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Review ArticleLippia javanica (Burm.f.) Spreng.: Traditional andCommercial Uses and Phytochemical and PharmacologicalSignificance in the African and Indian Subcontinent
Alfred Maroyi
Department of Botany, University of Fort Hare, Private Bag X1314, Alice 5700, South Africa
Correspondence should be addressed to Alfred Maroyi; [email protected]
Received 5 September 2016; Revised 25 October 2016; Accepted 20 November 2016; Published 1 January 2017
Academic Editor: Rainer W. Bussmann
Copyright © 2017 Alfred Maroyi.This is an open access article distributed under theCreative CommonsAttribution License, whichpermits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Lippia javanica occurs naturally in central, eastern, and southern Africa and has also been recorded in the tropical Indiansubcontinent. The potential of L. javanica as herbal or recreational tea and herbal medicine and its associated phytochemistryand biological properties are reviewed. The extensive literature survey revealed that L. javanica is used as herbal tea and hasethnomedicinal applications such as in colds, cough, fever,malaria, wounds, diarrhoea, chest pains, bronchitis, and asthma.Multipleclasses of phytochemicals including volatile and nonvolatile secondary metabolites such as alkaloids, amino acids, flavonoids,iridoids, and triterpenes as well as several minerals have been identified from L. javanica. Scientific studies on L. javanicaindicate that it has a wide range of pharmacological activities which include anticancer, antiamoebic, antidiabetic, antimalarial,antimicrobial, antioxidant, antiplasmodial, and pesticidal effects. Although many of the traditional uses of L. javanica have beenvalidated by phytochemical and pharmacological studies, there are still some gaps where current knowledge could be improved.Lippia javanica is popular as both herbal and recreational tea, but there is need for more precise studies to evaluate the safety andclinical value of its main active crude and pure compounds and to clarify their mechanisms of action.
1. Introduction
Lippia javanica (Burm.f.) Spreng. (Verbenaceae) (Figure 1(a))has a long history of traditional uses in tropical Africaas indigenous herbal tea or tisane (Figure 1(b)), refresh-ing beverage, or food additive based on its perceivedhealth and medicinal properties. Lippia javanica is rich involatile oil, particularly caryophyllene, carvone, ipsenone,ipsdienone, limonene, linalool, myrcene, myrcenone, oci-menone, p-cymene, piperitenone, sabinene, and tagetenone[1–5]. Research by Viljoen et al. [3] revealed that the essentialoil profiles of L. javanica are characterized by inter- andintraspecies variations because they are produced by differentmetabolic pathways. Using cluster analysis, Viljoen et al. [3]identified five chemotypes of L. javanica in South Africaand Swaziland, myrcenone-rich type (36–62%), carvone-richtype (61–73%), piperitenone-rich type (32–48%), ipsdienone-rich type (42–61%), and linalool-rich type (>65%). The
relative proportion of the chemical constituents of L. javanicaessential oil is important as this determines the biologicalproperties of the species chemotypes.
Lippia javanica belongs to the Verbena or vervain family(Verbenaceae) comprising approximately 32 genera and 840species [97]. The genus Lippia L. is named after AugustinLippi (1678–1701), an Italian botanist and natural historianwho was killed in Ethiopia at the age of 23 [98]. Phylogeneticrelationships within family Verbenaceae demonstrated thatgenus Lippia and other closely related genera, namely,AloysiaPaláu, Lantana L., and Phyla Lour., are not monophyletic[97]. The boundaries separating these four genera are his-torically weak, with many taxonomic researchers includingspecies belonging toAloysia, Lantana, and Phyla in the genusLippia [99]. Lippia and Lantana genera are the most difficultto separate, as species of these two genera show similaritiesin their inflorescences that are spicate, often subcapitateduring anthesis and elongating in fruit and pedunculated
HindawiEvidence-Based Complementary and Alternative MedicineVolume 2017, Article ID 6746071, 34 pageshttps://doi.org/10.1155/2017/6746071
https://doi.org/10.1155/2017/6746071
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2 Evidence-Based Complementary and Alternative Medicine
(a) (b)
Figure 1: (a) Lippia javanica (Burm.f.) Spreng. flowers and leaves (photo: BT Wursten) and (b) L. javanica herbal tea traded as Zumbani inZimbabwe (http://specialityfoods.co.zw/product/zumbani/).
[98]. According to de Campos et al. [100], the genus Lippiacomprises about 200 species of herbs, shrubs, and smalltrees distributed throughout south and central America andtropical Africa. Only 15 Lippia species have been recordedin tropical Africa [101]. The specific name “javanica” wasgiven by theDutch Botanist Nicolaas Laurens Burman (1734–1793) in 1768, whomistakenly thought that the type specimenwas collected in Java, Indonesia [102]. He placed the speciesin the genus Verbena, and the German botanist Sprengel(1766–1833) transferred Burman’s name to the genus Lippiain 1825 [103]. Lippia javanica is morphologically similar to L.scaberrima Sond. but is much taller and its bracts are shorterthan the flowers (Figure 1(a)), while L. scaberrima has manystems arising from ground level and is usually less than 0.5metres high, and its bracts are not longer than the flowers[104].
Lippia javanica is an erect woody perennial herb orshrub of up to 4.5m tall, with strong aromatic leaves whichgive off a lemon-like fragrance when crushed [105]. Stemsare brownish, usually erect or spreading with short stifftubercle-based whitish hairs and small glands, and branchedwith inflorescences in nearly all axils. Leaves are oppositeor in whorls of 3, blades lanceolate to oblong and denselypubescent, rounded and then cuneate at the base, andcrenate-serrate or closely serrulate on themargins except nearthe leaf base [106]. Flowers occur in conical or oblong spikes,purple or dull-reddish in fruit, dark brownish on drying [101,106]. The flowers are sessile or with short peduncles, lowerbracts of spikes ovate and upper bracts smaller, pubescent,glandular, and densely spreading [101]. The calyx is 2-lobed,half as long as the corolla, pubescent, and densely spreading.The corolla is white, yellowish-white to greenish (Figure 1(a)),usually with a yellow throat, glandular and pubescent outsidein the upper half, tube narrowly funnel-shaped from a narrowbase [101, 106]. Anthers are sulphur-yellow and nutlets arebrown and half ovoid [101, 106].
Lippia javanica occurs naturally in central, eastern, andsouthern Africa (Figure 2) and has also been recorded in thetropical Indian subcontinent [12, 13, 23, 39, 47, 61]. In sub-Saharan Africa, the species is native to Angola, Botswana,Central African Republic, Democratic Republic of Congo,Ethiopia, Kenya, Malawi, Mozambique, South Africa, Swazi-land, Tanzania, Uganda, Zambia, Zanzibar, and Zimbabwe.
1000 km
Figure 2: Lippia javanica naturally occurs in central, eastern, andsouthern Africa.
Lippia javanica has been recorded in low to high altitude(0–2350m above sea level) woodlands and wooded grass-lands, scrub bushland, and grassy rocky kopjes, in riverinevegetation, and on margins of dambos and swampy ground,sometimes on termite mounds, in montane grasslands, andon evergreen forest margins, also in disturbed ground besideroads, forest clearings, plantations, and cultivated land andbecoming a weed in derived rangelands [101, 106].This showsthat the plant is highly adaptable to a wide range of climatic,soil, and vegetation conditions.
2. Traditional Uses of Lippia javanica
Lippia javanica is used for a wide variety of traditional uses(Table 1). Based on literature, the most important traditionalapplications include its uses as herbal tea and ethnomedicinalapplications for (in descending order of importance) colds,cough, fever or malaria, wounds, repelling mosquitos, diar-rhoea, chest pains, bronchitis, and asthma (Figure 3). Thesedifferent uses are discussed in the following seven sections:
http://specialityfoods.co.zw/product/zumbani/
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Evidence-Based Complementary and Alternative Medicine 3
Table1:Tradition
aluses
ofLippiajavanica
incentral,easte
rn,and
southern
Africa.
Use
Plantp
art(s
)used
Mod
eofu
seCou
ntry
practised
Reference(s)
Food
uses
Food
additiv
eLeaves,twigs
Leaves
andtwigsb
oiledtogether
with
maize,cassava,groun
dnuts,andcommon
tea
(Cam
elliasin
ensis
(L.)Ku
ntze)
Kenya
[6]
Herbaltea
Leaves
Leaves
canbe
sundriedforlater
use
Botsw
ana,South
Africa,and
Zimbabw
e[7–11]
Leafyvegetable
Leaves
Eatenas
vegetablew
ithmeato
rfish
India
[12,13]
Respira
tory
problem
s
Asthma
Leaves,twigs
Decoctio
ntakenorallyor
smokeinh
aled
SouthAfrica,
Zimbabw
e[14
–17]
Blockedno
seLeaves
Leafdecoctionof
L.javanica
alon
etaken
orallyor
mixed
with
anyof
theses
pecies:
Brachylaenaun
ifloraHarv.,
Clau
sena
anisa
ta(W
illd).H
ook.f.ex
Benth.,C
lematis
brachiataTh
unb.,C
ombretum
molleR.
Br.exG.D
on,E
ucalyptusgrand
isW.H
ill,
Helichrysum
krau
ssiiSch.B
ip.,Krau
seolamosam
bicin
aPax&Hoff
m.,Plectra
nthu
sneochilusS
chltr.,Senecio
serratuloidesD
C.,orT
richilia
emetica
Vahl
takenorally
SouthAfrica
[18]
Bron
chitis
Leaves,roo
ts,andste
ms
Leafinfusio
nof
L.javanica
alon
etaken
orallyor
appliedto
skin
asointmento
rleafand
stem
infusio
nof
L.javanica
mixed
with
leaves
ofAr
temisiaafra
Jacq.exWilld.taken
orally
Botsw
ana,South
Africa
[15,19–22]
Chestp
ains
Leaves,roo
ts
Leaves
androotso
fL.javanica
alon
echewe
dor
decoctiontakenorallyor
used
inwashes
andpo
ultic
esor
smokeinh
aled
or“im
biza,”decoctionprepared
from
L.javanica
and
Cyrtanthus
obliquu
s(L.f.)
Aito
n,takenorallyor
leafdecoctionof
L.javanica
mixed
with
leaves
ofanyof
theses
pecies:B
rachylaena
transvaalensis
Hutch.exE.
Phillips&
Schw
eick.,C.
brachiata,E.
grandis,H
.kraussii,orT
.emetica
takenorallyor
leafjuice
takenorallywith
cloveso
fAllium
sativ
umL.
