Jo urn al o f C hin ese In te g r at ive Me dicin e Ma y V ol N o

R A

Chemical components of Centella asiatica and their bioactivities

Chengjian ZHENG Luping QIN
Depa r tment of Phar maco gnosy Scho ol of Phar macy Seco nd Militar y M edical University Sha ng hai Chin a

Keywords Centella asiatica triterpenes apiaceae biological activity chemical constituent

Zheng CJ Q in L P J Ch in Integ r Med Zh ong X i Yi J ie H e X ue Bao R eceived S eptem ber

published online M ay Free f ull text PD F is available at w w w jcimjournal co m

depressive sedative effect s of C as iatica prepara

1 INTRODUCTION
Cen tell a asiatica L U rba n a pr ost r ate
per ennial h erbaceous cr eeper belo ngs to t he genus
Cen tell a Apiceae flouris hing abund an tly i n
moist areas and dis t ribu ting widely in t r opical and
sub tr opical count ries up to an altit ude o f m co unt ries P opula rit y of C asi ati ca is m os tly due
T he plant is clonally pr opagated by pr oducin g
s tolons th at ar e cha racterized by long in ternodes
and n odes on w hich are bo rne renifo r mco rdate
leaves and ses sile flo w e rs in sim ple um bels I t is
com m only kn o w n as G ot u kola in Chin ese India n
Pen ny w o r t in Engli sh Bra hmi in H indi and
M anduukapa rani in Ay ur veda and u tilized as a n
impo r tant f olk m edicinal he rb b y na tives of Asia
sout hern and middle Af rica sout heas tern U nit ed
S tates and A us t ralia w it h a lon g hist o ry of
t herapeu tic uses since ancient times
In co m m on w it h mos t t raditional phyt ot hera
peutic ag en ts C asi atica is claimed to pos sess a
w ide r ange of p har m acolo gical effect s being used
f or w ounds heali ng m ental diso rders
tions as w ell as their a bility t o im pr ove ven ous in
su fficie ncy and mic roangiopathy
T he h erb is also a t raditional ve getab le in Ch i
na India Sri L anka and Indonesia and is being
int r odu ced as a cultivat ed veg etable in developed
t o it s efficacy and versatilit y especially r efe rring
t o it s repu tation as a w ound healing age nt a nd
brai n stim ulan t pr o mo ting br ain gr o w t h and im
pr ovin g lear ning and m em or y M any scien tist s i n
t he w or ld have bee n conductin g quite e xtensive e x
perim en tal and cli nical investig ations and focu sing
t heir in teres ts on sear ching f or som e pr omising
com po unds w ith high ef fectiv eness and lo w to xicit y
f or t h e benefit of humans health H er e w e r evie w
recen t advances in the chemi st r y and bioactivities
o f C asia tica pa rticula rly mentio ning its principal
active m as striterpenoid s
2 CHEMICAL CONSTITUENT
at her 2 1 Triterpenoids T rite rpene is a major and t he

oscler osis f ungicidal a ntibacterial antio xidan t mos t im po r tan t co m pon ent o f C asi atica r egarded

and anticancer purposes C asia tica has also as a ma rke r co nstit uent in ter ms o f qualit y cont r ol

been repo r ted to be usefu l in t he t reat ment of in
flam m atio ns dia rrhea asth ma t ubercu losis and
va riou s ski n lesio ns a nd ailments like lepr osy lu
pus psoriasis and keloid In addition nume ro us
cli nical rep o rts verify t he ulcerprev en tive and an ti
T he t rite rpenes ob tained f r om C asi atica are
main ly pent acyclic t riterpenic acids and t heir
res pective glycosides belonging t o ur sa ne o r
oleananet y pe including asiatic acid asiaticoside
madecassic acid madecassoside brahm oside brahmic

