Catharanthus roseus Leaf Extract Accelerates Healing of Wound Wistar Rat.

rndonezta'Jaurn qJ

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tsioned:cal

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Chief

Prof.

Dr.

dr. I

N

Adipura,

M.OH., Faculty ofMedicine

Udayana

University, Bali-Indonesia.

Vice

Editor

Prof.

Dr.

h.

I.

B. Putra Manuaba,

M.Phil., Postgaduatc

School

ofBiomedicine

Udayana

University

Bali

Indoncsia.

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\{ember\:

Prol

Dr. dr. i

Made

Bakta, Sp.PD(KEOM) (Bali-Indonesia); Prof. Dr.

C. Bauer

(Visiting

Professor Udayana

UniveNitl,;

Giessen

Germany);

Prcf. Dr. David

J

Young

CNational

Universitl' Brunai

Darussalam,

Brunai);

Prof

Dr- A.

Moritz

(Giesen

Gemany); Prof.

Dr.

R. Edward

Tiekink

(Malaya

Unive6ity,

Malaysia);

Prol

Dr. dr.

Pdhatini, Sp.PK(K)

(Surabaya-Indonesia);

Prol

Dr.

dr.

A. A.

Raka

Sudewi,

Sp.S(K)

(Bali-Indonesia);

Prof.

Dr.

Made Budiarsa,

MA

(Bali-Indonesia);

Prol

Dr.

&.

I

Ketut

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(Bali-lndonesia);

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Shukla

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(Japan);

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Ketut

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Prof

Andi Asadul

Islam

(Makasar Indonesia);

Prof

Dr.

dr.

Abdul Hafid

Bajanml, Sp.BS

(Surabaya-Tndonesia)i

Prof.

I

Ketur Siki

Kawiyana SpBO (Bali-lndonesia);

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dr.

Arlati,

MS.,Sp.PK(K) (Suabaya-Indonesia);

Prol

Dr.

Ir.

Odi

Pinontoan,

M.Si

(Manado-Indonesia);

Dr.

dr. F.

W.

Wagey,Sp.OC(K) (Manado-Indonesia); Prcf. drh.

I N

Mantik

Astawa, PhD (Ba1i-Indonesia);

Prof. Dr.

drh.

I

Made Damriyasa,

M.Si

(Ba1i-lndonesia);

Prol

Dr.

dr.

Soemamo,

Sp.MK(K.) (Malang-Indonesia);

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Dr. fu.

I

Putu

Astawa, M.Kes-,FlC

(Ba1i-Indonesia);

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drh.

I

Gusti Ngurah Kd Mahardika, PhD

(Ba1i-lndonesia);

Prof

Dr.

dr. cede

Raka

Widiana, Sp.PD(KGH)

(Bali Indonesia).

Prol

Ir.

I

Putu Wirawan, M.Sc.,

PhD

(Bali-Tndonesia);

Prof.

Dr.

dr. Wimpie

Pangkahila,

Sp.And

(Bali-IndoDesia);

Prol

K. Tuti

Parwati

Memti, Sp.PD-KPTI (Bali-Indonesia).

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TN,DONSSTAN

JOURNAL

OT

tsIOMEDICAL

SCIEN CES

(

W

S)

Volume

7

Number

1

January-June

2013

CONTENTS

1. HEADACHE. A SINONASAL SYMPTOM

AND

MORE.''

A

RFVIFW

ARTICLE..,,,..

L'6

Kout, A., and

Singh,

A.

2. INTERLEUKIN 1P, INTERLEUKIN-6,

AND

ANTAGONIST INTERLEUKIN 1

RECEPTOR AS

MEMORY IMPAIRMENT

RISK FACTOR 1N COMPLEX

PARTIAL F PI1EPsY...

710

Purwa-sdmotru,

D, P. G.,

sudewa-Dielantilt

A. A. G., dnd

suostika,

K 3.

A

NOVEL APPROACH OF VLROTHERAPY BASED HSF-1

shRNA

rN cANCER

rRADICAllON...

WOUND

WISTAR RAT.,,,...

