17
REVIEW ARTICLE A Review of Plant Species Assessed in vitro for Antiamoebic Activity or both Antiamoebic and Antiplasmodial Properties Poonam Sharma and Jayashri Devi Sharma* Medicinal Ecology, Environmental and Occupational Health, School of Environmental Sciences, Jawaharlal Nehru University, New Delhi 110067, India The resurgence of the protozoal diseases amoebiasis and malaria has been known to occur, from time to time, in endemic and epidemic proportions all over the world. Furthermore, the import of these indivi- dual pathogens to other areas from tropical regions encourages these protozoal diseases to occur on a global scale with considerable associated mortality and morbidity. From time immemorial, the cure of these diseases has been attempted with the use of traditional plant products, derived from such species as are available within local habitats and ecosystems, and dependent on their host community for their con- servation. Scientific validation and in vitro investigation, continues to be an important requirement for drug development, particularly with the emergence of resistance and cross resistance to some standard drugs used in such protozoal diseases. This paper provides a comparative compilation of the various stu- dies reported between 1982 and 1999, on plants with antiamoebic activities and those which possess both antiamoebic and antiplasmodial activities. The results suggest that it is advisable to increase efforts towards the conservation of such plants, in order to retain their economic and therapeutic significance. Copyright # 2001 John Wiley & Sons, Ltd. Keywords: antiamoebic plants; entamoeba histolytica; antiplasmodial plants; plasmodium falciparum; metronidazole; chloroquine. INTRODUCTION Amoebiasis is a major cause of morbidity and mortality in tropical areas. It is known to be a major health problem in China, Mexico, the Eastern portion of South America, South-East and West Africa, and the whole of South-East Asia including the Indian subcontinent (WHO, 1985, Adams and MacLeod, 1977). An estimated 480 million people, or 12% of the world’s population are infected with E. histolytica, and amoebiasis causes about 40 000 to 110 000 deaths per year worldwide. The occurrence of the disease is known to be more closely related to sanitation and socioeconomic status than to the location and climate of the region (Stanley 1996). Complex aetiological factors are poor life-style, environmental conditions in the tropics, and the non- availability of guaranteed conventional medical cure. In such situations people have commonly looked for natural symptomatic cures and resorted to self-medication from traditionally used plants as found in folklore. A number of traditionally found natural products that are believed to be of medicinal value have been further studied for scientific validation, and put through the rigors of standard drug use. Ipecacuanha, is an antiamoebic Brazilian root, first taken to Europe by Piso in 1658, and it was not until the mid nineteenth century that its principle alkaloid, emetine, was tested on dysenteric stools against E. histolytica and in the cure of amoebic dysentery. Glaucarubin, a quassinoid isolated from Simarouba glauca, was found to have in vitro amoebi- cidal activity and its chemistry and relative toxicity were reported in the late 1940’s (Van Assendelft et al., 1956). The development of standard drugs for different protozoal infections have some similarities. Metronida- zole, derived from a microbial product and described by Cosar and John in 1959 (Tanowitz et al., 1975) has become the drug of choice in amoebiasis, much as chloroquine once was in malaria. Losch in 1875 recorded the use of quinine enemas to treat patients with amoebiasis (Marshall et al., 1997). While emetine formulations derived from Ipecacuanha are mixtures of compounds, a direct antiamoebic effect of any single isolate is difficult to evaluate. The inherent difficulties of separating the role of a single plant compound in the activity of an extract, in testing antiprotozoal activity in general and antiamoebic activity in particular, are the following: 1. Mixtures of the common classes of compounds (alkaloids, terpenes, quinines) and other miscella- neous compounds are often present in most preliminary active extracts; PHYTOTHERAPY RESEARCH Phytother. Res. 15, 1–17 (2001) Copyright # 2001 John Wiley & Sons, Ltd. * Correspondence to: Dr J. D. Sharma, Medicinal Ecology, Environmental and Occupational Health, School of Environmental Sciences, Jawaharlal Nehru University, New Delhi 110067, India. E-mail: [email protected] Contract/grant sponsor: UGC Fellowship. Received April 2000 Revised July 2000 Accepted September 2000

A review of plant species assessedin vitro for antiamoebic activity or both antiamoebic and antiplasmodial properties

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REVIEW ARTICLE

A Review of Plant Species Assessedin vitro forAntiamoebic Activity or both Antiamoebic andAntiplasmodial Properties

Poonam Sharma and Jayashri Devi Sharma*Medicinal Ecology, Environmental and Occupational Health, School of Environmental Sciences, Jawaharlal Nehru University, New Delhi110067, India

The resurgence of the protozoal diseases amoebiasis and malaria has been known to occur, from time totime, in endemic and epidemic proportions all over the world. Furthermore, the import of these indivi-dual pathogens to other areas from tropical regions encourages these protozoal diseases to occur on aglobal scale with considerable associated mortality and morbidity. From time immemorial, the cure ofthese diseases has been attempted with the use of traditional plant products, derived from such species asare available within local habitats and ecosystems, and dependent on their host community for their con-servation. Scientific validation and in vitro investigation, continues to be an important requirement fordrug development, particularly with the emergence of resistance and cross resistance to some standarddrugs used in such protozoal diseases. This paper provides a comparative compilation of the various stu-dies reported between 1982 and 1999, on plants with antiamoebic activities and those which possess bothantiamoebic and antiplasmodial activities. The results suggest that it is advisable to increase effortstowards the conservation of such plants, in order to retain their economic and therapeutic significance.Copyright # 2001 John Wiley & Sons, Ltd.

Keywords:antiamoebic plants; entamoeba histolytica; antiplasmodial plants; plasmodium falciparum; metronidazole;chloroquine.

INTRODUCTION

Amoebiasis is a major cause of morbidity and mortalityin tropical areas. It is known to be a major health problemin China, Mexico, the Eastern portion of South America,South-East and West Africa, and the whole of South-EastAsia including the Indian subcontinent (WHO, 1985,Adams and MacLeod, 1977). An estimated 480 millionpeople, or 12% of the world’s population are infectedwith E. histolytica, and amoebiasis causes about 40000 to110000 deaths per year worldwide.

The occurrence of the disease is known to be moreclosely related to sanitation and socioeconomic statusthan to the location and climate of the region (Stanley1996). Complex aetiological factors are poor life-style,environmental conditions in the tropics, and the non-availability of guaranteed conventional medical cure. Insuch situations people have commonly looked for naturalsymptomatic cures and resorted to self-medication fromtraditionally used plants as found in folklore. A numberof traditionally found natural products that are believed tobe of medicinal value have been further studied for

scientific validation, and put through the rigors ofstandard drug use. Ipecacuanha, is an antiamoebicBrazilian root, first taken to Europe by Piso in 1658,and it was not until the mid nineteenth century that itsprinciple alkaloid, emetine, was tested on dysentericstools againstE. histolyticaand in the cure of amoebicdysentery. Glaucarubin, a quassinoid isolated fromSimarouba glauca, was found to havein vitro amoebi-cidal activity and its chemistry and relative toxicity werereported in the late 1940’s (Van Assendelftet al., 1956).

The development of standard drugs for differentprotozoal infections have some similarities. Metronida-zole, derived from a microbial product and described byCosar and John in 1959 (Tanowitzet al., 1975) hasbecome the drug of choice in amoebiasis, much aschloroquine once was in malaria. Losch in 1875 recordedthe use of quinine enemas to treat patients withamoebiasis (Marshallet al., 1997). While emetineformulations derived from Ipecacuanha are mixtures ofcompounds, a direct antiamoebic effect of any singleisolate is difficult to evaluate.

The inherent difficulties of separating the role of asingle plant compound in the activity of an extract, intesting antiprotozoal activity in general and antiamoebicactivity in particular, are the following:

1. Mixtures of the common classes of compounds(alkaloids, terpenes, quinines) and other miscella-neous compounds are often present in mostpreliminary active extracts;

PHYTOTHERAPY RESEARCHPhytother. Res.15, 1–17 (2001)

Copyright# 2001 John Wiley & Sons, Ltd.

* Correspondence to: Dr J. D. Sharma, Medicinal Ecology, Environmentaland Occupational Health, School of Environmental Sciences, JawaharlalNehru University, New Delhi 110067, India.E-mail: [email protected]/grant sponsor: UGC Fellowship.

Received April 2000Revised July 2000

Accepted September 2000

2. Differencesoccur in the selectivityandsensitivityof specific antiamoebicand antiplasmodialcom-pounds in various antiprotozoal cultures andstrains;

3. In vivo and in vitro differencesare found in thevirulence of various strains of E. histolytica(Gomeset al., 1997)resultingin variedpathogen-esis(Clark, 1998);

4. Two or manymorebiological componentsmaybeinvolved in the effect of the compoundtested,e.g.associationsof the amoebaewith bacterial flora(polyaxeniccultures)maymakeit difficult to provea direct antiamoebiceffect.

Reportedmethodsfor in vitro bioassayfor antiamoebicactivity havebeenbasedondifferentculturemethodsandtesting protocols and have used different strains ofamoebae.A survey of the various methodshas beenpublishedsince the initial isolation and culture of E.histolytica by Cavier in 1960 (Youssef, 1968) andupdatedto include the microdilution technique(Wrightet al., 1988).