Bang
ladesh,
Ethiop
ia,and
SouthAfrica
[14,18,23–27]
Colds
Leaves,twigs
Leafinfusio
nof
L.javanica
alon
etaken
orallyor
inhaledor
appliedas
anointmento
r“im
biza,”decoctionprepared
from
L.javanica
andC.
obliquu
s,takenorally
Botsw
ana,Ke
nya,
SouthAfrica,and
Zimbabw
e
[15,16,19,21,27–
32]
Cou
ghLeaves,
stems,and
twigs
Leaves
ofL.javanica
alon
echewed
orinfusio
ninhaledor
takenorallyor
appliedas
anointmento
rleafand
stem
infusio
nof
L.javanica
mixed
with
leaves
ofanyof
these
species:Ac
anthosperm
umgla
bratum
(DC.)W
ild.,A.
afra,B
.uniflora,B
.transvaalensis,
BrideliacatharticaBe
rtol.,C.
anisa
ta,C
.brachiata,C
.molle,
E.grandis,H.kraussii,K
.mosam
bicin
a,P.neochilus,Psidium
guajavaL.,S.serratuloides,Terminaliaseric
eaBu
rch.
exDC.,Tetradeniarip
aria(H
ochst.)
Cod
d,or
T.em
etica
takenorally
Botsw
ana,
Ethiop
ia,Sou
thAfrica,and
Zimbabw
e
[15,16,18–
21,26,30,32]
Influ
enza
Leaves,roo
tsDecoctio
ntakenorally
Mozam
biqu
e,SouthAfrica
[7,33–36]
Lung
infections
Leaves
Infusio
nstakenorally
SouthAfrica
[37]
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4 Evidence-Based Complementary and Alternative Medicine
Table1:Con
tinued.
Use
Plantp
art(s
)used
Mod
eofu
seCou
ntry
practised
Reference(s)
Measle
sLeaves,stems
Leafdecoctionof
L.javanica
alon
etaken
orallyor
body
washedwith
infusio
nor
leafand
stem
infusio
nof
L.javanica
mixed
with
leaves
ofA.
afra
takenorally
Kenya,South
Africa,and
Zimbabw
e[14
,20,38]
Pneumon
iaLeaves
Ointm
entrub
bedon
chestand
abdo
men
Zimbabw
e[14
]Re
spira
tory
disorders
Leaves
Decoctio
ntakenorally
India,SouthAfrica
[39–
41]
Runn
yno
seLeaves,roo
ts
Leafandroot
decoctionof
L.javanica
alon
etaken
orallyor
leafdecoctionof
L.javanica
mixed
with
leaves
ofanyof
theses
pecies:B
.transvaalensis,B
.cathartica
,C.anisata,C
.brachiata,E.
grandis,Hypoxisspp.,K
.mosam
bicin
a;P.guajava,S.serratuloides,P.
neochilus,or
T.em
etica
takenorally
SouthAfrica
[18]
Shortnesso
fbreath(dyspn
oea)
Leaves
Decoctio
ntakenorallyor
body
washedwith
decoction
Zimbabw
e[14
]
Sore
throat
Leaves
Leafdecoctionof
L.javanica
alon
etaken
orallyor
leafdecoctionof
L.javanica
mixed
with
leaves
ofE.
grandiso
rT.ripariatakenorally
SouthAfrica
[18]
Tonsillitis
Leaves
Leafdecoctionof
L.javanica
alon
etaken
orallyor
leafdecoctionof
L.javanica
mixed
with
leaves
ofE.
grandistaken
orally
SouthAfrica
[18]
Tuberculosis
Leaves
Leafdecoctionof
L.javanica
alon
etaken
orallyor
“imbiza,”decoctionprepared
from
L.javanica
andC.
obliquu
s,takenorally
SouthAfrica,
Ugand
a[24,42,43]
Gastro
intestina
ldise
ases
Amoebiasis
Leaves,twigs
Decoctio
ntakenorally
Kenya
[6]
Anthelm
intic
sLeaf
Infusio
nstakenorally
SouthAfrica
[40]
Diarrho
eaLeaves,roo
tsDecoctio
ntakenorally
Kenya,
Mozam
biqu
e,SouthAfrica
[17,29,34,37,44]
Gangrenou
srectitis
Leaves
Infusio
nstakenorally
SouthAfrica
[45]
Prop
hylacticagainstd
iarrho
eaLeaves
Infusio
ntakenorally
SouthAfrica
[40]
Vomiting
Leaves
Decoctio
ntakenorally
Zanzibar,Tanzania
[46]
Fever,malaria,and
asinsectrepellent
Fever
Leaves,
stems,and
twigs
Leafandtwigdecoctionof
L.javanica
alon
etaken
orallyor
leafandste
minfusio
nof
L.javanica
mixed
with
leaves
ofanyof
theses
pecies:A
.afra
,B.transvaalensis,C
.anisata,C
.molle,
E.grandis,P.gua
java,S.serratuloides,T.riparia,orT
.emetica
takenorally
SouthAfrica,
Zimbabw
e[14
,16,18,20]
Gettin
grid
oflice,insects,andlicea
ndas
mosqu
itorepellent
Leaves,twigs,
andwho
leplant
Usedin
washesa
ndpo
ultic
esor
asste
amor
sprayedor
burnttochasea
way
mosqu
itoes
Ethiop
ia,Sou
thAfrica,and
Zimbabw
e[4,26,34,47–51]
Malaria
Leaves,roo
tsDecoctio
ntakenorally
Mozam
biqu
e,SouthAfrica
[17,33,52]
Prop
hylacticagainstm
alaria
Leaves
Infusio
ntakenorally
SouthAfrica
[40]
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Evidence-Based Complementary and Alternative Medicine 5
Table1:Con
tinued.
Use
Plantp
art(s
)used
Mod
eofu
seCou
ntry
practised
Reference(s)
Wound
s,injurie
s,pain,and
skin
infec
tions
Abdo
minalpains
Leaves
Leaves
chew
edandjuices
wallowed
Zimbabw
e[14
]Ac
neLeaves
Not
specified
Botsw
ana
[22]
Antidotes
Roots
Usedas
antid
otefor
food
poiso
ning
Botsw
ana
[22]
Backache
Roots
Infusio
ntakenorally
SouthAfrica,
Zimbabw
e[14
,20]
Bleeding
from
then
ose(epistaxis)
Leaves
Freshleaves
inserted
into
nose
orpo
wderedleaves
sniffed
SouthAfrica,
Zimbabw
e[14
,53]
Boils
Leaves
Infusio
ntakenorally
SouthAfrica
[54]
Chickenpo
xLeaves
Usedin
washesa
ndpo
ultices
oras
steam
SouthAfrica
[50]
Earache
Leaves
Decoctio
ntakenorallymixed
with
leaves
ofE.
grandis
SouthAfrica
[18]
Febrile
rashes
Leaves
Infusio
nstakenorally
SouthAfrica
[40]
Headache,migraine
Leaves,roo
tsLeafandroot
decoctionof
L.javanica
alon
etaken
orallyor
leafdecoctionof
L.javanica
mixed
with
leaves
ofanyof
theses
pecies:B
.cathartica
,C.brachiata,E
.grand
is,T.rip
aria,
andT.em
etica
takenorally
Kenya,South
Africa,and
Zimbabw
e[14
,18,33,34,38]
Inflammation
Leaves
Not
specified
SouthAfrica
[41]
Pubics
ores
Leaves
Decoctio
ntakenorallymixed
with
leaves
ofAc
anthosperm
umau
strale(Lo
efl.)Ku
ntze
Swaziland
[55]
Scabies
Leaves,roo
tsInfusio
ntakenorallyor
used
inwashesa
ndpo
ultic
esor
asste
amSouthAfrica,
Zimbabw
e[14
,50,54]
Shingles
Leaves,twigs,
androots
Appliedas
anointment
SouthAfrica
[15]
Skin
disorders,such
asheatrash
scratches,sting
s,andbites
Leaves,twigs
Appliedas
anointmento
r“im
biza,”decoctionprepared
from
L.javanica
andC.
obliquu
s,takenorally
SouthAfrica
[21,27]
Sores
Leaves
Decoctio
nof
L.javanica
mixed
with
bark
ofAc
aciaburkeiBe
nth.,O
zoroaengle
riR.
Fern.
&A.Fern.,Scle
rocaryabirrea
(A.R
ich.)H
ochst.,Syzygium
cordatum
Hochst.ex
Krauss,
andTabernaemontana
elegans
Stapftaken
orally
SouthAfrica
[56]
Sore
eyes,cataracts
Leaves,roo
tsJuices
queezedinto
eyes
Botsw
ana,
Zimbabw
e[14
,22]
Sprained
joints
Roots
Root
powdera
ppliedto
scarificatio
nsarou
ndsprained
joints
SouthAfrica
[20]
Ulcers
Leaves
Juicetaken
orallywith
cloveso
fA.sativum
Bang
ladesh
[23]
Wou
nds
Leaves
Freshleaves
wrapp
edarou
ndwou
ndto
enhanceh
ealin
gor
infusio
ntakenorally
Kenya,South
Africa
[54,57]
Ethn
oveterinaryu
ses
Disinfectin
gsuspectedanthrax-infeste
dmeat
Who
leplant
Who
leplantsused
todisin
fectsuspectedanthrax-infeste
dmeat
SouthAfrica
[20]
Gettin
grid
ofticks
andother
ectoparasites
Leaves,twigs,
andwho
leplant
Crushedleaves
mixed
with
water
andsprayed,twigsu
sedas
bedd
ingin
fowlrun
sSouthAfrica,
Zimbabw
e[58–60]
Lice
repellant
Who
leplant
Who
leplantu
sedto
repelliceinpo
ultry
India
[61]
Milk
preservativ
eStem
Stem
appliedto
milk
gourdbefore
milk
ferm
entatio
nKe
nya
[62]
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6 Evidence-Based Complementary and Alternative Medicine
Table1:Con
tinued.
