Review Article Mallotus philippinensis Muell. Arg (Euphorbiaceae): Ethnopharmacology and ...

13 Pages·2014·3.3 MB·English

Hindawi Publishing Corporation
BioMed Research International
Volume 2014, Article ID 213973, 13 pages
http://dx.doi.org/10.1155/2014/213973
Review Article
Mallotus philippinensis
Muell. Arg (Euphorbiaceae):
Ethnopharmacology and Phytochemistry Review
MayankGangwar,1,2R.K.Goel,2andGopalNath1
1LaboratoryofGastrointestinalInfectionsandMolecularDiagnosis,DepartmentofMicrobiology,InstituteofMedicalSciences,
BanarasHinduUniversity,Varanasi221005,India
2DepartmentofPharmacology,InstituteofMedicalSciences,BanarasHinduUniversity,Varanasi221005,India
CorrespondenceshouldbeaddressedtoGopalNath;[email protected]
Received15February2014;Revised2May2014;Accepted2May2014;Published8July2014
AcademicEditor:KotaV.Ramana
Copyright©2014MayankGangwaretal. This is an open access article distributed under the Creative Commons Attribution
License,whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperly
cited.
MallotusphilippinensisMuell.Arg(Euphorbiaceae)arewidelydistributedperennialshruborsmalltreeintropicalandsubtropical
region in outer Himalayas regions with an altitude below 1,000m and are reported to have wide range of pharmacological
activities. Mallotus philippinensis species are known to contain different natural compounds, mainly phenols, diterpenoids,
steroids,flavonoids,cardenolides,triterpenoids,coumarins,isocoumarins,andmanymoreespeciallyphenols;thatis,bergenin,
mallotophilippinens,rottlerin,andisorottlerinhavebeenisolated,identified,andreportedinterestingbiologicalactivitiessuch
asantimicrobial,antioxidant,antiviral,cytotoxicity,antioxidant,anti-inflammatory,immunoregulatoryactivityproteininhibition
againstcancercell.Wehaveselectedallthepharmacologicalaspectsandtoxicologicalandallitsbiologicalrelatedstudies.The
presentreviewrevealsthatMallotusphilippinensisisavaluablesourceofmedicinallyimportantnaturalmoleculesandprovides
convincing support for its future use in modern medicine. However, the existing knowledge is very limited about Mallotus
philippinensisanditsdifferentpartslikesteam,leaf,andfruit.Further,moredetailedsafetydatapertainingtotheacuteandsubacute
toxicityandcardio-andimmunotoxicityalsoneedstobegeneratedforcrudeextractsoritspureisolatedcompounds.Thisreview
underlinestheinteresttocontinuethestudyofthisgenusoftheEuphorbiaceae.
1.Introduction bronchitis,abdominaldiseases,spleenenlargement,antimi-
crobial,antiparasitic,andsoforth(Figure18).
Mallotus (family: Euphorbiaceae) is a large genus of trees Someothermedicinalplantsreportedsimilaranticesto-
andshrubsdistributedchieflyinthetropicalandsubtropical dalactivityshowninTable1.Somemedicinalplantsexported
regions of the Old World with around 20 species in India from India are Aconitum species (root), Acorus calamus
[1].MallotusphilippinensisMuell.(commonlycalledKamala, (rhizome), Adhatoda vasica (whole plant), Berberis aristata
Kampillaka, and Kapila, and locally known as Shendri) is (root),Cassiaangustifolia(leafandpod),Colchicumluteum
a very common perennial shrub or small tree found in (rhizome and seed), Hedychium spicatum (rhizome), and
outer Himalayas ascending to 1500 meters. Mature fruits Heradeumcandicans(rhizome)[4].
have glandular hairs collected as reddish brown powder
whichiscollectedinclothbyshakingandrubbingthefruits
1.1.ScientificClassification. Considerthefollowing:
by hand. The collected material is fine, granular powder,
dull red, or madder red-colored and floats on water. This kingdom:Plantae,
plant is traditionally used for antifilarial [2], antibacterial,
subkingdom:Tracheobionta,
anti-inflammatory, and immune-regulatory activity [3] and
superdivision:Spermatophyta,
also used as purgative, anthelmintic, vulnerary, detergent,
maturant,carminative,alexitericandisusefulintreatmentof division:Magnoliophyta,
2 BioMedResearchInternational
Table1:Somemedicinalplantsreportedfortheantihelminticactivity.
S.no. Sources Partused Family Reference
1 Strobilanthesdiscolor Leaves Acanthaceae [56]
2 Trifoliumrepens Aerialshoot Fabaceae [57]
3 HouttuyniacordataThumb Leaves Piperaceae [58]
4 LasiaspinosaLinn Leaves,stalk,stem Araceae [59]
5 CentellaasiaticaLinn Leaves Apiaceae [60]
6 ClerodendrumcolebrookianumWalp Leaves Verbenaceae [61]
7 GynuraangulosaDC Leaves Asteraceae [61]
8 AloeveraLinn Leaves Liliaceae [61]
9 PsidiumguajavaLinn Leaves Myrtaceae [62]
10 CurcumalongaLinn Rhizomes Zingiberaceae [63]
11 OcimumsanctumLinn Oil/eugenol Lamiaceae [64]
12 Albiziaanthelmintica Steambark Mimosaceae [65]
13 Berliniagrandiflora Steambark Leguminosae [66]
14 NicotianatabacumL. leaves Solanaceae [67]
15 Calotropisprocera(Ait.)Ait. Flowers Asclepiadaceae [68]
class:Magnoliopsida, other species, both in forests and open scrubland. Kamala
treeiscommoninevergreenforest,especiallyinsecondary
subclass:Rosidae,
forest, and sometimes even dominant in the undergrowth.