Laboriousmicroscopicobservationswererecordedonthe effects of drugs upon motility and morphologyofcultivated parasites(Balamuth, 1952). Since not all-motile organismsmaybeableto reproduce,investigatorsfound it important to resort to subcultureto determinekilling asanendpoint(Tanowitzetal., 1975).Theabilityof a cell to grow andmultiply is a stringentcriterion forviability.

The colony method eliminated the need for micro-scopic observationand subculture.A new method forclonal growthof theseparasitesin semi-solidmediahasbeenusedextensively.This hashelpedin the identifica-tion of selectivityandmechanismsof actionongrowthofthe testcompounds(Gillin andDiamond,1981).

A plate method permitting a sharp demarcationbetweendirect andindirect antiamoebiceffectsof givencompoundswere attemptedon Amoebaabdou (‘DrugAmoeba’) (Kradolfer and Jarumilinta, 1965). Otherbiological componentslike E. coli, alreadyestablishedontheagarplates,were‘desensitized’to theactionof thevast majority of compoundsin this plate sensi-discmethod.

In broth cultures,emetine,the principal alkaloid ofipecacuanhawas shownby Vedder in 1911 to destroyamoebaein high dilutions (Rogers, 1912). Dilutionassaysusing liquid medium are time consumingandrequirerelatively largequantitiesof testcompounds,andwere used to evaluate standard antiamoebic drugs,emetine,2-3-dehydroemetine,metronidazole,5-chloro-8-hydroxyquinoline,antimalarialdrugs,Cinchonaalka-loids andquassinoids(Keeneet al., 1986).

A micromethodwasdevelopedbasedonmeasuringtheincorporation of tritiated thymidine into amoebaebyscintillation counting in microtitre plates(CedenoandKrogstad, 1983). A newer microdilution procedure,which does not require the use of radio-labelledcompoundsbut dependson a simpler spectroscopicmethodof measuringoptical densityand its correlationwith the numberof viable amoebaein a culture is alsoknownto showa goodcorrelationcoefficient(Wright etal., 1988).

Plant species have the potential to yield newantiamoebic agents. Development of this potentialrequiresthescreeningof largenumbersof plantextracts,

isolation and identification of the active compounds,uncoveringtheir mechanismof action, and the perfor-manceof toxicity tests to demonstrateselectiveanti-amoebiceffects.

PLANTS WITH ANTIAMOEBIC ACTIVITY

In past decadesscientific studies in the search forantiamoebicagentsfrom plant-derivedmaterialswerebased on the traditional usage of these materials.Ethnopharmacologicalresearchof this kind has led totheformationof syntheticmedicinesanddrugs.Themostactive plant extractsfrom effective use of plant partswereselectedfor extensivebiologicalandphytochemicalstudies.This further led to attemptsfor the isolationandcharacterizationof active principles. A compilation ofsuchstudiesis shownin Table1.

PLANTS WITH COMMON ANTIAMOEBIC ANDANTIPLASMODIAL ACTIVITY

Therich historicalheritageof traditionalknowledgeanddifferent indigenoussystemsof medicinebroughtaboutthe developmentof formulationscomprisingthe useofseveral plants for mixed protozoal infections. Plantextracts and compoundswhich possessantiamoebicactivity may also haveantiplasmodialactivity and viceversa, in such mixed infections since both classesoforganism are protozoans.The specificity of isolatedcompoundswhich test well for E. histolytica and P.falciparumarelistedin Table2. Someof theexamplesofisolatedalkaloids,terpenesand quinonesand miscella-neous compoundscan be seen to have comparableeffectivenessto well-knownstandarddrugs.

DISCUSSION

Of themanyplantswhichhavebeentestedovertheyearsby different workers,preparationsderivedfrom Simar-ouba amara, Brucea javanica, Strychnosusambarensisand Cryptolepis sanquinolentahave shown inhibitorypotencycomparableto the effective rangeof standarddrugsfor bothantiamoebicandantiplasmodialactivity.Aformol HCl and n-butanol extract of Gardenia jovistontanis also show promising antiamoebic activity.Quassinoids,bruceantinand brusatol,which havebeenisolatedfrom Bruceajavanica, show the besteffectivevalueagainstboththeprotozoa.Thealkaloid,gentianine,however,was found to be an artefactproducedduringextraction(Natarajanet al., 1974).

Among the various standard antiprotozoal drugs,metronidazoleand chloroquine,are the most effectiveasreportedin thesein vitro studies.It is fundamentalthatstandarddrugsmust be usedin assaysfor comparativepurposeswith theplantderivedisolates.Sofar thestudieswith metronidazoleshowanIC50 rangeof 1–2mg/mL andMIC of 0.312–0.625mg/mL against E. histolytica.Chloroquine diphosphatehas been found to have anED50 of 0.168mM and an IC50 of 0.156mM againstP.falciparum.

Preliminaryindicationsof specificityof actionduring

2 P. SHARMA AND J. D. SHARMA

Copyright# 2001JohnWiley & Sons,Ltd. Phytother.Res.15, 1–17(2001)

Tab

le1.

Aco

mpi

latio

nof

rese

arch

wor

ksh

owin

gin

vitr

ost

udie

swith

vario

usst

rain

sof

E.h

isto

lytic

afo

rsc

reen

ing

ofpl

ant

extr

acts

,diff

eren

tfr

actio

nsan

dpu

rified

com

poun

ds

S.

No

.B

ota

nic

al

na

me

(Fa

mily

)P

art

use

dE

xtr

act

/Cla

sso

fco

mp

ou

nd

Na

me

of

com

po

un

dD

ose

ef®

cie

ncy

E.

his

toly

tica

stra

inin

vit

roR

efe

ren

ce

1A

caci

aa

uri

culifo

rmis

Le

gu

me

sE

tha

no

lN

.D.

Lo

wa

ctiv

ity

at

E.

his

toly

tica

Un

iya

le

ta

l.(1

99

0)

(Mim

osa

cea

e)

10

00mg

/mL

ST

A2

Aca

lph

ap

hle

oid

es

IC5

0(m

g/m

L)

E.

his

toly

tica

Ca

lza

da

et

al.

(Eu

ph

orb

iace

ae

)E

nti

rep

lan

tM

eth

an

ol

N.D

.7

.23

HM

1-I

MS

S(1

99

8a

)3

Alc

ho

rne

aco

rdif

olia

MIC

(mg

/mL

)E

.h

isto

lyti

caT

on

ae

ta

l.(1

99

8)

(Eu

ph

orb

iace

ae

)L

ea

ve

sD

eco

ctio

nN

.D.

12

54

Alliu

msa

tiv

um

10

0%

killin

ga

tE

.h

isto

lyti

caM

ire

lma

ne

ta

l.(1

98

7)

(Lilia

cea

e)

Clo

ve

sC

rud

eg

arl

ic-e

xtr

act

oil

50mg

/mL

SA

W1

73

4R

/c1

AR

Allic

in3

0mg

/mL

MIC

(mg

/mL

)E

.h

isto

lyti

caB

ori

es

et

al.

(19

91

)5

An

no

na

che

rim

olia

Fru

its

Me

tha

no

lN

.D.

>1

00

Re

hm

an

An

no

na

mu

rica

taF

ruit

sM

eth

an

ol

>1

00

(An

no

na

cea

e)

EC

10

0(m

g/m

L)

E.

his

toly

tica

Sh

ah

et

al.

(19

87

)6

Ard

isia

ox

yp

hy

lla

Ro

ots

Dic

hlo

rom

eth

an

e2

00

BY

80

(My

rsin

ace

ae

)P

etr

ole

um

eth

er

20

0in

solu

ble

po

rtio

nR

ap

an

on

e2

00

7B

erb

eri

sa

sia

tica

MIC

(mg

/mL

)1

00

E.

his

toly

tica

SF

L3

So

hn

ie

ta

l.(1

99

5)

(Be

rbe

rid

ace

ae

)N

.A.

N.A

.N

.D.

8B

rick

ellia

pa

nic

ula

taIC

50

(mg

/mL

)E

.h

isto

lyti

caC

alz

ad

ae

ta

l.(1

99

9)

(Ast

era

cea

e)

N.A

.F

lav

on

oid

Xa

nth

om

icro

l2

74

.85

HM

1-1

MS

SM

IC(m

g/m

L)

E.

his

toly

tica

To

na

et

al.

(19

98

)9

Bri

de

lia

ferr

ug

ine

aR

oo

tb

ark

De

coct

ion

N.D

.6

2.5

(Eu

ph

orb

iace

ae

)S

tem

ba

rkD

eco

ctio

nN

.D.

25

01

0B

ruce

aja

va

nic

aIC

50

(mg

/mL

)E

.h

isto

lyti

caN

IH2

00

Ke

en

ee

ta

l.(1

98

6)

(Sim

aro

ub

ace

ae

)F

ruit

sQ

ua

ssin

oid

sB

uta

no

le

xtr

act

8.2

5B

ruce

an

tin

0.3

5B

ruce

ine

C1

0Q

ua

ssin

0.5

Ca

nth

in-6

-on

e2

3E

me

tin

e0

.07

2,3

-De

hy

dro

em

eti

ne

0.1

6M

etr

on

ida

zole

0.2

25

-Ch

loro

-8-h

yd

rox

yq

uin

olin

e0

.19

Am

od

iaq

uin

e0

.07

Me

pa

crin

e0

.58

Pri

ma

qu

ine

23

.2C

hlo

roq

uin

e2

4.8

Qu

inin

e1

4.8

Qu

inid

ine

16

.6Q

uin

idin

on

e7

.4C

inch

on

am

ine

14

.81

0-M

eth

ox

yci

nch

on

am

ine

4.5

3-E

piq

uin

am

ine

12

.9IC

50

(mg

/mL

)E

.h

isto

lyti

caH

M-1

Gillin

et

al.