L1

22

Supddmonobo,

t

G,

P.,

and

Wibowd'Mdnuobd,l

B.

T'

4,

ORAL

ADMINISTRATION

OF PEPPERMINT IN WISTAR

ALBINO

RATSI

Memory Boosting and

Regaining

...

.

....

-.

23-26

Jdsiro,

M.,

sdi-sdilesh,

K.,

ond Mukkdddn,

J, K.

5, THE RISK OF

SQUAMOUS

CELL

CARCINOMA ON HUMAN

PAPILLOMAVIRUS TYPE

16

INFECTION

IN

BALI"

""

27'29

Mdhendtd'Dewi

I

G.

A.

s,

dnd

suwiyoga,

I K.

6. COMBlNATION

OF TEMPEH

AND

CARROT PREVENT ATHEROSCLEROSIS

WISTAR RAT:

lndicated

by lncrease

of

HDL

and

Total Antioxidant,

Decrease

LDL,

F2_lsoprostan,

and

lL-6..-.

..

30'36

Ati-Agung,l

G.

A-,

Suryadhi, N. T.,3Mdntik,

N.

A.,

suteL

I

K', and

Portdmo,l.

B, G.

7.

CANTHARANTHUS ROSEUS LEAF EXTRACT ACCELERATES HEALING OF

31

40

Anom-Dadd,

t K.,

Beruta,

I

K.,

Putto-Monudbs,

l.

8.,

and

Dom

ydsa,l

M.

1

I

I^dnAeti.aa+^io1ut"t.)' 4tsi2fl2.d.LlzLsa:etu)et

ldw

7

,

N t1h17,2.r, 1,

Js

uata'Jui@

2073:

37'+c

Pri,af'ISSAli

2085

47 7 3,

t

ISSN : 2 3O2

-2906.

CANTILA.RA.NTHUS ROSEUS LEAT'

EXTRACT

ACCELERA.TES

IIEALING

OF

WOIJND

WISTAR RAT

'Anom-Dddd,l K.,tBeruto,

t

K.,2Putrd-Monudbo,

I. 8.,

ondlDamtiosa,I

M.

1

Focutty

ol

veterindry Medicine, Udayana lJniversity

'Faculty

ol Mathemothic

and

Natural

Science

lJdoyano University

ABSTRACT

Conthonntus

roseus (C. roseus) is a medical

plantth.t

has been used

to treat

various diseases. This

study was carried

to

deiermine

C

rosels

leaf extract able

to

acclerate

wound

healing

in wGtar rat.

FuLl

skin

tickness round wounds

were

created

on the

back

of the

rats.

Wound

healing was evaluated

after

treated with

15%

of

a

mixture

of

leaf

extraci

of

C

roseus

and

vaseline.

The rats

were divided into two

groups? each

group

consist

of

16

rats. Wound

healing was assesed in

five

and

fifteen

days

after

treatment

by

measuring

wound

area,

wound

closure, and counting

the

new capillary

vessel

number

(angiogenesis) The

result

of

the

study indicated

that

extract of C

roseus leaf accelerates

the

wound

healing in

wistar

rat

Coverage

rate

of

wound is faster on treated group than control group

(p<0.05).

Wound

closure

and angiogenesis

in early wound

healing

were higher in treated group than control eroup

(p<0.05)- These

results

suggested

that the first

phase

of

wound healing was shortened, and

the

proliferatlve

and

rnaturation

phases

were

advanced

by

methanol

extract of

C

roseus

leaf. Therefore,

it

can be

concluded

that

C

roseus

could

be

potential to help

in

topical

management of

wound

healing.

Kpy

wotdst

C. rcseus, wound. hPohng. _' olloqenesis.

o.aiooPne\is.

INTRODUCTION

Many indigenous pLants have been described for

therapy

of !arious

diseases.