Co rrespondence L uping QIN P hD P ro fesso r Tel Email lpqin s m mu edu cn

 Jo urn al o f C hi nese In t eg r a tiv e M edicin e M ay
acid brahminoside thankuniside i sot ha nkuniside
centellos ide madasiatic acid cen tic acid cenellic
acid bet ulinic acid indocentic acid etc Ear lie r
w ork on th is plan t has led to t he isolation of man y
t riterpenoid constit uen ts and Bri nkha us et a l has
already revie w ed t he che mical pro file of C asi ati ca
befo re t hus w e predo minantly collect phyt o
chemis t r y info r mation on novel com po unds isolat ed
f ro m C as ia tica in rece nt years Sh ukla et a l
separ ated a n e w ursane triterp enoid f r om C
asi ati ca and ex hibited it s dosedependen t g r o w th
inhibito r y activit y ag ainst lar vae of Spilarctia
o bliqu e L ater on M a t suda et a l isolat ed a
ne w oleanene t riterpe ne cent ellasapo genol A
and its olig o glycoside f r om C asia tica cultivated i n
Viet nam Con tinuou sly i n t h eir co m parative st ud y
o n t he g enet ype cultiva ted in S ri Lanka ho w ever
t hey obt ained t w o ne w ur sanet ype t riterpe neolig o
glycosides cen tellasaponins B a nd C a nd a n
oleananet ype trite rp ene olig o glycoside cent ellasa
ponin D K ur oda et a l also sepe rated ne w t rit
erpene glycosides f r om t he aerial par ts of C
asi ati ca and n one of t hese saponins revealed signifi
cant cytotoxicity M o reo ver Jia ng et al identified
f our n e w triterp en oid glycosides nam ed asiaticoside
C D E and F f r om t he Bu O H fr action of C
asi ati ca In addition dr a wing as sistance f r om t he
techn olo gy of bio t ran sf or m ation M onti et a l
pr epa red an array of novel derivatives of asia ticos i
de wit h m olecular diversit y and f unctional variety
Being t he chief bioactive substances in C
asi ati ca triterpenoid derivatives play an im por tant
role in t he aspect of medicinal app lication Sever al
o f t h eir t raditional uses have been scientifically
validated a nd so me o f t he active principles have
also been r epor ted
2 1 1 Wound healing properties A s an universal
use in w ound h ealing a nd va rio us skin disorde rs
effectivenes s of t he ex t racts and mon o mer s f r o m C
asi ati ca has been subjected t o and jus tified b y bo th
exp erimental and clinical evaluations
W ound healing is a com plex p hy siolo gical
pr oces s t hat r equires a se ries of st eps of w hich
gr anu lation colla gen mat ur ation and scar fo r ma
tio n ar e som e o f t he many phases E xt r acts of
C asia ti ca ha ve been sho wn to produce differ en t
actions on t he va riou s phases of w ound r epair
Scien tific s t udies pr oved t ha t t riterpenes
f ro m C as ia tica s tim ulated ex t racellu lar mat rix ac
cum ulation i n r at ex perimental w ounds as fur t he r
evidenced in v it ro by g eneexpr essio n alterna tio n i n
a h uman der mal fibr ob las t As iatic acid w as t he
o nly com ponent responsible fo r t he collage n
synt hesi s s tim u latio n w hile m adecassoside w as
ab le t o i ncrease sig nifican tly collagen secr etion
V o l N o
A d vanced st udies indicated t hat asiaticoside in
duce d type I collag en sy nt hesis via the activation of
t he T GF r ecept or I kinaseindep enden t Smad
pat h w ay wh ich f org ed a b asi s f or m olecu la r
unders tandin g of Centel las bioactivit y on w ound
healing
2 1 2 Brain stimulating effects A s co m m only
described bo th i n Chi nese and Indian medicine sys
tem C asia tica posses ses va rious CN S effect s
such as s ti m ulat o ryn er vi ne t onic rejuvenant sed
ative t ranquilize r esp ecially me mo r y im pr ove
men t and i ntellig ence pr o m oting pr oper ty So me of
t hese bioactivities hav e been dem onstr ated expe ri
men tally Scien tific findin gs ex hibited t hat t he
aqueo us ex t ract of C asi ati ca has cognitive enhan
cing ef fect and an an tioxidan t mechanism is