(19

82

)

PLANTS SHOWINGANTIAMOEBIC ACTIVITY 3

Copyright# 2001JohnWiley & Sons,Ltd. Phytother.Res.15, 1–17(2001)

Tab

le1.

Con

tinue

d

S.

No

.B

ota

nic

al

na

me

(Fa

mily

)P

art

use

dE

xtr

act

/Cla

sso

fco

mp

ou

nd

Na

me

of

com

po

un

dD

ose

ef®

cie

ncy

E.

his

toly

tica

stra

inin

vit

roR

efe

ren

ce

11

Bru

cea

an

tid

yse

nte

rica

Fru

its

Qu

ass

ino

ids

Bru

cea

nti

n0

.01

8(S

ima

ruo

ba

cea

e)

Sim

alila

cto

ne

D0

.04

7A

ila

nth

ino

ne

0.0

68

Gla

uca

rub

olo

ne

0.1

2G

lau

caru

bin

on

e0

.14

Aila

nth

on

e0

.14

Gla

uca

rub

in1

.57

12

Ca

jan

us

caja

nM

IC(m

g/m

L)

E.

his

toly

tica

To

na

et

al.

(19

98

)(F

ab

ace

ae

)L

ea

ve

sD

eco

ctio

nN

.D.

>5

00

13

Ca

rica

pa

pa

ya

MIC

(mg

/mL

)E

.h

isto

lyti

caT

on

ae

ta

l.(1

99

8)

(Ca

rica

cea

e)

Ma

ture

see

ds

De

coct

ion

N.D

.�7

.81

Imm

atu

rese

ed

sM

ace

rati

on

inw

ate

r6

2.5

14

Ca

ssia

®st

ula

IC5

0(m

g/m

L)

E.

his

toly

tica

36

4A

ntu

rlik

ar

et

al.

(19

93

)(C

ae

salp

ine

ace

ae

)S

ee

ds

Eth

an

ol

N.D

.1

09

.61

5C

ast

ela

tex

an

aIC

50(m

g/m

L)

E.

his

toly

tica

Ca

lza

da

et

al.

(19

98

a)

(Sim

aro

ub

ace

ae

)S

tem

ba

rka

nd

wo

od

Me

tha

no

lN

.D.

46

.84

HM

1-I

MS

S

16

Ca

ste

late

xa

na

Ae

ria

lp

art

sIC

50(m

g/m

L)

E.

his

toly

tica

He

inri

che

ta

l.(1

99

2)

(Sim

aro

ub

ace

ae

)E

tha

no

lN

.D.

31

±63

NIH

20

0D

ich

loro

me

tha

ne

N.D

.4

±8W

ate

rN

.D.

63

17

Ca

ste

lato

rtu

osa

IC5

0(m

g/m

L)

E.

his

toly

tica

Ca

lza

da

et

al.

(19

98

a)

(Sim

aro

ub

ace

ae

)S

tem

ba

rka

nd

wo

od

Me

tha

no

lN

.D.

41

HM

1-I

MS

S

18

Ce

iba

pe

nta

nd

raM

IC(m

g/m

L)

E.

his

toly

tica

To

na

et

al.

(19

98

)(B

om

ba

cea

e)

Ste

mb

ark

De

coct

ion

N.D

.1

25

19

Ce

ph

ae

lis

ipe

cacu

an

ha

Ro

ot

IC5

0(m

g/m

L)

E.

his

toly

tica

NIH

20

0W

rig

ht

et

al.

(19

89

)(R

ub

iace

ae

)A

lka

loid

sE

me

tin

e1

.7C

ep

ha

elin

e3

.26

Psy

cho

trin

e8

.19

20

Ce

nti

pe

da

min

ima

IC5

0(m

M)

E.

his

toly

tica

Yu

et

al.

(19

94

)(A

ste

race

ae

)W

ho

lep

lan

tS

esq

uit

erp

en

ela

cto

ne

Bre

vilin

A4

.5±9

21

Ch

en

op

od

ium

gra

ve

ole

ns

IC5

0(m

g/m

L)

E.

his

toly

tica

He

inri

che

ta

l.(1

99

2)

(Ch

en

op

od

iace

ae

)A

eri

al

pa

rts

Eth

an

ol

N.D

.1

25

±25

0N

IH2

00

Dic

hlo

rom

eth

an

eN

.D.

31

±63

Wa

ter

N.D

.>

25

02

2C

ho

ne

mo

rph

afr

ag

na

ns

MIC

(mg

/mL

)E

.h

isto

lyti

caS

FL

3C

ha

tte

rje

ee

ta

l.(1

98

7)

(Ap

ocy

an

ace

ae

)R

oo

tsS

tero

ida

la

lka

loid

Ch

on

em

orp

hin

e1

00

23

Cig

arr

illa

me

xic

an

aL

ea

ve

sIC

50(m

g/m

L)

E.

his

toly

tica

Ca

lza

da

et

al.

(19

98

a)

(Ru

bia

cea

e)

Me

tha

no

lN

.D.

45

.13

HM

1-I

MS

SIC

50

(mg

/mL

)E

.h

isto

lyti

caN

IH2

00

Ke

en

ee

ta

l.(1

98

6)

24

Cin

cho

na

led

ge

ria

na

Le

av

es

Fra

ctio

nA

N.D

.0

.21

4 P. SHARMA AND J. D. SHARMA

Copyright# 2001JohnWiley & Sons,Ltd. Phytother.Res.15, 1–17(2001)

Tab

le1.

Con

tinue

d

S.

No

.B

ota

nic

al

na

me

(Fa

mily

)P

art

use

dE

xtr

act

/Cla

sso

fco

mp

ou

nd

Na

me

of

com

po

un

dD

ose

ef®

cie

ncy

E.

his

toly

tica

stra

inin

vit

roR

efe

ren

ce

(Ru

bia

cea

e)

Fra

ctio

nB

N.D

.3

Fra

ctio

nC

N.D

.0

.52

IC5

0(m

g/m

L)

E.

his

toly

tica

NIH

20

0K

ee

ne

et

al.

(19

87

)2

5C

inch

on

ale

dg

eri

an

aL

ea

ve

sA

lka

loid

s3

-Iso

cory

na

nth

eo

l4

.13b,

17b-

18

,19

-D

eh

yd

roo

chro

lifu

an

ine

1.7

3b,

17a-

18

,19

-D

eh

yd

roo

chro

lifu

an

ine

3a,

17b-

Cin

cho

ph

yllin

e2

3a,

17a-

Cin

cho

ph

yllin

eC

inch

on

asp

s.A

lka

loid

s0

.96

(Ru

bia

cea

e)

2.2

26

Cis

siu

sa

relo

ide

sM

IC(m

g/m

L)

E.

his

toly

tica

To

na

et

al.

(19

98

)(V

ita

cea

e)

Le

av

es

De

coct

ion

N.D

.>

50

02

7C

lem

ati

sd

ioic

aIC

50

(mg

/mL

)E

.h

isto

lyti

caH

M1

-1M

SS

Ca

lza

da

et

al.

(19

98

b)

(Ra

nu

ncu

lace

ae

)L

ea

ve

sM

eth

an

ol

N.D

.1

29

4.1

92

8C

nid

osc

olu

ste

hu

aca

ne

nsi

sIC

50(m

g/m

L)

E.

his

toly

tica

Ca

lza

da

et

al.

(19

98

a)

(Eu

ph

orb

iace

ae

)E

nti

rep

lan

tM

eth

an

ol

N.D

.1

3.7

HM

1-I

MS

S2

9C

om

me

lin

ae

rect

aIC

50(m

g/m

L)

E.

his

toly

tica

Ca

lza

da

et

al.

(19

98

a)

(Co

mm

elin

ace

ae

)E

nti

rep

lan

tM

eth

an

ol

N.D

.2

9.5

3H

M1

-IM

SS

IC5

0(m

g/m

L)

E.

his

toly

tica

NIH

20

0S

ha

rma

an

dS

ha

rma

30

Co

mm

iph

ora

wig

hti

iG

um

-ole

o-

resi

nC

hlo

rofo

rmN

.D0

.22

(19

96

)

(Bu

rse

race

ae

)A

qu

eo

us

N.D

.0

.24

Pe

tro

leu

me

the

rN

.D.

0.8

83

1C

on

yza

®la

gin

oid

es

IC5

0(m

g/m

L)

E.

his

toly

tica

HM

1-I

MS

SC

alz

ad

ae

ta

l.(1

99

8a

)

(Ast

era

cea

e)

En

tire

pla

nt

Me

tha

no

lN

.D.