They are

a

source

of

synthetlc

and tradluonal

herba

medlcine.

ln

many couniries such as lndia, China and

ako

ndonesia the

traditional medical plants are

nil

the primary heahh care svstem in human and animal.t

c

roseus is one

of

the

tradiotiona

medical plants

that

empircallv

has

bFPn rFported

!o

o,

wo.no,pdln8.l

Recenty, we obsetued

thit

there was a co.siderable

chanse in sclenufic investisauon of the applicauon of

naturai

product,

such

as

herb

to

be

used

for

ethnopharmacoogy

thempeutic

applications.

The

presence

of

various aclive

compounds

ln

nrany indigenous

pants

has

!rged

to

evaluate these plants

with

a view

to

determlne potential

to

accelerate the

woJr d

--"t

I

I. wou"d

hedt n8

i.

t\4

pro,

e(

of .eparr

that

follows injury

to

the skin and other soft tissues.

To

studv woLrid repair, wound

healine

is

often

subdivided lnto three phases: an inflamnratory phase,

a

proliferatlve

phase,

and

a

maturation

phase or

remode ins.r

?

Alons

with

iiflammatory

phase, d,,

infammatory response occu6 and the ce ls below the

dermis be8in

to

increase co

lagen producton,

and

conesponden et I K

Ano

-Dado

Fd.ulty

ol

Veteinary Medicine, uddvdna Univetsity

uddydnd U nive rciv,Ba li-l ndonesio Email: anomdada@yahoo.colrr

followed by

the

epithe

ial

tissue regeneration. This was

ihen followi:d

by

the

prollferative phase

that

is

cha€cterized

by

ansiosenesis, collagen deposition,

4prr

pl dl

\d

ior

dnd

wou-d

(o_t'dct

o..

ang

ogelp\r\

is

the

irnportant process

of

generating new capillary

blood vesses

that

a fundamental

to

wound heallns,

new blood vessels originate from endotheLial

cels.

n

fibrop

asia

and

granu

ation

tissue

formation,

flbrob asts exert co lagen and fibronectin

io

form

a

new,

provisional extracel

ular

matrix.

subsequently epithellal c€

k

crawi across the wound bed to cover

it

and the wound ls conhacted by myofibroblasts, whjch

e'ip rhe wou_d -dgp. dnd

u.dF

go

'

o_

d' .ro

,

I

nB d

mechanism

simiartoihatin

smooth musc e

cells.irl

(.ro.pr.d o\nowrd

topol,daro

n

-danp\ia,

has

empiically been

used

to

treat

a

various of

diseases.

lt

has more than 400 known alkalolds.

so-e

of

which are

approved as antineoplaslic agents

to

treat various dlseas,as.6 Alkaloids and tannins are the

two

lmportant acuve

compounds

in

C.

roseus. vincamine js _{the major alkaloid that is wideLy used as a}

T"di!ind

aCert

The.oapu_d

..

o\Fly

pi"rad

.pnr-syntheuc derivative known as ethylapovincamlnate or

vlnpocetine.

lt

has actions

in

vasodilating, bood

th r n

ns

_ypogly

Frr dld

mpno

v-pnhdni ne Extracts

from the flower

of

C. roseus has

wolrd

h-dlngd.vityil

ipdraCup

p3apy

6rs.s,

"cr

ro

previous

report

on

wound

healing activlties

of

the extract

ofthe

c

roseus eaf. ln the studv we evaluated

-a

r^aa4p.ti^a^'Jo11r^t

L of

BiolteAitaL-fa:e4.et

)/d'bt12

7,

Nuillbs

1,

Jtuvary

JB!?2073:

37 40

the wound healng

ofthe Wist.r

rat after treated with the methano extract

ofthe

c. rcseus leaf.

MATERIALAND METHODS

Male

2nr.nthod

wistar

rats

weishins

of

24013.85

s,

were

purchased

from

Balai

Besar

veterne,

(BBV) DenDasar

Bali.

The anlmak

were

maintalied

in

ndivldua cage5 during the experime.t. animals were

clos.y

observed

for

any

infedion

and those which showed sisns of lnfection were separated and excluded from the study and rep aced.

Extract

was

obta

ned from

the

leaf

of chantaranthus roseus

at

UPT Laboralorlum

Anaitk

unlveEitas

Udavan..

