Intern
ati
o
n
a
l
Jo
urn
a
l
o
f
P
u
b
lic Hea
l
th Science (IJ
P
HS)
Vol
.
4,
N
o
.
4
,
D
ecem
b
er 20
1
5
, pp
. 25
6~
26
3
I
S
SN
: 225
2-8
8
0
6
2
56
Jo
urn
a
l
h
o
me
pa
ge
: h
ttp
://iaesjo
u
r
na
l.com/
o
n
lin
e/ind
e
x.ph
p
/
IJPHS
A Review on the Anti-diabetic Activity of
Androgr
aphis
pani
c
ulata
(Bu
r
m. f.) Nees b
a
sed
In-vivo
Study
Titi Kom
a
las
a
ri, Sa
btanti Harimurti
Department o
f
P
h
armacy
, Univer
sita
s Muhammadiy
a
h Yog
y
ak
arta, Indon
esia
Article Info
A
B
STRAC
T
Article histo
r
y:
Received Aug 04, 2015
Rev
i
sed
Sep
t
29
, 20
15
Accepted Nov 26, 2015
Diabet
es m
e
llitu
s (DM) is ricin
g
nowada
y
s. D
M
is a m
e
tabolic dease
a
se
c
h
a
r
ac
te
rize
d by inc
r
ea
sing of gluc
os
e
blood
le
vel for prolonge
d
time
.
Pa
tie
n
t
with DM m
u
st take m
e
dic
i
ne
for lo
wering glucose lev
e
ls in
whole life.
S
y
nthe
tic
ant
i
-d
iabe
tic
agen
t is
com
m
only
used and signif
i
cantly
ab
le
to
m
a
intain
the gl
ucose blood l
e
v
e
ls. However
,
m
a
n
y
side
effects will occur
during the tr
eatment. Further
,
peopl
e ar
e tr
ying
to find a
n
altern
at
ive
medicine for
DM treatment. This pape
r will
discuss about
an alternativ
e
m
e
dicine for a
n
ti-diab
et
ic ag
e
n
t that is ca
ll
e
d
Andrographis paniculata
(Burm. f.) Nees based
in-vivo
stud
y
.
Search data obtain
e
d from
PubMed,
PMC (
P
ubMed Central)
, Inter
n
ation
a
l Food and Research J
ournal, and
Google sear
ch
engine. Inclu
tion
and ex
clut
ion
criteria wer
e
used f
o
r selection
of journals. In
clution
cr
it
eria
w
e
re
tak
e
n is
in-
v
ivo
stud
y
of
Andrographis
paniculata
as an
ti-diab
etic, published in
2000-2014, and free full
text journal
or PubReader (f
ull tex
t
journal
in PubM
ed Central) in English or Indonesian
languag
e
. Bas
e
on reviewed
jou
r
nals th
at w
a
s conducted
,
anti-d
iabetic
agent
of
Andrographis paniculata
was found in extract,
in fraction
a
l coumpund
(i.e. androgr
aph
o
lide or its analo
gue AL-1: andro
g
rapholid
e-lipo
i
c acid),
and
in combination
with s
y
nth
e
tic dr
ug or other herb
al.
Therefo
r
e,
Andrographis
paniculata
is
po
t
e
nti
a
ll
y
dev
e
lop
e
d as
an
alt
e
rna
t
i
v
e an
ti-di
abe
tic
agent
.
Keyword:
Altern
ativ
e m
e
d
i
cin
e
An
dro
g
r
a
phi
s pa
ni
cul
a
t
a
An
dr
o
g
ra
p
hol
i
d
e
Diabetes m
e
llitus
Copyright ©
201
5 Institut
e
o
f
Ad
vanced
Engin
eer
ing and S
c
i
e
nce.
All rights re
se
rve
d
.
Co
rresp
ond
i
ng
Autho
r
:
Titi Ko
m
a
lasari,
Depa
rtem
ent of Pha
r
m
acy, Faculty of
Medi
cal and Healt
h
Sciences,
Uni
v
ersitas M
uhamm
adiyah Yogyaka
r
ta
,
Tam
a
n
Tir
t
o
,
K
a
sih
a
n
,
Ban
t
u
l
,
D
.
I
Yog
y
akar
ta,
5
518
3, Ind
o
n
e
sia, Ph
on
e (0
274
)
37
4320
.
Em
a
il: k
o
m
a
l
a
s
arit@g
m
ail.co
m
1.
INTRODUCTION
Di
abet
es m
e
l
lit
us (DM
)
i
s
a m
e
t
a
bol
i
c
di
sease i
n
w
h
i
c
h t
h
ere a
r
e hi
g
h
bl
o
od
gl
uc
ose
l
e
vel
s
ove
r
a
l
o
n
g
peri
o
d
.
DM
i
s
cha
r
act
eri
zed
by
hy
p
e
rgl
y
cem
i
c
regar
d
i
n
g t
o
t
h
e
dam
a
ge of m
e
t
a
bol
i
s
m
proc
ess o
f
carboh
yd
rates,
p
r
o
t
ein
s
or
fats th
at is cau
s
i
n
g th
e im
p
a
ired in
su
li
n
secretion
,
i
n
su
lin
activity o
r
a co
m
b
inatio
n
of
b
o
t
h
.
Di
a
b
e
t
es i
s
cl
assi
fi
ed i
n
t
o
t
w
o m
a
i
n
t
y
pes, t
h
at
are di
a
b
et
es t
y
pe
1
or
ID
D
M
(i
ns
ul
i
n
-
d
e
p
ende
nt
di
abet
es m
e
l
l
i
t
us) a
n
d t
y
pe 2
or
NI
DDM
(n
on
-i
ns
ul
i
n
-de
p
ende
nt
di
a
b
et
es
m
e
l
l
i
t
u
s) [
1
]
.
Ty
pe 1 o
f
D
M
occ
u
r
d
u
e
to
t
h
e
d
e
stru
ction
o
f
th
e
b
e
ta cells
an
d usu
a
lly fo
llo
wed
b
y
insu
lin
d
e
ficiency (ab
s
o
l
u
t
e in
su
li
n
deficiency
)
or in
the othe
r word
t
h
at the
body can not
produ
ce in
su
lin
.
Wh
ereas, typ
e
2
o
f
DM is a cond
ition
wh
en
th
e
bo
d
y
still ab
le to
p
r
o
d
u
ces insu
lin
h
o
wev
e
r th
ere
is in
terferen
ce
o
n
t
h
e pro
c
ess
o
f
insu
lin
secretio
n
d
u
e
to
th
e b
a
ckg
r
ou
nd
of in
sulin
resistan
ce (relativ
e in
su
lin d
e
ficien
cy). In ad
d
itio
n
to
th
e ab
ov
e two
types o
f
DM
, t
h
e
r
e are
al
so di
a
b
et
es c
a
use
d
by
dest
r
u
ct
i
o
n
o
f
b
e
t
a
cel
l
funct
i
o
n
d
u
e t
o
ge
net
i
c
f
act
ors,
desea
s
e
s
of
t
h
e
exoc
ri
ne
pa
nc
r
eas (s
uc
h as cy
st
i
c
fi
br
osi
s
)
,
a
n
d
ge
st
at
i
onal
DM
[
2
]
.