14

1.6

32

Co

ny

za®

lag

ino

ide

sIC

50

(mg

/mL

)E

.h

isto

lyti

caC

alz

ad

ae

ta

l.(1

99

9)

(Ast

era

cea

e)

N.A

.F

lav

on

oid

3,6

-Dim

eth

ox

yka

em

pfe

ol

10

5.3

HM

1-1

MS

S3

3C

ost

us

afe

rM

IC(m

g/m

L)

E.

his

toly

tica

To

na

et

al.

(19

98

)(Z

ing

ibe

race

ae

)J

uic

eD

eco

ctio

nN

.D.

12

53

4C

ross

op

tery

xfe

bri

fug

aM

IC(m

g/m

L)

E.

his

toly

tica

To

na

et

al.

(19

98

)(R

ub

iace

ae

)L

ea

ve

sD

eco

ctio

nN

.D.

12

5IC

50

(mg

/mL

)E

.h

isto

lyti

caH

M1

-1M

SS

Ca

lza

da

et

al.

(19

98

b)

35

Cu

ph

ea

pin

eto

rum

Ro

ot

Me

tha

no

l7

3.2

3(L

yth

race

ae

)F

lav

on

oid

Ka

em

pfe

rol

7.9

3Q

ue

rce

tin

11

4.3

IC5

0(m

g/m

L)

E.

his

toly

tica

HM

1-1

MS

SC

alz

ad

ae

ta

l.(1

99

9)

PLANTS SHOWINGANTIAMOEBIC ACTIVITY 5

Copyright# 2001JohnWiley & Sons,Ltd. Phytother.Res.15, 1–17(2001)

Tab

le1.

Con

tinue

d

S.

No

.B

ota

nic

al

na

me

(Fa

mily

)P

art

use

dE

xtr

act

/Cla

sso

fco

mp

ou

nd

Na

me

of

com

po

un

dD

ose

ef®

cie

ncy

E.

his

toly

tica

stra

inin

vit

roR

efe

ren

ce

36

Cu

ph

ea

pin

eto

rum

Ro

ot

Fla

vo

no

idK

ae

mp

fero

l7

.93

(Ly

thra

cea

e)

Qu

erc

eti

n1

14

.33

7D

atu

raa

rbo

rea

MIC

(mg

/mL

)E

.h

isto

lyti

caT

on

ae

ta

l.(1

99

8)

(So

lan

ace

ae

)L

ea

ve

sD

eco

ctio

nN

.D.

12

53

8D

ialu

me

ng

leri

an

um

MIC

(mg

/mL

)E

.h

isto

lyti

caT

on

ae

ta

l.(1

99

8)

(Ca

esa

lpin

ea

ece

ae

)S

tem

ba

rkD

eco

ctio

nN

.D.

62

.53

9D

race

an

are

¯e

xa

MIC

(mg

/mL

)E

.h

isto

lyti

caT

on

ae

ta

l.(1

99

8)

(Ag

av

ace

ae

)L

ea

ve

sD

eco

ctio

nN

.D.

62

.54

0D

yss

od

iap

ap

po

saIC

50(m

g/m

L)

E.

his

toly

tica

Ca

lza

da

et

al.

(19

98

a)

(Ast

era

cea

e)

En

tire

pla

nt

Me

tha

no

lN

.D.

14

4.6

HM

1-I

MS

SM

IC(m

g/m

L)

E.

his

toly

tica

To

na

et

al.

(19

98

)4

1E

up

ho

rbia

hir

taL

ea

ve

sM

ace

rati

on

inw

ate

rN

.D.

25

0(E

up

ho

rbia

cea

e)

Wh

ole

pla

nt

Ma

cera

tio

nin

wa

ter

N.D

.3

1.2

54

2F

uch

sia

mic

rop

hy

lla

Ste

m/L

ea

ve

sIC

50

(mg

/mL

)E

.h

isto

lyti

caH

M1

-1M

SS

Ca

lza

da

et

al.

(19

98

b)

(On

ag

race

ae

)M

eth

an

ol

N.D

.7

59

.87

43

Ga

rcin

iako

laM

IC(m

g/m

L)

E.

his

toly

tica

To

na

et

al.

(19

98

)(C

lusi

ace

ae

)S

tem

ba

rkD

eco

ctio

nN

.D.

12

54

4G

era

niu

mn

ive

um

IC5

0(m

g/m

L)

E.

his

toly

tica

Ca

lza

da

et

al.

(19

98

a)

(Ge

ran

iace

ae

)R

oo

tM

eth

an

ol

N.D

.8

.7H

M1

-IM

SS

IC5

0(m

M)

E.

his

toly

tica

Go

nza

lez-

Ga

rza

an

dS

aid

-Fe

rna

nd

ez

(19

88

)4

5G

oss

yp

ium

he

rba

ciu

mS

ee

do

ilN

.A.

Go

ssy

po

l0

.01

5H

M-1

:IM

SS

(Ma

lva

cea

e)

IC5

0(m

M)

E.

his

toly

tica

Go

nza

lez-

Ga

rza

et

al.

(19

93

)4

6G

oss

yp

ium

sp.

Se

ed

oil

N.A

.(ÿ

)-G

oss

yp

ol

0.0

1H

M-1

(Ma

lva

cea

e)

0.0

16

HK

-90

.03

8H

M-3

0.0

26

HM

-20

.02

9H

M-3

8IC

50(m

g/m

L)

E.

his

toly

tica

He

inri

che

ta

l.(1

99

2)

47

Go

ua

nia

po

lyg

am

aL

ea

ve

sE

tha

no

lN

.D.

12

5±2

50

NIH

20

0(R

ha

mn

ace

ae

)D

ich

loro

me

tha

ne

N.D

.1

25

±25

0W

ate

rN

.D.

>2

50

48

He

insi

ap

ulc

he

lla

MIC

(mg

/mL

)E

.h

isto

lyti

caT

on

ae

ta

l.(1

99

8)

(Ru

bia

cea

e)

Ro

ot

ba

rkD

eco

ctio

nN

.D.

15

.62

49

He

lia

nth

em

um

glo

me

ratu

mIC

50(m

g/m

L)

E.

his

toly

tica

HM

1-1

MS

SC

alz

ad

ae

ta

l.(1

99

8b

)

(Cis

tace

ae

)S

tem

/Le

av

es

Me

tha

no

lN

.D.

15

8.2

25

0H

elia

nth

em

um

glo

me

ratu

mIC

50(m

g/m

L)

E.

his

toly

tica

HM

1-1

MS

SC

alz

ad

ae

ta

l.(1

99

9)

(Cis

tace

ae

)S

tem

/Le

av

es

Fla

vo

no

ids

Tilir

osi

de

17

.45

51

He

lio

psi

slo

ng

ipe

sIC

50(m

g/m

L)

E.

his

toly

tica

Ca

lza

da

et

al.

(19

98

a)

(Ast

era

cea

e)

Ro

ot

Me

tha

no

lN

.D.

53

.12

HM

1-I

MS

S

6 P. SHARMA AND J. D. SHARMA

Copyright# 2001JohnWiley & Sons,Ltd. Phytother.Res.15, 1–17(2001)

Tab

le1.

Con

tinue

d

S.

No

.B

ota

nic

al

na

me

(Fa

mily

)P

art

use

dE

xtr

act

/Cla

sso

fco

mp

ou

nd

Na

me

of

com

po

un

dD

ose

ef®

cie

ncy

E.

his

toly

tica

stra

inin

vit

roR

efe

ren

ce

52

He

llia

nth

ella

IC5

0(m

g/m

L)

E.

his

toly

tica

Ca

lza

da

et

al.

(19

98

a)

qin

qu

en

erv

is(A

ste

race

ae

)R

oo

tM

eth

an

ol

N.D

.4

.61

HM

1-I

MS

S

Dilu

tio

nE

.h

isto

lyti

cain

-vit

roW

hit

e(1

93

3)

53

Ho

larr

he

na

inte

ge

rrim

aB

ark

an

dS

ee

ds

Alk

alo

idN

orc

on

ess

ine

1:5

00

0

(Ap

ocy

an

ace

ae

)C

on

ess

ine

1:2

0,0

00

IC5

0(m

g/m

L)

E.

his

toly

tica

Wri

gh

te

ta

l.(1

98

9)

54

Ho

larr

he

na

pu

be

sce

ns

Ba

rkA

lka

loid

sC

on

ess

ine

8.9

7N

IH2

00

(Ap

ocy

an

ace

ae

)C

on

ess

imin

e1

.87

Iso

con

ess

imin

e2

0.9

Co

nku

rch

ine

12

Co

ne

ssid

ine

2.2

9H

olo

na

min

e3

.96

MIC

(mg

/mL

)E

.h

isto

lyti

caT

on

ae

ta

l.(1

99

8)

55

Hy

me

no

card

iaa

cid

aS

tem

ba

rkD

eco

ctio

nN

.D.

31

.25

(Eu

ph

orb

iace

ae

)R

oo

tb

ark

De

coct

ion

N.D

.2

50

56

Ja

son

iag

luti

no

saA

eri

al

pa

rts

Ace

ton

eN

.D.

Sig

ni®

can

tin

hib

itio

na

t1

00mg

/mL

E.

his

toly

tica

Ra

hm

an

Villa

esc

usa

et

al.

(19

96

)

(Ast

era

cea

e)

57

Ja

tro

ph

acu

rca

sM

IC(m

g/m

L)

E.

his

toly

tica

To

na

et

al.