The extract was

dilted

with

ethanol.

The

eafes of

c

roieus were co Lected locaLly

in

BaLi

and identified by

the plart

taxonomist and curator.

Thefresh

eaves were shade drled and ground

into

a

powder

usins

an

electrlc bender.

the

fine

powder was

lrspended

in

methanol

for

24 houts at

room temperature. The mlxrure was

filtered

usinS 3

il',e mlslin

doth fo lowed by

fiter

paper (GF227). Th€ iLltrate vtur

I

a.ed in a water bath to drv at

40'c

and

ihe c ei:r .e,:,iue was used

forthe

nudy.

R1c were anesthetized

with

ketam ne, and their

dorir '.

-,ras

shaved. A fLrLlthickness

ro!.d

wound was pr€pared on the back of the rzt with a skin biopsy punch _{{10 mm} dianreter).

Ihe

animals were d:vded

nto two

€roups,

of

16 each. Group

l

anjmals were topicalLy treated

wlth

vasellre as

.

pacebo control. The anlmals of group 2 were topicaly

teated

with the ethanol extract of

C

roieus at a dose of 1s%

v/v

per

day

til

comp

ete

epitheljzation. The

wound

closure

rate was assessed by tracing the wound on days 1, 5

and 15 post wo!ndlng !sing transparency paper and a

permanent _{marker. The}

wo!nd

areas recorded were measured usins a graph paper. Flve and fifty days after

the creatio.

ofthe

wound. the rats were k I ed and the

wound

area exclsed.

The

tiss!e

was

fixed

in

10%

phosphate

brffered

formalli sol!tlon

The formalln-fixed tlssues were dehydrated, embedded

ln

paraffn,

..d

cut into 4mm ections. The sectlors were sta ned

wlth

hematoxyln and eosln

(H

E)

The number

of

lop

la-es sd ou.rpd

l

6

rd,

dd .

o

and

the

col agen area

in

the

granu at on

tissle

was

mea.

red.

The number of cap larles was counted in

tl.re4

pafts

of

the

granulat

on

tlssue.

The

area of

co lagen synthesk was derived from the area stained b ue bytheAzan stain.

D.ta

on wound

c osure,

capilary

n!nber,

and col agen

in the

granu ation ar€a were ana yzed with

5P55

and

expressed as

the

mean

!

S.D

or

S.E.lvl.

5i€ificant

differences

were

eva uated

accordiig to

RESULTS

'r,he _{wound area were measured}

oler

_{a perlod}

of

15 days to determine wheiher the

eltract

og C roserr

!ryrrywp6.uru!tr!]d

and

www.ballmedjca iourna

.com

P t

itr\t

ISSN: 2O8 5 .+7 7 3,

E'IssAri

2302

2906.

affecrs

the

progress

of

wound heallns

of

Wistar rai.

The results

of the

present

nudy

indicated

that

the extract

of

c

roseus _-paf has

an

abiity

to

sccelerate

wolnd

heallng in

the rat

(F _sure 1). At five days, the decrease

in

wound area

had

been

acce

erated

in treated aroup (Table 1).

Five days

afterlreatrnent

Flfleen days alter treatment

Figure 1

Wourd Hea ing ln Treaied Group and Control Gro!p

Flgure 1 shows the signif

ca.t

increase in the wound heallnC activity was obserued in

the

animals treated

with the

C

ro5e!5 ext.act compared

wlth

those who recelved the p _acebo

contro

treatments.

Tabel

Wound

healfs

effect ofextract c. roseus eaf in

WistarRatWound Model

12

5711012!

30 31117.76 0.00210

004

4.162 + 7 211 73.94!

19.1{

60.42 J 515

99.99r0.01

99.25

!

\

69

+ssnlfkantaip<0.05

Table 1 shows

the

effects of exftact

c

rorpus leafes adm nistered toplca ly at a dose of 1s%

v^

o.

wound area

ard

wound

closlre

in

Wittar

rat. ln the fu I

skin-thlckness

rouid

wound

model, c.

