fam
pic
in,
cla
rith
rom
yci
n
Ca
ntr
ell
et
al.
,1
99
8a
306 S. M. NEWTON ET AL.
Copyright# 2000JohnWiley & Sons,Ltd. Phytother.Res.14, 303–322(2000)
Tab
le1.
Con
tinue
d.
Pla
nt/
Na
tura
lp
rod
uct
Ori
gin
Pa
rtu
sed
Mo
de
lu
sed
/R
ou
teo
fa
dm
inis
tra
tio
nA
ctiv
eC
on
stit
ue
nt(
s)/e
xtr
act
(s)
Act
ivit
yS
ide
eff
ect
s/to
xic
ity
Re
ma
rks
Re
fere
nce
Bru
ce
aa
nti
dy
se
nte
rica
(Sim
aro
ub
ace
ae
)
±±
MT
1D
eh
yd
rob
ruce
an
tin
2B
ruce
an
tin
3D
eh
yd
rob
ruce
an
tari
n4
Bru
cea
no
l-F
5D
eh
yd
rob
ruce
an
tin
ol
(Qu
ass
ino
ids)
Inh
ibit
ion
at
12
.5m
g/m
L1
15
%2
9%
38
%4
3%
51
%
±A
ctiv
itie
so
fq
ua
ssin
oid
sw
ere
ve
rylo
w.
0±1
9%
inh
ibit
ion
at
12
.5m
g/m
LR
ifa
mp
icin
wa
su
sed
as
the
po
siti
ve
con
tro
ld
rug
Ra
hm
an
et
al.
,1
99
7
Bru
ce
aja
va
nic
a(S
ima
rou
ba
ce
ae
)±
±M
TB
ruce
osi
de
-D(Q
ua
ssin
oid
)7
%in
hib
itio
no
fM
Ta
t1
2.5
mg
/mL
±A
ctiv
itie
so
fq
ua
ssin
oid
sw
ere
ve
rylo
w.
0±1
9%
inh
ibit
ion
at
12
.5m
g/m
LR
ifa
mp
icin
wa
su
sed
as
the
po
siti
ve
con
tro
ld
rug
Ra
hm
an
et
al.
,1
99
7
Ca
llis
tem
on
cit
rin
us
(My
rta
ce
ae
)P
ue
rto
Ric
oL
ea
fM
Sm
MT
Mic
eA
rte
mia
salin
aL
ee
ch(B
rin
esh
rim
p)
Eth
an
ol
ex
tra
ctIn
hib
itio
nzo
ne
sfo
rM
Sm
ran
ge
dfr
om
27
mm
(10
00
mg
/m
L)
to8
mm
(25
mg
/mL
).M
Tse
nsi
tiv
ea
t1
00
mg
/mL
LC
50
=1
68
mg
(Bri
ne
shri
mp
)N
oto
xic
ity
tom
ice
wh
en
giv
en
50
0m
g/
10
0m
Lo
fp
lan
te
xtr
act
/m
ou
sei.p
.o
ve
r1
5d
ay
s
Sig
ni®
can
ta
ctiv
ity
.P
osi
tiv
e(s
tre
pto
my
cin
)a
nd
ne
ga
tiv
e(u
ntr
ea
ted
)co
ntr
ols
we
rein
clu
de
d.
Tra
nsi
tory
inh
ibit
ion
of
MT
sim
ila
rto
gro
wth
inh
ibit
ory
eff
ect
sfo
rkn
ow
nb
act
eri
ost
ati
ca
ge
nts
Fra
me
et
al.
,1
99
8
Ca
ne
lla
win
tera
na
(Ca
ne
lla
ce
ae
)G
ua
dL
ea
fM
TM
KM
A
Ca
ne
lla
l(S
esq
uit
erp
en
ed
iald
eh
yd
e)
iso
late
dfr
om
chlo
rofo
rme
xtr
act
MIC
(in
hib
ite
dm
ore
tha
n9
9%
of
ba
cte
ria
lp
op
ula
tio
n)
of
AC
wa
sg
rea
ter
tha
n1
00
mg
/mL
for
ea
chte
sto
rga
nis
m
±N
osi
gn
i®ca
nt
act
ivit
ya
ga
inst
MT
,M
A,
MK
Ra
sto
gi
et
al.
,1
99
8
Gu
ad
Oil
fro
mle
af
MT
MK
MA
Ess
en
tia
lo
ilm
ad
eu
po
fm
yrc
en
e,b-
farn
ese
ne
lin
alo
la
nd
ne
rolid
iol
(all
no
n-c
ycl
icte
rpe
no
ids)
MIC
(in
hib
ite
dm
ore
tha
n9
9%
of
ba
cte
ria
lp
op
ula
tio
n)
of
ess
en
tia
lo
ilw
as
gre
ate
rth
an
10
0m
g/m
Lfo
re
ach
test
org
an
ism
±N
osi
gn
i®ca
nt
act
ivit
yR
ast
og
ie
ta
l.,
19
98
Ca
nsco
rad
ecu
ssa
taS
ch
ult
(Ge
nti
an
ace
ae
)
Ind
ia±
MT
Alb
ino
rats
Xa
nth
on
e1
(Ma
ng
ife
rin
)X
an
tho
ne
2X
an
tho
ne
3X
an
tho
ne
4is
ola
ted
fro
me
tha
no
le
xtr
act
MIC
(co
nce
ntr
ati
on
req
uir
ed
for
gro
wth
inh
ibit
ion
)o
fto
tal
xa
nth
on
es
=1
0m
g/m
LM
ICo
fx
an
tho
ne
1a
lon
e=
20
0m
g/m
L
No
ob
vio
us
tox
icit
yo
rsi
de
eff
ect
sin
alb
ino
rats
wit
hto
tal
xa
nth
on
es
(50
mg
/kg
i.p
.)
Sig
ni®
can
ta
ctiv
ity
of
tota
lx
an
tho
ne
sa
nd
MIC
wa
sco
mp
ara
ble
toth
at
of
stre
pto
my
cin
Xa
nth
on
e1
sho
we
do
nly
we
ak
inh
ibit
ory
act
ivit
yU
sed
intr
ad
itio
na
lIn
dia
nm
ed
icin
eto
tre
at
tub
erc
ulo
sis
(Ch
op
rae
ta
l.,
19
56
)
Gh
osa
la
nd
Ch
au
dh
uri
,1
97
5;
Gh
osa
le
ta
l.,
19
78
Ce
nte
lla
asia
tica
Lin
n.
(Um
be
llif
era
e)
Ind
ia±
MT
No
red
uct
ion
inth
en
um
be
ro
fa
cid
-fa
stb
aci
lli
wit
hv
ari
ou
sco
nce
ntr
ati
on
so
fth
ea
ctiv
ee
xtr
act
±N
osi
gn
i®ca
nt
act
ivit
yo
nth
ea
cid
fast
ne
ssa
nd
via
bilit
yo
fM
Tin
vit
ro.
Asi
ati
cosi
de
(gly
cosi
de
)h
as
be
en
iso
late
dp
rev
iou
sly
fro
mth
isp
lan
ta
nd
ha
sb
ee
nu
sed
totr
ea
tle
pro
syp
ati
en
tsfr
om
ve
rye
arl
yti
me
s(B
oit
ea
ue
ta
l.,
19
49
;K
akk
ar,
19
88
)
He
rbe
rte
ta
l.,
19
94
Ce
tra
ria
isla
nd
ica
L.
(Pa
rme
lia
ce
ae
)Ic
ela
nd
±M
Au
Pro
to-l
ich
est
eri
nic
aci
dM
IC=
25
0m
g/m
L±
Re
pu
ted
tob
ee
ffe
ctiv
ein
tre
atm
en
to
fp
ulm
on
ary
tub
erc
ulo
sis
(Va
rtia
,1
97
3).
Co
ntr
ols
incl
ud
ed
rifa
mp
icin
,st
rep
tom
yci
n,
iso
nia
zid
Ing
olf
sdo
ttir
et
al.
,1
99
8
Ch
ae
na
cti
sd
ou
gla
si
Ho
ok
.(A
ste
race
ae
)B
rC
±M
TM
AM
eth
an
ol
ex
tra
ctC
om
ple
tein
hib
itio
no
fM
Ta
t5
0m
ge
xtr
act
/dis
c.S
ma
llzo
ne
of
cle
ari
ng
of
MA
at
50
mg
ex
tra
ct/d
isc.
±S
ign
i®ca
ntl
ya
ctiv
eM
cCu
tch
eo
ne
ta
l.,
19
97
Ch
ryso
ma
pa
uci¯
oscu
losa
Mic
hx
.(A
ste
race
ae
)
US
AR
oo
tM
TM
A1
(4Z
,8Z
)-M
atr
ica
ria
est
er
2(2
Z,8
Z)-
Ma
tric
ari
ae
ste
r3
(2Z
,8-d
eh
yd
ro)-
Ma
tric
ari
ae
ste
ra
nd
oth
er
rela
ted
com
po
un
ds
MIC
(MT
)=1
12
.5m
g/m
L2
25
mg
/mL
32
5m
g/m
LM
IC(M
A)=
15
0m
g/m
L2
25
mg
/mL
32
5m
g/m
L
±S
ign
i®ca
ntl
ya
ctiv
eP
osi
tiv
eco
ntr
ols
are
rifa
mp
icin
ag
ain
stM
Ta
nd
cla
rith
rom
yci
na
ga
inst
MA
Lu
et
al.,
19
98
ANTIMYCOBACTERIAL NATURAL PRODUCTS 307
Copyright# 2000JohnWiley & Sons,Ltd. Phytother.Res.14, 303–322(2000)
Tab
le1.
Con
tinue
d.
Pla
nt/
Na
tura
lp
rod
uct
Ori
gin
Pa
rtu
sed
Mo
de
lu
sed
/R
ou
teo
fa
dm
inis
tra
tio
nA
ctiv
eC
on
stit
ue
nt(
s)/e
xtr
act
(s)
Act
ivit
yS
ide
eff
ect
s/to
xic
ity
Re
ma
rks
Re
fere
nce
Ch
rysa
nth
um
sin
en
se
Sa
b.
(Aste
race
ae
)
Ch
ina
±M
TA
lco
ho
lic
ex
tra
ctM
IC=
1:5
0d
ilu
tio
n±
Sig
ni®
can
ta
ctiv
ity
Wa
ng
,1
95
0
Ch
rysa
nth
em
um
se
ge
tum
(Aste
race
ae
)±
Le
af
Ca
lyx
MT
an
do
the
rb
act
eri
al
spe
cie
sE
tha
no
le
xtr
act
MIC
=1
:80
dilu
tio
n±
Sig
ni®
can
ta
ctiv
ity
Lu
cas
et
al.
,1
95
1C
inn
am
om
um
ca
mp
ho
ra(L
au
race
ae
)
±±
MT
Eth
an
ol
ex
tra
ctM
IC(n
og
row
tho
rle
ssth
an
5co
lon
ies)
=1
:12
80
dilu
tio
nL
ike
lyto
be
too
tox
icfo
rcl
inic
al
use
(Wre
n,
19
88
).
Hig
ha
ctiv
ity
Gra
ng
ea
nd
Da
ve
y,
19
90
Cin
na
mo
mu
mze
yla
nic
um
(La
ura
ce
ae
)
±L
ea
fM
TW
ate
re
xtr
act
MIC
(co
mp
lete
gro
wth
inh
ibit
ion
)=
1:6
40
dilu
tio
n±
Sig
ni®
can
tly
act
ive
Fit
zpa
tric
k,1
95
4
Cla
do
nia
arb
uscu
laW
allr.
Ra
be
nh
.(C
lad
on
iace
ae
)
Ice
lan
d±
MA
uU
snic
aci
d(d
ibe
nzo
fura
nd
eri
va
tiv
e)
iso
late
dfr
om
die
thy
le
the
re
xtr
act
MIC
of
act
ive
con
stit
ue
nt
wa
s3
2m
g/m
L±
Act
ivit
yb
ut
low
er
tha
nth
eM
ICfo
rco
ntr
ol
dru
gs,
rifa
mp
icin
(2m
g/m
L),
stre
pto
my
cin
(0.2
5m
g/m
L)
an
dis
on
iazi
d(0
.03
mg
/mL
)E
ffe
ctiv
ein
the
tre
atm
en
to
fp
ulm
on
ary
tub
erc
ulo
sis
(Va
rtia
,1
97
3)
Ing
olf
sdo
ttir
et
al.