(19

98

)(E

up

ho

rbia

cea

e)

Le

av

es

De

coct

ion

N.D

.3

1.2

55

8J

ust

icia

insu

lari

sM

IC(m

g/m

L)

E.

his

toly

tica

To

na

et

al.

(19

98

)(A

can

tha

cea

e)

Le

av

es

De

coct

ion

N.D

.>

50

05

9K

oh

leri

ad

ep

pe

an

aIC

50(m

g/m

L)

E.

his

toly

tica

Ca

lza

da

et

al.

(19

98

a)

(Ge

sne

ria

cea

e)

Le

av

es

Me

tha

no

lN

.D.

12

0.9

2H

M1

-IM

SS

60

Le

pid

ium

vir

gin

icu

mIC

50(m

g/m

L)

E.

his

toly

tica

Ca

lza

da

et

al.

(19

98

a)

(Cru

cife

rae

)E

nti

rep

lan

tM

eth

an

ol

N.D

.1

05

HM

1-I

MS

S6

1M

alm

ea

de

pre

ssa

IC5

0(m

g/m

L)

E.

his

toly

tica

Ca

lza

da

et

al.

(19

98

a)

(An

no

na

cea

e)

Ste

mb

ark

an

dw

oo

dM

eth

an

ol

N.D

.4

53

.41

HM

1-I

MS

S

62

Ma

ng

ife

rain

dic

aM

IC(m

g/m

L)

E.

his

toly

tica

To

na

et

al.

(19

98

)(A

na

card

iace

ae

)S

tem

ba

rkD

eco

ctio

nN

.D.

�7.8

1M

IC(m

g/m

L)

E.

his

toly

tica

To

na

et

al.

(19

98

)6

3M

ap

rou

ne

aa

fric

an

aL

ea

ve

sD

eco

ctio

nN

.D.

62

.5(E

up

ho

rbia

cea

e)

Ro

ot

ba

rkD

eco

ctio

nN

.D.

31

.25

64

Mo

rin

da

mo

rin

do

ide

sM

IC(m

g/m

L)

E.

his

toly

tica

To

na

et

al.

(19

98

)(R

ub

iace

ae

)L

ea

ve

sD

eco

ctio

nN

.D.

15

.62

65

My

rta

nth

us

arb

ore

us

MIC

(mg

/mL

)E

.h

isto

lyti

caT

on

ae

ta

l.(1

99

8)

(Mo

race

ae

)L

ea

ve

sD

eco

ctio

nN

.D.

>5

00

66

On

go

kea

go

reM

IC(m

g/m

L)

E.

his

toly

tica

To

na

et

al.

(19

98

)(O

laca

cea

e)

Ste

mb

ark

De

coct

ion

N.D

.>

50

06

7P

ara

the

sis

chia

pe

nsi

sS

tem

/le

av

es

IC5

0(m

g/m

L)

E.

his

toly

tica

HM

1-1

MS

SC

alz

ad

ae

ta

l.(1

99

8b

)

PLANTS SHOWINGANTIAMOEBIC ACTIVITY 7

Copyright# 2001JohnWiley & Sons,Ltd. Phytother.Res.15, 1–17(2001)

Tab

le1.

Con

tinue

d

S.

No

.B

ota

nic

al

na

me

(Fa

mily

)P

art

use

dE

xtr

act

/Cla

sso

fco

mp

ou

nd

Na

me

of

com

po

un

dD

ose

ef®

cie

ncy

E.

his

toly

tica

stra

inin

vit

roR

efe

ren

ce

(My

rist

ica

cea

e)

Me

tha

no

lN

.D.

11

70

.68

68

Pa

rop

sia

bra

zze

an

aM

IC(m

g/m

L)

E.

his

toly

tica

To

na

et

al.

(19

98

)(F

laco

urt

iace

ae

)R

oo

tb

ark

De

coct

ion

N.D

.7

.81

69

Pe

nta

cle

tra

ma

cro

ph

ylla

MIC

(mg

/mL

)E

.h

isto

lyti

caT

on

ae

ta

l.(1

99

8)

(Mim

osa

cea

e)

Ste

mb

ark

De

coct

ion

N.D

.2

50

70

Ph

yto

lla

cad

od

eca

nd

raM

IC(m

g/m

L)

E.

his

toly

tica

To

na

et

al.

(19

98

)(P

hy

tolla

cace

ae

)L

ea

ve

sD

eco

ctio

nN

.D.

>5

00

EC

50

(mg

/mL

)E

.h

isto

lyti

caN

IH2

00

Ha

rris

an

dP

hillip

son

(19

82

)7

1P

icra

sma

ex

cels

aW

oo

dQ

ua

ssin

oid

Qu

ass

in0

.5(S

ima

rou

ba

cea

e)

Ind

ole

alk

alo

idC

an

thin

-6-o

ne

23

Eth

an

ol

10

00mg

/mL

E.

his

toly

tica

NIH

20

0G

ho

sha

le

ta

l.(1

99

6)

72

Pip

er

lon

gu

mF

ruit

sH

ex

an

e1

00

0mg

/mL

(Pip

era

cea

e)

Ch

loro

form

50

0mg

/mL

n-B

uta

no

l(S

olu

ble

)1

00mg

/mL

n-B

uta

no

l(i

nso

lub

le)

No

ta

ctiv

eP

ipe

rin

eN

ot

act

ive

73

Pip

er

sch

mid

tii

Wh

ole

pla

nt

He

xa

ne

N.D

.9

8%

at

10

00mg

/mL

E.

his

toly

tica

Jo

shi

et

al.

(19

90

)(P

ipe

race

ae

)tr

op

ho

zoit

es

kille

d7

4P

lum

ba

go

sca

nd

en

sIC

50(m

g/m

L)

E.

his

toly

tica

Ca

lza

da

et

al.

(19

98

a)

(Plu

mb

ag

ina

cea

e)

Ste

mb

ark

Me

tha

no

lN

.D.

11

7.9

HM

1-I

MS

SM

IC(m

g/m

L)

E.

his

toly

tica

Ah

me

de

ta

l.(1

99

6)

75

Pro

sop

isju

li¯

ora

N.A

.A

lka

loid

sJ

uli¯

ori

ne

10

(Le

gu

min

osa

e)

Ju

li¯

ori

cin

e1

0B

en

zen

ein

solu

ble

7.5

Alk

alo

ida

lp

ort

ion

MIC

(mg

/mL

)E

.h

isto

lyti

caT

on

ae

ta

l.(1

99

8)

76

Psi

diu

mg

ua

jav

aL

ea

ve

sD

eco

ctio

nN

.D.

62

.5(M

yrt

ace

ae

)S

tem

ba

rkD

eco

ctio

nN

.D.

�7.8

17

7P

tele

atr

ifo

lia

taIC

50(m

g/m

L)

E.

his

toly

tica

Ca

lza

da

et

al.

(19

98

a)

(Ru

tace

ae

)S

tem

ba

rka

nd

wo

od

Me

tha

no

lN

.D.

18

.94

HM

1-I

MS

S

78

Pte

rid

ium

aq

uilin

um

MIC

(mg

/mL

)E

.h

isto

lyti

caT

on

ae

ta

l.(1

99

8)

(Pte

rid

ace

ae

)T

wig

sD

eco

ctio

nN

.D.

>5

00

79

Qu

ass

iaa

fric

an

aM

IC(m

g/m

L)

E.

his

toly

tica

To

na

et

al.

(19

98

)(S

ima

rou

ba

cea

e)

Ro

ot

ba

rkD

eco

ctio

nN

.D.

31

.5IC

50(m

g/m

L)

E.

his

toly

tica

He

inri

che

ta

l.(1

99

2)

80

Qu

erc

us

ole

oid

es

Ba

rkE

tha

no

lN

.D.

12

5±2

50

NIH

20

0(F

ag

ace

ae

)D

ich

loro

me

tha

ne

N.D

.1

25

±25

0W

ate

rN

.D.

>2

50

81

Ra

tib

ida

lati

pa

lia

ris

IC5

0(m

g/m

L)

E.

his

toly

tica

Ca

lza

da

et

al.

(19

98

a)

(Ast

era

cea

e)

Ro

ot

Me

tha

no

lN

.D.

91

.72

HM

1-I

MS

S8

2R

au

wo

l®a

ob

stra

taM

IC(m

g/m

L)

E.

his

toly

tica

To

na

et

al.

(19

98

)(A

po

cya

na

cea

e)

Ro

ot

ba

rkD

eco

ctio

nN

.D.

31

.5

8 P. SHARMA AND J. D. SHARMA

Copyright# 2001JohnWiley & Sons,Ltd. Phytother.Res.15, 1–17(2001)

Tab

le1.

Con

tinue

d

S.