order:Euphorbiales,
Kamalatreewithstandsconsiderableshade;itisfrost-hardy
family:Euphorbiaceae, andresistanttodrought.
genus:Mallotus,
species:Mallotusphilippinensis. 1.5. Biophysical Limits. Kamala tree is mostly grown at an
∘
altitudeof0–1600matameanannualtemperatureof16–28 C
withmeanannualrainfallof800–2000mm.Plantswillgrow
1.2. Botanic Description. Trees are small to medium-sized
mostlyinawiderangeofsoiltypes,includinginfertilesoils,
monoecious in nature, up to 25m tall and with a bole up
limestone,acid,androckyland.
to 50cm in diameter, but usually much less in number
(Figure19(a)).Slashturningdeepred.Branchletsarereddish-
brownglandular. 2.VernacularNamesandTraditionalUses
Leaves are alternate and simple, more or less leathery,
ovate to lanceolate, cuneate to rounded with two glands at 2.1. Vernacular Names. The vernacular names are as fol-
base.Leavesaremostlyacuteoracuminateatapex,conspicu- lows: English: Kamala tree; Hindi: Kamala, Sindur, Rohini,
ously3-nerved,hairyandreddishglandularbeneath,petiole and Kambhal; Bengali: Kamala, Kamalagundi; Guajarati:
size 1–4cm long, puberulous and reddish-brown in color Kapilo; Kannad: Kampillaka, Kunkumadamara; Malayalam:
(Figure19(b)).Maleflowersinterminalandaxillaryposition, Sinduri,Manjana,Kuramatakku,Kampipala,andPonnagam;
2–10cm long, solitary or fascicled paniculates spikes, each Marathi: Shindur, Shendri, and Kapila; Punjabi: Kumila,
flowers are with numerous stamens, small; female flowers Kamal, Kambal, and Kamela; Tamil: Kapli, Kungumam,
have spikes or slender racemes, each flower with a stellate Kurangumanjanatti, Kamala, Manjanai, Kunkumam, and
hairy, 3 celled ovary with 3 papillose stigmas. Fruit is a Kamala;Telugu:Kunkuma,Chendra-sinduri,Kapila,Vassun-
depressed-globose;3-lobedcapsule;5,7mm,and10mm;stel- tagunda,Sundari,Vasanta,andKumkumamu;Arabic:Kinbil;
late;puberulous;withabundantorangeorreddishglandular Assam:Gangai,Puddum,andLochan;Oriya:Bosonto-gundi,
granules;3-seeded(Figure19(d)).Seedsaresubgloboseand Kumala,Sundragundi,andKamalagundi;Pers:Kanbela;San-
blackincolorand4mmacross(Figure19(e))[5]. thal:Rora.
1.3.Biology. Inthisgenus,Mallotusphilippinensis(M.philip- 2.2. Traditional Uses. According to Ayurveda, leaves are
pinensis) flowers mature from March to April and fruits bitter, cooling, and appetizer. All parts of plant like glands
mature in July-August. M. philippinensis has extra floral and hairs from the capsules or fruits are used as heat-
nectariesattractingants. ing,purgative,anthelmintic,vulnerary,detergent,maturant,
carminative, and alexiteric and are useful in treatment of
1.4.Ecology. M.philippinensishasawidespreadnaturaldis- bronchitis,abdominaldiseases,andspleenenlargement,and
tribution, from the western Himalayas, through India, Sri iftakenwithmilkorcurd(yoghurt),itcanbequiteusefulfor
Lanka, to southern China, and throughout Malesia to Aus- expellingtapeworms[6].KamalaorKampillakahisalsoused
tralia.Sometimesitisgregariousbutmoreusuallymixedwith asanoralcontraceptive.Thepowderandafewotherpartsof
BioMedResearchInternational 3
Table2:Cardenolideanditsderivatives. Table3:Lupeolanditsderivatives.
O CH2
O
H3C H CH3
Me CH3 CH3
H
R1 H
H CH3
R O
H
H OH H3C CH3
R2 O No. Name R1 References
H 6 Lupeol-3-acetate Ac [9]
7 Lupeol H [9]
No. Name R1 R2 References
1 Coroglaucigenin CH OH H [8]
2
2 CoroglaucigeninL-rhamnoside CH OH L-rham [8] CH2
2
3 Corotoxigenin CHO H [8] H3C
4 CorotoxigeninL-rhamnoside CHO L-rham [8] H
CH3 CH3 OH
Kamalaarealsousedinexternalapplicationstopromotethe H
healingofulcersandwounds.Theyareusedtotreatparasitic
affectionsoftheskinlikescabies,ringworm,andherpes. H CH3
AcO
H
2.3. Common Adulterants. Glandular hair powder of M. H3C CH3
philippinensis is commonly adulterated with Annato dye
(BixaorellanaLinn.),ferricoxide,brickdust,andferruginous Figure1:Betulin-3-acetate.
sand. Casearia tomentosa (stem bark powder), Carthamus
tinctorius(flowerpowder),Ficusbenghalensis(fruitpowder),
andFlemingiamacrophylla(hairsoffruits)arealsoreported H3C CH3
tobeusedasadulterantorsubstituteofKampillaka[7].