,1
99
8
Cle
ma
tis
inte
gri
folia
(Ra
nu
ncu
lace
ae
)±
Le
af
MT
Wa
ter
ex
tra
ctM
IC(c
om
ple
tein
hib
itio
n)
=1
:64
0d
ilu
tio
n±
Sig
ni®
can
ta
ctiv
ity
Fit
zpa
tric
k,1
95
4C
lem
ati
sv
irg
inia
na
(Ra
nu
ncu
lace
ae
)±
Le
af
MT
Wa
ter
ex
tra
ctM
IC(c
om
ple
tein
hib
itio
n)
=1
:64
0d
ilu
tio
n±
Sig
ni®
can
ta
ctiv
ity
Fit
zpa
tric
k,1
95
4C
op
tis
co
ine
nsia
Fre
nch
(Ra
nu
ncu
lace
ae
)
Ch
ina
Ro
ot
MT
Be
rbe
rin
eb
isu
lph
ate
(alk
alo
id)
MIC
=1
:80
0d
ilu
tio
nB
erb
eri
ne
hig
hly
tox
icb
yp
are
nte
ral
inje
ctio
n(C
ha
ng
,1
94
8)
Sig
ni®
can
ta
ctiv
ity
bu
th
igh
lyto
xic
Wa
ng
,1
95
0
Em
pe
tru
mn
igru
mL
.(E
mp
etr
ace
ae
)B
rC
Ste
mM
TM
AM
eth
an
ol
ex
tra
ctC
om
ple
tein
hib
itio
no
fM
Ta
nd
MA
at
50
mg
ex
tra
ct/d
isc
±S
ign
i®ca
nt
act
ivit
y.
Po
siti
ve
con
tro
l-is
on
iazi
dM
cCu
tch
eo
ne
ta
l.,
19
97
En
tad
aa
by
ssin
ica
A.
Ric
h(L
eg
um
ino
sa
e)
Ea
stA
fric
a(K
en
ya
)
Ste
mM
TM
AM
CM
IM
Te
an
d5
ba
cte
ria
lsp
eci
es
Me
tha
no
le
xtr
act
Co
nce
ntr
ati
on
of
2m
g/m
La
llo
we
dth
eg
row
tho
fm
ore
tha
n1
0%
of
the
ino
culu
mo
fth
e®
ve
my
cob
act
eri
al
spe
cie
s
±N
osi
gn
i®ca
nt
act
ivit
ya
ga
inst
the
my
cob
act
eri
a.
MIC
50
%(m
g/m
L)
ran
ge
dfr
om
0.5
±4d
ep
en
din
go
nb
act
eri
a
Fa
bry
et
al.
,1
99
8
Eri
ge
ron
ph
ila
de
lph
icu
sL
.(A
ste
race
ae
)
±±
MT
MA
Ma
tric
ari
ala
cto
ne
sM
IC(m
g/m
L),
for
bo
tho
rga
nis
ms,
ran
ge
dfr
om
12
.5ÿ
>1
00
for
ea
cho
fth
eco
mp
ou
nd
ste
ste
d
±S
ign
i®ca
nt
act
ivit
yo
fo
ne
pa
rtic
ula
rco
mp
ou
nd
(4Z
,8
Z-m
atr
ica
ria
est
er)
wh
ich
ga
ve
aM
ICo
f1
2.5
mg
/mL
ag
ain
stM
T
Lu
et
al.,
19
98
Eri
ge
ron
str
igo
su
sM
uh
l.(A
ste
race
ae
)U
SA
Ro
ots
MT
MA
Dic
hlo
rom
eth
an
ee
xtr
act
10
0%
inh
ibit
ion
ag
ain
stM
Ta
nd
MA
at
0.1
mg
/mL
±S
ign
i®ca
nt
act
ivit
yP
osi
tiv
eco
ntr
ols
Ðri
fam
pic
in,
cla
rith
rom
yci
nC
an
tre
lle
ta
l.,
19
98
aE
rio
dic
tyo
ng
luti
no
su
m(H
yd
rop
hy
lla
ce
ae
)
±L
ea
fM
TE
tha
no
le
xtr
act
Act
ive
(co
nce
ntr
ati
on
no
tst
ate
d)
±A
ctiv
ity
Als
oa
ctiv
ea
ga
inst
SA
Go
ttsh
all
et
al.,
19
49
Ery
thri
na
gib
bo
sa
(Pa
pilio
na
ce
ae
)P
an
am
a±
MT
MS
m1
Ph
ase
ollid
in2
Ery
thra
by
ssin
II3
Ery
gib
iso
-¯a
vo
ne
(All
¯a
vo
no
ids)
MIC
(MT
)1
8±2
5m
g/m
L2
8±2
5m
g/m
L3>
25
mg
/mL
MIC
(MS
m)
20
.78
mg
/mL
±±
Mit
sch
er
an
dB
ake
r,1
99
8a
308 S. M. NEWTON ET AL.
Copyright# 2000JohnWiley & Sons,Ltd. Phytother.Res.14, 303–322(2000)
Tab
le1.
Con
tinue
d.
Pla
nt/
Na
tura
lp
rod
uct
Ori
gin
Pa
rtu
sed
Mo
de
lu
sed
/R
ou
teo
fa
dm
inis
tra
tio
nA
ctiv
eC
on
stit
ue
nt(
s)/e
xtr
act
(s)
Act
ivit
yS
ide
eff
ect
s/to
xic
ity
Re
ma
rks
Re
fere
nce
Eu
ca
lyp
tus
bo
try
oid
es
Sm
ith
(My
rta
ce
ae
)
Bra
zil
Le
af
MD
RM
TM
Ta
nd
8o
the
rsp
eci
es
Ess
en
tia
lo
ilO
nly
the
slo
wg
row
ing
my
cob
act
eri
aw
ere
sen
siti
ve
usi
ng
10
mg
/mL
of
ess
en
tia
lo
il
±V
ery
we
ak
act
ivit
yM
ore
ira
et
al.,
19
97
;L
eit
ee
ta
l.,
19
98
Eu
ca
lyp
tus
ca
ma
du
len
sis
De
hn
(My
rta
ce
ae
)
Bra
zil
Le
af
MD
RM
TM
Ta
nd
8o
the
rsp
eci
es
Ess
en
tia
lo
ilO
nly
the
slo
wg
row
ing
my
cob
act
eri
aw
ere
sen
siti
ve
usi
ng
10
mg
/mL
of
ess
en
tia
lo
il.
MT
,M
Aa
nd
MD
RM
Tw
ere
sen
siti
ve
at
5m
g/m
Lo
fe
sse
nti
al
oil
±V
ery
we
ak
act
ivit
yM
ore
ira
et
al.,
19
97
;L
eit
ee
ta
l.,
19
98
Eu
ca
lyp
tus
cit
rio
do
raH
oo
k(M
yrt
ace
ae
)B
razi
lL
ea
fM
DR
MT
MT
an
d8
oth
er
spe
cie
so
fm
yco
ba
cte
ria
Ess
en
tia
lo
ilO
nly
slo
wg
row
ing
we
rese
nsi
tiv
ea
t5
mg
/mL
ex
cep
tM
K±
Ve
ryw
ea
ka
ctiv
ity
Mo
reir
ae
ta
l.,
19
97
;L
eit
ee
ta
l.,
19
98
Eu
ca
lyp
tus
de
glu
pta
Sm
ith
(My
rta
ce
ae
)B
razi
lL
ea
fM
DR
MT
MT
an
d8
oth
er
spe
cie
so
fm
yco
ba
cte
ria
Ess
en
tia
lo
ilM
Aa
nd
MS
cw
ere
sen
siti
ve
at
10
mg
/mL
of
ess
en
tia
lo
il.
All
oth
er
fast
an
dsl
ow
gro
win
go
ne
sw
ere
resi
sta
nt
±V
ery
we
ak
act
ivit
ya
ga
inst
MA
an
dM
S.
No
act
ivit
ya
ga
inst
all
oth
er
spe
cie
so
fm
yco
ba
cte
ria
Mo
reir
ae
ta
l.,
19
97
;L
eit
ee
ta
l.,
19
98
Eu
ca
lyp
tus
glo
bu
lus
La
bil
(My
rta
ce
ae
)B
razi
lL
ea
fM
DR
MT
MT
an
d8
oth
er
spe
cie
so
fm
yco
ba
cte
ria
Ess
en
tia
lo
ilO
nly
MD
R,
MT
,M
T,
MS
c,M
Aw
ere
sen
siti
ve
at
10
mg
/mL
±V
ery
we
ak
act
ivit
yM
ore
ira
et
al.,
19
97
;L
eit
ee
ta
l.,
19
98
±L
ea
fM
TE
tha
no
le
xtr
act
Act
ive
(co
nce
ntr
ati
on
no
tst
ate
d)
±V
ery
we
ak
act
ivit
yG
ott
sha
lle
ta
l.,
19
49
Eu
ca
lyp
tus
gra
nd
isS
mit
h(M
yrt
ace
ae
)B
razi
lL
ea
fM
DR
MT
MT
an
d8
oth
er
spe
cie
so
fm
yco
ba
cte
ria
Ess
en
tia
lo
ilO
nly
act
ive
ag
ain
sta
llsl
ow
gro
win
gm
yco
ba
cte
ria
,e
xce
pt
MA
an
dM
G,
at
5m
g/m
L
±V
ery
we
ak
act
ivit
yM
ore
ira
et
al.,
19
97
;L
eit
ee
ta
l.,
19
98
Eu
ca
lyp
tus
ma
cu
lata
Ho
ok
(My
rta
ce
ae
)B
razi
lL
ea
fM
DR
MT
MT
an
d8
oth
er
spe
cie
so
fm
yco
ba
cte
ria
Ess
en
tia
lo
ilO
nly
act
ive
ag
ain
sta
llth
esl
ow
gro
win
gm
yco
ba
cte
ria
at
5m
g/
mL
,e
xce
pt
MK
±V
ery
we
ak
act
ivit
yM
ore
ira
et
al.,
19
97
;L
eit
ee
ta
l.,
19
98
Eu
ca
lyp
tus
tere
tico
rnis
Sm
ith
(My
rta
ce
ae
)
Bra
zil
Le
af
MD
RM
TM
Ta
nd
8o
the
rsp
eci
es
of
my
cob
act
eri
a
Ess
en
tia
lo
ilO
nly
act
ive
ag
ain
sta
llth
esl
ow
gro
win
gb
act
eri
aa
t5
mg
/mL
,e
xce
pt
MK
an
dM
M
±V
ery
we
ak
act
ivit
yM
ore
ira
et
al.,
19
97
;L
eit
ee
ta
l.,
19
98
Eu
tha
mia
lep
toce
ph
ala
Gre
en
e(A
ste
race
ae
)
US
AA
eri
al
MT
MA
Dic
hlo
rom
eth
an
ee
xtr
act
10
0%
inh
ibit
ion
of
MT
an
dM
Aa
t1
mg
/mL
±A
ctiv
ity
Ca
ntr
ell
et
al.
,1
99
8a
Fe
rula
co
mm
un
is(U
mb
ellif
era
e)
Sa
ud
iA
rab
iaR
hiz
om
eM
IM
XM
CM
Sm
an
do
the
rb
act
eri
al
spe
cie
s
Fe
rule
no
l(C
ou
ma
rin
o-
sesq
uit
erp
en
e)
MIC
(mg
/mL
)o
fA
C=
1.2
5fo
re
ach
of
the
my
cob
act
eri
al
spe
cie
s
±S
ign
i®ca
nt
act
ivit
y.
Fe
rch
rom
on
ew
as
an
oth
er
com
po
un
did
en
ti®
ed
wh
ich
ha
da
nM
ICo
f5
0m
g/m
Lfo
re
ach
of
the
my
cob
act
eri
al
spe
cie
sa
nd
an
MIC
of
12
.5m
g/m
Lfo
re
ach
of
the
ba
cte
ria
lsp
eci
es
Use
din
tra
dit
ion
al
me
dic
ine
for
skin
infe
ctio
ns,
fev
er
an
dd
yse
nte
ry
Al-
Ya
hy
ae
ta
l.,
19
98
Fra
ga
ria
ve
sca
L.
va
r.b
racte
ata
He
lle
rD
av
is(R
osa
ce
ae
)
Br
CL
ea
fM
TM
AM
eth
an
ol
ex
tra
ctS
ma
llzo
ne
of
cle
ari
ng
of
MT
at
50
mg
ex
tra
ct/d
isc.
No
act
ivit
ya
ga
inst
MA
at
50
mg
ex
tra
ct/d
isc
±P
osi
tiv
eco
ntr
olÐ
iso
nia
zid
McC
utc
he
on
et
al.
,1
99
7
Ga
lip
ea
of®
cin
alis
(An
gu
stu
rav
era
)(R
uta
ce
ae
)
±±
MT
Eth
an
ol
ex
tra
ctM
IC(n
og
row
tho
rle
ssth
an
5co
lon
ies)
=1
:32
0d
ilu
tio
n±
Hig
ha
ctiv
ity
Use
dto
tre
at
dia
rrh
oe
aa
nd
fev
ers
Pre
pa
rati
on
list
ed
inth
eB
riti
shp
ha
rma
ceu
tica
lco
de
x,
19
34
.