No

.B

ota

nic

al

na

me

(Fa

mily

)P

art

use

dE

xtr

act

/Cla

sso

fco

mp

ou

nd

Na

me

of

com

po

un

dD

ose

ef®

cie

ncy

E.

his

toly

tica

stra

inin

vit

roR

efe

ren

ce

83

Ru

bu

sco

rlif

oliu

sS

tem

/IC

50(m

g/m

L)

E.

his

toly

tica

HM

1-1

MS

SC

alz

ad

ae

ta

l.(1

99

8b

)(R

osa

cea

e)

lea

ve

sM

eth

an

ol

N.D

.7

2.4

28

4S

ida

rho

mb

ifo

lia

MIC

(mg

/mL

)E

.h

isto

lyti

caT

on

ae

ta

l.(1

99

8)

(Ma

lva

cea

e)

Le

av

es

De

coct

ion

N.D

.6

2.5

85

IC5

0(m

g/m

L)

E.

his

toly

tica

Wri

gh

te

ta

l.(1

98

9)

Sim

aro

ub

aa

ma

raS

tem

Ch

loro

form

N.D

.2

.9N

IH2

00

(Sim

aro

ub

ace

ae

)B

uta

no

lN

.D.

6.8

9F

ruit

sQ

ua

ssin

oid

sA

ila

nth

ino

ne

0.0

63

Gla

uca

rub

ino

ne

0.1

68

2'-

ace

tox

y-g

lau

caru

bin

on

e0

.15

5H

ola

can

tho

ne

0.1

62

86

Sw

ite

nia

hu

millis

IC5

0(m

g/m

L)

E.

his

toly

tica

Ca

lza

da

et

al.

(19

98

a)

(Me

lia

cea

e)

Ste

mM

eth

an

ol

N.D

.1

78

.1H

M1

-IM

SS

87

Str

ych

no

sg

oss

we

ile

riR

oo

tb

ark

Qu

ate

rna

rya

lka

loid

Dip

loce

lin

e1

00

%in

hib

itio

na

t5

0mg

/mL

E.

his

toly

tica

Re

hm

an

Ga

squ

et

et

al.

(19

92

)

(Lo

ga

nia

cea

e)

88

%in

hib

itio

na

t1

.5mg

/mL

E.

his

toly

tica

Du

Va

nB

ee

ke

ta

l.(1

98

4)

Ta

be

rna

em

on

tan

aa

ura

nti

aca

20

±80

%

Le

af

an

dtw

igE

tha

no

lN

.D.

T.

chip

pii

20

±80

%L

ea

f8

0±1

00

%R

oo

tb

ark

0±2

0%

T.

con

tort

art

aS

tem

ba

rk8

0±1

00

%L

ea

f2

0±8

0%

T.

cra

ssa

Tw

ig0

±20

%T

.d

ich

oto

ma

Ste

mb

ark

20

±80

%T

.e

gla

nd

ulo

saL

ea

f2

0±8

0%

Le

af

20

±80

%T

.g

lan

du

losa

Ste

mb

ark

20

±80

%L

ea

f2

0±8

0%

T.

he

tero

ph

ylla

Ste

mb

ark

0±2

0%

Le

af

20

±80

%T

.lo

ng

i¯o

raT

wig

20

±80

%T

.o

rie

nta

lis

Le

af

an

dtw

ig2

0±8

0%

T.

pa

chy

sip

ho

nL

ea

fa

nd

twig

20

±80

%R

oo

tb

ark

80

±10

0%

T.

pe

nd

uli¯

ora

Ste

mb

ark

10

0%

Le

af

10

0%

T.

pso

roca

rpa

Ste

mb

ark

20

-80

%L

ea

f1

00

%R

oo

tb

ark

10

0%

T.

un

du

lata

Ste

mb

ark

80

±10

0%

PLANTS SHOWINGANTIAMOEBIC ACTIVITY 9

Copyright# 2001JohnWiley & Sons,Ltd. Phytother.Res.15, 1–17(2001)

Tab

le1.

Con

tinue

d

S.

No

.B

ota

nic

al

na

me

(Fa

mily

)P

art

use

dE

xtr

act

/Cla

sso

fco

mp

ou

nd

Na

me

of

com

po

un

dD

ose

ef®

cie

ncy

E.

his

toly

tica

stra

inin

vit

roR

efe

ren

ce

T.

ve

ntr

ico

saS

tem

ba

rk8

0±1

00

%L

ea

f0

±20

%(A

po

cya

na

cea

e)

Ste

mb

ark

89

Te

lox

ys

gra

ve

ole

ns

IC5

0(m

g/m

L)

E.

his

toly

tica

Ca

lza

da

et

al.

(19

98

a)

(Ch

en

op

od

iace

ae

)E

nti

rep

lan

tM

eth

an

ol

N.D

.9

.13

HM

1-I

MS

SIC

50(m

g/m

L)

E.

his

toly

tica

HM

1-1

MS

SC

alz

ad

ae

ta

l.(1

99

9)

90

Te

lox

ys

gra

ve

ole

ns

N.A

Fla

vo

no

ids

Pin

oce

mb

rin

80

.76

(Ch

en

op

od

iace

ae

)P

ino

stro

bin

18

4.4

59

1T

etr

ace

rap

og

ge

iM

IC(m

g/m

L)

E.

his

toly

tica

To

na

et

al.

(19

98

)(D

ille

ne

ace

ae

)L

ea

ve

sD

eco

ctio

nN

.D.

>5

00

IC5

0(m

M)

E.

his

toly

tica

Go

nza

lez-

Ga

rza

et

al.

(19

93

)9

2T

he

spe

psi

ap

up

ula

na

Se

ed

oil

N.A

.(�

)-G

oss

yp

ol

0.2

35

HM

-1(M

alv

ace

ae

)2

.08

6H

K-9

0.2

25

HM

-30

.45

5H

M-2

1.0

85

HM

-38

93

Tit

ho

nia

div

ers

ifo

lia

Le

av

es

Ma

cera

tio

nin

wa

ter

MIC

(mg

/mL

)E

.h

isto

lyti

caT

on

ae

ta

l.(1

99

8)

(Ast

era

cea

e)

N.D

.6

2.5

MIC

(mg

/mL

)E

.h

isto

lyti

caN

IH2

00

ax

en

ica

nd

Po

lyx

en

ic

Bh

uta

ni

et

al.

(19

87

)

94

Ty

lop

ho

rain

dic

aA

eri

al

pa

rts

Eth

an

ol

15

0a

nd

75

.0T

ylo

ph

ori

ne

hy

dro

chlo

rid

e6

.25

an

d6

.25

Ph

en

an

thro

ind

olizi

din

ea

lka

loid

sT

ylo

ph

ori

ne

6.2

5a

nd

6.2

5T

ylo

ph

ori

nin

e4

00

an

d4

00

De

me

thy

lty

lop

ho

rin

e2

5a

nd

50

4-M

eth

ox

y-1

4-

hy

dro

xy

tylo

ph

ori

ne

3.1

2a

nd

12

.5

Ace

tylt

ylo

ph

ori

ne

d-S

ep

tici

ne

50

an

d2

5E

tha

no

l4

00

an

d4

00

Ph

en

an

thro

ind

ol-

Ty

lop

ho

rah

irsu

taA

eri

al

pa

rts

izid

ine

alk

alo

ids

Ty

loh

irsu

tin

ine

30

0a

nd

15

0(A

scle

pia

da

cea

e)

13

a-M

eth

ylt

ylo

hir

suti

nin

e5

0a

nd

10

01

3a

-Me

thy

lty

loh

irsu

tin

idin

e2

5a

nd

12

.5T

ylo

hir

suti

nid

ine

40

0a

nd

N.D

.1

3a

-Hy

dro

xy

tylo

ph

ori

ne

20

0a

nd

N.D

.1

3a

-Hy

dro

xy

sep

tici

ne

50

an

dN

.D.

Iso

tylo

cre

bin

e8

00

an

d8

00

10 P. SHARMA AND J. D. SHARMA

Copyright# 2001JohnWiley & Sons,Ltd. Phytother.Res.15, 1–17(2001)

Tab

le1.

Con

tinue

d

S.

No

.B

ota

nic

al

na

me

(Fa

mily

)P

art

use

dE

xtr

act

/Cla

sso

fco

mp

ou

nd

Na

me

of

com

po

un

dD

ose

ef®

cie

ncy

E.

his

toly

tica

stra

inin

vit

roR

efe

ren

ce

14

-De

ox

y-1

3a

-m

eth

ylt

ylo

hir

suti

nid

ine

25

an

d2

5

12

.5a

nd

12

.59

5V

ite

xm

ad

ien

sis

MIC

(mg

/mL

)E

.h

isto

lyti

caT

on

ae

ta

l.(1

99

8)

(Ve

rba

na

cea

e)

Le

av

es

De

coct

ion

N.D

.>

50

09

6V

oa

can

ga

afr

ica

na

Ma

cera

tio

nin

wa

ter

MIC

(mg

/mL

)E

.h

isto

lyti

caT

on

ae

ta

l.(1

99

8)

(Ap

ocy

an

ace

ae

)R

oo

tb

ark

N.D

.6

2.5

MIC

(mg

/mL

)E

.h

isto

lyti

caS

FL

3S

oh

ni

et

al.

(19

95

)9

7W

ho

lefo

rmu

lati

on

con

tain

ing

N.A

.E

tha

no

lN

.D.

