Antinociceptive anti-inflammatory effect of Monotropein isolated from the root

Pharmaceutical Society of Japan

NII-Electronic Library ServicePharmaceuticalSociety

of Japan

October200SBioL

Pharm.

BuU.

28(10)

1915-1918{2005)1915

Antinociceptiye

Anti-infiammatory

Effect

of

Monotropein

the

Root

of

Morin

da

ofieinalisIsolated

from

Jongwon

CHoi,"

Kyung-Tae

LEE,b

Moo-irbung

CHoL,C

Jung-Hwan

NAM,d

Hyun-Ju

JuNG,d

Sun-Kyu

PARK,d

and Hee-Juhn

PARK"'d

'`CoUage

qf'

Pharmaqi

Dae.veon-Dong,

K)?ungsung

Univensit.v:

Busan

608-736,

Kbrea.'

bCollage

qf' Pharmacy

Dongdoemttn-ku,

IIoegi-Dong,

t<),ung-Hbe

Llai),ersity;

Slroul

i30-101,

Kbrea:

`'Department

qf'feod and Ntttrition,

Sbngy'i

Univens'iO,;

Pthosan-Dong

PPbnju

220-702,

Kbrea:

and tiDepartment

ofBotanical

Resources,

Sangti

Uhivet'siij,;

PPloosan-

Dong,

}V2)tu'tt

220-702,

Kt)rea.

Recejved

May

2,

2005;

acceptcd July

6,

2005

The

root ofMbrinda

ca7icinalis

(Rubiaceae)

is

used

to

treat

rheurnatoid

arthritis

and

impotence

in

the

tradi-

tional

Oriental

medicine.

To

identify

the

antinociceptiye

anti-infiammatory

components

of

this

crude

drug,

we

adopted

an

activity-directed

fractionation

approach.

The

active

fraction

of

the

BuOH

extract of ML

ctfiicinalis

roet

was

subjected

to

silica

get

and

ODS

colllmn

chromatography

to

yield two

diterpenes,

compounds 1

and 2

and these

were identified

as

monotropein and

deacetylasperulosidie

acid,

respectiyely.

The

iridoid

glycoside,

monotropein,

was

tested

for

its

anti-infiammatory

antinociceptive

effbcts using hot

plate- and writhing antinoci-

ceptive

assays

and

by

using

carrageenan-induced

anti-infiammatory

assays

in

mice

and

rats. Pretreatment

with

monotrope;n (at

20,

30

mglkgtd,

p.

o.)

significantly

reduced

stretching episodes and prolonged action timc

in

mice.

It

also

significantty

reduced

acute

paw

edema

by

carrageenan

in

rats.

These

results

indicate

that

monotropein

contributes

to

the

antinociceptiye

and

anti-inflammatory

action

ofMbrinala ctOicinans root.

Key

words Morinda

qMcinatis;

Rubiaeeae:

iridoid

glycoside;

monotropein;

antinociceptive;

anti-inflammatory

Morinda

citrlfolia

(Rubiaceae)

is

commonly known

as

noni

is

indigenous

to

the

Hawaian

and Tahitian

islands.

A

number

of

constituents

have

already

been

isolated

from

this

plant,

and

they

include

anthraquinones,

flavonoids,

iridoids

and oligosaccharides.i) Moreover,

it

has

been

established that

the

constituents of Hawaiian

noni differ

from

those

of noni

found

on the

Indian

sub-continent. Cimanga2)

reported on thc

isolation

of

iridoids

with complement-inhibitory activity

from

Morinda

spp,

Moreover,

the

roots

of

imrinda

qfiici-

nalis

(Rubiaceae)

continue

to

be

traditionally

used

to

treat

rheumatoid

arthritis,

diabetes

and

hypertension

in

North

East

Asia

rather

than

M,

citrij?)lia, which is

also

used in

tradi-

tiona]

medicine

and

said

to

have

similar

pharmaeologic

efl

fect.

Ring

et aL3) have

reported on the

anthraquinones from

a

CHCI]

extract

ofM.

q17icinatis.

Tb

isolate

the

active principle ofML qdicinalis, we used ac-

tivity-directed

fractionation.

The

main

iridoid

glycoside

iso-

lated

monotropein,

was also examined by

antinociceptive

assay

(hot

plate

test

and

writhing

test)

in

mice

and

anti-in-

fiammatory

assay

in

rats with carrageenan-induced edema.

Our

invcstigation

of

the

components

of

M

qfiicinatis,

re-

sulted

in

the

isolation

of iridoid

glycosides that

were some-

what

ditllerent

from

noni

constituents.

It

is

commonly

known

that

many

iridoid

glycosides or other natural glycosides are

easily

hydrolyzed

by

intestinal

bacteria.

Therefore,

we

adopted

oral

administration

approach for

in

vivo model to

find

the

exact

activc

compounds.

MMERIALS

AND

METHODS

Instruments

Melting

points

were

determined

on

an

Electrothermal

digitaL

me]ting point apparatus; optical reta-

tions

on a JASCO

DIP-360

digital

polarimeter

and IR

spectra

on

a

Bomem

MB-100

FILIR

spectrometer. iH-NMR

spectra

(6ppm,

J

in

Hz)

were recorded in

CD30D

using a Bruker

AM-500

spectromcter (500

MHz),

whereas i3C-NMR

spcctra

were

recorded

in

the

same

solvent using an AM-500

instru-

*

lb

whom correspondence

should

be

addressed.

e-mail/ment

at

125.5

MHz

with

tetramethylsilane

(TMS)

as

an

inter-

nal

standard.

Sample

purity

was

chccked

by

TLC

(Si

gel,

precoated

plates,

Merck,

PF2s,,

20

×20

cm,

O,25

mm).

Plant

Material

The

dried

roots

of Mbrinda

qfficinalis

(Rubiaceae)

were purchased from

the

Chun-Il

Herb

Store

in

Wbriju,

Gangwon

province,

Korea,

and the

plant was identi-

fied

by

Prof.

S.

Y.

Yun,

Department

ofBotanical Resources,

Sang'i

University,

Korea.

Extraction,

Fractionation

and

Isolation

Dried

pow-

dered

roots (2.5

kg)

were extraeted with MeOH

(2.5

1)

three

times

under

reflux.

The

extract

was then

filtered

and evapo-

rated

on

a

rotatory

evaporator

under

reduced

pressure,

The