Roseus tr€ated

anima s showed a siCnlficant reduction ln the wound

38

lrd'rMaiaaJ.t4MaL

of

Bir1tu&..aLsc.1"au€,!

yoluw

7, Ntunbea.

r,

fMy.f

L6)2

2013:

37

.40

area

(p<0.0s)and

a sisn ifica nt gre.ter wou nd closure (p < 0.0s) in five days after treatrnent, but in fifteen

days after treatment showed no sign

ficant

between

ireated and

contro

gro!p

ofthe

rats.

n contrast, controlgroup de ayed wound closure

relative

to

treatment

with v.selin.

Complete

wo!.d

hpor'8d

oo!.r"pd""

l6

rr.dreocoup

l-d

r

controls. There

was

a

greater number

of

capilla.y

v 6l

r

' Loo a.f -\ '4 ,.

ro.pL.

_-edLed

rnd.

n

contros,

and

the

capillarjes

were

distributed

at

the center of a wound .atherrhan at rhe edge of wound

i.

Table 2

The C!p I ary Number ofTreated and control croup

of

The Rat

?ri,at'IlsN:

2O85-1773,

f

65^'1 2302,2906.

presenr

study

indicated

that

the

leaf extract

of

c. roseus accelerates

wound

healing

by

eva uauon

of

wound area and

ansiosenesls. Angiogenesis

k

rhe

important process

n

wound hea ing

that

occured

i.

the

inflamatory

ph.se.

n

these phale

of

wound

hea

ins is

characterked

by

hemostasis

and

inf

anrm;tion,

followed by

epitheltzation, angiosenes s. The next phase is the prollferauve phase

that

characterDed by colagen

depostion.

n the fina

ph.se

or

mat!rationa

phase

that

also

caled

_as

remodeling phase, the wound undersoes contraction

resu tlng in a smal er amount of apparent scar

tits!e.

l.

the

fl.a

phase characterized

bygranuation

tssue

formauon

that

is

prlmarily

composed

of

colasen,

edema, libroblasts, and new

smal

blood vessels. The

methanol

extract

of the

eave

af

C.

roseus

demonstrated

a slgnficant

decrease

of

wound

area

and

slcnlficant

l.crease

of

wound

cloLrsure. Th€

evid€nce lndicates

that

the

jn

easing granu ation

tiss!e

formation. Thls formauon indicatine increased

The resu ts

ofthis

studV indicate

that

eaf extract

of

c

roseus that adminlstered toplca ly can accelerate

the

wound h€a lng

procesr

N4acroscoplc observation showed that the wound hea ing was

faner

in treated

grolp

than control

group.

lt

is m:rked

with

a

scab

wound dosure by a faster and hisher percentage

of

wound cosure

ofthe

wound area me!surernents

tris

proved that the leaf extract Tapakdara can ac.elerate

wound hea

i.g.

Similar results were never proven by

Nayik

€t a.,

(2006)

that

tapakdara

fower

extract acce erates

the

wound

hea

ing

process

in

sparatsle Dawley rats.3 M ce

that

were previoLslv

rnide

a

clt

then

administered

topica

y of

flower

extract tapakdara and ora

ly

at a dose

of

100 mc

/

kg body

weight

recovery

was

faster

when

compared with

control

mice, as indicated by

wound cosure

faster,

faner

epithe

iallzation

and

granulauon

iissue

_drv

weight higher

in

mlce

treited

rats

compared with

Phytochemical ana ysis

of

extracts

of

C. roseus

rowed hd, lh ol"..

o-

oi

triterpeneoida

and

various alkaloids.

One

of

the5e

components

is

r-asponslble

in

acceleratins

of

wo!nd

healln€

proce$.

Prevlous

studies report€d

that phytochemical compon€nts s!rch

as favanoida

and

trit€rpenoide known

to

acce erate the wound hea tng process, especia

ly

dLe

astrlsen

and

anrmcrobial

propeties.rl

c

The content of ph),tochemtcak ptays a

ro

e ln

wound

cortrnction

and

acc€ erates

epithelia

ization, severa othe. studies have

atso

shown

that

triterpenoida

wo!nd

healing properties such as those contained ln any orh€r herbat rem€dies such asCecropla pe lata, and Pe.tas tarceo ata.B

The resu

ts of

present

nudy

and previous studV

(Nayak

et

a

.,

2006) have shown

that

actjve compounds

in

C. roseus may be responsible

for

rhe

Day 5 Day 15

ConiroL

4,001 1,69

Treatment

11,5012,,?0*

8,75

!