In
tern
ation
a
l
Diab
etes Fed
e
rat
i
o
n
(IDF)
predicted
th
at
p
e
o
p
le with
DM
reach
ed
3
7
1
m
ill
io
n in
20
12
an
d 552
m
i
llio
n
in
20
30
. Th
e av
erag
e
o
f
th
e in
creasi
n
g
case
is 3
p
e
op
le ev
ery secon
d
[3],[4
]. Th
erefo
r
e, it is
necessa
ry
t
o
fi
nd
t
h
e i
n
t
e
grat
ed t
r
eat
m
e
nt
of
DM
by
usi
n
g
an alternative
medicine suc
h
as he
rbal m
e
dicine or
usi
n
g a
com
b
i
n
at
i
o
n
bet
w
ee
n t
h
e sy
nt
het
i
c
d
r
u
g
s
an
d
he
r
b
al
m
e
di
ci
ne.
Thi
s
pa
per
wi
l
l
di
scus
s i
n
t
e
n
s
i
v
el
y
Evaluation Warning : The document was created with Spire.PDF for Python.
I
J
PH
S I
S
SN
:
225
2-8
8
0
6
A Review o
f
t
h
e An
ti-d
i
ab
etic Activity o
f
And
r
og
rap
h
i
s
pan
icu
l
a
t
a
(Bu
r
m. f.)
Nees b
a
s
ed .... (Titi Ko
ma
l
a
sari)
25
7
ab
ou
t th
e an
ti-d
i
ab
etic activ
ity o
f
Andr
og
rap
h
i
s
p
a
n
i
c
u
l
at
a,
a plant
species that tradi
onally use
d
as
an
tid
iab
e
tic
agen
t, b
a
sed
o
n
in
-vivo
stud
y.
2.
R
E
SEARC
H M
ETHOD
Evi
d
e
n
ce B
a
se
d M
e
di
ci
ne
(E
B
M
) fr
om
Pub
M
ed, PM
C
(P
ubM
e
d
C
e
nt
ra
l
)
, I
n
t
e
r
n
at
i
o
na
l
Fo
od a
n
d
R
e
search
Jo
u
r
nal
,
a
n
d
G
o
og
l
e
search
en
gi
ne
fo
r
In
d
ones
i
an l
a
n
gua
ge
j
o
u
r
nal
o
n
t
h
e
t
opi
c
of
t
o
t
h
e
ant
i
-
d
i
ab
etic activ
ity o
f
A
ndr
o
g
r
a
phi
s pa
ni
c
u
l
a
t
a
(B
u
r
m
.
f.)
Nees were
u
s
ed
as th
e sou
r
ce of th
is literatu
re rev
i
ew.
An
dro
g
r
a
phi
s pa
nc
ul
at
a
,
d
i
ab
etes, an
ti-d
i
ab
etic activ
ity o
f
An
dr
o
g
ra
p
h
i
s
pa
ni
cul
a
t
a
,
an
d c
o
m
b
i
n
at
i
on
o
f
An
dro
g
r
a
phi
s pa
ni
cul
a
t
a
as a
n
t
i
-
di
a
b
et
i
c
were use
d
as t
h
e key
w
or
ds f
o
r s
earchi
ng t
h
e
jo
ur
nal
s
. I
n
cl
ut
i
o
n an
d
exclution criteria were used
for selec
tio
n
of th
e jo
urn
a
ls. In
clu
tion
crit
er
ia were th
e
j
ourn
a
ls th
at discu
s
s
about
in
-vivo
st
udy
of
And
r
og
raph
is pa
n
i
cula
ta
as ant
i
-
di
abet
i
c
, jo
u
r
nal
s
pu
bl
i
s
he
d i
n
20
0
0
-
2
01
4, an
d fre
e
ful
l
t
e
xt
jo
ur
n
a
l
or P
u
bR
ead
er (
f
ul
l
t
e
xt
jo
ur
nal
i
n
Pu
b
M
ed C
e
nt
ral
)
pu
bl
i
s
he
d i
n
En
gl
i
s
h
or
In
d
one
si
an
lan
g
u
a
g
e
. Mean
wh
ile th
e ex
clu
tio
n
criteria
were th
e
j
ournals th
at n
o
h
a
v
e
relatio
n
b
e
t
w
een
And
r
og
ra
ph
is
pa
ni
cul
a
t
a
t
o
an
ti-d
i
ab
etic activ
ity, j
ourn
a
l
of o
t
h
e
r h
e
b
a
l
med
i
cin
e
fo
r an
ti-d
i
ab
etic and
j
ourn
a
l
no
t pu
b
lish
in
200
0 – 201
4.
There
we
re se
v
e
n
jo
u
n
al
s ha
v
e
bee
n
re
vi
ewe
d
,
fi
ve
j
o
u
r
nal
s
pu
bl
i
s
he
d i
n
E
ngl
i
s
h an
d t
w
o
j
o
u
r
nal
s
i
n
In
d
onesi
a
n
. Ea
ch j
o
u
r
nal
t
h
en was ev
al
uat
e
d o
n
t
h
e resea
r
ch
ob
ject
i
v
es
,
researc
h
m
e
t
hods
, an
d pa
ra
m
e
t
e
rs
use
d
as
wel
l
as
t
h
e
di
scus
si
o
n
of
resea
r
ch
res
u
l
t
s
.
3.
R
E
SU
LTS AN
D ANA
LY
SIS
Recently, the
pha
rm
acologic
a
l and
non pha
r
m
acological
thera
p
ies
were
known as t
h
e
DM the
r
a
p
y.
The p
h
arm
acol
ogi
cal
t
h
era
p
y
i
s
com
m
onl
y usi
ng s
o
m
e
hy
pogl
y
cem
i
c
oral
dru
g
s s
u
ch as
sul
f
ony
l
ur
ea, gl
i
n
i
d
,
t
h
i
azol
i
d
i
n
e
d
i
o
nes,
bi
ng
ua
di
t
,
or
i
t
s
com
b
i
n
a
t
i
on
of
t
h
ese
d
r
ugs
. P
h
a
r
m
acol
ogi
cal
t
h
e
r
apy
i
s
al
so ca
n
be
do
ne
b
y
using
in
su
li
n
inj
ection
s
d
i
rectly o
r
with
DPP-4
i
n
h
i
b
ito
rs (in
s
u
lin sensitizin
g).