10

00

Bo

err

ha

via

dif

fusa

(Ny

cta

gin

ace

ae

)T

ino

spo

raco

rdif

olia

(Me

nis

pe

rma

cea

e)

Be

rbe

ris

asi

ati

ca(B

erb

eri

da

cea

e)

Te

rmin

alia

che

bu

la(C

om

bre

tace

ae

)Z

ing

ibe

ro

f®ci

na

le(Z

ing

ibe

race

ae

)IC

50

(mg

/L)

Gillin

an

dD

iam

on

d(1

98

1)

98

Sta

nd

ard

dru

gs

ÐM

ep

acr

ine

Qu

ina

crin

eH

Cl

0.0

6-0

.5E

.h

isto

lyti

caH

M-1

:IM

SS

5-n

itro

imid

azo

leM

etr

on

ida

zole

0.1

-2.0

Em

eti

ne

HC

l2

-Ja

nIC

50

(mg

/mL

)W

rig

ht

et

al.

(19

87

)9

9S

tan

da

rdd

rug

5-n

itro

imid

azo

leM

etr

on

ida

zole

0.3

2E

.h

isto

lyti

caN

IH2

00

Em

eti

ne

hy

dro

chlo

rid

e1

.23

4-a

min

oq

uin

olin

eC

Qd

iph

osp

ha

te1

5.1

Cin

cho

na

alk

alo

idQ

uin

ine

24

MIC

(mg

/mL

)M

ah

aja

ne

ta

l.(1

97

4)

10

0S

tan

da

rdd

rug

5-n

itro

imid

azo

leM

etr

on

ida

zole

0.3

12

-0

.62

5E

.h

isto

lyti

can

itro

imid

azo

leT

inid

azo

le0

.62

5-

1.2

5

N.A

.,n

ot

av

aila

ble

inlite

ratu

re;

N.D

.,p

ure

-co

mp

ou

nd

sw

ere

no

td

esc

rib

ed

.

PLANTS SHOWINGANTIAMOEBIC ACTIVITY 11

Copyright# 2001JohnWiley & Sons,Ltd. Phytother.Res.15, 1–17(2001)

Tab

le2.

Aco

mpa

rativ

eco

mpi

latio

nof

plan

tex

trac

tsan

dco

mpo

unds

asse

ssed

for

antia

moe

bic

and

antip

lasm

odia

lac

tivity

byin

vitr

osc

reen

ing

with

E.

hist

olyt

ica

and

P.

falc

ipar

um

S.

Bo

tan

ica

ln

am

eE

xtr

act

/Cla

sso

fco

mp

ou

nd

Do

see

f®ci

en

cyD

ose

ef®

cie

ncy

No

.(F

am

ily

)a

nd

Pa

rtu

sed

Na

me

of

com

po

un

din

P.

falc

ipa

rum

inE

.h

isto

lyti

caR

efe

ren

ce

ED

50

(mM

)E

D5

0(m

M)

Wri

gh

te

ta

l.(1

99

2)

1A

lsto

nia

an

gu

stif

olia

Alk

alo

ids

Als

ton

eri

ne

46

.37

5.3

(Ap

ocy

an

ace

ae

)A

lsto

ph

yllin

e8

2.5

67

.7M

acr

als

ton

ine

Ina

ctiv

ea

t1

78

Ina

ctiv

ea

t7

0M

acr

als

ton

ine

ace

tate

3.4

31

5.5

1M

acr

oca

rpa

min

e9

.36

8.1

21

1-M

eth

ox

ya

kua

mm

icin

e4

1.3

70

.5N

or¯

uro

cura

rin

e1

29

84

.1P

leio

carp

am

ine

20

.54

7.4

Villa

sto

nin

e2

.92

11

.8V

inca

ma

jin

e1

38

ina

ctiv

ea

t7

0S

tan

da

rdd

rug

sC

Qd

iph

osp

ha

te0

.16

8N

TE

me

tin

eh

yd

roch

lori

de

NT

2.0

4IC

50

(mg

/mL

)2

An

no

na

mu

rica

taE

tha

no

lN

.D.

63

He

inri

che

ta

l.(1

99

2)

(An

no

na

cea

e)

Dic

hlo

rom

eth

an

eN

.D.

31

-63

Wa

ter

N.D

.2

50

IC5

0(m

g/m

L)

Gb

ea

sso

re

ta

l.(1

99

0)

Eth

an

ol

N.D

.3

9.9

IC5

0(m

g/m

L)

IC5

0(m

g/m

L)

Wri

gh

te

ta

l.(1

98

8)

3B

ruce

aja

va

nic

aQ

ua

ssin

oid

sB

ruce

ine

A0

.01

10

.09

7(S

ima

rou

ba

cea

e)

Bru

cein

eB

0.0

11

0.3

06

Bru

cein

eC

0.0

05

0.2

79

Bru

cea

nti

n0

.00

08

0.0

19

Bru

cein

eD

0.0

15

0.3

86

Ya

da

nzi

osi

de

F5

2.3

3

IC5

0(m

M)

IC5

0(m

M)

Wri

gh

te

ta

l.(1

99

3)

4B

ruce

aja

va

nic

aQ

ua

ssin

oid

sB

ruce

an

tin

0.0

01

50

.03

5(S

ima

rou

ba

cea

e)

Bru

cein

eA

0.0

21

0.2

22

Bru

cein

eB

0.0

23

0.6

38

Bru

cein

eC

0.0

09

0.4

95

Bru

cein

eD

0.0

37

0.9

41

Bru

sato

l0

.00

60

.06

24

-Am

ino

qu

ino

lin

eC

Qd

iph

osp

ha

te0

.40

72

9.3

5-

Nit

roim

ida

zole

Me

tro

nid

azo

leN

T1

.87

MIC

(mg

/mL

)T

on

ae

ta

l.(1

99

8)

5C

ryp

tole

pis

san

gu

ino

len

taM

ace

rati

on

inw

ate

rN

.D.

�7.8

1(A

scle

pid

ea

cea

e)

IC5

0(m

g/m

L)

Ind

ole

qu

ino

lin

ea

lka

loid

Cry

pto

lep

ine

0.0

31

MA

C(m

g/m

L)

Mb

ela

et

al.

(19

92

)

12 P. SHARMA AND J. D. SHARMA

Copyright# 2001JohnWiley & Sons,Ltd. Phytother.Res.15, 1–17(2001)

Tab

le2.

Con

tinue

d

S.

Bo

tan

ica

ln

am

eE

xtr

act

/Cla

sso

fco

mp

ou

nd

Do

see

f®ci

en

cyD

ose

ef®

cie

ncy

No

.(F

am

ily

)a

nd

Pa

rtu

sed

Na

me

of

com

po

un

din

P.

falc

ipa

rum

inE

.h

isto

lyti

caR

efe

ren

ce

6G

ard

en

iajo

vis

ton

an

tis

Aq

.E

tha

no

lN

.D.

3.1

3(R

ub

iace

ae

)n

-Bu

tan

ol

N.D

.1

.56

Fo

rmo

lH

Cl

N.D

.1

.56

Eth

er

N.D

.6

.25

IC5

0(m

g/m

L)

We

en

en

et

al.

(19

90

)P

etr

ole

um

eth

er

N.D

.>

49

9D

ich

loro

me

tha

ne

N.D

.5

0±9

9M

eth

an

ol

N.D

.>

49

9

MIC

(mg

/mL

)T

on

ae

ta

l.(1

99

8)

7H

aru

ng

an

am

ad

ag

asc

ari

en

sis

De

coct

ion

N.D

.6

2.5

(Hy

pe

rica

cea

e)

IC5

0(m

g/m

L)

Ge

ssle

re

ta

l.(1

99

4)

Eth

an

ol

N.D

.2

9P

etr

ole

um

eth

er

10

Eth

yla

ceta

te1

0W

ate

r8

8

MIC

(mg

/mL

)T

on

ae

ta

l.(1

99

8)

8N

au

cle

ala

tifo

lia

De

coct

ion

N.D

.>

50

0(R

ub

iace

ae

)D

eco

ctio

nN

.D.

>1

25

Gb

ea

sso

re

ta

l.(1

98

9)

Wa

ter

N.D

.1

5mg�

IC5

0<

22

/mg

MIC

(mg

/mL

)S

ha

rma

an

dB

hu

tan

i(1

98

8)

9P

art

he

niu

mh

yst

ero

ph

oro

us

Se

squ

ite

rpe

ne

lact

on

eP

art

he

nin

10

-12

.5(A

ste

race

ae

)H

oo

pe

re

ta

l.(1

99

0)

IC5

0(m

g/m

L)

1.2

89

IC5

0(m

g/m

L)

IC5

0(m

g/m

L)

Wri

gh

te

ta

l.(1

98

8)

10

Sim

aro

ub

aa

ma

raQ

ua

ssin

oid

sG

lau

caru

bin

on

e0

.00

40

.16

8(S

ima

rou

ba

cea

e)

2'-

Ace

tylg

lau

caru

bin

on

e0

.00

80

.15

5A

ila

nth

ino

ne

0.0

15

0.0

63

Ho

laca

nth

on

e0

.00

70

.16

2M

etr

on

ida

zole

NT

0.3

2

IC5

0(m

M)

IC5

0(m

M)

Wri

gh

te

ta

l.(1

99

3)

11

Sim

aro

ub

aa

ma

raQ

ua

ssin

oid

sA

ila

nth

ino

ne

0.0

19

0.1

32

(Sim

aro

ub

ace

ae

)G

lau

caru

bin

on

e0

.00

80

.32

3

IC5

0(m

M)

IC5

0(m

M)

Wri

gh

te

ta

l.(1

99

4)

12

Str

ych

no

sh

en

nin

gsi

iA

lka

loid

sH

ols

tilin

e3

1.5

Ina

ctiv

ea

t6

3(L

og

an

iace

ae

)H

ols

tiin

e3

2.7

Ina

ctiv

ea

t6

5C

Qd

iph

osp

ha

te0

.15

6N

TE

me

tin

ed

ihy

dro

chlo

rid

e0

.13

3.0

7

PLANTS SHOWINGANTIAMOEBIC ACTIVITY 13

Copyright# 2001JohnWiley & Sons,Ltd. Phytother.Res.15, 1–17(2001)

Tab

le2.