Gra
ng
ea
nd
Da
ve
y,
19
90
ANTIMYCOBACTERIAL NATURAL PRODUCTS 309
Copyright# 2000JohnWiley & Sons,Ltd. Phytother.Res.14, 303–322(2000)
Tab
le1.
Con
tinue
d.
Pla
nt/
Na
tura
lp
rod
uct
Ori
gin
Pa
rtu
sed
Mo
de
lu
sed
/R
ou
teo
fa
dm
inis
tra
tio
nA
ctiv
eC
on
stit
ue
nt(
s)/e
xtr
act
(s)
Act
ivit
yS
ide
eff
ect
s/to
xic
ity
Re
ma
rks
Re
fere
nce
Ga
lip
ea
of®
cin
alis
(als
ok
no
wn
as
Cu
sp
ari
afe
bri
fug
aH
um
b)
(Ru
tace
ae
)(A
ng
ostu
rab
ark
)
±B
ark
MT
Eth
an
ol
ex
tra
ct(A
lka
loid
s)1
Cu
spa
rin
e2
Ga
lip
ine
34
-me
tho
xy
-2-n
-p
en
tylq
uin
ole
ine
4N
-Me
thy
l-2
-qu
ino
lon
e
MIC
(mg
/mL
)R
an
ge
dfr
om
6.2
5±6
29
de
pe
nd
ing
on
the
fra
ctio
na
nd
the
stra
ino
fM
T
±A
ctiv
e,
ho
we
ve
r,n
on
eo
fth
eco
mp
ou
nd
ssh
ow
ed
act
ivit
ya
sg
rea
ta
sth
etw
op
osi
tiv
eco
ntr
ols
use
dÐ
iso
nia
zid
an
dri
fam
pic
inT
rad
itio
na
lly
use
da
sa
bit
ter
ton
ica
nd
feb
rifu
ge
Sim
ila
ra
lka
loid
sfr
om
oth
er
Ga
lip
ea
spe
cie
sh
av
esh
ow
na
ctiv
ity
ag
ain
stL
eis
hm
an
ia,
Try
pa
no
som
a,
Pla
smo
diu
msp
eci
es
(Sp
ath
an
dP
ikl,
19
30
;F
ou
rne
te
ta
l.,
19
93
,1
99
4,
19
96
)a
nd
sna
ils
(Vie
ira
an
dK
ub
o,
19
90
)
Ho
ug
hto
ne
ta
l.,
19
99
Ge
um
ma
cro
ph
yllu
mW
illd
.va
r.m
acro
ph
yllu
m(R
osa
ce
ae
)
Br
C±
MT
MA
Me
tha
no
le
xtr
act
Co
mp
lete
inh
ibit
ion
of
MT
at
50
mg
ex
tra
ct/d
isc.
No
inh
ibit
ion
of
MA
at
50
mg
ex
tra
ct/d
isc
±S
ign
i®ca
nt
act
ivit
yP
osi
tiv
eco
ntr
olÐ
iso
nia
zid
McC
utc
he
on
et
al.
,1
99
7
Gle
hn
ialitt
ori
sF
.S
ch
mid
tssp
Le
ioca
rpa
(Ma
thia
s)
Hu
lt.
(Um
be
llif
ere
ae
)
Br
CR
oo
tM
TM
AM
eth
an
ol
ex
tra
ctC
om
ple
tein
hib
itio
no
fM
Ta
nd
MA
at
50
mg
ex
tra
ct/d
isc
±S
ign
i®ca
nt
act
ivit
yP
osi
tiv
eco
ntr
ol±
iso
nia
zid
McC
utc
he
on
et
al.
,1
99
7
Gly
cy
rrh
iza
gla
bra
L.
(Le
gu
min
ose
ae
)C
hin
a±
MT
MS
mL
ico
iso
-¯a
vo
ne
(Fla
vo
no
id)
Le
ssa
ctiv
ea
ga
inst
MS
m(5
0m
g/
mL
)th
an
MT
(25
mg
/mL
)±
±M
itsc
he
ra
nd
Ba
ker,
19
98
a,b
Gu
aia
cu
mo
f®cin
ale
(Zy
go
ph
ylla
ce
ae
)±
±M
TE
tha
no
le
xtr
act
MIC
(no
gro
wth
or
less
tha
n5
colo
nie
s)=
1:1
60
dilu
tio
nL
ike
lyto
be
tox
icfo
rcl
inic
al
use
Hig
ha
ctiv
ity
Gra
ng
ea
nd
Da
ve
y,
19
90
Ha
rris
on
iaa
by
ssin
ica
Oliv
.(S
ima
rou
ba
ce
ae
)
Ea
stA
fric
a(K
en
ya
)
Ro
ot
MT
MA
MC
MT
eM
Ia
nd
6b
act
eri
al
spe
cie
s
Me
tha
no
le
xtr
act
No
sig
ni®
can
ta
ctiv
ity
ag
ain
stth
em
yco
ba
cte
ria
±A
ga
inst
the
fast
gro
win
gb
act
eri
a,
the
ex
tra
ctsh
ow
ed
MIC
sa
nd
MB
Cs
of�8
mg
/mL
Fa
bry
et
al.
,1
99
8
He
racle
um
ma
xim
um
Ba
rtr.
(Um
be
llif
era
e)
Br
CR
oo
tM
TM
AM
eth
an
ol
ex
tra
ctC
om
ple
tein
hib
itio
no
fM
Ta
nd
MA
at
50
mg
an
d1
0m
ge
xtr
act
/d
isc
±S
ign
i®ca
nt
act
ivit
y.
Po
siti
ve
con
tro
lÐis
on
iazi
dM
cCu
tch
eo
ne
ta
l.,
19
97
Hu
mu
lus
lup
ulu
s(C
an
na
bin
ace
ae
)±
Flo
we
rM
TE
tha
no
le
xtr
act
Act
ive
(co
nce
ntr
ati
on
no
tst
ate
d)
±S
ign
i®ca
nt
act
ivit
yA
ctiv
ity
als
oto
wa
rds
SA
an
dE
CG
ott
sha
lle
ta
l.,
19
49
Hy
dra
sti
sca
na
de
nsis
(Go
lde
nS
ea
l)(R
an
un
cu
lace
ae
)
Ea
ste
rnN
ort
hA
me
rica
Ro
ot
MS
mM
AC
BC
Ga
nd
va
rio
us
ba
cte
ria
lsp
eci
es
Eth
an
ol
ex
tra
ctB
erb
eri
ne
(alk
alo
id)
MIC
of
AC
MS
m=
25
mg
/mL
BC
G=
20
0m
g/m
LM
AC
=5
0m
g/m
L
±A
ctiv
e.
Be
rbe
rin
eh
as
be
en
de
mo
nst
rate
dto
red
uce
the
infe
ctiv
ity
of
ba
cte
ria
,fu
ng
ia
nd
pro
tozo
ain
an
ima
lsa
nd
hu
ma
ns
by
inh
ibit
ing
the
ad
he
ren
ceo
fm
icro
org
an
ism
sto
the
ho
stce
lls
(Am
ine
ta
l.,
19
69
;P
rein
ing
er,
19
75
;S
ub
ba
iah
an
dA
min
,1
96
7;
Su
ne
ta
l.,
19
88
)
Ge
ntr
ye
ta
l.,
19
98
No
rth
Am
eri
ca±
MS
mM
TM
A
Be
rbe
rin
e(a
lka
loid
)M
ore
act
ive
inv
itro
ag
ain
stM
Sm
(25
mg
/mL
)th
an
ag
ain
stM
T
±T
he
an
ti-T
Be
ffe
ctw
as
pro
ba
bly
du
eto
the
larg
ea
mo
un
to
fb
erb
eri
ne
con
tain
ed
inth
ep
lan
tM
itsc
he
ra
nd
Ba
ker,
19
98
a,b
Hy
pe
ricu
mca
lycin
um
(Hy
pe
rica
ce
ae
)±
Le
af
MT
Eth
an
ol
ex
tra
ctA
ctiv
e.
(co
nce
ntr
ati
on
no
tst
ate
d)
±S
ign
i®ca
nt
act
ivit
yG
ott
sha
lle
ta
l.,
19
49
Hy
pe
ricu
mp
erf
ora
tum
L.
(Hy
pe
rica
ce
ae
)
Br
C±
MT
MA
Me
tha
no
le
xtr
act
Sm
all
zon
eo
fcl
ea
rin
go
fM
Ta
t5
0m
ge
xtr
act
/dis
c.G
rea
tly
inh
ibit
ed
gro
wth
of
MA
at
10
mg
ex
tra
ct/d
isc
±S
ign
i®ca
nt
act
ivit
ya
t1
0m
ge
xtr
act
/dis
cto
wa
rds
MA
Po
siti
ve
con
tro
lÐis
on
iazi
d
McC
utc
he
on
et
al.
,1
99
7
Inu
lah
ele
niu
mL
.(A
ste
race
ae
)U
SA
Ro
ot
MT
Dic
hlo
rom
eth
an
ea
nd
he
xa
ne
ex
tra
cts
10
0%
inh
ibit
ion
ag
ain
stM
Ta
t0
.1m
g/m
L±
Sig
ni®
can
ta
ctiv
ity
Po
siti
ve
con
tro
lsÐ
rifa
mp
icin
,cl
ari
thro
my
cin
Ca
ntr
ell
et
al.
,1
99
8a
310 S. M. NEWTON ET AL.
Copyright# 2000JohnWiley & Sons,Ltd. Phytother.Res.14, 303–322(2000)
Tab
le1.
Con
tinue
d.
Pla
nt/
Na
tura
lp
rod
uct
Ori
gin
Pa
rtu
sed
Mo
de
lu
sed
/R
ou
teo
fa
dm
inis
tra
tio
nA
ctiv
eC
on
stit
ue
nt(
s)/e
xtr
act
(s)
Act
ivit
yS
ide
eff
ect
s/to
xic
ity
Re
ma
rks
Re
fere
nce
±R
oo
tM
T1
ala
nto
lact
on
e2
iosa
lan
tola
cto
ne
31
1,1
3-d
ihy
dro
iso
ala
nto
lac-
ton
e(E
ud
esm
an
olid
es)
iso
late
dfr
om
he
xa
ne
,d
ich
loro
me
tha
ne
an
dm
eth
an
ol
ex
tra
cts.
10
0m
g/m
Lcr
ud
eh
ex
an
ea
nd
chlo
rofo
rme
xtr
act
se
xh
ibit
ed
10
0%
inh
ibit
ion
of
MT
.1
00
mg
/mL
me
tha
no
le
xtr
act
ex
hib
ite
d8
3%
inh
ibit
ion
MIC
of
AC
(mg
/mL
)=
13
22
32
3>
12
8
±S
ign
i®ca
nt
act
ivit
yR
ifa
mp
icin
wa
su
sed
as
the
po
siti
ve
con
tro
lU
sed
intr
ad
itio
na
lm
ed
icin
efo
rtr
ea
tme
nt
of
lun
gd
iso
rde
rsa
nd
ag
ain
stT
B(M
oe
rma
n,
19
86
)E
ud
esm
an
olid
es
are
als
ofo
un
din
Mo
nta
no
asp
eci
osa
an
dR
ud
be
ckia
sub
tom
en
tosa
Ca
ntr
ell
et
al.
,1
99
6b
Ipo
mo
ea
pu
rga
(Ja
lap
a)
(Co
nv
olv
ula
ce
ae
)
±±
MT
Eth
an
ol
ex
tra
ctM
IC(n
og
row
tho
rle
ssth
an
5co
lon
ies)
=1
:16
0.
Pa
rtia
lin
hib
itio
n=
1:3
20
dilu
tio
n
Ha
sp
urg
ati
ve
pro
pe
rtie
sS
ign
i®ca
ntl
ya
ctiv
e,
bu
tm
ay
be
un
suit
ab
led
ue
top
urg
ati
ve
pro
pe
rty
Gra
ng
ea
nd
Da
ve
y,
19
90
Ju
nip
eru
sco
mm
un
isL
.(C
up
ressa
ce
ae
)B
rC
±M
TM
AM
eth
an
ol
ex
tra
ctG
rea
tly
inh
ibit
ed
gro
wth
of
MT
at
50
mg
ex
tra
ct/d
isc.
Sm
all
zon
eo
fcl
ea
rin
go
fM
Aa
t5
0m
ge
xtr
act
/dis
c
±S
ign
i®ca
nt
act
ivit
y.