4,92 5,25

t

4,46

n this

stldy, the

process of

wornd

healins was

also eva uated histo ogka

ly. At

the

five

and fifteen [image:6.596.57.266.406.539.2]

days, the amount of granu ation

tssue

had increased

rema*ably

n keated

wo!ids.

Figure 2

Histo

ogyofthe PartofWo!nd

(H EStain)

Contro _{Group {A)and Treated Group {B),} capttary

vese

s (arrow)

FlSure

2

shows

the

neovascu

arkation

of

the granu ation tssue. The

c.pilary

vesseh were counted

in

F

E stained h sto

ogica

sect ons {Tab

e

2).

tt

wds

cear

that

the

number

of

capilary

vesse

s

was

significanty _{increased {p < 0.051 in} the treated group

than control

group

at

flve

davs

after

treatmenr.

However, there was no difference

in

the

nlmber of

capillary vessek between convoi and treated wounds at fifteen days aftertreatment.

DtSCUSSTON

C ,o,u r

l-or1

ndonesia,

rindopor

(sr

awetij,

kembong tenbasa

{sunda),

kemborg fopok doro

(.laiva).

the

e.fes and/or the whole plant is used as househo d remedv

for

various

diseases. Traditiona

lV,

in

ndia

rhe

flowers/leafes

are

used

to

control

daberes.

The

lAADne+iaa4oatt^'51'oftsLo"Lda.aLsaka.avoluruz7

'

Nutalrer t,

Jdturatt i&t\''

2a13:

37

'+o

wound

healing activity.s Tannins,

trlterpenoids

and alkaloids are presence at the extract of whole plant of

c

roseus by phytoch€mica analysis.

Microscoplc

examination

of

histological preparations

of the

formauon

of

new

blood vess'"ls (angiosenesis), showed

that

the

angiogenesis

in

the

treated group

at

day

s

was

sl8nificantlv

more

compared

with the

control

group

However,

in

this

study

found

that

angiogenesls

ln the

daY_to

1s

for

treatment group was less compared

wlth

the control group. Data anciogenesls in the treatment and conrrol

in daytols

thls was not

statisticallY sisnificantlY

differeni.

Thk

is certainly due to the

treat

ent group

save

the

wound

healing process

is

faster

than

the control group, so

that

in

the

treated group

did

not

form new bood

vessek

again The

research was sLrpported

by a

study

of

Fujlta

et

al,

(2003),

whl.h

proves

that

the

seaweed

extract

Lithosporus

erythrorhisoi

which

also coitain

tannins

and

tritrefenoid

can

rcceLerate

wound

healing .haracterDed bv increased number of new capilaries

in the

injured ar€a.5

Thls

ihe

flndings

in this

studv re nforce

that

angiogenesis plays an lmportant role ln

wound h€alins

process,

as

also

noi€d

bv

several

previous

investiSators

as

weLl

as

role

oi

the

sympathetic nerves ocated in the skin ako has a role ln wound healing.lolr

coNctustoN

The

present

study

has

demonnrated

that

an

ethano

extract

of

c

.oseus Leaf has properties that render

it

capabe

of

promoting accelerated wound

healn€ actlvity

compared

with

placebo

controls

Wound contraction,

increased

tensile

strength,

increased hydroxyprol

ne

content and

antimicrobial

activity supporl

further

eva uauon

of

c

roseui in the

topica I treatme nt a nd management ofwounds

ACKNOWLEDGEMENT

The

study,

as

pari

of

the

Dissertalion, was

slpported

by the

Directorate General

of

l-ligh

Educatjons, Republic

of

lndonesia.

we

securely thank allwho have gives assistance during the study.

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