CH3 CH3
3.ChemicalConstituents
H H
H
Major phytochemicals present in this genus contain dif-
ferent natural compounds, mainly phenols, diterpenoids,
steroids, flavonoids, cardenolides, triterpenoids, coumarin, CH3 CH3
isocoumarins, and many more to discover. Present knowl- O
edge about this endangered species of medicinal plant is CH3
stilllimitedwithrespecttoitsphytochemistryandbiological CH3
activity.However,someresearchershavecontributedtowards
Figure2:Friedelin.
isolationofsomenovelconstituentsandtheiractivity.Oneof
themajorchemicalconstituent,thatis,rottlerinofM.philip-
pinensis, is listed below with its chemical structure and its
the heartwood of M. philippinensis yielded triterpenoids:
major biological activities along with other phytochemicals
betulin-3-acetate (Figure1) as a major compound, lupeol
(Figure18).
acetate (Table3), and lupeol (Table3) [9]. Friedelane-type
triterpenoidsareverycommoninMallotusspecies.Friedelin
3.1. Cardenolides. M. philippinensis seeds contain cardeno- (Figure2) was obtained from the stem bark of M. philip-
lides. The seeds of M. philippinensis were found to contain pinensis [10]. Most of the genera of family Euphorbiaceae,
after fermentation four cardenolides (Table2), of which such as Drypetes [11] or Celaenodendron [12] also contain
two were newly reported: corotoxigenin L-rhamnoside and friedelin in rich amount. Friedelin is common and is also
corogl-aucigeninL-rhamnoside[8]. foundinplantsfromotherorders.Otherknownpentacyclic
terpenoids,thatis,acetylaleuritolicacid(Figure3)foundto
3.2. Triterpenoids. Some Mallotus species were found to be reported in the petroleum and ether extracts from bark
haveacharacteristicfeatureofpentacyclictriterpenoidswith of M. philippinensis [9]. The first olean-18-ene triterpene
a 6/6/6/6/5 ring system. The petroleum ether extract of oxidizedatC-22(Figure4)wasisolatedfromthestembark
4 BioMedResearchInternational
H3C CH3 CH3
H3C
CH3 CH3
CH3 CH3 H CO2H CH3 CH3 H
H H CH3
AcO HO
H
H
H3C CH3 H3C CH3
Figure3:Acetylaleuritolicacidoraleuriticacidacetate. Figure5:𝛼-Amyrin.
H3C CH3
Et
H CH3 H3C
i-Pr
CH3 H
CH3 CH3 OH
O CH3 H
H CH3
H3C O H H
H
H3C CH3 R O
Figure4:3b-Acetoxy-22b-hydroxyolean-18-ene. Figure6:𝛽-Sitosterol.
of M. Philippinensis [10]. Apart from above triterpeniods, OH
ursane-typetriterpenoid:a-amyrin(Figure5)reportedfrom
thepetroleumetherandetherealextractsofM.philippinensis
OH
bark[9]. OH
O
MeO
3.3. Steroids. Common steroid, b-sitosterol (Figure6), was OH
isolatedfrompetroleumetherextractsoftheheartwoodand O
barkofM.philippinensis[9].Daucosterolwasobtainedfrom HO
etherextractfrombarkofM.philippinensis[9].
O
Figure7:Bergenin.
3.4. Phenolic Compounds. Isocoumarins, Bergenin
(Figure7), an isocoumarin, was isolated in 1972 from
theheartwoodofM.philippinensis.Thiscompoundwasalso
obtained from the bark and the leaves of M. philippinensis
[9].
Twonewchalconederivatives(flavonoids),kamalachal-
cones A and B (Figures 8-9) with a unique ring system H3C CH3
caused by dimerization between a dimethylchromene ring
and a phenoxyl group, were isolated from kamala (M. O H3C
H CH3
philippinensis) [13]. Three other novel chalcone derivatives,
mallotophilippensC,D,andE(Figures10,11,12,13and14), O O O
wereisolatedfromthefruitsofM.philippinensis[14],lignans,
H
chalcones,anddimericchalconederivatives[15]. O
HO
Fourphloroglucinolderivatives(kamalins),rottlerin,and
H
isorallorottlerin (Figures 15 and 16) were isolated from M. CH
3 HO OH
philippinensis [16]. Isorottlerin (Figure17) was also men-
tionedinM.philippinensis[17].
CH
3
Fruit and bark of plant contain condensed tannins
responsibleforantioxidantactivity.Methanolicbarkextract Figure8:KamalachalconeA.