Use
Plantp
art(s
)used
Mod
eofu
seCou
ntry
practised
Reference(s)
Otheruses
Anaem
iain
pregnancy
Leaves
Decoctio
ntakenorally
Zanzibar,Tanzania
[46]
Broo
mWho
leplant
Who
leplantscutand
tiedtogether
tomaker
ough
broo
ms
SouthAfrica
[53]
Cancer
Leaves
“Imbiza,”decoctionprepared
from
L.javanica
andC.
obliquu
s,takenorally
SouthAfrica
[27]
Cerem
onial
Leaves,w
hole
plant
Usedbefore
andaft
erfuneralsor
placed
onpatie
nts’bedaft
ercircum
cisio
nKe
nya,South
Africa
[31,58,63]
Con
vulsion
sLeaves
Leaves
rubb
edon
face
Zimbabw
e[14
,64]
Diabetes
Leaves
“Imbiza,”decoctionprepared
from
L.javanica
andC.
obliquu
s,takenorally
SouthAfrica
[27]
Fatig
ueor
tiredness
Leaves
Leafdecoctionof
L.javanica
mixed
with
leaves
ofA.
glabratum
orE.
grandiso
rT.riparia
takenorally
SouthAfrica
[18]
Fence
Who
leplant
Plantedarou
ndho
mesteads
Ethiop
ia[26]
Fodd
erLeaves
Leaves
eatenby
goats
Kenya
[31]
Fuelw
ood
Who
leplant
Who
leplantu
sedas
fuelw
ood
Zanzibar,Tanzania
[46]
Hum
anim
mun
odeficiency
virus(HIV
)or
acqu
iredim
mun
odeficiency
synd
rome
(AID
S)symptom
sLeaves
“Imbiza,”decoctionprepared
from
L.javanica
andC.
obliquu
swhich
istakenorally
SouthAfrica
[65,66
]
Kidn
eyprob
lems
Root
50groot
powd
erbo
iledin
2litreso
fwater;patient
takesa
cupof
thismixture
once
per
dayfor3
days
Swaziland
[67]
Madness
Leaves,w
hole
plant
Body
washedwith
leafinfusio
nMalaw
i,Zimbabw
e[14
,68]
Marasmicinfants
Roots
Infusio
nsused
tobath
infants
SouthAfrica,
Zimbabw
e[14
,20]
Night
blindn
ess
Leaves
Face
washedwith
infusio
nZimbabw
e[14
]Nightmares
Not
specified
Not
specified
Zimbabw
e[64]
Pre-,intra-,andpo
stpartum
complications
Stem
,roo
tsSm
earp
owdero
froo
torstem
Kenya
[69]
Preventin
god
oursor
beingused
indo
ors
tofre
shen
air
Leaves,w
hole
plant
Leaves
sprin
kled
intoiletsto
prevento
dourso
rwho
leplantp
lacedin
vase
orroom
Kenya,South
Africa
[31,35,58]
Protectio
nagainstd
ogsa
ndcrocod
iles
Leaves
Leaves
smearedon
body
SouthAfrica
[70]
Psycho
tropicb
ehaviour
Leaves
Infusio
ntakenorally
Swaziland
[71]
Removingbadluck
Leaves
Face
andhand
swashedwith
infusio
nof
L.javanica
leaves
mixed
with
C.molleleaves
Swaziland
[72]
Sleeplessn
ights
Leaves
Leafdecoctionof
L.javanica
mixed
with
leaves
ofE.
grandisand
T.rip
ariatakenorally
SouthAfrica
[18]
Todrivea
way
badspirits
Leaves
Body
washedwith
infusio
nZimbabw
e[14
]To
preventinfantsfro
mcontracting
illnesscaused
byfather
ormother
committingadultery
Leaves
Leaves
rubb
edon
forehead,elbow
s,andkn
eesa
fterc
ommittingadultery
Zimbabw
e[14
]
Venerealdiseases
Roots
Decoctio
ntakenorally
Mozam
biqu
e[44]
Weakjoints
Leaves
Decoctio
ntakenorally
Zimbabw
e[14
]
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Evidence-Based Complementary and Alternative Medicine 7
0 2 4 6 8 10 12 14 16
Asthma
Bronchitis
Chest pains
Diarrhoea
Mosquito repellent
Wounds
Fever/malaria
Herbal tea
Cough
Colds
Times found in literature
Figure 3: Main ethnobotanical applications of Lippia javanica in central, eastern, and southern Africa. An ethnobotanical use is countedonly once per publication.
Food Uses; Respiratory Problems; Gastrointestinal Diseases;Fever, Malaria, and Insect Repellent; Wounds, Injuries, Pain,and Skin Infections; Ethnoveterinary Uses; and Other Uses.
2.1. Food Uses. Leaves and twigs of Lippia javanica are usedas food additives in Kenya [6] and leafy vegetable in India[12, 13]. Lippia javanica is popular as herbal tea, particularlyin Botswana, South Africa, and Zimbabwe [7–11]. Lippiajavanica herbal tea is prepared by steeping fresh or driedleaves, stems, or twigs in boiling water and letting them standfor two to five minutes to release flavour, with or withoutmilk and sugar added according to taste. A stronger brew,known as a decoction, is prepared by boiling fresh or driedleaves, stems, or twigs for more than five minutes. The herbaltea prepared from L. javanica leaves, stems, or twigs has alemon or vanilla aroma and is often used as a common tea(i.e., C. sinensis) substitute or a few leaves, stems, or twigsare added to C. sinensis to provide a lemon or vanilla aroma.According to Sõukand and Kalle [87], herbal tea or tisaneis an English term used to denote a decoction or infusionmade of herbs for medicinal purposes. When L. javanica isused as medicinal herbal tea, it is consumed for a limitednumber of days to treat a specific condition like asthma inZimbabwe [14], bronchitis in South Africa [19], chest painsin Zimbabwe and South Africa [14, 24], colds in Kenya,South Africa, and Zimbabwe [19, 20, 28–30], cough in SouthAfrica and Zimbabwe [19, 20, 30, 53], and other diseases(see Table 1). From literature, it seems L. javanica herbaltea evolved over the years from medicinal tea decoctionsor infusions to nonmedicinal uses, where the herbal teais now drunk for recreation and enjoyment. According toShikanga et al. [7], L. javanica tea is appreciated throughoutits distributional range as a general health tonic and alsobecause it is naturally caffeine-free and has a calming andrelaxing effect. Research done by other workers, for example,Manenzhe et al. [2], Shikanga et al. [7], Parrant [8], Olivieret al. [81], Motlhanka and Makhabu [9], and Bhebhe et al.[10, 11], revealed that L. javanica is a popular recreational teain southern Africa, consumed on a daily basis within a food
context, while medicinal infusions or tisanes of L. javanicaare taken for a specific medical purpose. During the past20 years, the use of herbal teas has increased globally [107]because of their functional properties and consumer interestin the health promoting properties of such beverages [108].The other advantage associated with L. javanica usage is thatthe leaves can be sun-dried and later boiled in water anddrunk as herbal tea [9].
Most of L. javanica used as herbal tea in rural andperiurban communities in central, eastern, and southernAfrica is still collected from the wild, although small-scale cultivation has become necessary as it is marketed asherbal tea in Botswana under the brand name “Mosukudu”or “Mosukujane” [109] and in Zimbabwe as “Zumbani”(Figure 1(b)). Although considerable quantities of L. javanicaare sold in local markets in Botswana and Zimbabwe andalso traded on the Internet, there is no data on presentproduction levels, traded volumes, values, and export figuresin these two countries. Research by Whiteside [110] showedthat sales of L. javanica tea bags generated an income ofR20300.00 (US$5718) during 1994/1995 in Botswana. Thereis increased demand for L. javanica herbal tea especiallyin the light of growing health consciousness worldwide,with the estimated potential demand for the species and itsproducts around 100 tonnes per year on the local marketand 1000 tonnes per year on the export market (http://bio-innovation.org/work/fever-tea-tree/). Considering the rapidgrowth of the herbal tea industry worldwide and the increas-ing demand for L. javanica products, there is need for theimprovement of L. javanica products as well as developmentof new products. Therefore, L. javanica has potential to makethe transition from limited local use to commercial andinternational product. Lippia javanica has been identifiedas one of the few plant species that should be integratedin the domestication process in farming systems in sub-Saharan Africa to supportmedicinal, nutritional, and incomesecurity of local communities [107, 111]. According to VanWyk [111], L. javanica is of commercial value as herbal tea andhealth drinks. Therefore, commercialization of L. javanica is
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8 Evidence-Based Complementary and Alternative Medicine
unlikely to be viable if the product is sorely harvested fromthe wild. In the same line commercialization of L. javanicamight be more worthy if other products other than tea arederived from the plant.
2.2. Respiratory Problems. The different parts of L. javanica,for example, the leaves and twigs, are used for the treatmentof asthma, coughs, colds, influenza, pneumonia, tuberculosis,and bronchial problems in Bangladesh, Botswana, Ethiopia,Kenya, South Africa, and Zimbabwe [14–16, 19, 20, 23, 25, 26,28–32, 53, 112]. In Bangladesh, leaf infusion of L. javanica istaken orally mixed with 3-4 pieces of cloves ofA. sativum, 2-3times daily as remedy for chest pains [23]. In Ethiopia, leavesof L. javanica are chewed with butter as remedy for chestpains and cough [26]. In India, L. javanica leaf decoctionis taken orally as remedy for respiratory disorders [39]. InKenya, leaves are sniffed [31] or half glass of hot leaf infusionis taken orally three times a day [28, 29] as remedy for coldsand cough. Research done by Davids et al. [19] in SouthAfrica revealed that about 50 g of leaves is added to a cupof boiling water to produce an infusion which is taken orallyas remedy for coughs, colds, and bronchial problems or theinfusion is applied to the skin or mixed with Vaseline tomake an ointment. In South Africa, leaf or twig decoctionis taken orally for asthma, colds, and cough [16, 53], leavesare used in washes and poultices for chest pains [25], andleaves are boiled for 5 minutes and one cup of extract is takenorally thrice a day for chest pains and tuberculosis [24, 42].According to York [18], two handfuls of L. javanica leaves areboiled in two litres of water and patient is steamed once ortwice a day to treat coughs, chest pain, headaches, fever, chills,a sore throat, or a blocked nose. This decoction can also betaken orally by drinking half a cup daily [18]. Alternatively,a handful of L. javanica roots or leaves are mixed with ahandful leaves of A. glabratum or B. transvaalensis or B.uniflora or B. cathartica or C. anisata or C. brachiata orC. molle or E. grandis or H. kraussii or Hypoxis spp. or K.mosambicina or P. neochilus or P. guajava or S. serratuloides orT. sericea or T. riparia or T. emetica to treat blocked nose,chest pain, cough, earache, fatigue, fever, influenza, headache,runny nose, sleepless nights, sore throat, tiredness, andtonsillitis [18]. Leaf and stem infusion of L. javanica are takenorally together with A. afra by the Zulu people in SouthAfrica as remedy for bronchial ailments, colds, and cough[20]. “Imbiza,” a popular herbal decoction prepared from L.javanica and C. obliquus, is used by the Zulu people in SouthAfrica as herbal tonic and an immune booster and also forthe treatment of cancer, chest pains, colds, diabetes, HIV orAIDS symptoms, skin infections, and tuberculosis [27]. Insome communities in South Africa, L. javanica leaf or rootinfusion is taken orally as remedy for influenza and malaria[33] and respiratory disorders [40, 41]. In Zimbabwe, leafor root decoction is taken orally or smoke of burnt leavesand roots is inhaled as remedy for chest pains [14] and leafand twigs are boiled in water and infusion is taken orally asremedy for colds and cough [30]. According to Gelfand etal. [14], Shona people in Zimbabwe rub leaf ointment of L.javanica on the chest and abdomen as remedy for pneumoniaand leaf decoction is taken orally and body washed with leaf
decoction as remedy for shortness of breath or dyspnoea. InSouth Africa, a leaf and stem infusion of L. javanica are takenorally together with leaves of A. afra as remedy for measles[20].