inv olved A dditionally C as ia tica leaf
ex t ract w as no t o nly s ho w ed t o im pro ve spa tial
lear ning per fo r mance and enhance m em or y reten
tion i n ne onatal r at s duri ng g r o w t h spur t period
but also f ou nd efficien t in e nhancing hippocam pal
C A ne ur onaldendritic a rborization in rat s t hus
pr o viding evidence to sho w t he ef fect of t his plan t
ex t ract on t he brain regions involved in lea rning
and m em or y
2 1 3 Treatment of venous hypertension and
microangiopathy S t udies d one in acco rdance w ith
standa rdized scientific crite ria have sho w n t h at
t riterpenic co m p on ent s in C asi atica e xhibit a pos
itive effect in the t reatm ent o f venous insu fficiency
and micr oangiopat hy and se veral prosp ective
placebocon t rolled r and omized t rials convinced t he
effectiven es s of t he to tal t riterpenic fr action of C
asi atica by im pr ovin g mic rocir culation ede ma a nd
decr easin g capillar y per meability
2 1 4 Actions on gastric ulcer M any scie ntific
findings sug gest th e potential use of C asi ati ca
and it s active in g redie nt as an tig ast ric ulcers
drugs Che ng et a l displayed t he healin g effect s
o f C as iatica w a ter e xt ract and asiaticoside on
acetic acid induced gas tric ulce rs in rats by signifi
can tly attenuating t he m yeloper o xidase activity
pr o m otin g epith elial cell pr olifer ation and angio
genesi s and upr eg ulatin g expression o f basic fi
br ob las t g r o w th fact or in t he ulcer ti ssues there
f or e st r engt hening t he m ucosal defensive fact ors
Cen tell a ex tr act w as also repo r ted t o s ho w an ti
ulcer o genic activity a gai nst va riou s physical a nd
ch emical facto rs such as et h an ol aspirin cold
res t raint st ress and py loric ligatio n induce d gast ric
ulcers i n rat s In addition Gu o et a l sho w ed
t hat C asi atica w ater ex tr act and asiaticoside have
an an tiinflam ma to r y pr oper ty t hat i s brough t
ab ou t by inhibition of N O sy n t hesis and t hus facili
tates ulcer healin g
 Jo urn al o f C hin ese In te g r at ive Me dicin e Ma y
2 1 5 Anticancer activity A s anticancer drugs of
plant o rigi n a re gai ning p opularit y man y scien tist s
cast ligh t o n C as ia tica in searc h of p otential bio
active molecules agains t tumor Babu et al found
crude ex t ract of C asi ati ca as w ell as it s pa rtially
purified fr action s e x hibited selective cy to to xicity in
vit ro and a n tit um our pr o per ties in v i vo Syne rgis
tic inhibito r y effect of asia ticoside co m bined w ith
vinc ristin e on pr olife ration o f several cancer cell
lines w as al so repo r ted sho w ing asiaticoside as a
biochemical m odulato r can induce ap op t osis
Besides t he w at er e xt ract of C asi atica w as dis
played t o e xer t a chem opreve ntive effect on colo n
t um orig enesis Fur t her m o re asiatic acid w as
sug gested t o be a g oo d candida te fo r t he t her apeu
tic int er ven tion of human skin ca nce r
2 1 6 Other ef fects In addition to a bove
men tioned activities t riterpe noids i n C asi ati ca
w er e also claimed t o be effectively applied f or an ti
bilharzial an tifer tility a ntiherpes sim plex virus
radio pro tection cosm etics im m uno modulato r y
and antag onizing liver fibr osi s
A dmitting of no e xception C as iatica
despite of it s m ultifarious fav or able uses has bee n
inevitable t o s ho w several adver se effects incl u
di ng m utag enicit y aller gic con tact der ma titis and
hep ato to xicit y perhaps m ainly evoked by its t rit
erpenoid s co mponents
2 2 Essential oil Closely related to t he species
H ydr ocoty le lik e m ost m em be rs o f t h e fa mily
A piaceae C asi atica w as char acterized by t he
pr esence of essential oil Qin et al identified
v ola tile co m p onent s by GCM S f r om C as iatica
o f w hich t he main constituen ts w er e cary o