BioMedResearchInternational 5
15
7󳰀 O O 11 13 14
H3C CH 12
3
3󳰀 8
HO 4󳰀 2󳰀 OH HO 7 9 O 2
O H3C
H CH3
3
O 5󳰀 1󳰀 6 10
O O 6󳰀 5 4
H
OH OH
HO O
H Figure11:MallotophilippenBor1-[6-(3-acetyl-2,4,6-trihydroxy-5-
HO CH2 HO OH methyl-benzyl)-5,7-dihydroxy-2,2-dimethyl-2H-chromen-8-yl]-2-
methyl-butan-1-one.
CH
H3C OH 3
CH
3 OH
HO
O
H
Figure9:KamalachalconeB. O
15 HO O
7󳰀 O O 11 13 14
8󳰀 12
HO 4󳰀 3󳰀 2󳰀 OH HO 7 8 9 O 2 OH
Figure 12: Mallotophilippen C or (1-[6-(3,7-dimethyl-octa-2,6-
5󳰀 1󳰀 6 10 3 dienyl)-5,7-dihydroxy-2,2-dimoethyl-2H-chromen-8-yl]-3-(4-hy-
6󳰀 5 4 droxy-phenyl)-propenone),R=H.
OH OH
OH
Figure10:MallotophilippenAor1-[5,7-dihydroxy-2,2-dimethyl-6-
(2,4,6-trihydroxy-3-isobutyryl-5-methyl-benzyl)-2H-chromen-8-
yl]-2-methyl-butan-1-one. OH
O
of M. philippinensis subjected to characterization through
HO O
columnchromatographyonaSephadexLH-20columnusing
ethanol and acetone-water as the mobile phases, tannins
andphenolswerequantified.Barkextractcontains541mg/g
of total phenolics and infractions ranging from 54mg/g
OH
(fractionI)to927mg/g(fractionVI)andcondensedtannins
were detected in fractions II–VI [18, 19]. In 1989, leaves of Figure 13: Mallotophilippen D or 3-(3,4-dihydroxy-phenyl)-1-[6-
M.philippinensiswerereportedfortanninsandotherrelated (3,7-dimethyl-octa-2,6-dienyl)-5,7-dihydroxy-2,2-dimethyl-2H-
compoundsbySaijoetal.[20]. chromen-8-yl]-propenone,R=OH.
3.5.OtherCompounds. Unsaturatedfattyacids,thatis,triply-
unsaturedhydroxyacidkamlolenicacid,differentfattyacids,
and glyceride [21] have been reported from Kamala (M. nerve-muscle(n.m.)preparationofSetariacerviandonthe
philippinensis)seedoil. survival of microfilariae in vitro. Both the extracts result in
Resinouscolouredmaterialcontainsactivepartsofrott- inhibition of spontaneous motility of whole worm and the
lerinandisorottlerin.Italsocontainshomorottlerine,redrole n.m.preparationofS.cervicharacterizedbyinitialstimula-
50%,yellowrole5%,manure2%,volatileoils,tannin,gum, tionfollowedbydepressioninamplitude.Thetoneandrate
citricacid,andoxalicacid. ofcontractionsremainedvisiblyunaffected.Aqueousextract
athigherconcentrationshowedimmediatereductionintone.
4.PharmacologicalActivities Theconcentrationrequiredtoinhibitthemovementsofn.m.
preparation was 1/5th for aqueous and 1/11th for alcoholic
4.1.AntifilarialActivity. Theeffectofaqueousandalcoholic extract compared to that for the whole worm, suggesting a
leaveextractsofM.philippinensis(Lam.)Muell.wasstudied cuticular permeability barrier. The stimulatory response of
on the spontaneous movements of the whole worm and acetylcholinewasblockedbyaqueousextractonwholeworm
6 BioMedResearchInternational
OH
HO OH
O
OH
O
HO
HO O
HO O
OH O
OH
Figure14:MallotophilippenEor1-[5,7-dihydroxy-2-methyl-6-(3-
methyl-but-2-enyl)-2-(4-methyl-pent-3-enyl)-2H-chromen-8-yl]- Figure16:Isoallorottlerin.
3-(3,4-dihydroxy-phenyl)-propenone.
OH O
OH
O
O O
O HO HO
OH OH
O OH OH
HO
O
Figure15:Rottlerin.
Figure17:Isorottlerin.
movements.OnthemicrofilariaetheLC50 andLC90 were18
Klebsiella pneumonia, Candida albicans, and Saccharomyces
and20ng/mLforaqueousand12and15ng/mLforalcoholic
cerevisiae.Twenty-eightplantextractsshowedactivityagainst
extracts, respectively [2]. Further study will be required to
at least one of the test organisms used in the screening.
evaluatethesameactivitywithitsphytochemicals.