Wh
ile
no
n-p
h
a
rm
aco
lo
g
i
cal
th
erap
ies are so
m
e
act
iv
ities
th
at can
h
e
lp
t
o
m
a
in
tain
n
o
r
mal g
l
u
c
o
s
e b
l
o
o
d
lev
e
ls such
as ch
an
g
i
ng
th
e
l
i
f
est
y
l
e
and behavi
or (i
.e
. av
oi
di
n
g
sm
oki
n
g
an
d al
coh
o
l
)
,
t
a
ki
ng a g
o
o
d
di
et
, and d
o
i
n
g a phy
si
cal
ex
erci
se
[5]
.
One
al
t
e
rnat
i
v
e t
h
era
p
y
f
o
r
DM
i
s
usi
n
g
h
e
rbal
m
e
di
ci
ne, w
h
i
c
h
has
be
en c
hos
en
by
com
m
uni
t
y
.
Treatm
e
nt with he
rbal m
e
dicine is
m
o
re eas
ily accepted by comm
unity s
i
nce
it is considered to
ha
ve low side
effect
s w
h
e
n
p
r
o
p
erl
y
use
d
(p
ro
per
d
o
sage
, i
ndi
cat
i
o
ns, t
i
m
i
ng, m
a
nne
r o
f
use an
d acc
ur
acy
of det
e
rm
inat
i
o
n
m
a
terial from
her
b
al m
e
dicine) [
6
]
.
Num
b
ers
of
re
search
on m
e
dicinal plants
that pote
n
tially d
e
v
e
l
o
p
e
d as an
an
ti-d
i
ab
etic ag
en
t
were
conducted.
Me
dicinal plants can be use
d
a
s
an
altern
ati
v
e treatm
e
n
t
for
DM is sam
b
ilo
to
(
An
dr
og
r
a
p
h
i
s
pa
ni
cul
a
t
a
) [6]. Besides as
anti-dia
b
etic agent,
And
r
og
ra
ph
is pa
n
i
cu
lata
had al
so
be
en wi
del
y
st
u
d
i
e
d as
an
alg
e
tic, an
tiox
i
d
a
n
t
s [6
], an
t
i
-m
a
l
arial [7
],
an
tib
acterial, an
d h
e
p
a
topro
t
ecto
r
[8
].
An
dro
g
r
a
phi
s
p
ani
c
u
l
a
t
a
i
s
con
t
ain
i
ng
so
m
e
p
h
y
to
con
s
titu
en
t co
m
p
oun
d su
ch as flav
ono
id
s,
di
t
e
rpe
n
oi
ds, a
nd
pol
y
p
h
e
nol
[9]
,
[
10]
. T
h
e m
a
jor c
o
m
pou
nds i
n
si
de t
h
e
An
dro
g
r
a
phi
s pa
ni
cul
a
t
a
which
is
has a bi
ol
o
g
i
cal
act
i
v
i
t
y
i
s
a di
t
e
rpene l
act
o
n
e
gr
ou
p,
whi
c
h
consi
s
t
s
o
f
an
dr
o
g
ra
ph
ol
i
d
e,
neoa
n
d
r
o
gra
p
h
o
l
i
d
e
,
14-deoxyandrogra
pholide
,
a
n
drogra
pin, 14-acet
ylandrogra
pholide,
14-deoxy
dehi
droa
nd
rogra
p
holide, and
hom
oan
d
r
o
gra
p
h
o
l
i
d
e.
An
d
r
o
g
ra
p
hol
i
d
e i
s
a
di
t
e
rpe
n
e l
act
one c
o
m
pou
nd
t
h
at
m
o
st
dom
i
n
ant
,
ap
p
r
o
x
i
m
at
ely
4
%
o
f
th
e
wh
o
l
e p
l
an
t
[9
]. Th
is and
r
og
raph
o
l
id
e is an
activ
e co
m
p
o
und
as
an
tid
iab
e
tes
[11
]
.
Vari
o
u
s
stud
ies related to
t
h
e
p
h
a
rm
aco
lo
g
i
cal activ
ity of
A
n
dro
g
r
a
phi
s
p
a
n
i
c
ul
at
a
(especially
andrographolide as com
pounds that
ha
ve
pharm
acologica
l activity as a
n
ti-dia
b
etic agent)
had
bee
n
carrie
d
out
bot
h
in
-vivo
and
in
vitro
stu
d
y
. So
m
e
o
f
th
em
h
a
d
b
een th
roug
h
clin
ical trials in
h
u
m
an
s abou
t safet
y
and
afficacy. T
h
e c
h
em
ical structur
e of
a
n
drogra
pholide
ca
n be
seen on
Fi
gure 1 [12].
Evaluation Warning : The document was created with Spire.PDF for Python.
I
S
SN
:
2
252
-88
06
IJPHS Vol. 4, No. 4, D
ecem
ber 2015
:
256 – 263
25
8
Fig
u
r
e
1
.
Ch
emical str
u
ctu
r
e of
an
dr
ogr
apho
lid
e
[
1
2
]
3.
1.
Physi
c
ochemi
cal
pr
oper
ti
es
of
an
dro
g
r
a
p
h
ol
i
d
e
And
r
og
raph
o
l
i
d
e is th
e m
a
in
co
m
p
o
und
in
An
dro
g
r
a
phi
s pa
ni
cul
a
t
a
, es
pecially on t
h
e
leaves.
The
IUP
A
C
nam
e
of a
n
dr
og
ra
ph
ol
i
d
e i
s
3
α
,
14
, 1
5
, 18-
tetr
ah
y
d
rox
y
-
5
β
, 9
β
h, 1
0
α
-l
ab
da-
8
, 12
-
d
i
e
n-
1
6
-
o
i
c
aci
d
γ
-
lactone
(Figure 1). T
h
e m
o
lecular
f
o
r
m
u
l
a o
f
andr
og
r
a
pho
lid
e is C
20
H
30
O
5
with m
o
lec
u
lar
weigh
t
is
3
5
0
.
4
gram
/m
ole. Androgra
pholide
is not ve
ry s
o
luble in wate
r,
soluble in
acetone
, chloroform
,
ether and e
t
hanol
(ho
t
eth
a
no
l).
Cristallin
e o
f
an
dro
g
rapho
lid
e is h
i
g
h
l
y stab
le fo
r m
o
re th
an
3
m
o
n
t
h
s
with
th
e m
e
ltin
g
p
o
i
n
t
is
23
5.
3 °C
. T
h
e
puri
t
y
of a
n
d
r
o
g
ra
p
hol
i
d
e c
a
n be det
e
rm
ined
by
Thi
n
-L
ay
er C
h
r
o
m
a
t
o
gra
p
hy
(TLC
)
[12]
,
Hi
g
h
Pe
rf
orm
a
nce Li
qui
d C
h
r
o
m
a
t
ograp
hy
(H
PLC
)
[
13]
,
or
Li
q
u
i
d
C
h
rom
a
t
ogra
phy
-
M
ass Spect
ro
m
e
t
r
y
(LC
M
S) [
12]
.