Based on literature, inhalation of smoke from L. javanicaappears to be a popular remedy for asthma, chest pains,colds, and chronic coughs in Botswana, South Africa, andZimbabwe [14, 15, 20, 32]. In Botswana, L. javanica leafinfusion vapour is inhaled as remedy for colds and cough[32]. In SouthAfrica, for example, leaves and twigs are burnedand smoke is inhaled as remedy for asthma and cough [15]or steam from leaf infusions is inhaled or hot leaf infusionsare taken orally against colds and cough [20]. In Zimbabwe,smoke of burnt leaves and roots is inhaled as remedy for chestpains [14].
2.3. Gastrointestinal Diseases. The leaf and root decoction orinfusions of L. javanica are used as remedies of the digestivesystem diseases such as cholera, diarrhoea, and dysentery.For example, in Mozambique, root decoction is taken orallyas remedy for a type of diarrhoea commonly known as“chinhamucaca” which is characterized by milky diarrhoeaaccompanied by vomiting in children [44]. Leaf decoctionis used as herbal medicine for diarrhoea in Kenya [113]. InSouth Africa, the leaves of L. javanica are crushed and mixedwith cold or hot water and the mixture is then sieved and aquarter of a cup (75mL) is taken twice a day until diarrhoeasubsides [34]. The Venda people in South Africa use leafinfusions as prophylactic against diarrhoea [40]. Researchdone by Palgrave et al. [37] in South Africa revealed that teainfusions of the L. javanica leaves are used as remedies forHIV/AIDS opportunistic infections such as lung infectionsand diarrhoea. Previous research inMozambique [114], SouthAfrica [115], and Zimbabwe [116] showed that gastrointestinaldisorders, particularly cholera, diarrhoea, and dysentery areamong human diseases often treated with herbal medicines.For those patients diagnosed as having intestinal worms inVenda, South Africa, a leaf infusion of L. javanica leavesis used as an anthelmintic [40]. Therefore, these findingsillustrate that herbal medicines including L. javanica can playan important role in basic health care of local communitiesthrough treatment and management of cholera, diarrhoea,and dysentery.
2.4. Fever, Malaria, and Insect Repellent. Traditionally, L.javanica is commonly used to treat fever and malaria andrepel insects throughout its distributional range [4, 14, 16,17, 33–35, 40, 48–50, 58–60]. In South Africa, a decoctionof fresh or air dried leaves is used to wash or steam bodyparts infested with lice [50]. In India, the whole plant is usedto repel lice in poultry [61]. In South Africa and Zimbabwe,whole plant or leaves are burnt to repel mosquitoes [4, 34,35, 48, 49, 58]. In South Africa and Zimbabwe, L. javanicais widely used to get rid of ticks and other ectoparasites; forexample, ticks are sprayed with crushed leaves mixed withwater or twigs are used as bedding in fowl runs [58–60].Leaf and twig decoction of L. javanica are taken orally asremedy for fever [16]. The Venda people in South Africa useleaf infusions of L. javanica as prophylactic against malaria
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Evidence-Based Complementary and Alternative Medicine 9
[40]. In Zimbabwe, leaf decoction is taken orally as remedyfor fever [14].
Lippia javanica is also cultivated on a commercial scale bya rural community in Giyani, the Limpopo province, SouthAfrica, for the production of mosquito-repellent candles[117]. Clinical studies using human volunteers showed thatL. javanica repels no less than 95% of mosquitos, whereasmost mosquito repellents repel only 42% of them [118].Based on these findings, the Council for Scientific andIndustrial Research (CSIR), South Africa, signed a benefitsharing agreement with traditional healers allowing for thecommercial cultivation of L. javanica aimed at establishingan indigenous oil industry for rural development and large-scale production of antimosquito candles and other insectrepellents. The mosquito repellent is registered as a patentunder the Fertilisers, Farm Feeds and Stock Remedies Act(Act 36 of 1947) as a pest repellent [119]. These findings andthe establishment of a large-scale production of antimosquitocandles and other insect repellents strengthen the view thatL. javanica is a potential source of antipesticidal agentsand to some extent validate the traditional use of the plantspecies for insect pest control. Pesticidal plants such as L.javanica are increasingly being used as alternatives wheresynthetic products are unaffordable or are not available or areineffective. A number of studies have indicated that the use ofL. javanica as a pesticide is a long-standing tradition passeddown from generation to generation [120].
2.5. Wounds, Injuries, Pain, and Skin Infections. Lippia javan-ica is used as remedy for a variety of skin infections andinjuries in Kenya, South Africa, Swaziland, and Zimbabwe.In SouthAfrica, leaf infusions are used to treat skin disorders,such as boils, chicken pox, febrile rashes, heat rashes,measles,scabies, scratches, and stings [20, 21, 40, 50, 54]. In Kenya,about 50 g of fresh leaves is wrapped around a fresh woundto enhance healing [57] and, in South Africa, leaf infusionsare taken orally as remedy for wounds [54]. In SouthAfrica, powder from burnt roots of L. javanica is appliedto scarifications made around sprained joints to facilitatehealing [20]. In Kenya and Zimbabwe, leaf infusion is takenorally to treatmeasles or a patient is washedwith leaf infusion[14, 38]. The Zulu people in South Africa take a mixtureof chopped handful leaves of L. javanica with the sameamount of bark of A. burkei,O. engleri, S. birrea, S. cordatum,and T. elegans boiled in two litres of water as an enemafor the treatment of sores [56]. In Swaziland, about 30 g ofL. javanica leaves and similar amount of Acanthospermumaustrale Kuntze are boiled in 5 litres of water and decoctionis taken as remedy for sores [55]. In Zimbabwe, root ashesof L. javanica mixed with fat are applied to the skin ofa patient with scabies [14]. Wound healing is a processwhich involves distinct overlapping phases of coagulation,inflammation, proliferation, and tissue remodelling [121].The same authors argued that a set of complex biochemicalevents takes place in a closely orchestrated cascade to repairthe wound and any errors in the wound healing processcan lead to delayed healing or formation of hypertrophicscars. Abubakar [122] argued that colonization of woundsby opportunistic microorganisms usually delays the wound
healing process and/or may lead to infectious condition.Therefore, application of L. javanica on wounds and skininfections leads to disinfection, debridement, and provisionof a suitable environment for aiding the wound healingprocess. Lippia javanica has potential for therapeutic use inwound and skin diseases management, but there is needfor research on the safety, phytochemistry, and biologicalproperties of the species.
2.6. EthnoveterinaryUses. The leaves, stems, twigs, andwholeplants of L. javanica are used as ethnoveterinary medicinein India, Kenya, South Africa, and Zimbabwe. The Xhosapeople in the Eastern Cape province, South Africa, use L.javanica leaves for the disinfection of meat that has beeninfected with anthrax [20]. In Kenya, the stem of L. javanicais used to preserve milk by applying it to the gourd beforemilk fermentation [62]. In India, whole plants are used aslice repellants while, in South Africa and Zimbabwe, crushedleaves mixed with water are used to get rid of ticks and twigsare used as bedding in fowl runs to get rid of ectoparasites[58–60].
2.7. Other Uses. Lippia javanica is used as a good luck charm,to treat persons experiencing bad dreams, to ward off evilspirits, to protect one from lightening, and to protect thehome (Table 1). In Zimbabwe, L. javanica leaves are preparedas an infusion to treat persons experiencing nightmares [64].In both South Africa and Zimbabwe, evil spirits are cleansedby washing the body of an affected person by leaf infusion ofL. javanica [14, 123]. In Swaziland, 50 g leaves of L. javanicaand C. molle are ground into a powder and 5 litres of wateris added and face and hands are washed to remove badluck when exposed to a corpse [71]. In South Africa, thewhole plant is placed on a patient’s bed after the circumcisionceremony [58], to prevent odours and freshen surroundingair. A mixture of L. javanica leaves and roots is used toclean tools and hands before and after funerals, the stemsand leaves are used as brooms to sweep grave sites, and theentire plant is also used when coming from the mortuaryto remove bad spirits [58, 124]. The corpse is washed withL. javanica infusion after death to prevent odours formingor if the corpse has an odour, women place pieces of L.javanica in the nostrils of the corpse and sweep the roomwith twigs where the person was sleeping [58]. In KwaZuluNatal, South Africa, if the meat started to smell it will beboiled with L. javanica leaves to take away the smell [58].TheXhosa people in the Eastern Cape province, South Africa, useL. javanica leaves for the disinfection of meat that has beeninfected with anthrax [20]. In KwaZulu Natal, South Africa,leaves are sprinkled in toilets to prevent odours [58]. Leavesof L. javanica are sprinkled in houses for pleasant smell inthe Limpopo province, South Africa [35], and Kenya [31]. InKwaZulu Natal, South Africa, it is believed that a person canrepel snakes by placing a small stem with leaves on his orher head [58]. In Malawi, Swaziland, and Zimbabwe, peopleshowing sign of mental disorder, madness, or hystericaloutbursts are required towash their bodies with leaf infusions[14, 67, 68, 71].
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10 Evidence-Based Complementary and Alternative Medicine
Table 2: Nutritional composition of Lippia javanica leaves.