On the basis of the results obtained, study concludes that
the crude extracts of M. philippinensis exhibited significant
4.2. Antifertility Activity. Seeds extract of M. philippinensis
antimicrobial activity [3] and properties that support folk-
exhibitsadverseeffectsondifferentreproductiveparameters
loricuseinthetreatmentofsomediseasesasbroad-spectrum
of female rats. According to the study, extract reduces
antimicrobialagents.Steambarkofplantanditschloroform
serum FSH and LH levels, probably by affecting hypotha-
fractions and the methanolic extract significantly inhibit
lamic/pituitary axis in experimental animals. This reduced
the pathogenic bacteria with significant zones of inhibition
level may affect follicular development, quality of ovulated
comparabletothestandarddrugused.However,thehexanic
eggs,corpusluteumformation,estruscycle,andmaintenance
extractdidnotshowanysignificantactivity[24].Glandular
of pregnancy in rats [22]. This antifertility effect of plant
hair of fruits of Mallotus exhibits significant antibacterial
extract is supposed to be caused by rottlerin (Figure15), a
activityagainsthumanpathogenicbacteriawithMICranging
phloroglucinolderivative.Acetylrottlerinmaybeactive,but
15–20mg/mL. This extract does not show any inhibition
isorottlerin(Figure17)iseitherinactiveorslightlyactive[23].
against different species of candida. This shows that fruit
Effectofpurerottlerincanbefurtherstudiedsoastoclarify
extractpossessesantibacterialactivitywithoutanyantifungal
thepotentialofphloroglucinolderivatives.
potential.Theresultsofthestudymayjustifytheuseofthe
plantagainstbacterialpathogens.Thisprobablyexplainsthe
4.3. Antibacterial and Antifungal Activity. A series of 61 useoftheseplantsbytheindigenouspeopleagainstanumber
Indian medicinal plants belonging to 33 different families ofinfections[25].
usedinvariousinfectiousdisorderswerescreenedfortheir However, ethanolic extract shows potent anti-Heli-
antimicrobial properties. Screening was carried out at 1000 cobacterpyloriactivityattheconcentrationof15.6–31.2mg/L
and 500𝜇g/mL concentrations by agar dilution method againsteightH.pyloristrains.Furtherpurificationofextract
againstBacilluscereusvarmycoides,Bacilluspumilus,Bacillus revealed that rottlerin exhibits potent bactericidal effect
subtilis,Bordetellabronchiseptica,MicrococcusLuteus,Staphy- with minimal bactericidal concentration (MBC) of 3.12–
lococcusaureus,Staphylococcusepidermidis,Escherichiacoli, 6.25mg/Lagainstdifferentresistantstrainsofclarithromycin
BioMedResearchInternational 7
M. philippinensis
Fruit
✓Antifertility
O
CH3 ✓Antimicrobial
HO OH O CH3 ✓Protein inhibition
H3C HO CH3 ✓Antituberculosis activity
✓Antiallergic activity
O OH OH ✓Antiproliferative activity
Rottlerin
✓Antiparasitic (cestodal)
Figure18:Rottlerinanditsmajorbiologicalactivities.
andmetronidazoleincludingJapaneseandPakistanistrains 4.6.ProteinInhibitionImplicatedinCancerProcesses. Protein
[17]. kinaseisinhibitedwithsomespecificityforPKCbyrottlerin,
a compound isolated from Mallotus. Inhibition of PKC
appears due to a strong competition between rottlerin and
4.4. Anti-Inflammatory and Immunoregulatory Activity.
ATP.CaM-kinaseIIIissuppressedbyrottlerinaseffectively
Chalcones derivatives from the fruits of M. philippinensis as PKC 𝛿, among different protein kinases tested. Novel
and mallotophilippens C, D, and E (Figures 12, 13, and
inhibition property and improved selectivity for a distinct
14) inhibit nitric oxide (NO) production and inducible
PKCisoenzymeofrottlerinaresuggestivefromitschemical
NO synthase (iNOS) gene expression by a murine
structure [27, 28]. Rottlerin is also very potent in blocking
macrophage-likecellline(RAW264.7),whichwasactivated
otherkinasesincludingAkt/PKBandp38MAPK[29–31].It
by lipopolysaccharide (LPS) and recombinant mouse
alsoinhibitshumanTcellresponses[32],reducesMUC5AC
interferon-gamma (IFN-gamma). Further investigations
expression in human epithelial cells [33], abrogates reactive
suggest the downregulation of cyclooxygenase-2 gene,
oxygenspeciesproductioninhepaticstellatecells[34],and
interleukin-6 gene, and interleukin-1b gene expression.
prevents histamine-induced H1-receptor gene expression in
The above results show that these chalcones have good
HeLa cells [35]. However, still very limited information is
anti-inflammatoryandimmunoregulatoryeffects[26].
available of rottlerin towards cancer disease and its mecha-
nismofaction.
4.5. Antioxidant Activity and Antiradical Activity. Different
fractions of bark and fruit of Mallotus were studied for 4.7. Hepatoprotective Activity. Methanolic extract of M.
its total antioxidant activity (TAA) and antiradical activity philippinensisleavesdecreasestheCCl4-inducedelevationin
against DPPH on a Sephadex LH-20 column using ethanol biochemical parameters (SGOT, SGPT, SALP, direct biliru-
andacetone-waterasmobilephase.Amongdifferentextracts, bin,totalbilirubin,andMDA)onpretreatmentatdoses100–
barkfractionshowedthestrongestantiradicalactivity(TAA 200mg/kgandalsoreversedthefunctionalandantioxidant
value—5.27 mmol Trolox equiv./g) and reducing power. parameters.Thisstudysuggeststhatleaveextractwaseffec-
Another extract, that is, phenolic fraction, shows TAA tiveinfunctionalimprovementofhepatocytes.Histopatho-
ranging from 0.58mmol Trolox/g (fraction I) to 6.82mmol logical studies also suggest the hepatoprotective activity of
Trolox/g(fractionIV);thisisthestrongestfractionshowing plant[36].