A
r
yan
i
r
e
po
r
t
ed
th
at th
e andr
og
r
a
ph
o
lid
e l
e
v
e
l o
f
An
drog
raph
is pa
n
i
cu
la
ta
at different areas in
In
d
onesi
a
has
vari
at
i
o
n o
n
con
s
ent
r
at
i
o
n
,
st
art
i
ng f
r
o
m
6.
25% i
n
B
a
ny
u
w
an
gi
t
o
14
.6
9% i
n
Su
rabay
a
.
Ide
n
tification
was c
o
nducted for
96% etha
nolic
e
x
tract
from
m
aceration process [13]
.
The
An
d
r
og
ra
ph
is
pa
ni
cul
a
t
a
e
x
tract that can
be
use
d
as
the a
n
ti-diabetic ag
e
n
t is a e
x
tract t
h
at containing
andrographolide not
less th
an 15
% [1
4
]
.
3.
2.
Mech
anism
of inducti
on
of
diabe
t
es in r
a
ts
During
th
e stud
y o
f
an
ti-d
i
abetic activ
it
y o
f
An
dro
g
r
a
phi
s pa
ni
cul
a
t
a
,
rat was use
d
as the anim
al for
th
e test. In
variou
s stud
ies o
n
an
ti-d
i
ab
etic activ
ity o
f
a d
r
u
g
on
in
-vivo
study,
m
o
st researchers use
st
rept
oz
ot
o
s
i
n
(STZ
) [
1
5]
,[
16
]
or al
l
o
xan
[
1
7]
t
o
i
n
duce
i
n
sul
i
n resi
st
a
n
ce. Al
l
o
xa
n us
ual
l
y
used t
o
i
n
d
u
ce
typ
e
1
d
i
ab
etes (IDDM
),
bu
t later rev
ealed th
at allo
x
a
n
is no
t selectiv
e for rat
p
a
n
c
reatic b
e
ta cells.
W
h
ile
STZ can be us
ed to induce
b
o
t
h
t
y
pes of
di
abet
es (I
DDM
and N
I
D
D
M
)
with a toxic effect on the be
ta sel
[1
8]
,[
1
9
]
.
In fe
w st
udi
es [
1
1]
,
[
1
9
]
-
[
2
2]
t
h
at
was i
n
cl
u
d
ed
in
th
is rev
i
ew,
for in
du
ction
th
e in
su
li
n
resi
stan
ce
was usi
ng
hi
g
h
fruct
ose-
fat
fe
d. Th
e i
n
sul
i
n
resi
st
ence oc
cured
du
e to
th
e in
crease
o
f
fatt
y acid
m
e
tab
o
lis
m
in
th
e cells (in
t
racellu
lar) and resu
lting
fatty acid
Co
A,
d
i
acylg
lycero
l
, an
d
caram
i
d
e
s. Th
e
resu
lts o
f
th
i
s
metab
o
lis
m
ca
u
s
ing
a d
ecrease o
f
th
e ab
ility o
f
in
su
lin
re
cep
t
ors and
activ
ate th
e PI 3-kin
a
se p
r
o
t
ein
th
at can
decrease
t
h
e
ac
t
i
v
i
t
y
of
GL
U
T
-4
as
gl
u
c
ose
t
r
ans
p
ort
e
r
[2
3]
. T
h
e c
o
m
p
o
s
i
t
i
on
of
t
h
e
hi
gh
f
r
uct
o
se
-fat
fe
d a
r
e
feed
(8
0%
), l
a
rd
(1
5%
), a
nd
duc
k e
gg y
o
l
k
(5%
)
[
2
0]
or
wi
t
h
a com
b
i
n
at
i
on o
f
f
r
uct
o
se (3
6%
), l
a
r
d
(1
5%
),
and egg y
o
lks
(5%) [11].
3.
3.
T
oxi
ci
t
y
e
val
u
a
ti
on
of
And
r
og
rap
h
is Pa
nicula
ta
To ens
u
re that
the
Andr
og
ra
phi
s p
a
n
i
c
ul
at
a
and andrographolide as an
anti-diabetic agent can
be
u
s
ed
safely, it
h
a
d
b
een
co
ndu
cted
a research
on
th
e lev
e
ls o
f
to
x
i
city in
so
m
e
tes
t
su
b
j
ects with
a v
a
riety o
f
adm
i
ni
st
rat
i
on r
out
e
[
12]
.
Det
a
i
l
ex
pl
anat
i
o
n
of t
oxi
c
ef
fect
s
of
An
dr
o
g
ra
p
h
i
s
pa
ni
cul
a
t
a
and
andrographolide can
be
seen in Ta
ble
1.
Evaluation Warning : The document was created with Spire.PDF for Python.
I
J
PH
S I
S
SN
:
225
2-8
8
0
6
A Review o
f
t
h
e An
ti-d
i
ab
etic Activity o
f
And
r
og
rap
h
i
s
pan
icu
l
a
t
a
(Bu
r
m. f.)
Nees b
a
s
ed .... (Titi Ko
ma
l
a
sari)
25
9
Tabl
e
1.
D
o
sag
e
an
d t
o
xi
ci
t
y
of
And
r
og
raphis pa
n
i
cu
la
ta
a
n
d
i
t
s
m
a
jor
na
t
u
ral
pr
od
uct
a
n
d
r
og
rap
h
o
l
i
d
e
[
12]
Pr
oduct nam
e
Dosage/dur
ation/r
oute
E
xper
i
m
e
ntal m
o
d
e
ls
T
oxic
effects
Andr
ogr
apholide
10
m
g
/kg for
3 weeks
Hu
m
a
n
No
Andr
ogr
apholide
500
m
g
/kg bw for
7 day
s
i.
p.
M
i
ce
No
Andr
ogr
apholide
25-
75 µM
Platelets
No cy
totoxicity
A
ndrogra
phis p
ani
culata
20
m
g
/kg bw for
60 day
s
,
or
al
Rats
No
Andr
ogr
apholide
22-
55 µg/k
g,
i.
v.
M
i
ce
L
o
wer
i
ng
m
o
r
t
ality
A
ndrogra
phis p
ani
culata
1g/kg/
day
for
4,
6,
and 8 weeks
Rats
No
Andr
ogr
apholide
100
m
g
/kg,
i.
p.
M
i
ce
No
Andr
ogr
apholide
10
m
g
/kg,
i.
v
Rats
No
Note
: i
.
p.:
i
n
t
r
ape
ri
t
one
al
; i
.
v.: i
n
t
r
ave
n
o
u
s
;
an
d
bw
:
b
o
d
y
w
e
i
ght
.
3.
4.