Con

tinue

d

S.

Bo

tan

ica

ln

am

eE

xtr

act

/Cla

sso

fco

mp

ou

nd

Do

see

f®ci

en

cyD

ose

ef®

cie

ncy

No

.(F

am

ily

)a

nd

Pa

rtu

sed

Na

me

of

com

po

un

din

P.

falc

ipa

rum

inE

.h

isto

lyti

caR

efe

ren

ce

Me

tro

nid

azo

leN

T1

.87

IC5

0(m

g/m

L)

IC5

0(m

g/m

L)

Wri

gh

te

ta

l.(1

99

1)

13

Str

ych

no

su

sam

ba

ren

sis

Alk

alo

ids

Usa

mb

are

nsi

ne

0.3

80

.49

(Lo

ga

nia

cea

e)

3'4

'-D

ihy

dro

usa

mb

are

nsi

ne

0.0

12

.18

Nb

-me

thy

lusa

mb

are

nsi

ne

Ch

lori

de

2.3

94

.12

Usa

mb

ari

ne

18

,19

-Dih

yd

rou

sam

ba

rin

eo

xa

late

1.8

50

.46

Str

ych

no

pe

nta

min

e1

.07

0.6

5S

try

chn

op

en

tam

ine

me

tha

ne

sulp

ho

na

teIs

ost

rych

no

pe

nta

min

eb

ase

0.0

97

.7A

kag

eri

ne

0.0

91

0.1

Tu

bu

losi

ne

NT

10

.76

.98

17

.10

.02

NT

IC5

0(m

M)

IC5

0(m

M)

Wri

gh

te

ta

l.(1

99

4)

14

Str

ych

no

su

sam

ba

ren

sis

Alk

alo

ids

5,6

-Dih

yd

ro¯

av

op

ere

irin

e3

.02

24

.31

(Lo

ga

nia

cea

e)

Iso

stry

chn

op

en

tam

ine

0.7

65

19

.5S

try

chn

ofo

lin

e1

3.8

Ina

ctiv

ea

t5

2S

try

chn

op

en

tam

ine

0.1

64

14

Str

ych

no

pe

nta

min

em

eth

an

esu

lph

on

ate

0.1

41

5.7

Usa

mb

are

nsi

ne

3',4

'-D

ihy

dro

usa

mb

are

nsi

ne

0.8

81

.13

Nb

-me

thy

lusa

mb

are

nsi

ne

chlo

rid

e0

.02

35

.02

Usa

mb

ari

ne

5.3

45

9.2

21

8,1

9-D

ihy

dro

usa

mb

ari

ne

ox

ala

te�4

.11

1.0

21

.98

1.2

IC5

0(m

M)

IC5

0(m

M)

Wri

gh

te

ta

l.(1

99

4)

15

Str

ych

no

sv

ari

ab

ilis

Alk

alo

ids

O-A

cety

liso

reti

culin

e2

2.1

Ina

ctiv

ea

t6

6(L

og

an

iace

ae

)Is

ore

ticu

lin

e�9

2In

act

ive

at

74

Re

tulin

al/is

ore

tulin

al

36

Ina

ctiv

ea

t7

5R

etu

lin

e�9

2In

act

ive

at

74

Iso

stry

chn

ob

ilin

e2

.07

Ina

ctiv

ea

t4

1D

ide

hy

dro

iso

stry

chn

ob

ilin

em

on

om

eth

an

esu

lph

on

ate

1.6

7In

act

ive

at

35

14 P. SHARMA AND J. D. SHARMA

Copyright# 2001JohnWiley & Sons,Ltd. Phytother.Res.15, 1–17(2001)

Tab

le2.

Con

tinue

d

S.

Bo

tan

ica

ln

am

eE

xtr

act

/Cla

sso

fco

mp

ou

nd

Do

see

f®ci

en

cyD

ose

ef®

cie

ncy

No

.(F

am

ily

)a

nd

Pa

rtu

sed

Na

me

of

com

po

un

din

P.

falc

ipa

rum

inE

.h

isto

lyti

caR

efe

ren

ce

12

'-H

yd

rox

yis

ost

rych

no

bilin

em

on

om

eth

an

esu

lph

on

ate

1.5

8In

act

ive

at

34

Str

ych

no

bilin

e1

.03

Ina

ctiv

ea

t3

5IC

50

(mM

)IC

50

(mM

)M

ars

ha

lle

ta

l.(1

99

4)

16

N.A

.B

isb

en

zyliso

qu

ino

lin

eF

un

ife

rin

e0

.63

10

8(M

en

isp

erm

ace

ae

)a

lka

loid

sT

ilia

ge

ne

6.3

2>

41

1D

ap

hn

olin

e0

.96

46

.4A

rom

olin

e1

.36

10

5H

om

oa

rom

olin

e3

.46

>8

2.2

Ox

ya

can

thin

eH

Cl

1.0

67

4.4

Th

aliso

pid

ine

0.0

94

1.2

Ph

ae

nth

ine

1.4

64

3.6

Te

tra

nd

rin

e0

.57

NT

Iso

tetr

an

dri

ne

0.1

6N

TT

etr

an

dri

ne

me

thio

did

e>

65

.4>

32

.7P

ycn

am

ine

0.8

33

1.9

Fa

ng

chin

olin

e1

.43

10

4B

erb

am

ine

0.4

51

7.8

Ob

am

eg

ine

0.7

45

5.4

Din

kla

cori

ne

3.9

25

4.8

Iso

cho

nd

od

en

dri

ne

22

>4

21

Tri

gille

tim

ine

42

.1>

44

8C

ocs

olin

e1

.16

NT

4-A

min

oq

uin

olin

eC

ocs

ulin

ine

�88

.9>

22

25

-Nit

roim

ida

zole

Iso

trilo

bin

e2

.06

18

.8C

ocs

ulin

em

eth

iod

ide

>1

7.8

>3

55

Gille

tin

e1

.81

38

.3In

sula

rin

ep

icra

te2

.07

>2

94

CQ

dip

ho

sph

ate

0.2

NT

Em

eti

ne

hy

dro

chlo

rid

eN

T2

.23

Me

tro

nid

azo

leN

T1

.87

CQ

,ch

loro

qu

ine

;MA

C,m

inim

um

am

oe

bic

ida

lco

nce

ntr

ati

on

;N.A

.,n

ota

va

ila

ble

inlite

ratu

re;N

.D.,

aft

er

cru

de

ex

tra

ctio

ns

pu

reco

mp

ou

nd

sw

ere

no

td

ete

cte

d;N

T,n

otte

ste

din

the

stu

dy

.

PLANTS SHOWINGANTIAMOEBIC ACTIVITY 15

Copyright# 2001JohnWiley & Sons,Ltd. Phytother.Res.15, 1–17(2001)

screeningof plant material should to be followed bystudies of their cytotoxicity. In vitro amoebicidalorplasmodicidalactivity canbe comparedwith cytoxicityto guinea-pigear keratinocytes(GPK cells), KB cells,HeLacells,andothercell lines,humanerythrocytesetc,measuredas DNA- and protein-synthesisinferred fromtheinhibition of theuptakeof tritiatedthymidinein vitro.Some measureof specificity can also be obtainedbycomparisonsof cytotoxicity betweennon-specificcul-tures.Someantiamoebiccompoundswhich have beenisolated from plants have also been shown to becytotoxic, with little evidencethat toxicity with quassi-noids may not parallel antiamoebicactivity and haveamore favourable therapeutic ratio. Such cytotoxicitystudiesmay also be useful in the evaluationof naturalproductsas leadsfor the synthesisof evenmoreusefulderivativesandfor studieson structure–activityrelation-ships, drug sensitivity, multi-drug resistanceand evenresistancereversal.

CONCLUSION

Over100plantspeciesandnumerouscompoundsderivedfrom themhavebeenevaluatedfor antiamoebicactivityor for both antiamoebic and antiprotozoal activity.Compositeor non-specificactivity of plant extractsisapparentlysignificant in traditional usesand cures.Inareas of limited resources,maintaining a minimum‘freedom from disease’or its containmentwith the useof such composite formulations may be more cost-effective than repeateddiagnostic and prognostic in-vestigations,and the cost of the drug along with itsdevelopment.In developingcountriesit is still economic-ally importantfor thepeopleto resortto plant remedies.Studiessuchasthosereportedin this reviewmayhelptorestoreconfidencein theuseof suchtraditionalplants.

Acknowledgements

We sincerelyacknowledgeMr Basantfor computerizingthe text andformatting the tables.This work waspursuedwith the help of UGCFellowshipgrantedto PoonamSharmatowardsherPhDProgramme.

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