antiradicalactivityagainstDPPHandreducingpower.TAA
of other extracts ranged from 0.05 to 1.79mmol Trolox 4.8. In Vitro Cytotoxicity against Human Cancel Cell. Glan-
equiv./g[18,19]. dular hair extract of Mallotus fruit powder was assayed
8 BioMedResearchInternational
(a) (b)
(c) (d)
(e)
Figure19:Mallotusphilippinensis.(a)Matureplant;(b)leaf;(c)initialinflorescenceofseedsetting;(d)maturefruitstwig;(e)maturefruit
withseed.
against14humancancercelllinesamongdifferentfractions; philippinensis fruit extract of 800mg/kg twice daily for 3
95%ethanolicextractshowedthehighestcytotoxiceffectas days was observed to have curative efficacy against mature
compared to 50% ethanolic and aqueous portion. Further, adult worms of Hymenolepis diminuta. The total follow-up
thechromatographicanalysisofthesaidfractionaffordeda periodof90daysdidnotshowanyfurtherexcretionofeggs
polyphenolicmoleculerottlerininMallotusplant[37]. in the faeces of treated rats. Praziquantel at the dosage of
5mg/kgalsoproducedasimilareffect[40].Invitroscolicidal
4.9.AnticestodalActivity/VeterinaryApplications. M.philip- activityofM.philippinensis(Lam.)MuellArg.fruitglandular
pinensis fruit was found to be very effective against gas- hair extract against hydatid cyst Echinococcus granulosus
trointestinal cestodes in Beetal goats and other ruminants. protoscolecesatconcentrations10and20mg/mLshowsthe
Comparativeanticestodalefficaciesofsingleoraldosetreat- mortalityrate97%to99%,respectively,for60mintreatment,
mentswiththepowderedfruitofM.philippinensis(125,250, while up to 93% mortality was observed with 20mg/mL
and375mg/kg),itswaterormethanolextracts(equivalentto for only 10min treatment. This proves that the extract has
375mg/kg),andthetotalglycosides(25,50,and100mg/kg) significantscolicidalactivitywithalmostnoassociatedside
were determined in naturally cestode-infected Beetal goats effects[41].Invivoanimalmodelexperimentwillbefurther
[38]. An ethnobotanical survey has been conducted for requiredtoproveitseffectagainstHydatidcyst.
anthelmintics in ruminants, so as to document the plants
used to treat and control helminthes. Mallotus has been 4.10.PurgativeActivityandAnthelminticActivity. Asignifi-
frequentlyusedtotreathelminthosisinruminants[39]. M. cantpurgativeeffectafteranoraldose(120mg/kg)inratswas
BioMedResearchInternational 9
assessedfromresinsisolatedfromplant.Itseffectwasevalu- ringsisolatedfromsensitizedguineapigs.Thisexperiments
ated from the weight of faeces as well as from surface area provesantiallergiceffectofrottlerinbyblockingIgE-induced
of blotting paper soaked by liquid faeces. The anthelmintic mast cell degranulation. This report suggests the use of
effect on tape worm was evaluated in albino rates, from rottlerin in mast cell-mediated allergic disorders including
the resin of the plant showed lethal effect of 35.69% and urticariaandallergicasthma[48].
78.21% respectively in small intestine in concentrations 60
and120mg/kgrespectively[42,43]. 4.13.Anti-LeukaemicActivity. RootextractofM.philippinen-
siswastestedonhumanpromyelocyticleukemiaHL-60cell
proliferation,cellcycleregulators,andapoptosisinorderto
4.11. Antituberculosis Activity. Organicextract ofplant after
investigate its antileukemic effect. Hexane fraction showed
bioassay-directed fractionation yields five compounds, the
mostactiveofwhichagainstMycobacteriumtuberculosiswas promising toxicity against p53-deficient HL-60 cells (IC50
1.5mg dry roots equivalent/mL medium) after 72h and,
anewcompound,8-cinnamoyl-5,7-dihydroxy-2,2-dimethyl-
interestingly,inhibitionofcellproliferationwasprecededby
6-geranylchromene for which the name mallotophilippen
the upregulation of the protooncogenes Cdc25A and cyclin
F is suggested. The second compound 8-cinnamoyl-2,2-
D1 within 24 hours suggesting its antileukemic effect in
dimethyl-7-hydroxy-5-methoxychromenewasisolatedfrom
HL-60 cells. After isolation and identification by GC-MS,
anaturalsourceforthefirsttime,whiletheremainingthree
polyphenolswerethemaincompoundsofthehexaneextract
compounds, rottlerin, isoallorottlerin, or isorottlerin and
thatinhibitedproliferationandinducedapoptosis[49].