Com
p
ari
s
on
o
f
A
n
dro
g
r
a
phi
s
p
a
ni
cul
a
t
a
e
x
tr
act and
an
drograph
olide
Eth
a
no
lic ex
tract o
f
An
dr
o
g
r
ap
hi
s pa
ni
cul
a
t
a
i
n
rat
s
t
h
a
t
i
nduce
d
by
st
rept
oz
ot
oci
n
(
S
TZ)
had a
si
gni
fi
ca
nt
ef
fe
ct
on
bl
o
o
d
gl
uco
s
e l
e
vel
s
a
n
d
dec
r
ease
d
t
h
e act
i
v
i
t
y
o
f
t
h
e e
n
zy
m
e
gl
ucose-
6
-
p
h
o
sp
h
a
t
a
se.
H
o
w
e
v
e
r, af
ter 14
d
a
ys
o
f
admin
i
str
a
tio
n
,
t
h
e h
ypog
lycemi
c
activ
ity w
a
s
d
eclin
e
[
1
5
]
.
Nu
gr
o
ho
et al
rep
o
rte
d
that
An
dro
g
r
a
phi
s pa
ni
cul
a
t
a
ga
ve an e
ffect
o
n
l
o
weri
n
g
bl
oo
d
gl
uc
os
e
lev
e
ls in
typ
e
2
o
f
d
i
ab
etic rats in
du
ced
b
y
h
i
gh
fru
c
t
o
se-fat fed
.
Th
is st
u
d
y
co
mp
ared
th
e ab
ility o
f
An
dro
g
r
a
phi
s pa
ni
cul
a
t
a
ext
r
act
and an
dr
og
rap
h
o
l
i
d
e as act
i
v
e com
poun
d
for l
o
weri
ng
b
l
oo
d gl
uc
ose l
e
vel
s
on
va
ri
o
u
s
d
o
s
e [
11]
. T
h
e
opt
i
m
u
m
dosa
g
e f
o
r et
ha
n
o
l
i
c
ext
r
act
o
f
An
dro
g
r
a
phi
s pa
ni
cul
a
t
a
w
a
s 43
4.6
m
g
/
kg bw [
20]
. M
a
l
e
W
i
st
ar r
a
t
s
were use
d
f
o
r ani
m
al
s t
e
st
.
The rat
s
were
di
vi
de
d i
n
t
o
fi
ve gr
o
u
p
s
t
h
at
were
gi
ve
n a
hi
gh
f
r
u
ct
ose
-fat
fe
d
f
o
r
5
5
day
s
a
n
d
1
n
o
rm
al
gr
ou
p
(n
ot
s
u
ppl
i
e
d
)
.
T
h
e
fi
ve
g
r
ou
ps
co
nsi
s
t
s
o
f
t
w
o
gr
o
ups
was
gi
v
e
n a
pu
ri
fi
ed
e
x
t
r
act
(at
t
h
e
d
o
se
of
4
3
4
.
6 m
g
/
k
g b
w
a
n
d 1
3
0
3
.
8
m
g
/
kg
b
w
t
w
i
ce
dai
l
y
, oral
y
)
,
t
w
o
gr
ou
ps
of
and
r
o
g
r
ap
h
o
l
i
d
e (at
t
h
e
dos
e of
1.
5 m
g
/
kg
b
w
an
d 4
.
5
m
g
/
kg b
w
t
w
i
ce dai
l
y
) an
d t
h
e
metf
o
r
m
i
n
g
r
ou
p at th
e
do
se
o
f
45
m
g
/ kg
bw
o
r
aly, t
w
ice
d
a
ily as a stan
dar
d
[1
1
]
.
The res
u
lt showed t
h
at
either extract of
A
ndr
o
g
r
a
p
h
i
s
p
ani
c
u
l
a
t
a
or t
h
ei
r act
i
v
e co
m
poun
d i
.
e
an
dro
g
rapho
lide h
a
s an
activ
ity to
redu
ce th
e g
l
u
c
o
s
e lev
e
l
an
d
red
u
ce t
h
e
lip
id
lev
e
ls (p
<0
.0
5). Th
ese
resu
lts
were i
d
ent
i
f
i
e
d
by
m
easuri
ng
t
h
e i
n
crea
se o
f
bl
o
o
d
gl
ucos
e
l
e
vel
s
p
r
ep
ra
n
d
i
a
l
an
d p
o
st
pr
andi
al
aft
e
r 5
5
day
s
com
p
ared t
o
t
h
e co
nt
r
o
l
g
r
ou
p a
n
d m
e
t
f
orm
i
n gr
o
u
p.
The
r
e was no
signif
icant
differe
n
ce
between
hypoglycem
ic effects
of
A
ndr
ogr
a
phi
s
p
a
n
i
c
ul
at
a
ex
t
r
act an
d syn
t
h
e
sis an
dro
g
r
a
pho
lid
e on
th
e do
se that h
a
d
been tested
[11].
Th
e m
ech
an
ism o
f
an
ti-h
y
p
e
rg
lycem
ic
an
d
r
o
g
rap
h
o
lid
is no
t d
e
term
in
ed
well yet. Ho
wev
e
r so
m
e
o
f
th
e p
a
ram
e
ters u
s
ed
to
d
e
termin
e th
e activ
i
t
y o
f
Andr
o
g
r
a
p
h
i
s
p
ani
c
u
l
a
t
a
as anti-diabetic
are as follow: (1)
pre
p
ra
n
d
i
a
l
an
d
p
o
st
pra
ndi
al
bl
o
od gl
u
c
os
e
l
e
vel
s
[
11]
,
[
20]
(
2
)
ex
pre
s
si
on of GL
UT
-4 pr
ot
ei
n
i
n
m
u
scle
t
i
ssues [
20]
,
[
1
7
]
(3
)
hy
p
ogl
y
c
em
i
c
acti
v
i
t
y
of
gl
i
b
en
kl
a
m
i
d
e [2
0]
and
(4
) H
O
M
A
-I
R
i
nde
x (
ho
m
e
ost
a
t
i
c
model assess
ment-ins
ulin resistance
) [1
9]
.
HOM
A-
IR
i
n
dex i
s
rarel
y
use
d
f
o
r i
ndi
c
a
t
o
r
of i
n
sul
i
n
resi
st
ance.
T
h
i
s
i
n
dex i
s
c
a
l
c
ul
at
ed by
m
u
l
tip
lyin
g
fastin
g
g
l
u
c
o
s
e and
fasting
in
su
lin
lev
e
ls th
e
n
di
vi
de
by
a con
s
t
a
nt
.
Whe
n
t
h
e
HOM
A-
IR
i
n
d
e
x i
s
lo
w, it
m
ean
s th
at an
ti-d
i
ab
eti
c
activ
ity o
f
t
h
e com
pou
n
d
/
e
xt
ract
hi
g
h
er.