phyllene fa rnesol and elemene Subsequently
t hey f ound t he volatile oil ex tr act displayed an tide
pressan t effect in m ouse Recen t a nalyses of t he
v ola tile fr action of t his medicinal plan t g r o w in g i n
Sou t h Af rica r evealed monote rpenoid h ydr o
ca rb ons o xy genated m o noterpenoids ses
quiterpenoid hy dr oca rb on s o xy genated sesquit
erpenoid s a nd su lfide sesquiterpe noid
hum ulene cary ophyllene and bicyclog er ma
crene w er e the predo minan t constit utes T he v ola
tile e x tr act ex hi bite d a bro ad spect rum of an ti bac
terial activities against bot h Gra mpositive and
G ramnegative or gani sms
2 3 Flavonoids Besides t riterpenoids a nd es sen
tial oil C as iatica has also been repo r ted t o con
tain numer ous fla vo noids including quercetin and
kaem p fer ol catechin rutin and na rin gin as a
major pa rt of the to tal phenolic con ten t s so me of
w hich a re majo r co n t ribut o rs i n pa rticu lar to t he
an tioxidative activity o f C asia tica Base d o n
t he hyp ot hesis of fr ee radical mediated t oxicity i n
V ol N o
o xidative s t ress pr ocess and depending on it s
an tioxid ant pr oper ties C asi ati ca has been re
cen tly indicated to s ho w an tilipid pe ro xidative and
f ree ra dical scavenging activities In addi
tion M atsuda et a l isolate d a flav o nol pet ule
tin and kaem p fer ol ODglucur onide f r om t he
aerial par ts o f C asi ati ca c ultivat ed in Vietnam
bo t h of wh ich e xhibited po ten t i nhibito r y activit y
on aldose reductase in rats A nd bio flav onoids of
C asi ati ca ha ve ever been e xhibited t o be effica
cious in ve nou s in sufficiency pr o bab ly due to t heir
actions on m ucopolysaccharide metabolism
2 4 Other components C ohe ren t resear ches on
C asi ati ca also revealed the presence of polysac
ch arides poly ynealkene a min o acid s fatt y
acids sesquiterpenes al kaloid s st er ols car ote
noids tanni n chlo r ophyl pectin i no r ga nic salt s
etc
3 SUMMARY
In vie w of it s versatile medicinal prope rties
t he requir eme nt of C asia tica in p har m aceu tical in
dustries has bee n sharply inc reasin g th us leading
t o t h e o ver e x ploitation of t his herb It has already
been lis ted as t hr eat ene d species by t he In terna
tional U nion fo r Co nser vation o f Nat ure a nd
Na tional Resour ces I U CN and an enda nger ed
species T he refo re a pplicatio n of tiss ue cult ure
appr oaches fo r r apid m ultiplication of elite clones
and ger mp lasm con ser vatio n is of vital im p o rt ance
In recent year s C asia tica re generation has been
achiev ed by u sing leaf derived callu s ste m seg
men t s and nodal seg ment s as e xp lant s s h oot tip
and su spen sion cult ures pr oviding a pr erequisite
f or t he gener ation of bioactive secondar y pr oduct s
f ro m t his species H o w e ver f urt her st udies are
still needed t o be done for t he eval uatio n of t he ge
netic r eso urces of t he p lant fo r variation in m o r
phological g ro w t h and he rb a nd yiel d relat ed
ch aracters t o identify high herb and m adecassol
yielding populations suita ble fo r u se in ag r ono mical
and plant breeding pr og ra ms
A great pro gress has been m ade ove r t he past
decades in st ud y of biologically active co m ponent s
and bioactivities o f C asia tica bu t t he r esu lts are
still unsatisfact or y E ven t hough t his highly pre
cious herb is surr ounded w it h m ultifa rious claims
t he unde rlying m ec hanisms inv olved in its physio
lo gical effect s a re lacki ng M or e scien tific data are
required befo re r eco m mendation fo r increase in it s
utilization can be given w it h confidence
REFERENCES
Su guna L S iva ku ma r P Ch andrakasan G Effects o f
Cen tel la asi atica ext ract o n der mal w ound healing in
 Jo urn al o f C hi nese In t eg r a tiv e M edicin e M ay V o l N o