Po
siti
ve
con
tro
l-is
on
iazi
dM
cCu
tch
eo
ne
ta
l.,
19
97
Ju
nip
eru
se
xce
lsa
M.B
ieb
.(C
up
ressa
ce
ae
)
Sa
ud
iaA
rab
iaL
ea
fM
Sm
MI
MX
MC
Eth
an
ol
ex
tra
ctfo
llo
we
db
yp
art
itio
nb
etw
ee
nn
-he
xa
ne
an
da
ceto
nit
rile
Eth
an
ol
ex
tra
ctio
ny
ield
ed
the
com
po
un
ds,
1F
err
ug
ino
l2
Sa
nd
ara
cop
ime
ric
aci
d3
Hin
oki
no
l4
3b-
hy
dro
xy
-sa
nd
ara
cop
i-m
eri
ca
cid
MIC
(mg
/mL
)=1
5m
g/m
La
ga
inst
ea
chsp
eci
es
23
2m
g/m
L(o
nly
test
ed
on
MS
m)
3In
act
ive
(on
lyte
ste
do
nM
Sm
)4
No
tte
ste
d
±S
ign
i®ca
nt
act
ivit
y,
pa
rtic
ula
rly
of
com
po
un
d1
,a
ga
inst
all
the
my
cob
act
eri
um
spe
cie
sa
nd
com
po
un
d2
ag
ain
stM
Sm
.C
on
tro
lsin
clu
de
dst
rep
tom
yci
na
nd
iso
nia
zid
(MIC
=1
0m
g/m
L)
Mu
ha
mm
ad
et
al.,
19
92
Ju
nip
eru
sp
roce
raH
och
st
(Cu
pre
ssa
ce
ae
)
Sa
ud
iA
rab
iaB
ark
MI
MX
MC
MS
ma
nd
ba
cte
ria
ge
ne
ra
Eth
an
ol
ex
tra
ct,
wh
ich
wa
sfu
rth
er
pa
rtit
ion
ed
be
twe
en
chlo
rofo
rma
nd
aq
ue
ou
sM
eC
N.
Ch
loro
form
fra
ctio
ny
ield
ed
dit
erp
en
es,
17b-
Hy
dro
-x
ya
bie
ta-8
,13
-die
n-1
1,1
2-
dio
ne
Oth
er
ab
ieta
ne
de
riv
ati
ve
so
fco
mp
ou
nd
1w
hic
hw
ere
test
ed
incl
ud
ed
(�)-
ferr
ug
ino
la
nd
(�)-
tota
rol
2C
ryp
totr
ien
olic
aci
d3
Iso
cup
ress
ica
cid
MIC
of
com
po
un
d1
=1
.25
mg
/mL
for
ea
chsp
eci
es
of
my
cob
act
eri
aM
ore
po
ten
tth
an
its
ab
ieta
ne
de
riv
ati
ve
s.(M
IC=
5.0
mg
/mL
an
d2
.5m
g/m
Lfo
r(�
)-fe
rru
gin
ol
an
d(�
)-to
taro
lre
spe
ctiv
ely
)A
lso
act
ive
ag
ain
stth
eg
en
era
of
ba
cte
ria
±S
ign
i®ca
ntl
ya
ctiv
eb
ut
less
po
ten
tth
an
the
po
siti
ve
con
tro
l,a
mik
aci
nsu
lph
ate
(MIC
=0
.25
mg
/mL
ag
ain
ste
ach
spe
cie
s.)
Ho
we
ve
r,M
ICv
alu
es
for
stre
pto
my
cin
an
dis
on
iazi
dw
ere
hig
he
ra
t1
0m
g/m
L.
Co
mp
ou
nd
s2
an
d3
we
ren
ot
test
ed
ag
ain
stth
em
yco
ba
cte
ria
bu
tco
mp
ou
nd
2w
as
we
akl
ya
ctiv
ea
ga
inst
the
ba
cte
ria
spe
cie
sa
nd
com
po
un
d3
wa
sin
act
ive
Mu
ha
mm
ad
et
al.,
19
96
Ka
rwin
sk
iah
um
bo
ldti
an
a(R
ha
mn
ace
ae
)
US
AR
oo
tM
Sm
an
d6
oth
er
typ
es
of
ba
cte
ria
Dic
hlo
rom
eth
an
ea
nd
eth
an
ol
ex
tra
ct.
Ka
rwin
ap
hth
ol
AK
arw
ina
ph
tho
lB
Ka
rwin
ap
hth
ol
Ain
hib
ite
dg
row
tho
fM
Sm
at
12
.5m
g/m
La
nd
Ka
rwin
ap
hth
ol
Ba
t5
0m
g/m
L
±S
ign
i®ca
nt
act
ivit
y.
Se
ed
sa
rep
ois
on
ou
sb
ut
fru
itp
ulp
ise
dib
le.
Use
dlo
cally
inM
ex
ico
totr
ea
tco
nv
uls
ion
s(U
she
r,1
97
4)
Mit
sch
er
et
al.
,1
98
5
La
va
nd
ula
an
gu
sti
folia
Mill.
(la
ve
nd
er)
(La
bia
tae
)
Fra
nce
Flo
we
rM
CM
FM
KM
MM
Sc
Ess
en
tia
lla
va
nd
ino
oils
Dia
me
ter
of
the
zon
es
of
inh
ibit
ion
(in
mm
)ra
ng
ed
fro
m2
0±3
5d
ep
en
din
go
nth
ey
ea
rth
esa
mp
les
we
reh
arv
est
ed
an
dth
esp
eci
es
test
ed
ag
ain
st.
±S
ign
i®ca
nt
an
tim
yco
ba
cte
ria
la
ctiv
ity
on
all
the
spe
cie
sE
xtr
act
sa
lso
we
reco
mp
ara
ble
toth
est
an
da
rds
Sta
nd
ard
sin
clu
de
dA
mik
aci
na
nd
Ka
na
my
cin
Ga
bb
rie
lli
et
al.,
19
88
ANTIMYCOBACTERIAL NATURAL PRODUCTS 311
Copyright# 2000JohnWiley & Sons,Ltd. Phytother.Res.14, 303–322(2000)
Tab
le1.
Con
tinue
d.
Pla
nt/
Na
tura
lp
rod
uct
Ori
gin
Pa
rtu
sed
Mo
de
lu
sed
/R
ou
teo
fa
dm
inis
tra
tio
nA
ctiv
eC
on
stit
ue
nt(
s)/e
xtr
act
(s)
Act
ivit
yS
ide
eff
ect
s/to
xic
ity
Re
ma
rks
Re
fere
nce
Le
uca
sv
olk
en
sii
Gu
rke
(La
bia
tae
)K
en
ya
Ae
ria
lM
TM
eth
an
ol
ex
tra
ct1
(E)-
ph
yto
l2
Ph
yta
no
l3
(Z)-
ph
yto
l4
Mix
ture
of
E)-
an
d(Z
)-p
hy
tol
5G
era
nio
l6
Fa
rne
sol
MIC
12
mg
/mL
22
mg
/mL
32
mg
/mL
42
mg
/mL
56
4m
g/m
L6
8m
g/m
L
±S
ign
i®ca
nt
act
ivit
yfr
om
all
the
com
po
un
ds.
(E)-
ph
yto
l,p
hy
tan
ol,
(Z)-
ph
yto
la
nd
the
mix
ture
of
(E)-
an
d(Z
)-p
hy
tol
we
reth
em
ost
act
ive
an
dth
eir
act
ivit
ies
we
rein
sam
era
ng
ea
se
tha
mb
uto
l(0
.95
±3.8
mg
/mL
)
Ra
jab
et
al.
,1
99
8
Lo
ma
tiu
md
isse
ctu
mN
utt
(Um
be
llif
era
e)
Br
CR
oo
tM
TM
AM
eth
an
ol
ex
tra
ctC
om
ple
tein
hib
itio
no
fM
Ta
nd
MA
at
50
mg
ex
tra
ct/d
isc
±S
ign
i®ca
nt
act
ivit
y.
Po
siti
ve
con
tro
l±is
on
iazi
dM
cCu
tch
eo
ne
ta
l.,
19
97
Lo
nic
era
jap
on
ica
Th
.(C
ap
rifo
lia
ce
ae
)C
hin
a±
MT
±M
IC(c
om
ple
tein
hib
itio
n)
=1
:50
dilu
tio
n±
Sig
ni®
can
ta
ctiv
ity
Wa
ng
,1
95
0
Lu
pin
us
hir
su
tus
(Le
gu
min
osa
e)
±R
oo
tM
Ta
nd
oth
er
ba
cte
ria
lsp
eci
es
Eth
an
ol
ex
tra
ctM
IC=
1:8
0d
ilu
tio
n±
Sig
ni®
can
ta
ctiv
ity
Lu
cas
et
al.
,1
95
1L
up
inu
sp
oly
ph
yllu
s(L
eg
um
ino
sa
e)
±L
ea
fS
tem
Ro
ot
MT
an
do
the
rb
act
eri
al
spe
cie
sE
tha
no
le
xtr
act
MIC
=1
:80
dilu
tio
n±
Sig
ni®
can
ta
ctiv
ity
Lu
cas
et
al.
,1
95
1
Ma
gn
olia
acu
min
ata
(Ma
gn
olia
ce
ae
)U
SA
Ba
rkM
TM
AD
ich
loro
me
tha
ne
ex
tra
ct1
00
%in
hib
itio
na
ga
inst
MT
an
dM
Aa
t0
.1m
g/m
L±
Sig
ni®
can
tly
act
ive
.P
osi
tiv
eco
ntr
ols
Ðri
fam
pin
,cl
ari
thro
my
cin
Ca
ntr
ell
et
al.
,1
99
8a
Ma
gn
olia
gra
nd
i¯o
raa
nd
Ma
gn
olia
vir
gin
ian
a(M
ag
no
lia
ce
ae
)
±±
MT
MA
1C
ost
un
olid
e2
Pa
rth
en
olid
e3
1(1
0)-
ep
ox
yco
stu
no
lid
e(G
erm
acr
an
olid
es)
MIC
(mg
/mL
)v
sM
Ta
nd
MA
resp
ect
ive
lya
re1
32
,1
28
21
6,
64
36
4,
12
8
±S
ign
i®ca
nt
act
ivit
yP
art
he
no
lid
ew
as
the
mo
sta
ctiv
eg
erm
acr
an
olid
ea
ga
inst
bo
thM
Ta
nd
MA
Oth
era-
me
thy
len
e-g
-la
cto
ne
-be
ari
ng
sesq
uit
erp
en
ela
cto
ne
sa
rem
od
era
tely
act
ive
ag
ain
stM
Tw
ith
MIC
so
f6
4m
g/m
La
nd
be
low
Po
siti
ve
con
tro
lsin
clu
de
rifa
mp
icin
an
dcl
ari
thro
my
cin
Fis
che
re
ta
l.,
19
98
Ma
gn
olia
gra
nd
i¯o
raL
.(M
ag
no
lia
ce
ae
)U
SA
Flo
we
rF
ruit
Le
af
MT
MA
Dic
hlo
rom
eth
an
ee
xtr
act
10
0%
inh
ibit
ion
of
MT
at
10
00
mg
/mL
.8
4%
±92
%in
hib
itio
no
fM
Ad
ep
en
din
go
np
art
of
pla
nt
use
d
±W
ea
ka
ctiv
ity
Ca
ntr
ell
et
al.
,1
99
8a
Ma
mm
ea
am
eri
ca
na
(Gu
ttif
era
ce
ae
)P
ue
rto
Ric
oL
ea
fM
Sm
MT
Mic
eA
rte
mia
salin
aL
ea
ch(B
rin
esh
rim
p)
Eth
an
ol
ex
tra
ct1
0m
min
hib
itio
nzo
ne
at
25
mg
/d
isc
for
MS
m.
Act
ivit
yto
wa
rds
MT
at
50
mg
LC
50
=2
24
.6m
g/m
L(B
rin
esh
rim
p).
No
tox
icit
yto
mic
ea
t5
00
mg
/10
0m
Lo
fp
lan
te
xtr
act
mo
use
giv
en
i.p
.o
ve
r1
5d
ay
s
Sig
ni®
can
tly
act
ive
Ba
cte
rici
da
lin
hib
ito
ryp
att
ern
on
MT
gro
wth
com
pa
rab
leto
tha
to
fst
rep
tom
yci
n(u
sed
as
ap
osi
tiv
eco
ntr
ol)
Fra
me
et
al.
,1
99
8
Ma
ng
ife
rain
dic
a(A
na
ca
rdia
ce
ae
)P
ue
rto
Ric
oL
ea
fM
Sm
Mic
eA
rte
mia
salin
aL
ea
ch(B
rin
esh
rim
p)
Eth
an
ol
ex
tra
ct1
2m
min
hib
ito
nzo
ne
at
10
00
mg
/d
isc
for
MS
m.