An
dri
a
wa
n
et al
[1
9
]
co
ndu
cte
d
a
n
ex
p
e
rim
e
n
t
o
n
an
ti-d
i
ab
etic activ
ity o
f
An
dro
g
r
a
phi
s p
a
n
i
c
ul
at
a
i
n
duc
ed by
hi
g
h
f
r
u
ct
ose
-fat
fe
d
usi
n
g
HOM
A-IR as t
h
e p
a
ram
e
ter. Th
e resu
lt was a little d
i
fferen
t
th
an
prev
i
o
u
s
stud
y. Th
e
b
e
st do
se t
o
d
e
crease
th
e
HOM
A-IR ind
e
x was
ob
tain
ed fro
m
p
u
rified ex
tract o
f
A
ndr
o
g
r
a
phi
s
p
a
n
i
c
ul
at
a
c
o
m
p
ared to t
h
e
an
dro
g
rapho
lide as th
e activ
e b
i
o
l
o
g
i
cal constitu
en
t [1
9
]
at
th
e
d
o
se
was
1
303
.8
m
g
/k
g
b
w
. Thu
s
, t
h
e
p
u
re
b
i
o
l
og
ical activ
e co
m
p
o
u
n
d
(syn
tetic co
m
p
o
und
)
fro
m
a p
l
an
t is
n
o
t
al
ways b
e
tter than
th
ei
r ex
tract. Th
is
may happen because
of in this
plan
t c
ont
aining
other c
o
m
pounds that
work sy
nergi
s
tically to reduce t
h
e
gl
uc
ose bl
o
o
d
l
e
vel
.
3.
5.
Co
mbination o
f
And
r
og
ra
phis pa
nicula
t
a
p
u
rified e
x
tr
act
w
i
th me
tf
orm
i
n
Her
b
al
m
e
di
cine
wel
l
k
n
o
w
n
ab
out
i
t
s
sa
fet
y
, h
o
we
ver
n
u
m
bers of
her
b
al
m
e
di
ci
ne ar
e n
o
t
wi
d
e
l
y
kn
o
w
n
by
t
h
e
com
m
uni
t
y
, especi
al
l
y
i
n
ex
t
r
act
s do
sage
f
o
rm
. The
use
of
her
b
al
m
e
di
ci
ne al
o
n
e i
s
not
en
oug
h to
o
v
e
rco
m
e
m
e
tab
o
lic d
i
seases su
ch as DM. Based on
th
at, so
m
e
t
i
m
e th
e co
mmu
n
ities co
m
b
ine th
e
her
b
al
m
e
di
cines an
d sy
nt
h
e
t
i
c
dru
g
s.
Ho
weve
r,
pr
o
b
l
e
m
s
m
a
y
occur
du
ri
n
g
t
h
e t
r
eatm
e
nt
. Ther
e i
s
an
i
n
t
e
ract
i
on
bet
w
een
her
b
al
a
nd sy
nt
het
i
c
d
r
u
g
s,
whe
r
e
herbal m
e
dicine can im
prove
the effective
n
e
ss of
sy
nt
het
i
c
d
r
u
g
s
o
r
c
ont
ra
ri
l
y
[
24]
.
Syam
sul
et
al [20] ha
d done a researc
h
on the effi
cacy of the com
b
ination of purified
An
dro
g
r
a
phi
s
pa
ni
cul
a
t
a
and m
e
tfo
r
min
in
DM typ
e
2 of rat.
Th
e m
a
le
rats
o
f
Sp
ragu
e-Dawley strain
was
u
s
ed
fo
r th
e
ani
m
al
s t
e
st
. The di
a
b
et
i
c
rat
s
were i
n
d
u
ce
d by
hi
gh
fr
uc
tose-fat fed. In this study as
m
u
ch as 36 rat
s
were
di
vi
de
d
i
n
t
o
6
gr
o
ups:
o
n
e
gr
ou
p
o
f
no
rm
al
rat
s
an
d
5
g
r
o
u
p
s
of
di
a
b
et
i
c
r
a
t
s
. Di
a
b
et
i
c
ra
t
s
gr
o
u
p
s
c
onsi
s
t
i
n
g
o
f
a
n
e
g
a
tiv
e
co
n
t
ro
l
group
,
p
o
s
itiv
e con
t
rol g
r
ou
p (d
iab
e
t
i
c rats
were g
i
v
e
n m
e
tfo
r
m
i
n
45
m
g
/k
g
b
w
), t
h
e
gr
o
up
gi
ve
n p
u
ri
fi
e
d
ext
r
act
of
An
d
r
og
raph
is pa
n
i
cu
la
ta
at th
e d
o
s
e of
43
4.6
m
g
/k
g b
w
, the g
r
oup
g
i
ven
Evaluation Warning : The document was created with Spire.PDF for Python.
I
S
SN
:
2
252
-88
06
IJPHS Vol. 4, No. 4, D
ecem
ber 2015
:
256 – 263
26
0
com
b
i
n
at
i
on
of
m
e
t
f
orm
i
n at
t
h
e
dos
e o
f
4
5
m
g
/
kg b
w
a
n
d
pu
ri
fi
ed
ext
r
ac
t
of
An
dr
og
ra
p
h
i
s
p
a
n
i
c
ul
at
a
at
the
dos
e o
f
43
4.
6
m
g
/
kg b
w
(c
o
m
bi
nat
i
on 1)
, a
nd t
h
e l
a
st
g
r
o
up
was
gi
v
e
n a
hal
f
d
o
se
of m
e
t
f
orm
i
n (2
2.
5
m
g
/
kg
bw a
n
d p
u
ri
fi
e
d
ext
r
act
of
A
n
dro
g
r
a
phi
s pa
ni
cul
a
t
a
at
t
h
e dos
e o
f
4
3
4
.
6
m
g
/
kg bw
).
Al
l
gro
u
p
s adm
i
ni
st
ere
d
oral
l
y
t
w
i
ce a
day
.
T
h
e c
ons
ent
r
asi
o
n
of
t
h
e an
dr
og
ra
ph
ol
ide in t
h
e ext
r
act that was
us
ed
not less t
h
a
n
15%
[14
]
. Th
e
p
a
rameter u
s
ed
in
th
e d
e
term
in
ati
o
n
o
f
h
ypo
g
l
y
c
e
m
ic act
iv
ity
in
th
is stu
d
y
was th
e ex
pressi
o
n
o
f
GLU
T
-
4
pr
ot
ei
n i
n
m
u
scl
e
t
i
ssue.
The m
o
r
e
of
GL
UT-
4
pr
ot
ei
n e
x
p
r
es
si
on
occ
u
r
r
ed t
h
e m
o
re gl
uc
o
s
e wa
s
tran
sp
orted to
m
u
scle tissu
e, so
t
h
at
th
e
b
l
ood
g
l
u
c
o
s
e lev
e
l will d
e
crease
[2
0
]
.
C
o
m
b
i
n
at
i
on
o
f
m
e
t
f
orm
i
n and
pu
ri
fi
ed
ext
r
act
of
An
dr
og
r
a
p
h
i
s
pa
ni
c
u
l
a
t
a
dr
opp
ed
th
e m
e
tf
o
r
m
i
n
activ
ity sig
n
i
fican
tly (p
<0
.0
5) after
55
day
s
. The
decreas
e
of m
e
t
f
orm
i
n
act
i
v
i
t
y
was
m
i
ght
re
gar
d
i
n
g
t
o
t
h
e
d
r
op
o
f
m
e
tfo
r
min
ab
sorp
tion
.