the so-called “red compound,” 8-cinnamoyl-5,7-dihydroxy-
2,2,6-trimethylchromene, had been already isolated from
thisplant.Isolatedcompoundswereidentifiedby2D-NMR 4.14. Antiproliferative Activity. Antiproliferative effect was
and C-13 NMR [44]. Ethanolicextract of plant was assayed evaluated against Thp-1 cell lines from the isolated com-
󸀠
for antimycobacterial activity against M. smegmatis by disc pounds of M. philippinensis fruit extract, in which 4 -
diffusion assay. Further antituberculosis potential of leaves hydroxyrottlerinshowed54%growthinhibitionofThp-1cell
extractwasidentifiedbyradiometricBACTECassay;result line[50].Otherisolatedcompoundswerealsotestedagainst
revealedthatethanolicextractofM.philippensisshowedanti- differentfungiandwerefoundtobeveryeffectiveIC50values.
tuberculosisactivityagainstvirulentandavirulentstrainsof
M.tuberculosisH37RvandM.tuberculosisH37Rawithmin-
−1
imuminhibitoryconcentrationsof0.25and0.125mgmL , 4.15. Anti-HIV Activity. Four phloroglucinol derivatives,
respectively. The inhibition in growth index values of M. named mallotophenone (5-methylene-bis-2,6-dihydroxy-
tuberculosis was observed in the presence of ethyl acetate 3-methyl-4-methoxyacetophenone), mallotochromene (8-
−1
fraction at a minimum concentration of 0.05mgmL . It acetyl-5,7-dihydroxy-6-(3-acetyl-2,4-dihydroxy-5-methyl-6-
suggests that ethanolic and ethyl acetate fraction of plant methoxybenzyl)-2,2-dimethylchromene), mallotojaponin
possesses significant antimycobacterial activity [45]. Steam (3-(3,3(dimethylallyl) S-(3(acetyl-2,4-dihydroxy-5-methyl-
bark of M. philippinensis has also been reported for its 6-methoxybenzyl)-phloracetophenone),andmallotolerin(3-
antitumor promoting effect, which was due to the presence (3-methyl-2-hydroxybut-3-enyl)-5-(3-acetyl-2,4-dihydroxy-
of3𝛼-Hydroxy-D:A-friedooleanan-2-one[46]. 5-methyl-6-methoxybenzyl)-phloracetophenone), were
tested for their ability to inhibit the activity of human
immunodeficiency virus- (HIV-) reverse transcriptase.
4.12. Antiallergic Activity. M. philippinensis fruit contains
The mode of inhibition of mallotojaponin was found
two new phloroglucinol derivatives, mallotophilippens
to be competitive with respect to the template primer,
A and B (Figures 10 and 11) which were identified, using
(rA)n (dT)12–18, and noncompetitive with respect to the
chemical and spectral data, as 1-[5,7-dihydroxy-2,2-di-
triphosphatesubstrate,dTTP.TheK valueofmallotojaponin
methyl-6-(2,4,6-trihydroxy-3-isobutyryl-5-methyl-benzyl)- i
for HIV-reverse transcriptase was determined to be 6.1𝜇M
2H-chromen-8-yl]-2-methyl-butan-1-one and 1-[6-(3-
[51].
Acetyl-2,4,6-trihydroxy-5-methyl-benzyl)-5,7-dihydroxy-2,2
-dim-ethyl-2H-chromen-8-yl]-2-methyl-butan-1-one,respe-
ctively. These compounds inhibited the production of 4.16. Antitumor Activity. Four known friedelane-type trit-
nitric oxide (NO) and inducible NO synthase (iNOS) gene erpenoids, friedelin, 3-hydroxy-D:A-friedoolean-3-en-2-
expression by a murine macrophage-like cell line (RAW one, 2𝛽-hydroxy-D:A-friedooleanan-3-one, and 3𝛼-hy-
264.7), which was activated by lipopolysaccharide (LPS) droxy-D:A-friedooleanan-2-one, and two known lupane-
and recombinant mouse interferon-g (IFN-g). Further, type triterpenoids, lupeol and betulin, were isolated from
phloroglucinolderivativesinhibithistaminereleasefromrat the stem bark of M. philippinensis and were tested for
peritonealmastcellsinducedbycompound48/80.Thisstudy their inhibitory effects on Epstein-Barr virus early antigen
suggests its anti-inflammatory activity [47]. Rottlerin has (EBV-EA)activationinducedby12-O-tetradecanoylphorbol
beentestedinanimalmodelsofIgE-dependentanaphylaxis 13-acetate (TPA). The inhibitory effect of compounds 2
and the antiallergic mechanisms of action in mast cells. (IC50 =292molratio/32pmol/TPA)and4(IC50 =288)was
Antiallergic action of rottlerin has been tested in passive stronger than those of the other compounds tested and the
cutaneous anaphylaxis and passive systemic anaphylaxis positive control, curcumin (IC50 = 343). Compound 3𝛼-
mousemodelsandinanaphylacticcontractionofbronchial hydroxy-D:A-friedooleanan-2-onestronglyinhibitedmouse
10 BioMedResearchInternational
skintumorpromotioninaninvivotwo-stagecarcinogenesis Mallotus philippinensis has been widely used as tradi-
model[46]. tionalmedicineinseveralpartsofcountriesincludingIndia.