Act
ive
tow
ard
sM
Ta
t2
50
mg
LC
50=
10
00
mg
/mL
(Bri
ne
shri
mp
)A
ctiv
e.
Lo
wd
eg
ree
of
tox
icit
ya
t5
00
mg
/10
0m
Lo
fp
lan
te
xtr
act
/mo
use
giv
en
i.p
.o
ve
rfo
r1
5d
ay
sS
tre
pto
my
cin
use
da
sp
osi
tiv
eco
ntr
ol
Ba
cte
rio
sta
tic
act
ivit
yto
wa
rds
MT
at
25
0m
g/m
L
Fra
me
et
al.
,1
99
8
Ma
rch
an
tia
po
lym
orp
ha
(Ma
rch
an
tia
ce
ae
)
Pu
ert
oR
ico
Le
af
MS
mM
TM
ice
Art
em
iasa
lin
aL
ea
ch(B
rin
esh
rim
p)
Eth
an
ol
ex
tra
ct7
mm
inh
ibit
ion
zon
ea
t5
0m
g/
dis
cfo
rM
Sm
.A
ctiv
eto
wa
rds
MT
at
10
0m
g
LC
50
=1
00
0m
g/m
L(B
rin
esh
rim
p)
No
tox
icit
yin
mic
ea
t5
00
mg
/10
0m
Lo
fp
lan
te
xtr
act
mo
use
giv
en
i.p
.o
ve
r1
5d
ay
s
Sig
ni®
can
tly
act
ive
.L
ow
tox
icit
y.
Tra
nsi
tory
inh
ibit
ion
of
MT
gro
wth
sim
ila
rto
the
gro
wth
inh
ibit
ory
eff
ect
sfo
rkn
ow
nb
act
eri
ost
ati
ce
ffe
cts.
Str
ep
tom
yci
nu
sed
as
ne
ga
tiv
eco
ntr
ol
Fra
me
et
al.
,1
99
8
Me
lia
vo
lke
nsii
Gu
rke
(Me
lia
ce
ae
)
Ke
ny
aS
ee
ds
MT
Me
tha
no
le
xtr
act
11
2b
hy
dro
xy
kula
cto
ne
26b
hy
dro
xy
kula
cto
ne
3K
ulo
na
te
MIC
(mg
/mL
)1
16
24
31
6
Ho
we
ve
rit
isp
ois
on
ou
sa
th
igh
er
do
sele
ve
ls(K
okw
aro
,1
97
6)
Sig
ni®
can
tly
act
ive
.U
sed
info
lkm
ed
icin
eto
alle
via
tep
ain
-te
ap
rep
are
dfr
om
ba
rk.
Ku
lon
ate
pre
vio
usl
yis
ola
ted
fro
mM
elia
aze
da
rach
(Ch
ian
ga
nd
Ch
an
g,
19
73
;O
chi
et
al.
,1
97
7)
Ca
ntr
ell
et
al.
,1
99
9a
312 S. M. NEWTON ET AL.
Copyright# 2000JohnWiley & Sons,Ltd. Phytother.Res.14, 303–322(2000)
Tab
le1.
Con
tinue
d.
Pla
nt/
Na
tura
lp
rod
uct
Ori
gin
Pa
rtu
sed
Mo
de
lu
sed
/R
ou
teo
fa
dm
inis
tra
tio
nA
ctiv
eC
on
stit
ue
nt(
s)/e
xtr
act
(s)
Act
ivit
yS
ide
eff
ect
s/to
xic
ity
Re
ma
rks
Re
fere
nce
Mo
mo
rdic
ach
ara
nti
aL
.(C
ucu
rbit
ace
ae
)P
ue
rto
Ric
oL
ea
fM
Sm
MT
Mic
eA
rte
mia
salin
aL
ea
ch(B
rin
esh
rim
p)
Eth
an
ol
ex
tra
ct3
0m
min
hib
itio
nzo
ne
at
50
0m
g/
dis
cfo
rM
Sm
.A
ctiv
ea
ga
inst
MT
at
50
0m
g
LC
50
=3
3m
g/m
L(s
hri
mp
).N
oto
xic
ity
inm
ice
at
50
0m
g/1
00
mL
of
pla
nt
ex
tra
ct/m
ou
seg
ive
ni.p
.o
ve
r1
5d
ay
s
Sig
ni®
can
tly
act
ive
Fra
me
et
al.
,1
99
8
Mo
ne
se
su
ni¯
ora
L.
(Eri
ca
ce
ae
)B
rC
Ae
ria
lM
TM
AM
eth
an
ol
ex
tra
ctC
om
ple
tein
hib
itio
no
fM
Ta
nd
MA
at
50
mg
an
d1
0m
ge
xtr
act
/d
isc
±S
ign
i®ca
nt
act
ivit
y.
Po
siti
ve
con
tro
l-is
on
iazi
dM
cCu
tch
eo
ne
ta
l.,
19
97
My
rica
asp
len
i¯o
ra(M
yri
ca
ce
ae
)±
Le
af
MT
EC
SA
Eth
an
ol
ex
tra
ct,
Bo
ilin
gw
ate
re
xtr
act
Act
ive
ag
ain
stM
Tw
ith
bo
the
xtr
act
s(c
on
cen
tra
tio
nn
ot
sta
ted
).N
oa
ctiv
ity
ag
ain
stE
Ca
nd
SA
±S
ign
i®ca
nt
act
ivit
yG
ott
sha
lle
ta
l.,
19
49
Nu
ph
ar
lute
aL
.(N
ym
ph
ace
ae
)B
rC
Rh
izo
me
MT
MA
Me
tha
no
le
xtr
act
Co
mp
lete
inh
ibit
ion
of
MT
at
50
mg
ex
tra
ct/d
isc.
Sm
all
zon
eo
fcl
ea
rin
go
fM
Aw
ith
50
mg
ex
tra
ct/d
isc
±S
ign
i®ca
nt
act
ivit
ya
t5
0m
g/m
LP
osi
tiv
eco
ntr
ol-
iso
nia
zid
McC
utc
he
on
et
al.
,1
99
7
Ocim
um
sa
nctu
mL
inn
.M
an
t(U
nk
no
wn
)
±L
ea
fM
T(t
wo
resi
sta
nt
stra
ins)
Aq
ue
ou
sC
om
ple
tein
hib
itio
no
fa
llst
rain
sw
ith
a1
:1d
ilu
tio
no
fth
ee
xtr
act
±S
ign
i®ca
nt
act
ivit
y.
Co
ntr
ols
incl
ud
ed
stre
pto
my
cin
,is
on
iazi
da
nd
eth
am
bu
tol
Re
dd
ie
ta
l.,
19
86
Op
lop
an
ax
ho
rrid
us
Sm
ith
Miq
.(A
ralia
ce
ae
)
Br
CIn
ne
rb
ark
MT
MA
Me
tha
no
le
xtr
act
Co
mp
lete
inh
ibit
ion
of
MT
an
dM
Aw
ith
10
mg
ex
tra
ct/d
isc
±S
ign
i®ca
nt
act
ivit
yP
osi
tiv
eco
ntr
ol-
iso
nia
zid
McC
utc
he
on
et
al.
,1
99
7
Op
lop
an
ax
ho
rrid
us
(De
vil's
clu
b)
(Ara
lia
ce
ae
)
No
rth
Am
eri
caIn
ne
rb
ark
MT
Iso
nia
zid
resi
sta
nt-
MA
Oth
er
ba
cte
ria
la
nd
fun
ga
lsp
eci
es
1F
alc
ari
nd
ol
2F
alc
ari
no
l3
Op
lop
an
dio
l4
Act
ive
oil
1(C
20H
28O
4)
5A
ctiv
eo
il2
(C2
0H
30O
4)
All
po
lyy
ne
sis
ola
ted
fro
me
xtr
act
ion
wit
hm
eth
an
ol
follo
we
db
yd
ich
loro
me
tha
ne
All
act
ive
con
stit
ue
nts
me
tha
no
la
nd
chlo
rofo
rme
xtr
act
sw
ere
act
ive
at
aco
nce
ntr
ati
on
of
10
mg
/dis
ca
ga
inst
MT
an
dis
on
iazi
dre
sist
an
tM
AF
alc
ari
no
la
nd
act
ive
oil
2(C
20H
30O
4)
com
ple
tely
inh
ibit
ed
gro
wth
of
MT
an
dis
on
iazi
dre
sist
an
tM
Aa
t2
0m
g/d
isc
±A
llco
mp
ou
nd
ssi
gn
i®ca
ntl
ya
ctiv
ea
ga
inst
MT
Use
db
y®
rst
na
tio
ns
pe
op
lein
tra
dit
ion
al
me
dic
ine
for
av
ari
ety
of
ailm
en
tssu
cha
sd
iab
ete
s,rh
eu
ma
tism
,tu
be
rcu
losi
s,co
lds,
he
ad
ach
es
an
dlu
ng
ailm
en
ts(T
urn
er,
19
82
;T
urn
er
et
al.
,1
99
0)
Ko
ba
isy
et
al.
,1
99
7
Pa
na
xg
inse
ng
(Ara
lia
ce
ae
)±
Ro
ot
MT
Me
tha
no
le
xtr
act
,e
tha
no
le
xtr
act
,e
the
re
xtr
act
My
cob
act
eri
al
gro
wth
inh
ibit
ed
by
10
0m
g/m
Le
the
re
xtr
act
an
db
y5
00
mg
/mL
of
eth
an
ol
an
dm
eth
an
ol
ex
tra
cts
±G
inse
ng
isu
sed
intr
ad
itio
na
lm
ed
icin
eC
ha
ng
et
al.,
19
79
Pa
rme
lia
sa
xa
tilis
L.
(Pa
rme
lia
ce
ae
)±
±M
Au
Sa
lazi
nic
aci
dM
IC=
25
0m
g/m
L±
We
ak
act
ivit
yC
on
tro
lsin
clu
de
dri
fam
pic
in,
stre
pto
my
cin
,is
on
iazi
d
Ing
olf
sdo
ttir
et
al.,
19
98
Pe
nta
slo
ng
i¯o
raO
liv
.(R
ub
iace
ae
)R
wa
nd
aR
oo
tM
TM
AC
MS
iS
LM
Eth
an
ol
ex
tra
ctS
ho
we
da
ctiv
ity
ag
ain
stM
Ta
nd
MS
ia
t1
00
0m
g/m
LN
oa
ctiv
ity
ag
ain
sta
llo
the
rsp
eci
es
±W
ea
ka
ctiv
ity
.U
sed
inR
wa
nd
ese
tra
dit
ion
al
me
dic
ine
for
the
tre
atm
en
to
fp
ulm
on
ary
dis
ea
ses
(Va
nP
uy
ve
lde
et
al.
,1
97
5,
19
77
,1
98
2)
Co
ntr
ols
usi
ng
con
ve
nti
on
al
an
ti-t
ub
erc
ulo
sis
dru
gs
Va
nP
uy
ve
lde
et
al.
,1
99
4
Pe
tasit
es
jap
on
ica
s(C
om
po
sit
ae
)±
Ro
ot
MT
Eth
an
ol
ex
tra
ctM
IC=
1:8
0d
ilu
tio
n±
Sig
ni®
can
ta
ctiv
ity
Lu
cas
et
al.
,1
95
1
ANTIMYCOBACTERIAL NATURAL PRODUCTS 313
Copyright# 2000JohnWiley & Sons,Ltd. Phytother.Res.14, 303–322(2000)
Tab
le1.
Con
tinue
d.
Pla
nt/
Na
tura
lp
rod
uct
Ori
gin
Pa
rtu
sed
Mo
de
lu
sed
/R
ou
teo
fa
dm
inis
tra
tio
nA
ctiv
eC
on
stit
ue
nt(
s)/e
xtr
act
(s)
Act
ivit
yS
ide
eff
ect
s/to
xic
ity
Re
ma
rks
Re
fere
nce
Pic
rasm
aa
ila
nth
oid
es
(Sim
aro
ub
ace
ae
)±
±M
T1
Nig
aki
he
mia
ceta
l2
Nig
aki
lact
on
e-L
3N
eo
qu
ass
in4
Nig
aki
he
mia
ceta
l-A
5Q
ua
ssin
6N
iga
kila
cto
ne
-H7
Nig
aki
lact
on
e-E
8P
icra
sin
-A(Q
ua
ssin
oid
s)
Inh
ibit
ion
sa
t1
2.5
mg
/mL
are
11
2%
29
%3
8%
48
%5
7%
65
%7
5%
84
%
±A
ctiv
itie
so
fq
ua
ssin
oid
sw
ere
ve
rylo
wra
ng
ing
fro
m1
±19
%in
hib
itio
na
t1
2.5
mg
/mL
Po
siti
ve
con
tro
l-ri
fam
pic
in
Ra
hm
an
et
al.