Th
is resu
lt was fo
und
on
th
e first co
m
b
in
atio
n
and
seco
nd
co
m
b
in
ati
o
n20
.
Hence
,
f
u
rt
her
st
udy
on i
n
t
e
r
act
i
on b
e
t
w
ee
n
m
e
t
f
orm
i
n and p
u
r
i
f
i
e
d e
x
t
r
act
of
An
drog
ra
ph
is p
a
n
i
cu
l
a
ta
is
neede
d
t
o
a
voi
d t
h
e
i
n
t
e
ract
i
o
n
bet
w
ee
n m
e
tfo
r
m
i
n and
An
dro
g
r
a
phi
s p
a
n
i
c
ul
at
a
ex
tract.
3.
6.
Co
mbination o
f
And
r
og
ra
phis pa
nicula
t
a
purified e
x
tr
act with other
he
rbal me
dicine
Du
ri
n
g
t
h
e
o
p
t
i
m
i
zati
on o
f
t
h
e DM
t
h
e
r
a
p
y
oft
e
n u
s
ed
a c
o
m
b
i
n
at
i
on
of
several
he
rbal
m
e
di
ci
nes.
N
u
g
r
oh
o
et al
[2
1]
ha
d do
n
e
a
resear
ch o
n
t
h
e
e
ffect
s of
c
o
m
b
i
n
at
i
on
o
f
n-
he
xane
i
n
sol
ubl
e frac
t
i
on o
f
eth
a
no
lic ex
tract o
f
And
r
og
ra
ph
is pa
n
i
cu
lata
(H
IF
A) wi
t
h
ot
he
r he
rbal
m
e
di
ci
nes t
o
im
prove t
h
ei
r
ant
i
-
diabetic effect. In that study,
HIFA
com
b
i
n
e
d
wi
t
h
cu
rc
um
inoi
d fract
i
on
o
f
C
u
rc
um
a xa
n
t
horri
z
a
(CFC)
and
HIFA c
o
m
b
ine
d
with ethyl ac
etate
sol
u
bl
e f
r
act
i
on
of
p
r
o
p
o
l
i
s
(ESP
).
Fi
gu
re 2 i
s
s
h
owi
ng t
h
e co
m
b
i
n
at
i
on of
HIF
A
a
nd C
F
C
pro
v
i
d
es t
h
e best
hy
p
ogl
y
c
em
i
c
effect
com
p
are t
o
HI
FA t
h
at
gi
ven
si
ngl
y
o
r
i
n
c
o
m
b
i
n
at
i
on
with ESP.
Wh
ile at HIFA co
m
b
inatio
n
with
ESP sho
w
s
a hi
gh
er dec
r
e
a
se i
n
serum
gl
ucose l
e
vel
s
t
h
an
HI
FA si
n
g
l
y
, eve
n
t
h
o
u
gh t
h
e i
n
creas
e i
s
not
si
gni
fi
cant
l
y
.
Th
us t
h
i
s
com
b
i
n
at
i
o
n (
H
I
F
A-C
F
C
)
was
p
o
t
e
nt
i
a
l
l
y
deve
l
ope
d as t
h
e o
n
e o
f
ch
ose
n
t
h
era
p
y
usi
ng
her
b
al
m
e
di
ci
ne [
21]
.
Figure 2
.
Effect o
f
m
e
tfo
r
min
(po
s
itiv
e co
n
t
ro
l), sing
le
treat
men
t
o
f
HIFA, co
m
b
in
atio
n
HIFA-CFC,and
com
b
i
n
at
i
on H
I
FA
-ES
F
on
bl
oo
d gl
uc
ose
l
e
vel
s
(m
g/
dL)
i
n
hig
h
-
f
r
u
ctose
-fat-
fed
rats
(a)
an
d the
pe
rce
n
tage
of
re
duct
i
o
n i
n
bl
o
o
d
gl
uco
s
e l
e
vel
s
(
b
) [
2
1]
Othe
r herbal that can be com
b
ined with
Andr
o
g
r
a
p
h
i
s
p
ani
c
u
l
a
t
a
is
Cen
t
ella
a
s
ia
tica
L.
Cen
t
ell
a
a
s
ia
tica
ef
fect
i
v
el
y
for ant
i
-
di
abet
i
c
i
n
di
abet
i
c
rat
s
i
ndu
ced by
st
rept
o
z
ot
osi
n
base
d on m
easurem
ent
of
serum
l
e
vel
s
of
gl
uc
ose an
d t
h
ei
r he
pat
i
c gl
y
c
oge
n l
e
vel
s
[1
6]
. Al
k
a
l
o
i
d
s, fl
a
v
on
oi
ds
, t
e
rpe
n
oi
ds, a
n
d
saponi
ns are found in the
Cen
t
ella
a
s
ia
tica
wh
ich
are
scattered
th
rou
gho
u
t
th
e p
l
an
t. Im
p
o
r
tan
t
activ
e
com
pou
nd
i
n
Cen
t
ella
a
s
i
a
tica
is asiatico
s
i
d
e, a triterp
en
co
m
p
o
u
n
d
[25
]
.
An
dr
o
g
ra
p
hol
i
d
e-e
n
ri
c
h
ed e
x
tract of
An
drog
rap
i
s pa
n
i
cu
la
ta
(AEEAP) co
m
b
in
ed
with
asiatico
s
id
e-
e
n
r
i
ch
e
d
ex
tr
ac
t o
f
Cen
t
ella
a
s
ia
tica
(
A
EE
C
A
)
gave
an a
n
t
i
-
di
a
b
et
i
c
eff
ect
on
di
abet
i
c
rat
s
i
n
duce
d
b
y
hi
gh
-
fr
uctose
fat
fed
[
22]
.
Androgra
pholi
d
e-e
n
ric
h
ed e
x
tract of
A
n
d
r
ogr
a
phi
s pa
ni
cul
a
t
a
(
A
E
E
A
P
) was m
a
de by
usi
ng a
several tim
es
of fractionation of n-he
xa
ne
, ethyl acet
ate and etha
nol. As well as
the pre
p
arati
on
of
asiaticoside-e
n
riche
d
extract
of
Cen
t
ella
a
s
i
a
tica
(
A
EEC
A
)
was si
m
i
l
a
r to t
h
e
pre
p
arat
i
on
of
AEE
A
P
.
It
was
esti
m
a
ted
th
at in
th
e two
ex
tracts
were and
r
og
rap
h
o
l
id
e and
asiatico
s
id
e with hig
h
lev
e
ls
o
f
activ
e
co
nstitu
en
t, resp
ectiv
ely.
Evaluation Warning : The document was created with Spire.PDF for Python.