Caloric and nutritional composition Values ReferenceAsh 1.60 ± 0.001 g [13]Calorific value 50.64 ± 5.63 kcal [13]Crude fat 0.16 ± 0.001 g [13]Crude fibre 2.63 ± 0.002 g [13]Crude protein 1.22 ± 0.0004 g [13]Dry matter 15.46 ± 1.40 g [13]Moisture 90.44 ± 0.26 g [13]Total carbohydrate 6.55 ± 0.26 g [13]Vitamin C 22.42 ± 0.001mg [13]Ca 2856–9225 𝜇g g−1 [27]Mg 1598–5619 𝜇g g−1 [27]Fe 75–750 𝜇g g−1 [27]Mn 40.1 ± 1.16 𝜇g g−1 [27]Zn 15.6–27.3 𝜇g g−1 [27]Cu 3.0–8.5 𝜇g g−1 [27]Cr 0–2.7 𝜇g g−1 [27]Se 2.57 ± 0.19 𝜇g g−1 [27]Pb 0.38–1.19 𝜇g g−1 [27]Cd 0.53 ± 0.05 𝜇g g−1 [27]Co 0.19 ± 0.01 𝜇g g−1 [27]
3. Phytochemical Constituents and NutritionalComposition of Lippia javanica
Multiple classes of phytochemicals including volatile andnonvolatile secondary metabolites, such as alkaloids, aminoacids, flavonoids, iridoids, and triterpenes as well as severalminerals, have been identified from L. javanica [1–5, 7, 13, 27,73, 78, 81, 83–86, 88–94, 120, 123, 125–127]. Leaves, flowers,and twigs of L. javanica have a wide variety of the so-calledclassic nutrients, such as minerals, carbohydrates, proteins,fats, and vitamins (Table 2). Lippia javanica leaves are a goodsource of minerals such as cadmium, calcium, chromium,cobalt, copper, iron, magnesium, manganese, selenium, andzinc [27]. These authors assessed the levels of the elementsin L. javanica leaves and found the elements to be in thedecreasing order of Ca > Mg > Fe > Zn > Mn > Cu > Se >Cr > Pb > Co > Cd for total concentrations and Ca > Mg> Fe > Zn > Cu > Cr > Pb for water extractable forms. Theseresults corroborate an observation made by Sedaghathooret al. [128] that Ca and Mg are among the most abundantelements in tea plants. These mineral elements are importantin human nutrition since L. javanica is used as herbaltea and food additive (Table 1). Calcium, magnesium, iron,manganese, and zinc play a major role in activating someenzymes and regulating many responses of cells to stimuli[129]. Some of the mineral elements identified from L.javanica leaves are required by the human body for repair ofworn out cell tissues and strong bones and teeth and buildingof red blood cells and other related tissues.Therefore, since L.javanica has appreciable concentrations of mineral elementssuch as calcium, magnesium, iron, manganese, and zinc
(Table 2) which are essential for enzyme metabolism, thesemineral elements could enhance the nutritional and curativeproperties of the species.
Bhebhe et al. [10] determined the total phenolic and tan-nin content and radical scavenging activities of L. javanica,comparing it with Aspalathus linearis (Burm.f.) R. Dahlgren(Rooibos�), a commercial South African herbal tea, andother popular herbal teas in Zimbabwe (Table 3). Adansoniadigitata L., Fadogia ancylantha Schweinf., Ficus sycomorus L.,and Myrothamnus flabellifolius Welw. are indigenous herbalteas consumed in Zimbabwe. The tannin content of L.javanica is very low when compared to A. linearis (Rooibos)(Table 3). Lippia javanica has higher radical scavenging activ-ity than A. linearis (Table 3) which is probably due to highertotal phenolic content in comparison to A. linearis which is apopular herbal tea consumed by 10% of the global herbal teamarket [10]. In another study, Bhebhe et al. [11] determinedand compared the effect of several solvents, namely, hotwater, 50% methanol, ethanol, 50% ethanol, acetone, 50%acetone, and ethyl acetate, on phenolic composition and freeradical scavenging activity in common black tea, C. sinensis,and five other well-known herbal teas including L. javanica.In all the seven solvents used, L. javanica had higher totalphenolic content than C. sinensis implying that L. javanicais competitive to the black tea in terms of phenolic content.Shikanga et al. [7] found leaf extracts of L. javanica to havehigher phenolic content of 14.8 mg/g gallic acid equivalentof dry weight than flowers (9.9mg/g) and twigs (8.3mg/g).Phenolic compounds found in plants are known to play animportant role as antioxidants in exhibiting the medicinalproperties such as antibiotic, anti-inflammatory, anticancer,and antiallergic properties [10, 66, 130, 131].
The compounds isolated from L. javanica are docu-mented and listed in Appendix A and their structures arepresented in Appendix B. Simple phenolic compounds andcaffeic acid and its derivatives are some of the compoundsthat have been identified in L. javanica and examplesinclude coumarin 1, 3,4-dihydroxy-𝛽-phenylethoxy-O-[4-𝛽-caffeoyl-𝛼-rhamnopyranosyl-(1,3)-O-𝛽-glucopyrano-side], commonly referred to as verbascoside 2, and 3,4-dihydroxy-𝛽-phenylethoxy-O-[6-𝛽-caffeoyl-𝛼-rhamnopy-ranosyl-(1,3)-O-𝛽-glucopyranoside] commonly referredto as isoverbascoside 3 isolated by Olivier et al. [81] from theaerial parts of the species. Nonvolatile diterpenes, known asiridoid-glycosides, have also been isolated from L. javanicaby Rimpler and Sauerbier [82] represented by theveside-Na4 and theveridoside 5. Mujovo et al. [83] isolated a longchain alkane “4-ethylnonacosane” 6 and four flavanonesapigenin 7, cirsimaritin 8, 6-methoxyluteolin 4-methylether 9, and 6-methoxyluteolin 3,4,7-trimethyl ether 10from ethanolic extracts of L. javanica leaves. Madzimureet al. [120] identified an array of phenolic glycosides andflavonoids which include crassifolioside 11, luteolin 12,diosmetin 13, chrysoeriol 14, tricin 15, isothymusin 16,eupatorin 17, 5-dimethyl noboletin 18, genkwanin 19,salvigenin 20, and an alkaloid xanthine 22. Ludere et al.[84] isolated lippialactone 21 from the ethyl acetate extractof aerial parts of L. javanica. Neidlein and Staehle [85] andDlamini [86] isolated 19 amino acids, compounds 23 to
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Evidence-Based Complementary and Alternative Medicine 11
Table 3: Total phenolic content (TPC) as gallic acid equivalents (GAE) and tannin content as leucocyanidin equivalents (LE) and free radicalscavenging activity (FRSA) of herbal tea extracts (after Bhebhe et al. [10]).
Plant species TPC g GAE/100 g Tannin content of LE/100 g Percentage FRSA IC50g/mL
Lippia javanica 12.46 ± 4.31 0.12 ± 0.01 83.77 ± 0.8 0.016Aspalathus linearis 6.69 ± 0.83 0.94 ± 0.04 67.27 ± 0.25 0.053Adansonia digitata 0.79 ± 0.28 1.69 ± 0.01 43.07 ± 1.0 0.132Fadogia ancylantha 2.88 ± 0.48 0.20 ± 0.12 70.0 ± 0.40 0.051Ficus sycamores 14.02 ± 0.01 1.98 ± 0.12 86.13 ± 0.85 0.009Myrothamnus flabellifolius 4.75 ± 0.33 1.04 ± 0.01 80.93 ± 0.75 0.019
41 in Appendix A, from L. javanica. At least 131 differentclasses of essential oil compounds (compounds 42–172 inAppendices A and B) have been isolated from L. javanica byseveral researchers [3–5, 83, 85, 86, 88–94, 123]. Hutchingsand van Staden [96] isolated a toxic triterpenoid saponin,icterogenin 173, from L. javanica leaves. These differentclasses of essential oil compounds have been associatedwith various therapeutic activities such as anaesthetic,analgesic, anti-inflammatory, antimicrobial, cardiovascular,decongestant, digestive, expectorant, hepatoprotective, andsedative activities as well as stimulant of nervous systemand tonifying effects [132]. Meanwhile flavonoids possessseveral pharmacological properties including antibacterial,anticancer, anti-inflammatory, antioxidant, antiviral, andhepatoprotective effects [133] which play important rolesin human health. Flavonoid such as apigenin 7 is reportedto possess antibacterial [134] and hepatoprotective [135]properties. Apigenin 7 and luteolin 12 are reported to possessanti-inflammatory and analgesic effects [133], affecting thefunction of enzyme systems involved in the generation ofinflammatory processes, especially tyrosine and serine-threonine protein kinases [136, 137]. It has also been reportedthat apigenin 7 prevents HIV-1 activation via a novelmechanism that involves inhibition of viral transcription[138] and luteolin 12 demonstrated synergistic effects withanother flavonoid kaempferol against herpes simplex virus[133]. Kamiya [139] documented the importance of essentialamino acids such as lysine, valine, isoleucine, and histidinein terms of the risks to health if they are deficient.The authoralso documented their biological effects which includemuscle protein maintenance, potentiation of immunefunction, tissue repair acceleration after burn or trauma,protecting liver from toxic agents, lowering blood pressure,modulating cholesterol metabolism, and stimulating insulinor growth hormone secretion. Therefore, L. javanica leavesand other plant parts which have shown to be rich inflavonoid and polyphenolic compounds, amino acids, andessential oil could play an important role in the treatmentand management of diseases such as hypertension andinflammation listed in Table 1.
4. Pharmacological Activities
Scientific studies on L. javanica indicate that it has a widerange of pharmacological activities (Table 4), which include
anticancer [140], antidiabetic [141], antimalarial [4, 49, 142],antimicrobial [2, 3, 7, 17, 73–75, 77, 83, 84, 126, 143],antioxidant [7, 10, 11, 75, 77, 125], antiplasmodial [2, 79,80, 84, 144, 145], and pesticidal effects [1, 2, 59, 95, 120,146–150] and cytotoxicity [2, 73, 79, 120] activities. Table 4summarizes some of the pharmacological studies undertakenon L. javanica extracts aimed at evaluating some of theethnomedicinal uses of the species documented throughoutits distributional range (see Table 1). Some of the listedpharmacological activities may not relate directly to thedocumented ethnomedicinal uses of the species but mayprovide some insight into the species’ potential therapeuticvalue and bioactive properties and application.
4.1. Anticancer Activity. Fouche et al. [140] reported anti-cancer activity of dichloromethane root extract of L. javanicaagainst three human cells, exhibiting TGI value of 1.82𝜇g/mLfor breast MDA-MB-435, 1.86 𝜇g/mL for breast MDA-N, and2.09 𝜇g/mL for melanoma MALME-3M. Based on literature,a couple of terpenoid compounds that have been isolatedfrom L. javanica are known to have antitumor properties.For example, linalool 120 is known to have antitumoractivity which plays a protective role against hepatotoxicityand the compound has anti-inflammatory activities as well[151]. Research by Yang et al. [152] showed limonene 92 tohave inhibitory effect on pancreatic and mammary tumors.Another terpenoid compound, 𝛼-pinene 44, is known toinhibit translocation of NF-𝜅B or p65 protein into nuclei ofLPS-stimulated THP-1 cells [153]. These findings serve as ascientific validation for the use of L. javanica as a componentof a herbal concoction known in KwaZulu Natal province as“imbiza,” prepared by mixing L. javanica with C. obliquus asherbal medicine for cancer [27].
4.2. Antidiabetic Activity. Arika et al. [141] determined the invivo antidiabetic activity of aqueous leaf extracts of L. javan-ica in white male alloxan-induced albino mice. The aqueousleaf extracts of L. javanica at all dose levels significantlylowered the blood glucose levels in both oral and intraperi-toneal routes. The antidiabetic effect of L. javanica couldhave been due to the observed presence of flavonoids. Thepolyhydroxylated flavonol enhances lipogenesis and glucoseuptake in the adipocytes and flavanoids have demonstratedinsulinmimetic properties as the compound is known to beeffective at controlling blood sugar levels. These findings
-
12 Evidence-Based Complementary and Alternative Medicine
Table4:Summaryof
pharmacologicalactiv
ities
ofthee
xtractsisolated
from
different
partso
fLippiajavanica.