,1
99
7
Pie
ris
¯o
rib
un
da
(Eri
ca
ce
ae
)±
Le
af
MT
Wa
ter
ex
tra
ctM
IC(c
om
ple
tein
hib
itio
n)
=1
:64
0d
ilu
tio
n±
Sig
ni®
can
ta
ctiv
ity
Fit
zpa
tric
k,1
95
4P
ieri
sja
po
nic
a(E
rica
ce
ae
)±
Le
af
MT
Wa
ter
ex
tra
ctM
IC(c
om
ple
tein
hib
itio
n)
=1
:64
0d
ilu
tio
n±
Sig
ni®
can
ta
ctiv
ity
Fit
zpa
tric
k,1
95
4P
ilo
ca
rpu
sra
ce
mo
su
s(R
uta
ce
ae
)G
ua
d±
MT
MK
MA
Pilo
carp
ine
(alk
alo
id)
MIC
(mg
/mL
)w
as
gre
ate
rth
an
10
0fo
re
ach
test
org
an
ism
±N
osi
gn
i®ca
nt
act
ivit
ya
ga
inst
MT
,M
A,
MK
Ra
sto
gi
et
al.
,1
99
8
Pin
us
co
nto
rta
(Pin
ace
ae
)B
rC
±M
TM
AM
eth
an
ol
ex
tra
ctC
om
ple
tein
hib
itio
no
fM
Tw
ith
50
mg
ex
tra
ct/d
isc.
Sm
all
zon
eo
fcl
ea
rin
go
fM
Aw
ith
50
mg
ex
tra
ct/d
isc
±S
ign
i®ca
nt
act
ivit
ya
t5
0m
ge
xtr
act
/dis
cfo
rM
TM
cCu
tch
eo
ne
ta
l.,
19
97
Pip
er
cu
be
ba
(Pip
era
ce
ae
)In
do
-n
esi
a±
MT
Eth
an
ol
ex
tra
ctM
IC(n
og
row
tho
rle
ssth
an
5co
lon
ies)
=1
:32
0d
ilu
tio
n±
Hig
hsp
eci
®c
act
ivit
y.
Use
dto
tre
at
pu
lmo
na
rya
nd
uri
na
ryin
fect
ion
sa
nd
isa
nti
ba
cte
ria
lin
vit
ro(W
ren
,1
98
8)
Gra
ng
ea
nd
Da
ve
y,
19
90
Po
lysti
tch
um
mu
nit
um
Ka
ulf
(Po
lyp
od
iace
ae
)
Br
C±
MT
MA
Me
tha
no
le
xtr
act
Sm
all
zon
eo
fcl
ea
rin
go
fM
Ta
nd
MA
wit
h5
0m
ge
xtr
act
/dis
c±
Po
siti
ve
con
tro
l-is
on
iazi
dM
cCu
tch
eo
ne
ta
l.,
19
97
Po
pu
lus
tre
mu
loid
es
(Sa
lica
ce
ae
)B
rC
±M
TM
AM
eth
an
ol
ex
tra
ctC
om
ple
tein
hib
itio
no
fM
Tw
ith
50
mg
ex
tra
ct/d
isc.
Sm
all
zon
eo
fcl
ea
rin
go
fM
Aw
ith
50
mg
ex
tra
ct/d
isc
±S
ign
i®ca
nt
act
ivit
yo
f5
0m
ge
xtr
act
/dis
ca
ga
inst
MT
.P
osi
tiv
eco
ntr
ol-
iso
nia
zid
McC
utc
he
on
et
al.
,1
99
7
±±
MT
Eth
an
ol
ex
tra
ctM
IC(n
og
row
tho
rle
ssth
an
5co
lon
ies)
=1
:32
0d
ilu
tio
n.
Pa
rtia
lin
hib
itio
no
fM
Ta
t1
:64
0
Ap
pe
ars
tob
en
on
-to
xic
.H
as
be
en
giv
en
by
inh
ala
tio
nto
tre
at
pu
lmo
na
ryin
fect
ion
s(N
iku
lin
et
al.,
19
79
)
Hig
ha
ctiv
ity
Gra
ng
ea
nd
Da
ve
y,
19
90
Pro
po
lis
Ch
ile
Re
sin
MT
MA
Me
tha
no
le
xtr
act
pa
rtit
ion
ed
be
twe
en
dic
hlo
rom
eth
an
ea
nd
wa
ter
Org
an
icp
ha
sey
ield
ed
17
com
po
un
ds.
Act
ive
on
es
incl
ud
ed
,1
Vis
cid
on
e-1
4-a
ceta
te2
Co
nif
ery
la
lde
hy
de
3D
ihy
dro
be
nzo
fura
nlig
an
ald
eh
yd
e
MIC
(mg
/mL
)o
fcr
ud
ee
xtr
act
=1
28
mg
/mL
for
bo
thsp
eci
es
MIC
(mg
/mL
)o
fco
mp
ou
nd
s=
16
4m
g/m
L(M
Ta
nd
MA
)2
64
mg
/mL
(MT
)a
nd
12
8m
g/m
L(M
A)
36
4m
g/m
L(M
T)
an
d1
28
mg
/mL
(MA
)
±S
ign
i®ca
nt
act
ivit
yo
fa
llco
mp
ou
nd
sa
ga
inst
MT
an
dco
mp
ou
nd
1a
ga
inst
MA
Co
ntr
ols
incl
ud
ed
rifa
mp
icin
an
dcl
ari
thro
my
cin
Va
lcic
et
al.
,1
99
9
Pri
mu
lam
ala
co
ide
s(P
rim
ula
ce
ae
)±
Flo
we
rP
ed
un
cle
MT
Eth
an
ol
ex
tra
ctM
IC=
1:8
0d
ilu
tio
n±
Sig
ni®
can
tly
act
ive
Lu
cas
et
al.
,1
95
1
314 S. M. NEWTON ET AL.
Copyright# 2000JohnWiley & Sons,Ltd. Phytother.Res.14, 303–322(2000)
Tab
le1.
Con
tinue
d.
Pla
nt/
Na
tura
lp
rod
uct
Ori
gin
Pa
rtu
sed
Mo
de
lu
sed
/R
ou
teo
fa
dm
inis
tra
tio
nA
ctiv
eC
on
stit
ue
nt(
s)/e
xtr
act
(s)
Act
ivit
yS
ide
eff
ect
s/to
xic
ity
Re
ma
rks
Re
fere
nce
Pru
nu
sm
um
e(R
osa
ce
ae
)U
SA
Ho
ng
Ko
ng
Be
rry
MT
Cit
ric
aci
dM
alic
aci
da
nd
va
rio
us
oth
er
aci
ds
Cit
ric
aci
de
xtr
act
inh
ibit
ed
gro
wth
of
MT
on
ag
ar,
giv
ing
a7
.1m
mm
ea
nra
dia
lw
idth
of
inh
ibit
ion
.T
his
wa
sh
igh
est
of
all
aci
ds
test
ed
Bio
act
ivit
yis
rath
er
low
wh
en
com
pa
red
wit
hd
rug
ssu
cha
sIN
H
±C
itri
ca
cid
wa
ssh
ow
nto
ha
ve
spe
ci®
ca
nd
sig
ni®
can
ta
ctiv
ity
ag
ain
stM
TU
sed
intr
ad
itio
na
lC
hin
ese
me
dic
ine
(Li
Sh
ih-
Ch
en
,1
93
0;
Ka
riy
on
ea
nd
Kim
ura
,1
96
2)
Ro
pe
ra
nd
Ma
.,1
96
8;
Ma
an
dR
op
er,
19
68
Pu
nic
ag
ran
atu
mL
.(P
un
ica
ce
ae
)C
hin
a±
MT
Alc
oh
ol
ex
tra
ctM
IC(c
om
ple
tein
hib
itio
n)
=1
:50
dilu
tio
n±
Sig
ni®
can
ta
ctiv
ity
Wa
ng
,1
95
0
Py
rus
atr
osa
ng
uin
ea
(Ro
sa
ce
ae
)±
Le
af
MT
an
do
the
rb
act
eri
al
spe
cie
sE
tha
no
le
xtr
act
MIC
=1
:80
dilu
tio
n±
Sig
ni®
can
ta
ctiv
ity
Lu
cas
et
al.
,1
95
1R
au
wo
l®a
bia
uri
cu
lata
(Ap
ocy
na
ce
ae
)
Gu
ad
±M
TM
AM
K
Lo
chn
eri
n(I
nd
ole
alk
alo
id)
MIC
wa
s1
00
mg
/mL
for
ea
chte
sto
rga
nis
m±
No
sig
ni®
can
ta
ctiv
ity
ag
ain
stM
T,
MA
,M
KR
ast
og
ie
ta
l.,
19
98
Rh
eu
mo
f®cin
ale
(Po
lyg
on
ace
ae
)±
Ro
ot
MT
Eth
an
ol
ex
tra
ctA
ctiv
e(c
on
cen
tra
tio
nn
ot
sta
ted
)±
Sig
ni®
can
ta
ctiv
ity
Go
ttsh
all
et
al.,
19
49
Rh
am
nu
sca
tha
rtic
a(R
ha
mn
ace
ae
)±
±M
TE
tha
no
le
xtr
act
MIC
(no
gro
wth
or
less
tha
n5
colo
nie
s)=
1:1
60
dilu
tio
nH
as
ap
urg
ati
ve
pro
pe
rty
Hig
hsp
eci
®c
act
ivit
yb
ut
pu
rga
tiv
ep
rop
ert
yG
ran
ge
an
dD
av
ey
,1
99
0R
osa
ca
nin
a(R
osa
ce
ae
)±
Le
af
Ste
mF
low
er
MT
an
do
the
rb
act
eri
al
spe
cie
sE
tha
no
le
xtr
act
MIC
=1
:80
dilu
tio
n±
Sig
ni®
can
ta
ctiv
ity
Lu
cas
et
al.
,1
95
1
Ro
sa
nu
tka
na
Pre
sl
va
r.n
utk
an
a(R
osa
ce
ae
)
Br
C±
MT
MA
Me
tha
no
le
xtr
act
Sm
all
zon
eo
fcl
ea
rin
go
fM
Ta
nd
MA
wit
h5
0m
ge
xtr
act
/dis
c±
Po
siti
ve
con
tro
l±is
on
iazi
dM
cCu
tch
eo
ne
ta
l.,
19
97
Ru
db
eck
iasu
bm
en
tosa
(Aste
race
ae
)
±R
oo
tL
ea
fS
tem
Flo
we
r
MT
1A
llo
lan
tola
cto
ne
32
ox
oa
llo
ala
nto
lact
on
eis
ola
ted
fro
md
ich
loro
me
tha
ne
ex
tra
ct
10
0m
g/m
Ld
ich
loro
me
tha
ne
ex
tra
cto
fro
ot
ga
ve
a9
9%
inh
ibit
ion
.M
IC(m
g/m
L)
=1
32
21
28
±S
ign
i®ca
nt
act
ivit
yR
ifa
mp
icin
wa
su
sed
as
the
po
siti
ve
con
tro
lC
om
po
un
ds
pre
vio
usl
yis
ola
ted
fro
mE
up
ato
riu
mq
ua
dra
ng
ula
rae
(Oku
na
de
an
dW
iem
er,
19
85
)
Ca
ntr
ell
et
al.
,1
99
9b
Sa
lix
ca
pre
a(S
alica
ce
ae
)±
Flo
we
rM
Ta
nd
oth
er
ba
cte
ria
lsp
eci
es
Eth
an
ol
ex
tra
ctM
IC=
1:8
0d
ilu
tio
n±
Sig
ni®
can
ta
ctiv
ity
Lu
cas
et
al.
,1
95
1S
alv
iaH
yp
arg
eia
Fis
ch
.E
tM
ey
.(L
ab
iata
e)
Ea
ste
rnT
urk
ey
Ro
ot
MT
an
db
act
eri
al
stra
ins
Hy
pa
rge
nin
Fis
ola
ted
fro
ma
ceto
ne
ex
tra
ctA
ctiv
ity
ag
ain
stM
Ta
t2
50
mg
/mL
±A
ctiv
ea
ga
inst
MT
Act
ive
als
oa
ga
inst
va
rio
us
ge
ne
rao
fb
act
eri
aw
ith
MIC
va
lue
s(m
g/m
L)
ran
gin
gfr
om
62
.5±1
25
Ulu
be
len
et
al.,
19
88
Sa
lvia
mu
ltic
au
lis
Va
hl.