rats Indian J E x p Biol memo r y in mice Physiol Behav

A ppa rao M VR Srinivasan K R ao K et a l T he effect
of mand ookpa rni Centella asi atica on t he ge neral
mental ability M edh ya of men tally retarded children
J Res India n M ed
O yedeji O A A f olaya n AJ C hemical co mpositio n and
antibacterial activit y o f t he essential oil o f Centella
asia tica gro win g in So ut h A f rica P har m Biol
Ja yashree G Kurup M G Sudar slal V S et a l A n ti
oxida nt activity of Centell a as ia tica o n lympho mabear
ing mice Fito tera pia
Ba bu T D K ut tan G Padikkala J C yt oto xic and an ti
t umo r pr ope rties of cer tain texa of umbelliferae w ith
s pecific refer ence to Centella asi atica L urba n J
Et hno ph armacol
B rinkha us B Lindner M Schuppan D Ch emical ph ar
macological and clinical profile of t he East A sian medi
cal pla nt Centel la asi atica Ph yt omedicine
Shuk la Y N Srivastava R T ripa thi A K et a l Charac
ter ization of an ursane tr iterpenoid f ro m Centella
asia tica w ith g ro w th inhibito ry activit y against Spila rc
tia bliqua Phar m Biol gastr ic u lcers in rats Life Sci
M atsud a H M orik aw a T U eda H et al Medicinal
foo dstu ffs XXVI Inhibito rs o f aldose reductase and
ne w t riterpene and its oligoglycoside centellasapogenol A
and ce ntellasaponin A f rom Centell a asi atica Go tu
Kola H eterocycles Biol
M atsud a H M orik aw a T U eda H et al Medicinal
foo dstu ffs XXVII Sap onin co nstit uen ts o f g ot u kola
st ruct ur es of ne w ur san e and olean anet ype t riter
pe ne oligo glycosides centellasa ponins B C a nd D
f rom Cen tel la asi atica cultivated in Sri Lanka C hem
Pha rm B ull T okyo inducing ap op tosis of t umo r cells and enhancing an ti
K ur oda M Mimaki Y Ha rada H et a l Five n ew
t riterpene g lycosides f rom Centell a asi atica N at M ed
B unpo P Katao ka K A rimochi H et a l Inhibito ry
Jiang ZY Zh ang X M Zh ou J N e w tr ite rpenoid glyco
sides f ro m Centel la asi atica Helv C him Acta
M on ti D Candido A Silva M M C et a l Bioca talyzed
gene ration of molecular diversit y selective mo dification
of t he sap onin asiaticoside Ad v S yn th Catal
Shet ty BS Udupa S L U dupa A L et a l Ef fect o f
Cen tel la as ia tica L U mbelliferae o n n or mal and de xa
meth ason esuppres sed wo und healing in Wista r albin o
rats Int J L o w Ex t rem Wo unds
C oldren CD Has him P A li J M et al Ge ne ex pres sion
c hanges in t he human fibro blast induced b y Centella
asia tica t riterpen oids Planta M ed
Lee J Jung E K im Y et a l A siaticoside induces hu
man colla gen I syn t hesis t hro ug h T GFbeta recept or I
kinase T betaRI K inaseind epend ent s mad signalin g
Plan ta Med Won g SP Leo ng L P K o h J H W Antio xid ant activities
Rao SB Ch etana M U ma Devi P Cen tel la as ia tica
t reatment during post natal perio d enhances learning and
Veere ndra Kuma r M H Gup ta Y K E ffect of diffe ren t
ext racts of Cen tel la asi atica o n co gnition and marke rs o f
oxida tive st ress in r ats J Et hno ph armacol
M o handas R ao K G M uddanna Rao S G uru madh va
Rao S Cen tel la as iat ica linn induced behavioural
c han ges during g ro w t h spur t period in neon atal r ats
Neuroanat omy
M o handas R ao K G M uddanna Rao S G uru madh va
Rao S Centell a asi atica L leaf ext ract t reatmen t
during t he g ro wt h spur t period enh ances hippocampal
C A neuro nal dendritic arbo rization in rats E vid Based
Com plemen t A lternat M ed
De Sa nctis M T Belcar o G Inca ndela L et al T reat
ment of edema and increased ca pilla ry filt ration in
veno us h yp er tension w ith to tal trite rp enic f ractio n o f
Cen tel la as ia tica a clinical prospective placebo
co nt r olled r and omized d oseran ging t rial An giolo gy
Suppl S
Chen g CL Gu o JS Luk J et a l T h e healing effects o f
Cen tel la ext ract a nd asiaticoside o n acetic acid induced
Sairam K Rao C V G oel RK E ffect of Centella
asia tica Linn on ph ysical and ch emical facto rs induced
gastr ic ulce ration and secretio n in rats Indian J E xp
Guo JS C hen g CL K oo MW Inhibito ry effects o f
Cen tel la as ia tica w ater ex tract a nd asiaticoside o n in
ducible nitric o xide syn t hase durin g gast ric ulcer healing
in rats Planta M ed
H uan g Y H Zhan g S H Zhen RX et a l A siaticoside
t umo r activit y of vincristine Ai Zhen g
Ch inese w ith abst ract in En glish
ef fects o f Cen tel la as ia tica on azox ymeth aneinduced
aberr ant c ry pt focus fo rmation a nd carcino genesis in t he
in testines of F rats Food Chem To xicol
Pa rk BC Bosire K O Lee E S et al A siatic acid in
duces ap op tosis in SK M EL human mela noma cells
Cancer Lett
Q in L P D ing RX Zh ang WD et a l Es se ntial oil f rom
Cen tel la asia tica and its an tid epres san t activit y Di Er
Jun Y i D a X ue Xue Bao C hi
nese
Zainol M K A bdH amid A Yusof S et a l An tio xida
tive activity and t otal phenolic com po unds of leaf r oo t
and petiole of f our acces sions of Centell a asi atica L
Urba n Food Chem
H us sin M AbdulHamid A Mo hamad S et a l P ro
tective effect of Cen tel la asia tica ex tract a nd p ow de r on
oxida tive st res s in r ats Foo d Chem
of aqueo us ext racts of selected plan ts Foo d Ch em