Activ
ityteste
dEx
tract
Plantp
art
Mod
elEff
ect
Reference
Antiamoebic
Piperitenon
e162
Leaves
Microdilutio
nassay
Activ
ewith
IC50valueo
f25𝜇
g/mLagainstE
.histolytica
[73]
Antibacteria
lPiperitenon
e162
Leaves
Microdilutio
nassay
Activ
ewith
MIC
valueo
f50𝜇
g/mLagainstA
.calcoaceticu
s,M.kristin
ae(50𝜇
g/mL),S.typhi(25𝜇
g/mL),and
S.aureus
(12𝜇
g/mL)
[73]
Antibacteria
l(Antiproteus)
Methano
lLeaves
Disc
diffu
sion
assay
Activ
ewith
MIC
valueo
f313𝜇g/mLagainstP.m
irabilis
and926𝜇
g/mL
againstP.vulgaris
[74]
Water
Leaves
Disc
diffu
sion
assay
Exhibitedweakactiv
ityagainstP.m
irabilis
with
MIC
valueo
f1873𝜇g/mLand1768𝜇g/mLagainstP.vulgaris
[74]
Antibacteria
l
Aceton
eLeaves
Microdilutio
nassay
Activ
eagainstE.
coliwith
MIC
valueo
f0.64m
g/mL,E.
faecalis(0.64),P.
aeruginosa
(0.32
),andS.aureus
(0.64).Totalactiv
ityMIC
values
werea
sfollo
ws:E.
coli(127
mg/mL),E
.faecalis
(127
mg/mL),P.aeruginosa
(253
mg/mL),and
S.aureus
(127
mg/mL)
[75]
Aceton
eLeaves
Microdilutio
nassay
Activ
eagainstB.
cereus
with
MIC
valueo
f3mg/mL,Ba
cillusp
umilu
s(6
mg/mL),B
.subtilis(>12mg/mL),S.aureus(12mg/mL),E
.faecalis
(6mg/mL),E
.cloacae
(6mg/mL),E
.coli(6m
g/mL),Pantoea
agglo
meran
s(12mg/mL),P.aeruginosa(12m
g/mL),Shigella
flexneri
(1.5mg/mL),A
erom
onas
hydrophila(12m
g/mL),P.m
irabilis
(>12mg/mL),K
.pneum
oniae(12mg/mL),Salmonellacholeraesuis
(6mg/mL),and
Serratiamarcescens(>12mg/mL)
[17]
Hexane
Leaves
Microdilutio
nassay
Activ
eagainstB.
cereus
with
MIC
valueo
f12m
g/mL,B.
pumilu
s(12m
g/mL),B
.subtilis(12m
g/mL),S.aureus(6m
g/mL),E
.faecalis
(12m
g/mL),E
.cloacae
(12m
g/mL),E
.coli(6m
g/mL),P.agglomeran
s(12m
g/mL),P.aeruginosa(12m
g/mL),S.flexneri(6
mg/mL),A
.hydrophila(12m
g/mL),P.m
irabilis
(12m
g/mL),K
.pneum
oniae
(12m
g/mL),S.choleraesuis(6
mg/mL),and
antia
moebice
ffect
(12m
g/mL)
[17]
Methano
lLeaves
Microdilutio
nassay
Activ
eagainstB.
cereus
with
MIC
values
of1.5
mg/mL,B.
pumilu
s(6
mg/mL),B
.subtilis(>12mg/mL),S.aureus(12mg/mL),E
.faecalis
(3mg/mL),E
.cloacae
(6mg/mL),E
.coli(6m
g/mL),P.agglomeran
s(12m
g/mL),P.aeruginosa(12m
g/mL),S.flexneri(1.5mg/mL),A
.hydrophila(6
mg/mL),P.m
irabilis
(>12mg/mL),K
.pneum
oniae
(12m
g/mL),S.choleraesuis(6
mg/mL),and
S.marcescens(12mg/mL)
[17]
Essentialoil
Leaves
Microdilutio
nassay
Activ
eagainstB.
cereus
with
MIC
values
of6m
g/mL,B.
pumilu
s(6
mg/mL),B
.subtilis(3mg/mL),S.aureus(1.5
mg/mL),E
.faecalis
(3mg/mL),E
.cloacae
(12m
g/mL),E
.coli(6m
g/mL),P.agglomeran
s(6
mg/mL),P.aeruginosa(12m
g/mL),S.flexneri(3mg/mL),A
.hydrophila(3mg/mL),P.m
irabilis
(>12mg/mL),K
.pneum
oniae
(3mg/mL),S.choleraesuis(1.5mg/mL),and
S.marcescens(>12mg/mL)
[17]
-
Evidence-Based Complementary and Alternative Medicine 13
Table4:Con
tinued.
Activ
ityteste
dEx
tract
Plantp
art
Mod
elEff
ect
Reference
Methano
lLeaves
Microdilutio
nassay
Activ
eagainstE.
faecaliswith
MIC
valueo
f0.14
mg/mL
[7]
Methano
lLeaves
Microdilutio
nassay
Activ
eagainstE.
coliwith
MIC
valueo
f0.31
mg/mL
[7]
Methano
lLeaves
Microdilutio
nassay
Activ
eagainstP.aeruginosa
with
MIC
valueo
f0.42m
g/mL
[7]
Methano
lLeaves
Microdilutio
nassay
Activ
eagainstS.aureus
with
MIC
valueo
f0.13
mg/mL
[7]
Antifu
ngal
Aceton
eLeaves
Microdilutio
nassay
Activ
eagainstC.
albicans
with
MIC
valueo
f>7.5m
g/mL,C.
krusei
(1.88m
g/mL),and
C.neoforman
s(>7.5
mg/mL)
[7]
Hexane
Leaves
Microdilutio
nassay
Activ
eagainstC.
albicans
with
MIC
valueo
f>3.75
mg/mL,C.
krusei
(3.75m
g/mL),and
C.neoforman
s(>7.5
mg/mL)
[7]
Aceton
eLeaves
Microdilutio
nassay
Activ
eagainstC.
kruseiwith
MFC
valueo
f7.5mg/mL
[7]
Dichlorom
ethane
Aeria
lparts
Microdilutio
nassay
Activ
eagainstFu
sariu
mproliferatum
with
MIC
valueo
f0.14
mg/mLand
Fusariu
mverticillioides(0.19mg/mL)
[76]
Hexane
Aeria
lparts
Microdilutio
nassay
Activ
eagainstF.proliferatum
with
MIC
valueo
f0.23m
g/mLandF.
verticillioides(0.45
mg/mL)
[76]
Methano
lAe
rialp
arts
Microdilutio
nassay
Activ
eagainstF.proliferatum
with
MIC
valueo
f1.77m
g/mLandF.
verticillioides(0.43
mg/mL)
[76]
Methano
lAe
rialp
arts
Microdilutio
nassay
Activ
eagainstF.proliferatum
with
MIC
valueo
f>2.50
mg/mLandF.
verticillioides(>2.50
mg/mL)
[76]
Antim
ycob
acteria
l
Aceton
eLeaves
Microdilutio
nassay
Activ
ewith
MIC
valueo
f0.47m
g/mLandtotalactivity
of10mL/g
againstM
.smegmatis
[77]
Dichlorom
ethane
Leaves
Microdilutio
nassay
Activ
ewith
MIC
valueo
f1.25m
g/mLandtotalactivity
of23
mL/g
againstM
.smegmatis
[77]
Hexane
Leaves
Microdilutio
nassay
Activ
ewith
MIC
valueo
f0.62m
g/mLandtotalactivity
of13mL/g
againstM
.smegmatis
[77]
Methano
lLeaves
Microdilutio
nassay
Activ
ewith
MIC
valueo
f1.25m
g/mLandtotalactivity
of7m
L/gagainst
M.smegmatis
[77]
-
14 Evidence-Based Complementary and Alternative Medicine
Table4:Con
tinued.