(La
bia
tae
)T
urk
ey
Ro
ot
MT
1N
ora
bie
tan
e1
2N
ora
bie
tan
e2
3N
ora
bie
tan
e3
4N
ora
bie
tan
e4
5A
bie
tan
e1
6A
bie
tan
e2
7P
rim
ara
ne
All
iso
late
dfr
om
an
ace
ton
eso
lub
lee
xtr
act
MIC
15
.6m
g/m
L2
0.4
6m
g/m
L3
2.0
mg
/mL
41
.2m
g/m
L5
1.2
mg
/mL
60
.89
mg
/mL
77
.3m
g/m
L
±A
llsi
gn
i®ca
ntl
ya
ctiv
eb
ut
No
rab
ieta
ne
s2
,4
,5
,a
nd
Ab
ieta
ne
2a
rem
ost
po
ten
tT
est
com
po
un
ds
1±7
ga
ve
com
pa
rab
lev
alu
es
tost
an
da
rda
nti
-tu
be
rcu
lar
ag
en
tsi.e
.ri
fam
pic
inS
alv
iasp
eci
es
use
din
tra
dit
ion
al
me
dic
ine
an
dh
av
eb
ee
na
sso
cia
ted
wit
ha
nti
ba
cte
ria
l,a
nti
tub
erc
ulo
us,
an
da
nti
ph
log
isti
ca
ctiv
itie
s(L
ine
ta
l.,
19
89
)
Ulu
be
len
et
al.,
19
97
Sa
lvia
of®
cin
alis
(La
bia
tae
)±
Le
af
MT
Eth
an
ol
ex
tra
ctA
ctiv
e±
Sig
ni®
can
ta
ctiv
ity
.A
lso
act
ive
ag
ain
stS
AG
ott
sha
lle
ta
l.,
19
49
Sa
ng
uin
ari
aca
na
de
nsis
(Pa
pa
ve
race
ae
)
±R
oo
tM
TE
tha
no
le
xtr
act
Act
ive
±S
ign
i®ca
nt
act
ivit
y.
Als
oa
ctiv
ea
ga
inst
SA
Go
ttsh
all
et
al.,
19
49
Sa
ng
uis
orb
ao
f®cin
alis
L.
(Ro
sa
ce
ae
)
Ch
ina
±M
TA
lco
ho
le
xtr
act
MIC
(co
mp
lete
inh
ibit
ion
)=
1:5
0d
ilu
tio
n±
Sig
ni®
can
ta
ctiv
ity
Wa
ng
,1
95
0
ANTIMYCOBACTERIAL NATURAL PRODUCTS 315
Copyright# 2000JohnWiley & Sons,Ltd. Phytother.Res.14, 303–322(2000)
Tab
le1.
Con
tinue
d.
Pla
nt/
Na
tura
lp
rod
uct
Ori
gin
Pa
rtu
sed
Mo
de
lu
sed
/R
ou
teo
fa
dm
inis
tra
tio
nA
ctiv
eC
on
stit
ue
nt(
s)/e
xtr
act
(s)
Act
ivit
yS
ide
eff
ect
s/to
xic
ity
Re
ma
rks
Re
fere
nce
Sa
nto
lin
ach
am
ae
cy
pa
rissu
s(A
ste
race
ae
)
±R
oo
tM
Ta
nd
oth
er
ba
cte
ria
lsp
eci
es
Eth
an
ol
ex
tra
ctM
IC=
1:8
0d
ilu
tio
n±
Sig
ni®
can
ta
ctiv
ity
Lu
cas
et
al.
,1
95
1
Sa
ussu
rea
lap
pa
(Aste
race
ae
)±
±M
TM
AD
eh
yd
roco
stu
sla
cto
ne
MIC
(mg
/mL
=2
(MT
)1
6(M
A)
±S
ign
i®ca
nt
act
ivit
yC
an
tre
lle
ta
l.,
19
98
b
Sch
iza
nd
rach
ine
nsis
(Sch
isa
nd
race
ae
)C
hin
aB
err
yM
TC
itri
ca
cid
,M
alic
aci
da
nd
va
rio
us
oth
er
aci
ds
Cit
ric
aci
din
hib
ite
dg
row
tho
fM
To
na
ga
rg
ivin
ga
me
an
rad
ial
wid
tho
f7
.1m
m.
Th
isw
as
the
hig
he
sto
fa
lla
cid
ste
ste
d.
Bio
-act
ivit
yis
rath
er
low
wh
en
com
pa
red
wit
hd
rug
ssu
cha
sIN
H
±C
itri
ca
cid
wa
ssh
ow
nto
ha
ve
low
act
ivit
ya
ga
inst
MT
Ho
we
ve
rth
eh
yd
razi
de
s(f
rom
oth
er
aci
ds)
pro
du
cee
ve
ng
rea
ter
act
ivit
yth
an
the
pa
ren
ta
cid
sU
sed
intr
ad
itio
na
lC
hin
ese
me
dic
ine
(Li
Sh
ih-
Ch
en
,1
93
0;
Ka
riy
on
ea
nd
Kim
ura
,1
96
2)
Ro
pe
ra
nd
Ma
,1
96
8M
aa
nd
Ro
pe
r,1
96
8
So
lan
um
so
do
ma
eu
mL
.(S
ola
na
ce
ae
)
Lib
ya
Be
rry
MI
So
lso
do
min
eA
So
lso
do
min
eB
(Py
rro
lea
lka
loid
s)
So
lso
do
min
eA
MIC
=1
0m
g/m
LS
ols
od
om
ine
Bh
ad
no
act
ivit
yo
nM
I
No
cyto
tox
ica
ctiv
ity
tow
ard
sV
ero
cells
(do
sen
ot
sta
ted
)
Sig
ni®
can
ta
ctiv
ity
of
So
lso
do
min
eA
tow
ard
sM
I.S
ols
od
om
ine
sA
an
dB
did
no
tsh
ow
inv
itro
an
tim
ala
ria
l,a
nti
fun
ga
lo
rcy
toto
xic
act
ivit
y(c
on
cen
tra
tio
ns
no
tst
ate
d).
El
Sa
ye
de
ta
l.,
19
98
So
lid
ag
oca
na
de
nsis
L.
(Aste
race
ae
)±
±M
TM
AC
-10
-O-a
cyla
ted
ma
tric
ari
ae
ste
rsa
nd
ad
eh
yd
ro-
ma
tric
ari
ae
ste
r
MIC
va
lue
s(m
g/m
L)
for
MT
an
dM
Ara
ng
ed
fro
m1
2.5
to>
10
0m
g/m
l
±S
ign
i®ca
nt
act
ivit
yL
ue
ta
l.,
19
98
So
lid
ag
oru
go
sa
Mill.
(Aste
race
ae
)N
ort
hA
me
rica
Ro
ot
Ae
ria
lM
TM
A(D
ite
rpe
ne
s)1
Ko
lav
en
ol
2H
ard
wic
kiic
aci
d3
Hy
dro
xy
ma
no
ol
4M
on
oa
ceta
te5
Dia
ceta
te6
En
tab
ieti
ca
cid
iso
late
dfr
om
the
dic
hlo
rom
eth
an
ee
xtr
act
MIC>
10
0m
g/m
La
ga
inst
MT
an
dM
Afo
ra
ll6
com
po
un
ds
test
ed
±A
llsh
ow
no
sig
ni®
can
ta
nti
-my
cob
act
eri
al
act
ivit
yC
om
po
un
d2
als
op
rese
nt
inH
ard
wic
kia
pin
na
taC
om
po
un
d4
als
op
rese
nt
inJ
un
ipe
rus
pse
ud
osa
bin
a
Lu
et
al.,
19
95
So
lid
ag
oa
rgu
taA
it.
(Aste
race
ae
)U
SA
Ro
ot
MT
MA
Dic
hlo
rom
eth
an
ee
xtr
act
10
0%
inh
ibit
ion
ag
ain
stM
Ta
t0
.1m
g/m
L.
80
%in
hib
itio
na
ga
inst
MA
at
0.1
mg
/mL
±S
ign
i®ca
ntl
ya
ctiv
eP
osi
tiv
eco
ntr
ols
incl
ud
eri
fam
pic
ina
nd
cla
rith
rom
yci
n
Ca
ntr
ell
et
al.
,1
99
8a
Sp
ila
nth
es
ma
uri
tia
na
A.
Ric
h.
DC
.(A
ste
race
ae
)
Ea
stA
fric
a(K
en
ya
)
Ro
ot
Flo
we
rM
TM
AM
CM
Te
MI
an
db
act
eri
al
stra
ins
Me
tha
no
le
xtr
act
Co
nce
ntr
ati
on
of
2m
g/m
La
llo
we
dth
eg
row
tho
fm
ore
tha
n1
0%
of
the
ino
culu
mo
fth
e5
my
cob
act
eri
al
stra
ins
±N
osi
gn
i®ca
nt
act
ivit
ya
ga
inst
the
my
cob
act
eri
aF
ab
rye
ta
l.,
19
98
Ste
reo
ca
ulo
na
lpin
um
(Ste
reo
ca
ulo
na
ce
ae
)
Ice
lan
d±
MA
u1
Atr
an
ori
n2
Lo
ba
ric
aci
d
MIC
=1
25
0m
g/m
L2
12
5m
g/m
L
±C
on
tro
lsin
clu
de
dri
fam
pic
in,
stre
pto
my
cin
,is
on
iazi
dIn
go
lfsd
ott
ire
ta
l.,
19
98
316 S. M. NEWTON ET AL.
Copyright# 2000JohnWiley & Sons,Ltd. Phytother.Res.14, 303–322(2000)
Tab
le1.
Con
tinue
d.
Pla
nt/
Na
tura
lp
rod
uct
Ori
gin
Pa
rtu
sed
Mo
de
lu
sed
/R
ou
teo
fa
dm
inis
tra
tio
nA
ctiv
eC
on
stit
ue
nt(
s)/e
xtr
act
(s)
Act
ivit
yS
ide
eff
ect
s/to
xic
ity
Re
ma
rks
Re
fere
nce
Str
ob
ila
nth
us
cu
sia
(Aca
nth
ace
ae
)C
hin
a/
Ta
iwa
n±
1M
T2
MS
m3
MA
C
Try
pta
nth
rin
(in
do
le-
qu
ina
zolin
on
ea
lka
loid
)M
IC1
1m
g/m
L2
4m
g/m
L3
2m
g/m
L(1
an
d3
usi
ng
BA
CT
EC
me
tho
da
nd
2u
sin
ga
ga
rd
ilu
tio
nm
eth
od
)
±P
ote
ncy
of
com
po
un
din
sam
era
ng
ea
sth
at
of
an
titu
be
rcu
lar
dru
gs
alr
ea
dy
inu
se,
i.e
.st
rep
tom
yci
na
nd
eth
am
bu
tol
Po
siti
ve
con
tro
lsin
clu
de
dv
ari
ou
sst
an
da
rda
nti
tub
erc
ula
rd
rug
sA
ctiv
ea
ga
inst
MD
RM
TC
hin
ese
/Ta
iwa
ne
sem
ed
icin
al
pla
nt.
Ha
sfo
lklo
ric
rep
uta
tio
nfo
rth
eto
pic
al
tre
atm
en
to
fa
thle
tes
foo
t
Mit
sch
er
an
dB
ake
r,1
99
8a
Ch
ina
/T
aiw
an
±1
MT
2M
A3
MS
m
Try
pta
nth
rin
(in
do
le-
qu
ina
zolin
on
ea
lka
loid
)M
ore
po
ten
ta
ga
inst
MT
(1m
g/
mL
)a
nd
MA
(4m
g/m
L)
tha
na
ga
inst
MS
m(6
mg
/mL
)
±H
igh
sig
ni®
can
ta
ctiv
ity
.A
lso
act
ive
ag
ain
std
rug
sen
siti
ve
an
dd
rug
resi
sta
nt
MT
an
dM
AC
.C
om
po
un
da
lso
iso
late
dfr
om
Po
lyg
on
um
tin
cto
riu
ma
nd
Isa
tis
tin
cto
ria
Mit
sch
er
an
dB
ake
r,1
99
8b
Sy
rin
ga
vu
lga
ris
(Ole
ace
ae
)±
Le
af
Flo
we
rM
TE
tha
no
le
xtr
act
MIC
=1
:80
dilu
tio
n±
Sig
ni®
can
ta
ctiv
ity
Lu
cas
et
al.
,1
95
1S
yzg
ium
jam
bo
s(M
yrt
ace
ae
)P
ue
rto
Ric
oL
ea
fM
Sm
MT
Mic
eA
rte
mia
salin
aL
ea
ch(B
rin
esh
rim
p)
Eth
an
ol
ex
tra
ct3
0m
min
hib
itio
nzo
ne
at
50
0m
g/
dis
cfo
rM
Sm
.A
ctiv
ea
ga
inst
MT
at
50
0m
g
LC
50
=9
3m
g/m
l(b
rin
esh
rim
p).