Everypartofthisplantpossessesitsspecificmedicinalprop-
ertiesandisusedmainlyinayurvedatofightagainstintestinal
4.17. Wound Healing and Mesenchymal Stem Cell (MSC)
wormsindomesticandgrazinganimalswhenadministered
Proliferation. BarkextractofMallotusphilippinensishasbeen
withjaggery.However,onlyafewreportsareattributedtothis
tested in vitro for wound healing activity by examining the
plantanditsdifferentpartsandthereisalargescopeforinves-
proliferation and migration of MSCs. KUM6 cells prolifer-
tigation.Hence,itisrequiredtoexploremoreofitspotential
ation and migration have been enhanced at 0.16–4𝜇g/mL
withinthefieldofmedicinalandpharmaceuticalsciencesfor
and unregulated the activity of MSCs by secreting various
novelandfruitfulapplicationofthisplantinformofnatural
cytokines to wounded site from bone marrow to systemic
formulation. Along with this medicinal importance, this
circulationandfinallyremodelwoundedtissues[52].
plant is used against human pathogens including H. pylori,
anti-inflammatory activity, antioxidant, antiradical, protein
4.18. Toxicities. Seeds of M. philippinensis ethereal extract inhibition, hepatoprotective, antiallergic, anti-HIV activity,
haveadverseeffectonvariousparametersoffemalerats.Even andmanymore.Phytochemicalinvestigationrevealedthata
theextractreducesserumlevelsofgonadotropinsintreated large number phenol derivatives and several miscellaneous
animals at high dose of 100mg/kg body weight. Reduced compounds from different classes have been isolated from
weights of ovary and uterus, follicular development, and thisspecies.Thephenols,diterpenoids,steroids,flavonoids,
increasedatreticfollicularintheovaryareduetosubnormal cardenolides, triterpenoids, coumarins, and isocoumarins
levelsofsteroidhormones.Thus,pregnancyisverydifficult are mostly distributed in all parts of the plant. The other
infemaleratstreatedwithkamalaseedextract[22]. major isolated pure compounds from this species mostly
belong to phenolic group exhibiting most of the biological
activity. Various types of extracts from different parts and
4.19. Colouring Agent-Dye. Glandular hairs of fruit are
single compounds derived from this species have been
mostlyusedasanorangedyeforsilk[53,54].
foundtopossessbiologicalactivities,includingantioxidant,
antimicrobial, anti-inflammatory, cytotoxicity, and immune
5. PharmacognosticEvaluationof modulatory.Fruitandbarkofplantcontaincondensedtan-
Mallotusphilippinensis ninsresponsibleforantioxidantactivity.Somenovelchalcone
derivatives, mallotophilippens C, D, and E, were isolated
Morphological study shows that fruit depresses globose from the fruits of M. philippinensis. Mallotoxin or rottlerin
andisthree-lobedcapsule,5–7mm×8–10–12mm,stellate- hasgreatanticancerouspotential.Amongtheever-anticancer
puberulose, and with abundant orange or reddish glan- agents,rottlerinappearstohavegreatpotentialityforbeing
dular granules. Seeds are subglobose and black in color. used in chemotherapy. Rottlerin will become a potential
Organolepticpropertyoftheredfruitshowsthatitistasteless molecule for research in future to treat cancerous cell as it
andodourless.Microscopicdescriptionshowedthepresence will affect cell machineries involved in apoptosis, survival,
of epicarp, which contained a compactly packed layer of and autophage. This suggests the view that this species has
mucilaginous cells, and mesocarp composed of columnar
potentialtobeabeneficialchemotherapeuticremedy.
cellswhicharecloselyarranged.Itspolygonalcellsarecom-
Although the data and other reports provided that this
pactly arranged in 2-3 layers. Presence of lignified vascular
medicinal plant is of great biological use in different phar-
arrangementhasbeenobservedinthetransversesection[55].
macologicalactivitiesincludinganticancer,furtherresearch
isneededindifferentareasregardingthetoxicityandefficacy
6.ConclusionandFuturePerspective of pure phytochemicals isolated from different parts of this
plant.Moredatawillbeneededfrompreclinicalandclinical
Medicinalplantshavebeenclinicallyusedanditsinteresthas studies on humans to clarify its potency and safety, as
beendramaticallyincreasedoverthepastdecadesthroughout lack of knowledge with respect to its adverse effects and
the world and its formulations are increasingly cited in methodological accuracy in the literature limits towards
media.Dailyconsumptionofthenaturalproductsandtheir its standardized formulation. Furthermore, the mechanism
formulations by an extensive number of patients lead to of action of the phytochemicals and extract of Mallotus
serious concern for scientist to study its efficacy and safety. philippinensis is unclear; more exhaustive studies will be
Because of extensive use and its benefits, natural products performed to explore its mechanism and structure activity
inmanycountriesareregulatedbothasmedicinalproducts relationshipamongvariousconstituents.
and as food supplements, often labeled as natural food Inconclusion,thisreviewconfirmsthegreatpotentialof
supplements. Mallotus philippinensis. As very limited information is still
Traditional use and its growing demand for Mallotus known for this species, it leads us to continue the study on
philippinensisanditsotherspeciesleadtocompilethisreview different species of Mallotus plant and its interesting phar-
and commented on the current knowledge provided by macological properties. Further natural product chemistry
clinicalandpreclinicalresearchontheeffectofthisplant. of isolated moiety and its structural analysis of compounds