Activ
ityteste
dEx
tract
Plantp
art
Mod
elEff
ect
Reference
Antioxidant
Water
Leaves
DPP
Hassay
Exhibitedactiv
itywith
EC50valueo
f358𝜇g/mL
[7]
Water
Leaves
—Ex
hibitedactiv
itywith
209ascorbicacid
equivalent
(mg/gdryweight)
[7]
Water
Leaves
ABT
Sassay
Activ
ewith
TEAC
valueo
f1.5mmol/10
0g[78]
Water
Leaves
DPP
Hassay
Activ
ewith
TEAC
valueo
f1462.54
mmol/10
0g[78]
Water
Leaves
FRAPassay
Activ
ewith
TEAC
valueo
f2.38m
mol/10
0g[78]
Antiplasm
odial
Hexane,chloroform
Roots
Microdilutio
nassay
Activ
eagainstP.falciparum
chloroqu
ines
ensitivew
ithIC50valueo
f12.25±0.72𝜇g/mL
[79]
Ethylacetate
Roots
Microdilutio
nassay
Activ
eagainstP.falciparum
chloroqu
ines
ensitivew
ithIC50valueo
f12.12±0.79𝜇g/mL
[79]
Methano
lRo
ots
Microdilutio
nassay
Activ
eagainstP.falciparum
chloroqu
ines
ensitivew
ithIC50valueo
f1.35±0.06𝜇g/mL
[79]
Hexane,chloroform
Roots
Microdilutio
nassay
Activ
eagainstP.falciparum
chloroqu
iner
esistantw
ithIC50valueo
f18.59±0.26𝜇g/mL
[79]
Ethylacetate
Roots
Microdilutio
nassay
Activ
eagainstP.falciparum
chloroqu
iner
esistantw
ithIC50valueo
f15.80±0.26𝜇g/mL
[79]
Methano
lRo
ots
Microdilutio
nassay
Activ
eagainstP.falciparum
chloroqu
iner
esistantw
ithIC50valueo
f1.75±0.17𝜇g/mL
[79]
Dichlorom
ethane
Roots
pLDHassay
Activ
eagainstP.falciparum
with
IC50valueo
f3.8𝜇g/mL
[80]
Dichlorom
ethane/m
ethano
lRo
ots
pLDHassay
Activ
eagainstP.falciparum
with
IC50valueo
f27𝜇
g/mL
[80]
Methano
lRo
ots
pLDHassay
Activ
eagainstP.falciparum
with
IC50valueo
f24𝜇
g/mL
[80]
Water
Roots
pLDHassay
Activ
eagainstP.falciparum
with
IC50valueo
f>100𝜇
g/mL
[80]
Dichlorom
ethane
Stem
spL
DHassay
Activ
eagainstP.falciparum
with
IC50valueo
f4.5𝜇g/mL
[80]
Dichlorom
ethane/m
ethano
lStem
spL
DHassay
Activ
eagainstP.falciparum
with
IC50valueo
f21.8𝜇g/mL
[80]
Methano
lStem
spL
DHassay
Activ
eagainstP.falciparum
with
IC50valueo
f29.8𝜇g/mL
[80]
Water
Stem
spL
DHassay
Activ
eagainstP.falciparum
with
IC50valueo
f>100𝜇
g/mL
[80]
Free
radicalscaveng
ing
activ
ity
Water
—DPP
Hassay
Activ
ewith
IC50valueo
f0.059±0.02
g/mL
[11]
50%methano
l—
DPP
Hassay
Activ
ewith
IC50valueo
f0.04±0.001g/mL
[11]
Ethano
l—
DPP
Hassay
Activ
ewith
IC50valueo
f0.025±0.001g/mL
[11]
50%ethano
l—
DPP
Hassay
Activ
ewith
IC50valueo
f0.027±0.005g/mL
[11]
Aceton
e—
DPP
Hassay
Activ
ewith
IC50valueo
f0.057±0.004g/mL
[11]
50%aceton
e—
DPP
Hassay
Activ
ewith
IC50valueo
f0.022±0.001g/mL
[11]
Ethylacetate
—DPP
Hassay
Activ
ewith
IC50valueo
f0.066±0.001g/mL
[11]
Toxicity
Methano
lLeaf
Brines
hrim
plethality
assay
40%mortalityrecorded
after
48hexpo
sure
towards
Artemianauplii
[74]
Methano
lRo
ots
Brines
hrim
plethality
assay
Activ
eagainstP.falciparum
chloroqu
ines
ensitivew
ithIC50valueo
f843.0𝜇
g/mL
[79]
Methano
lRo
ots
Brines
hrim
plethality
assay
Activ
eagainstP.falciparum
chloroqu
iner
esistantw
ithIC50valueo
f650.3𝜇
g/mL
[79]
-
Evidence-Based Complementary and Alternative Medicine 15
strengthen the view that L. javanica is a potential source ofantidiabetic agents and to some extent validate the traditionaluse of the plant species mixed with C. obliquus to form aherbal concoction known in KwaZulu Natal province, SouthAfrica, as “imbiza” used against diabetes [27].
4.3. Antimalarial Activity. Govere et al. [142] found thattopical application of L. javanica alcohol extract leads to76.7% protection against Anopheles arabiensis for 4 hours.Lippia javanica has been used as a mosquito repellent by therural communities in Zimbabwe for a long time and previousstudies have shown that essential oils from the species havevery strong and lasting repellent activity against female A.arabiensis [64]. Research by Lukwa et al. [4] revealed thattopical application of 5mg/cm2 of L. javanica leads to 100%protection againstAnopheles aegypti for 8 hours.Mavundza etal. [154] screened dichloromethane and ethanol leaf extractsof L. javanica for adulticidal activity againstA. arabiensis.Theauthors observed dichloromethane and ethanol activities of45% and 55%mosquitomortality, respectively.These findingsstrengthen the view that L. javanica is a potential source ofantimalarial agents and to some extent validate the traditionaluse of the plant species as mosquito repellent in India [47],South Africa [34, 49, 58], and Zimbabwe [4, 48].
4.4. Antioxidant Activity. Leaf infusions of L. javanica exhib-ited antioxidant activity with EC
50value of 358𝜇g/mL and
contained 14.8mg/mL of dry weight gallic acid equivalentphenolic compounds [7]. The EC
50value of 358 𝜇g/mL
obtained for L. javanica by Shikanga et al. [7] compareswell to those of many commercial teas, including antioxidantcapacity of Rooibos Fresh Pack� herbal teas (A. linearis)with the best antioxidant activity of 333 𝜇g/mL. The highantioxidant activities displayed by L. javanica infusions canbe partially attributed to the high levels of verbascoside 2(1.5mg/g dry weight) reported by Olivier et al. [81] in theleaf extract of the species. Earlier research by Muchuwetiet al. [125] reported 74.4% inhibition of the DPPH radicalby an ethanolic leaf extract of L. javanica. Lekganyane etal. [75] reported antioxidant activity in L. javanica and theacetone extracts of the species displayed antioxidant activityon BEA chromatogram [77]. Bhebhe et al. [10] reported theantioxidant activities of L. javanica based on the DPPH,reducing power and inhibition of phospholipid peroxidationassays. Free radical scavenging activity of L. javanica isattributed to phenolic compounds since these compoundshave an ideal structural chemistry for free radical scavengingactivity [155]. Bhebhe et al. [11] determined the effect ofseveral solvents on the free radical scavenging activity ofL. javanica using the DPPH assay. Free radical scavengingactivity expressed as IC
50ranged from 0.022 ± 0.001 g/mL to
0.066 ± 0.001 g/mL; see Table 4.
4.5. Antiplasmodial Activity. Prozesky et al. [144] evaluatedL. javanica leaf acetone extract for in vitro antiplasmodialactivity using PfUP1, a chloroquine resistant strain of themalaria parasite Plasmodium falciparum by means of theflow cytometric test. The IC
50value for L. javanica was
4.26 𝜇g/mL. Manenzhe et al. [2] evaluated essential oil,
piperitenone 162, isolated from L. javanica for antiplasmodialactivity using chloroquine diphosphate as positive controland found it active against a chloroquine sensitive strainof P. falciparum in micromolar concentrations with IC
50of
8 𝜇g/mL. Clarkson et al. [80] evaluated L. javanica rootsand stems extracts for in vitro activity against P. falciparumusing the parasite lactase dehydrogenase (pLDH) assay andchloroquine diphosphate (Sigma) as the positive control.Thedichloromethane, methane, and water extracts showed IC
50
values ranging from 3.8 to >100 𝜇g/mL; see Table 4. Omolo etal. [145] screened the essential oil of L. javanica for fumiganttoxicity to Anopheles gambiae which exhibited LD
50of 4.3 ×
10−3mg cm−3. Ayuko et al. [79] showed that L. javanica rootextracts have antiplasmodial activity against P. falciparumwith IC
50ranging from 1.35 to 18.59 𝜇g/mL; see Table 4.
Lippialactone 21, derived from the ethyl acetate extract ofaerial parts of L. javanica, exhibited some activity againstthe chloroquine sensitive D10 strain of P. falciparum withan IC
50value of 9.1 𝜇g/mL and is also mildly cytotoxic [84].
Compared to chloroquine, the compound is approximately2000 times less active against the D10 strain of P. falciparum[84].
4.6. Antimicrobial Activities. Lippia javanica is widely usedin the treatment of a wide range of infectious diseasescaused by microorganisms. Viljoen et al. [3] determined theantimicrobial properties of L. javanica by evaluating the timekill studies of the species’ essential oil using the disc diffusionassay on three respiratory pathogens Klebsiella pneumoniae,Cryptococcus neoformans, and Bacillus cereus. This studyshowed that the killing rate was greatest for K. pneumoniaefollowed by C. neoformans and very little reduction of micro-bial populations was observed for B. cereus. The efficacy of L.javanica oil for K. pneumoniae showed a killing rate within30 minutes for the concentrations 0.25, 0.5, 0.75, and 1%,C. neoformans showed a killing rate for concentrations 0.5,0.75, and 1% within 1 hour, and the lowest concentration of0.25% took 8 hours before a bactericidal effect was notedwhile B. cereus showed some reduction in colonies [3]. Thepositive antimicrobial activity of L. javanica as revealed bythe time kill study could be attributed to linalool 120 whichaverages between 65 and 70% in yield [3, 5, 88, 90] and hasknown antimicrobial properties [93, 156–159].These findingssomehow corroborate the traditional use of L. javanica asherbal medicine for a wide range of bacterial and fungalrespiratory ailments indicated in Table 1.
Manenzhe et al. [2] evaluated essential oil, piperitenone162, isolated from L. javanica for antibacterial activityon cultures of Bacillus subtilis, Staphylococcus aureus, andEscherichia coli using imipenem, cefazolin, and ampicillinas positive controls. The authors found piperitenone 162to inhibit S. aureus and E. coli at 1% dilution. Acetone,hexane, and methanol leaf extracts and essential oil isolatedfrom L. javanica showed some activity against fifteen Gram-positive and Gram-negative bacteria with MIC values rang-ing from 1.5 to >12mg/mL [60]; see Table 4. In a similarstudy, Samie et al. [73] demonstrated that a pure compoundpiperitenone 162 isolated from L. javanica has antibacte-rial activities against Acinetobacter calcoaceticus, Micrococcus
-
16 Evidence-Based Complementary and Alternative Medicine
kristinae, Salmonella typhi, and S. aureus using dimethylsulphoxide and kanamycin as controls, with MIC valuesranging from 12 to 50 𝜇g/mL; see Table 4. Shikanga et al. [7]evaluated the antibacterial activity of L. javanica methanolicleaf extract against S. aureus, Enterococcus faecalis, E. coli,and Pseudomonas aeruginosa using the serial microdilutionmethod with gentamycin (Virbac�) and acetone as positiveand negative controls, respectively. Lippia javanica displayedantibacterial activities with MIC values ranging from 0.13to 0.42mg/mL against all four pathogens; see Table 4. Theobtained minimum inhibitory concentrations are promising,since natural products with MIC values below 1mg/mLare generally considered to be noteworthy findings [160].Lippialactone 21, derived from the ethyl acetate extract ofaerial parts of L. javanica, exhibited some activity against theE. coli and S. aureus at a concentration of 10mg/mL [84].Lekganyane et al. [75] reported antibacterial activity of L.javanica acetone leaf extracts against E. coli, E. faecalis, P.aeruginosa, and S. aureus with MIC values ranging from 0.32to 0.64mg/mL and total activity of the same species rangingfrom 127 to 253mg/mL; see Table 4. Methanol and water leafextracts of L. javanica exhibited some antiproteus activityagainstProteusmirabilis andProteus vulgariswithMICvalues7.5mg/mL;see Table 4. Thembo et al. [76] investigated the antifungalactivity of aqueous and organic extracts of L. javanica usinga serial microdilution assay. Generally, extracts of L. javanicaexhibited weak activity; see Table 4.