No
tox
icit
yto
mic
ea
t5
00
mg
/10
0m
lo
fp
lan
te
xtr
act
/mo
use
giv
en
i.p
.o
ve
r1
5d
ay
s.
Sig
ni®
can
ta
ctiv
ity
Fra
me
et
al.
,1
99
8
Ta
be
rna
em
on
tan
acit
rifo
lla
(Ap
ocy
na
ce
ae
)
Gu
ad
±M
TM
AM
K1
Ibo
ga
ine
2V
oa
can
gin
e(I
nd
ole
alk
alo
ids)
MIC
(mg
/mL
)1
50
,1
00
,5
0,
25
0,
50
,1
00
for
MT
,M
A,
MK
resp
ect
ive
ly
±S
ign
i®ca
nt
act
ivit
yb
yb
oth
com
po
un
ds
Ra
sto
gi
et
al.
,1
99
8
Ta
xu
sca
na
de
nsis
(Ta
xa
ce
ae
)±
Le
af
MT
Eth
an
ol
ex
tra
ctM
IC=
1:8
0d
ilu
tio
n±
Sig
ni®
can
ta
ctiv
ity
Lu
cas
et
al.
,1
95
1T
etr
ad
en
iari
pa
ria
Ho
ch
st.
Co
dd
.(L
am
iace
ae
)
Rw
an
da
Le
af
MT
MA
CM
Si
SL
M
Dit
erp
en
ed
iol
ine
tha
no
le
xtr
act
Sig
ni®
can
ta
ctiv
ity
of
AC
ag
ain
stM
T,
ran
gin
gb
etw
ee
n2
5±1
00
mg
/m
L,
de
pe
nd
ing
on
the
stra
inN
oa
ctiv
ity
fro
mA
Ea
ga
inst
MA
Ca
nd
SL
Ma
t1
00
0m
g/m
L.
±U
sed
inR
wa
nd
ese
tra
dit
ion
al
me
dic
ine
inth
etr
ea
tme
nt
of
pu
lmo
na
ryd
ise
ase
s(V
an
Pu
yv
eld
ee
ta
l.,
19
75
,1
97
7,
19
82
)C
on
tro
lsu
sin
gco
nv
en
tio
na
la
nti
tub
erc
ulo
sis
dru
gs
Va
nP
uy
ve
lde
et
al.
,1
99
4
Te
rmin
alia
sp
ino
sa
En
gl.
(Co
mb
reta
ce
ae
)E
ast
Afr
ica
(Ke
ny
a)
Ste
mM
TM
AM
CM
Te
MI
an
db
act
eri
al
stra
ins
Me
tha
no
le
xtr
act
Co
nce
ntr
ati
on
of
2m
g/m
La
llo
we
dth
eg
row
tho
fm
ore
tha
n1
0%
of
the
ino
culu
mo
fth
e5
my
cob
act
eri
al
stra
ins
±N
osi
gn
i®ca
nt
act
ivit
ya
ga
inst
my
cob
act
eri
aF
ab
rye
ta
l.,
19
98
Te
ucri
um
ch
am
ae
dry
s(L
ab
iate
ae
)
±W
ho
lep
lan
tM
TE
tha
no
le
xtr
act
MIC
=1
:80
dilu
tio
n±
Sig
ni®
can
tly
act
ive
Lu
cas
et
al.
,1
95
1
Tri
ph
asia
trif
olia
(Ru
tace
ae
)G
ua
dL
ea
fM
TM
AM
K
Iso
me
ran
zin
He
racl
en
ol
(Co
um
ari
ns)
iso
late
dfr
om
chlo
rofo
rme
xtr
act
MIC
wa
s�1
00
mg
/mL
for
ea
chte
sto
rga
nis
ma
nd
act
ive
con
stit
ue
nt
±N
osi
gn
i®ca
nt
act
ivit
yR
ast
og
ie
ta
l.,
19
98
ANTIMYCOBACTERIAL NATURAL PRODUCTS 317
Copyright# 2000JohnWiley & Sons,Ltd. Phytother.Res.14, 303–322(2000)
Tab
le1.
Con
tinue
d.
Pla
nt/
Na
tura
lp
rod
uct
Ori
gin
Pa
rtu
sed
Mo
de
lu
sed
/R
ou
teo
fa
dm
inis
tra
tio
nA
ctiv
eC
on
stit
ue
nt(
s)/e
xtr
act
(s)
Act
ivit
yS
ide
eff
ect
s/to
xic
ity
Re
ma
rks
Re
fere
nce
Xim
en
iaca
ffra
So
nd
.(O
laca
ce
ae
)E
ast
Afr
ica
(Ke
ny
a)
Ro
ot
MT
MA
MC
MT
eM
Ia
nd
ba
cte
ria
lst
rain
s
Me
tha
no
le
xtr
act
Ex
tra
ctco
nce
ntr
ati
on
so
f2
mg
/m
La
llo
we
dth
eg
row
tho
fm
ore
tha
n1
0%
of
ea
cho
fth
e5
my
cob
act
eri
al
stra
ins
±N
osi
gn
i®ca
nt
act
ivit
ya
ga
inst
my
cob
act
eri
aF
ab
rye
ta
l.,
19
98
Zin
gib
er
of®
cin
ale
(Gin
ge
r)(Z
ing
ibe
race
ae
)
±R
hiz
om
eM
TM
A1
10
-gin
ge
rol
28
-gin
ge
rol
36
-gin
ge
rol
iso
late
dfr
om
dic
hlo
rom
eth
an
ee
xtr
act
MIC
(mg
/L)
12
5(M
A)
50
(MT
)2
50
(MA
)5
0(M
T)
3>
10
0(M
A)>
10
0(M
T)
±1
0-G
ing
ero
lw
as
the
mo
sta
ctiv
eco
mp
ou
nd
for
the
inh
ibit
ion
of
MA
.H
ow
ev
er
this
com
po
un
dw
as
less
act
ive
ag
ain
stM
T
His
ero
dt
et
al.
,1
99
8
BC
G,B
aci
llu
sC
alm
ett
eG
ue
rin
;Br
C,B
riti
shC
olu
mb
ia;D
MS
O,d
ime
thy
lsu
lph
ox
ide
;EC
,Esc
he
rich
iaco
li;G
ua
d,G
ua
de
lou
pe
;IC
50
50
%in
hib
ito
ryco
nce
ntr
ati
on
(co
nce
ntr
ati
on
req
uir
ed
toin
hib
itg
row
tho
fth
eb
act
eri
alp
op
ula
tio
nb
y5
0%
);IN
H,i
son
ico
tin
ica
cid
hy
dra
zid
e;L
C5
0,5
0%
leth
alc
on
cen
tra
tio
n(c
on
cen
tra
tio
nre
qu
ire
dto
kill
50
%o
fth
ep
op
ula
tio
no
fo
rga
nis
ms)
;MA
,M
yco
ba
cte
riu
ma
viu
m;
MA
u,
My
cob
act
eri
um
au
rum
;M
AC
,M
yco
ba
cte
riu
ma
viu
mco
mp
lex
;M
BC
,m
inim
um
ba
cte
rici
da
lco
nce
ntr
ati
on
;M
C,
My
cob
act
eri
um
che
lon
ae
/ch
elo
ne
i;M
DR
,m
ult
i-d
rug
resi
sta
nt;
MF
,M
yco
ba
cte
riu
mfo
rtu
itu
m;
MG
,M
yco
ba
cte
riu
mg
ord
on
ae
;M
I,M
yco
ba
cte
riu
min
tra
cellu
lare
;M
IC,
min
imu
min
hib
ito
ryco
nce
ntr
ati
on
;M
K,
My
cob
act
eri
um
kan
saii
;M
M,
My
cob
act
eri
um
ma
rin
um
;M
Sc,
My
cob
act
eri
um
scro
fula
ceu
m;
MS
i,M
yco
ba
cte
riu
msi
mia
e;
MS
m,
My
cob
act
eri
um
sme
gm
ati
s;M
T,
My
cob
act
eri
um
tub
erc
ulo
sis;
MT
e,
My
cob
act
eri
um
terr
ae
;M
X,
My
cob
act
eri
um
xe
no
pi;
SA
,S
tap
hy
loco
ccu
sa
ure
us;
SL
M,
Sim
iae
-lik
em
yco
ba
cte
riu
m;
TB
,tu
be
rcu
losi
s.
318 S. M. NEWTON ET AL.
Copyright# 2000JohnWiley & Sons,Ltd. Phytother.Res.14, 303–322(2000)
compoundsto inhibit M. tuberculosiswithin culturedhumanmacrophages.This may be carriedout usingthemethodologyof CrowleandMay (1990).
PLANT SPECIESINVESTIGATED FORANTIMYCOBACTERIA L ACTIVITY
Thecrudeextractsof manyplantspecies,especiallythosewith ethnomedicaluseshavebeenassessedfor in vitroantimycobacterialpropertiesbut relatively few activecompoundshavebeenisolated.In manycases,work willhave beendiscontinuedbecausethe extractsexhibitedlittle or no activity at the highestconcentrationstested.For the purposeof this review,we haveselectedmostlythosespecieswhich havebeentestedfor activity againstone or more speciesof mycobacteriaand which havebeenfurther investigatedto determinethe natureof theconstituentslikely to beresponsiblefor theactivity. Thisinformation,summarizedin Table1, hasbeencompiledmainly from the literatureof the last20–30years.
An extensiveliteraturesearchwascarriedoutusingtheScienceCitation Index of BIDS (Bath InformationDataServices), 1981to dateandPubMed(Medline),1966to date.
The keywordsused(in variouscombinations)in thesearchwere: Plants;Natural; Remedies;Chinesemedi-cine;Traditional;Herbal;Indianmedicine;Tuberculosis;Mycobacteria; Antimycobacterial; Antituberculosis;Tuberclebacilli.
Furthermore,detailedsearchesthroughjournalssuchas Reviews of Aromatic and Medicinal Plants, forpapersand articles which are not included in the twodatabases(BIDS and Medline), were also included.Note that in some of the studiescited such as thosereported by Cantrell et al., 1998a; Fitzpatrick, 1954;Grange and Davey, 1990; Lucas et al., 1951, largenumbersof plant specieswere tested but only thosethat appear to have the most potent activities areincluded. In addition, a recentarticle (preparedat thesametime as this presentreview article) by Lall andMeyer (1999) has also reportedsignificant antimyco-bacterial activity of someplants which are not incor-porated into Table 1. An attempt has been made tosummarizeall the relevantinformationavailableso thatspeciescan be assessedfor their potential as leadstoanti-TB agents.In studieswherestandardanti-TB drugshavebeenusedaspositivecontrols,this is indicatedinthe remarkscolumn of the table as the resultsmay be
more reliable than those from studieswhere controlswerenot included.
PLANT SPECIESAS A SOURCE OF NEWANTIMYCOBACTERIAL AGENTS
Comparedwith microorganisms,plantspecieshavesofarproveddisappointingasa sourceof potentantibacterialagents.However, as is well illustrated in Table 1, anumberof plant extractsandcompoundsdo havepotentantimycobacterialproperties.Examplesof the specieswhichappearto beamongthemostactiveincludeAlliumsativum,Borrichia frutescens,Ferula communis,Her-acleum maximum, Karwinskia humboldtiana, Leucasvolkensii,Monesesuniflora, Oplopanaxhorridus,SalviamulticaulisandStrobilanthuscusia.
In somecases,compoundshavebeenisolatedwhichhaveantimycobacterialactivitiescomparableto standardanti-TB drugs, for example (E)- and (Z)-phytol andphytanol which were isolated from Leucas volkensii(Rajabetal., 1998).It is hopedthatnaturalproductssuchas the latter may prove to be useful agentsfor TBtreatmentor may be lead compoundsfrom which newdrugsmaybedeveloped.Bromhexineis asemi-syntheticderivative of the alkaloid vasicine,which is found inAdhatodavasica, anIndianshrubthathaslongbeenusedin India for the treatmentof TB. Although bromhexineand its metaboliteambroxolhavebeenwidely usedasmucolytics, these compoundsexert a pH dependentinhibitory effectagainstM. tuberculosisin vitro andtheyarealsoconcentratedin macrophages.It is suggestedthattheymaybeusefulasadjuctsin TB therapy(GrangeandSnell,1996).
CONCLUSION
The data compiled in Table 1 reveal that extractsofplant speciesfrom a wide rangeof families havebeenshown to have significant in vitro antimycobacterialactivities and that a number of active plant-derivedcompoundsbelongingto variouschemicalclasseshavebeenisolated.Thesefindingsshouldstimulatethesearchfor novel natural product leads towards new anti-TBagents.
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