4.7. Antimycobacterial Activity. Mujovo et al. [83] evaluatedL. javanica compounds against a drug-sensitive strain ofMycobacterium tuberculosis using the radiometric respira-tory techniques. Of all the isolated compounds, only onetriterpenoid carboxylic acid, euscaphic acid 172, exhibitedantimycobacterial activity with MIC value of 50𝜇gmL−1against this strain. In a similar study, the leaf extract ofL. javanica exhibited antimycobacterial activity against M.smegmatis in an evaluation which used microdilution assayand rifampicin as control [77]. Acetone extract was thebest extractant with MIC value of 0.47mg/mL; it extractedantibacterial agents which was indicated by the lowest MICvalue [77]. Masoko and Nxumalo [77] also evaluated thetotal activity ofL. javanicawhich averaged 13mL/g suggestingthat the extract prepared from one gram of L. javanicacould be diluted to a volume of 13mL and will still inhibitM. smegmatis efficiently. According to Semenya and Maroyi[115], tuberculosis caused by M. tuberculosis is a seriousdisease requiring effective strategies and tools to controland manage it. Therefore, preliminary evaluations done byMujovo et al. [83] and Masoko and Nxumalo [77] serve asa scientific validation for the use of L. javanica in traditionalmedicine for treatment of tuberculosis and other respiratoryailments in South Africa [24, 27, 115] and Uganda [43] as wellas their efficiency in tuberculosis drug discovery.
4.8. Antiviral Activity. Mujovo et al. [83] found that (E)-2(3)-tagetenone epoxide 42 and piperitenone 162 inhibitedthe HIV-1 reverse transcriptase enzyme by 91% and 53%,respectively, at 100 𝜇gmL−1 based on a nonradioactive HIVRT colorimetric ELISA kit. Little is known about the HIV RTactivity of L. javanica extracts or compounds, but flavonoidsare known to be active against viral RT and also as potentinhibitors of the cellular alpha and beta DNA polymerase[83], while luteolin 12 is active against HIV RT [164, 165].Lippia javanica is traditionally used to treat HIV/AIDSsymptoms in South Africa [65, 66] and several viral andHIV/AIDS opportunistic diseases and infections such asbronchitis [15, 19–22], chicken pox [50], diarrhoea [17, 34,37, 44, 113], measles [14, 20, 38], pneumonia [14], shingles[15], and venereal diseases [44]. Despite significant advancesin the utilization of L. javanica in southern Africa overthe years for numerous viral diseases (Table 1), very littleantiviral evaluations have been done on crude extracts andpurified compounds of the species. There is need, therefore,for more pharmacological research as L. javanica could beharbouring potent (RT) inhibitors which could be useful forthe development of new pharmaceutical products importantfor use against viral diseases and infections.
4.9. Pesticidal Effects. Magano et al. [95] evaluated the repel-lent effects of hexane extracts of L. javanica essential oilusing the in vitro tick climbing repellency bioassay on adultsof Hyalomma marginatum rufipes Koch ticks. The authorsfound that 107mg/mL caused repellency index of 100% at onehour and 30 minutes. In a similar study by Madzimure et al.[120], L. javanica aqueous leaf extracts at 10% and 20% w/vwere effective at controlling cattle ticks (Amblyomma species,
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Evidence-Based Complementary and Alternative Medicine 17
Boophilus species, Hyalomma species, Rhipicephalus appen-diculatus, and Rhipicephalus evertsi evertsi) and were as goodas the positive control amitraz-based acaricide Trickbuster�.These authors found no parasites on microscopic exami-nation of the Giemsa-stained thin blood smear collectedfrom treated cattle implying that the animals did not sufferfrom clinical tick-borne diseases. Similarly, Nyahangare etal. [59] tested the pesticidal activity of L. javanica waterextracts against cattle ticks. The authors found no significantdifference between cattle treated with a commercial syntheticacaricide and those under L. javanica treatment. Martinez-Velazquez et al. [166] evaluated pesticidal effects of twoessential oils, namely, 𝛾-terpinene 82 and 𝜌-cymene 99,isolated from Lippia graveolens Kunth against 10-day-oldRhipicephalus (Boophilus) microplus (Canestrini) tick larvaeusing the larval packet test bioassay. The two essential oilsproduced highmortality ranging from90 to 100% in all testedconcentrations of 20 to 1.25% (v/v).Therefore, L. javanica canprovide an effective tick control option where synthetic prod-ucts are unavailable or unaffordable particularly in remoterural areas in sub-Saharan Africa. Lippia javanica is popularfor tick control and management among resource-poorsmallholder farmers in South Africa [58, 95] and Zimbabwe[59, 60, 120]. While these preliminary evaluations may serveas confirmation that L. javanica has some bioactivities againstticks, a comprehensive method of tick control is requiredfor the resource-constrained smallholder farmers based onethnopharmacological properties of L. javanica.
McGaw et al. [146] screened L. javanica for the anthel-mintic test systems using the free living nematodeCaenorhabditis elegans. The crude ethanol and hexaneextracts showed some activity at a concentration of 2mg/mL,with the 7-day incubation assay appearing to be moresensitive than the shorter assay. Earlier research by Mwangiet al. [1] indicated that L. javanica was active against Aedesaegypti larvae and Sitophilus zeamais Motschulsky (maizeweevil). Katsvanga and Chigwiza [147] reported that L.javanica is an effective natural pesticide which can be used tocontrol aphid species (Brevicoryne brassicae). In their study,Katsvanga and Chigwiza [147] found that 1 : 1 powderedaqueous leaf extract of L. javanica reduced B. brassicae by53.2% against 78.3% and 96.7% of two synthetic pesticides,Aphid kill and Bexadust “L,” respectively. Chikukura etal. [149] found L. javanica powdered leaf extracts to haveinsecticidal properties with potential to control graindamage by 21–33%. Mashela et al. [148] reported that theapplication of ground L. javanica leaves to soil in nematode-infested (Meloidogyne incognita) pots reduced the nematodenumbers by 79–92% and significantly increased fresh fruityield, dry shoot mass, plant height, and stem diameter ofthe tomato plants, as well as levels of potassium, nitrogen,and manganese in leaf tissue. Muzemu et al. [150] evaluatedwater extracts of L. javanica leaf powder for pesticidal effectsagainst rape (Brassica napus L.) aphids, B. brassicae, andtomato (Solanum lycopersicum Lam.) red spider mites, andTetranychus evansi as alternatives to conventional pesticides.Lippia javanica reduced B. brassicae and Tetranychus evansiby 12.5% and 63%, respectively [150].The study demonstratedthat L. javanica has pesticidal effects on B. brassicae and T.
evansi. The reduced number of B. brassicae and T. evansicould be due to L. javanica’s extracts having repellent, toxic,and antifeedant effects since the species has essential oilswith pesticidal properties [2]. Therefore, these findingsindicate that L. javanica has both nematicidal and plantgrowth-promoting properties.
4.10. Toxicity and Cytotoxicity Activity. Lippia javanica isknown to cause liver damage and photosensitisation in live-stock, resulting in stock losses [167]. Triterpenoids isolatedfrom the genus Lippia are icterogenic and cause jaundice asa result of liver damage [167]. The characteristic swelling,yellowing, and later peeling of unpigmented skin are due tothe presence of phylloerythrin, a photodynamic porphyrinthat reacts with sunlight and causes severe cell damage [167].The compound is normally formed when chlorophyll isbroken down by microorganisms in the rumen, but it nowaccumulates in the liver as a result of the damage caused bytriterpenoids [167]. In view of the known toxicity of Lippiaspecies, the prolonged use of high doses of L. javanica ispotentially harmful [167]. Lippia javanica showed low toxicityafter 48 h exposure with the percentage of mortality below50% [74].
Ayuko et al. [79] evaluated the toxicity of L. javanicausing a brine shrimp cytotoxicity assay with LC
50value of
1138 ± 1.33 𝜇g/mL. Ayuko et al. [79] found the cytotoxicity toantiplasmodial activity ratios for the methanolic extracts ofthe two tested strains to be 843.0 and 650.3, and since theseare greater than 100, it may be concluded that the extractsare of low toxicity. Samie et al. [73] demonstrated that apure compound piperitenone 162 isolated from L. javanicaessential oil has low cytotoxicity activity against intestinaladenocarcinoma cells (i.e., the HCT-8 monolayers with IC
50
of 265.6 ± 5.3 𝜇g/mL). Lukwa [64] evaluated the toxicity of L.javanica aqueous leaf extracts using sexually mature BALB/cmice with the placebo as control. Within 48 hours, all micefed with the L. javanica leaf aqueous extract at 12.5–37.5% v/vwere lethargic, and the overall mortality was 37.5%. Previousresearch byManenzhe et al. [2] showed that hydrodistillationof L. javanica leaves, flowers, and stems produced oil thatwas poisonous against P. falciparumwhen diluted to 1% (v/v).These findings imply that, despite its apparent safety, waterextracts of L. javanica leaves may have deleterious healthimplications on humans and animals if consumed at veryhigh doses.
Many compounds that have been isolated from L. javan-ica including phenolic glycosides, flavonoids, and essentialoils are not known to have acute toxic properties withthe exception of icterogenin 173. Icterogenin 173 has beenshown to inhibit biliary excretion in rabbits [168]. Reports inliterature indicate that the consumption of xanthine 22 hasresulted in mammalian toxicity. According to Madzimure etal. [64], xanthine 22 is a demethylated derivative of caffeinewith pharmacological actions such as central nervous system(CNS) stimulation, relaxation of smooth muscle (especiallybronchial muscle), myocardial stimulation, peripheral vaso-constriction, and diuresis. Considering the widespread useof L. javanica as herbal tea and medicine, it is important
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18 Evidence-Based Complementary and Alternative Medicine
to determine if any toxicological effects can occur from itschronic or subchronic usage.
4.11. Other Activities. Mpofu et al. [169] determined the effectof inclusion of L. javanica leaf meal in broiler diets ongrowth performance, carcass characteristics, and fatty acidprofiles. The authors found that the L. javanica fed broilershad higher total polyunsaturated fatty acids and n-3 fattyacids.The findings from the study showed that inclusion of L.javanica in broiler diets at 5 g/kg feed has positive influenceson growth performance, carcass characteristics, and fattyacid profiles of broiler meat and, therefore, L. javanica haspotential as growth-promoting feed additive in broilers.Samie et al. [73] evaluated antiamoebic activity of a purecompound piperitenone 162 isolated from L. javanica essen-tial oil against Entamoeba histolytica using microdilutionmethod with metronidazole as the positive control, diluents(i.e., culture medium with an appropriate concentration ofdimethyl sulphoxide as the negative control), and a blank(i.e., culture medium without dimethyl sulphoxide). Samieet al. [73] demonstrated that piperitenone 162 had markedantiamoebic activity with IC
50value of 25 𝜇g/mL. More
research is required as L. javanica could be harbouring potentantiamoebic properties which could be useful for managingamoebiasis, an infection that remains a sign