I
J
PH
S I
S
SN
:
225
2-8
8
0
6
A Review o
f
t
h
e An
ti-d
i
ab
etic Activity o
f
And
r
og
rap
h
i
s
pan
icu
l
a
t
a
(Bu
r
m. f.)
Nees b
a
s
ed .... (Titi Ko
ma
l
a
sari)
26
1
Thi
s
st
u
d
y
wa
s do
ne by
c
o
m
b
i
n
i
n
g
AEE
A
P
and
AEEC
A
at
3 dose
rat
i
o
(i
.e. AE
EAP:
AEEC
A =
70:
30
, 5
0
:
5
0,
a
nd
3
0
:
7
0,
resp
ect
i
v
el
y
)
com
p
ared t
o
t
h
e si
n
g
l
e
d
o
se
of
AE
EAP,
AE
EC
A,
and m
e
t
f
orm
i
n. T
h
e
en
tire test
g
r
oup
,
eith
er sing
le do
se
or t
h
eir co
m
b
in
a
tio
n
p
r
o
v
i
d
e
resu
lts
with
sign
ifican
tl
y
lo
wer b
l
ood
su
gar
l
e
vel
s
(P
< 0
.
0
5
)
.
T
h
e
best
re
sul
t
s
we
re
obt
a
i
ned
fr
om
a com
b
i
n
at
i
on AE
EAP a
n
d
AEE
C
A at
rat
i
o
=
7
0
:
3
0
b
y
decreasi
n
g
t
h
e
bl
o
o
d
gl
uco
s
e l
e
vel
s
t
o
6
8
.
1
3
%
,
hi
g
h
er t
h
a
n
t
h
e si
ngl
e
d
o
s
e
o
f
m
e
t
f
orm
i
n
t
h
at
onl
y
62
.6
3%.
I
n
ad
d
ition
,
ex
cept lo
wering
th
e
b
l
oo
d g
l
u
c
ose l
e
v
e
ls, t
h
e co
mb
in
ation
o
f
AEECA an
d AEEAP
was si
gn
ifican
tly
decrese
the le
vels of choleste
ro
l, LDL, trig
ly
serid
e
s [2
2
]
.
3.
7.
A
n
a
l
og
ue of
androg
ra
pho
lide
Stu
d
y
o
n
an
ti-d
i
ab
etic activ
ity o
f
An
dr
o
g
ra
phi
s pa
ni
cul
a
t
a
was
not only
at the active com
pound, i.e.
andrographolide. Reseacher s
t
art to study the analogue of
androgra
pholid known as androgra
pholide lipoic
aci
d. Thi
s
a
n
al
og
ue i
s
p
o
t
e
nt
i
a
l
l
y
devel
ope
d
fo
r t
h
e al
t
e
rna
t
i
v
e agent
on
d
i
abet
es t
r
eatm
e
nt
. A
n
dr
og
ra
p
hol
i
d
e
lip
o
i
c acid (AL-
1)
is a r
e
su
lt
of
th
e conj
ugatio
n
o
f
andr
og
r
a
ph
o
lid
e and lip
o
i
c ci
d
(LA
)
[2
6
]
wh
ich bo
th
of
th
em h
a
v
e
an
ti
-d
iab
e
tic activ
i
t
y. Lip
o
i
c acid
itself is a
h
ealth
sup
p
l
em
en
t
th
at u
s
ed
ex
ten
s
iv
ely in
German
y
an
d used in th
e treatm
e
n
t
o
f
sy
m
p
to
m
a
tic d
i
ab
etic n
e
u
r
op
a
t
hy over 20 years. By l
o
oking at t
h
e a
d
vant
ages
of
each c
o
m
pone
nt (i.e
. a
n
drograph
olide
and li
poic a
c
id), Z
h
ang
et al
[17]
had done a
res
earch on t
h
e e
f
ficacy
and possi
blelilty of m
echanism
s
act
ion
of t
h
e conjugate
c
o
m
pound
of androgra
pholide
a
n
d lipoic a
c
id.
Research
on the efficacy of AL-1
was usi
ng
anim
a
l
s test. BALB/c fem
a
le
mice were induced
usi
ng
allo
x
a
n to
h
a
ve d
i
ab
etic m
i
c
e
. On
ly rats
with
b
l
ood
g
l
u
c
o
s
e lev
e
ls h
i
gh
er t
h
an 16
.7
mM was u
s
ed in
th
is
expe
ri
m
e
nt
. Furt
her,
t
h
e
rat
s
were
di
vi
de
d
i
n
t
o
6 g
r
ou
ps:
i
.
e. co
nt
r
o
l
g
r
ou
p
(n
ot
gi
ve
n
al
l
oxa
n),
t
h
e
gr
o
u
p
gi
ve
n AL
-1
(at
doses
of 2
0
,
4
0
, an
d 8
0
m
g
/
kg b
w
, res
p
ect
i
v
el
y
)
, t
h
e gr
ou
p
gi
ven a
n
d
r
og
r
a
ph
ol
i
d
e (at
d
o
s
e of
50 m
g
/
kg b
w
t
h
at
was eq
ual
t
o
m
o
l
a
r dose o
f
80 m
g
/
kg bw AL
-1
), an
d t
h
e gr
o
up
gi
ve
n
gi
ben
k
l
a
m
i
de
at
1.2
m
g
/k
g
b
w
as th
e po
sitiv
e co
ntro
l. All g
r
ou
ps were g
i
v
e
n
throug
h
in
trag
ast
r
ic rou
t
e o
n
ce
a d
a
y fo
r 6
d
a
ys. The
p
a
ram
e
ters u
s
ed
fo
r an
ti-d
i
abetic activ
ity
o
f
AL-1
was
by
m
easuri
n
g
t
h
e fast
i
ng bl
o
o
d
g
l
ucose
,
ser
u
m
insul
i
n
lev
e
ls, GLUT-4
p
r
o
t
ein
expressio
n
, th
e ab
i
lity
o
f
d
y
sfu
n
ctio
n
p
r
ev
en
tiv
e o
r
d
e
stru
ctio
n
o
f
b
e
ta cells b
y
pat
o
l
o
gi
c a
n
d i
m
m
unohi
st
och
e
m
i
cal
anal
y
s
i
s
o
f
t
h
e
m
ouse
panc
reas
[
17]
.
B
l
oo
d gl
uc
ose
l
e
vel
s
of di
a
b
e
t
i
c
rat
s
t
h
at
were fed
wi
t
h
AL
-1 at
t
h
e d
o
se
of
80 m
g
/
kg b
w
wer
e
t
h
e
gr
o
up t
h
at
i
n
t
e
nsi
v
el
y
dec
r
ea
se o
n
t
h
e
bl
o
o
d
gl
uco
s
e l
e
ve
l
s
on t
h
e day
of
0,
w
h
i
c
h
was a
b
o
u
t
6
5
%
. Thi
s
chan
ge
was 2
t
i
m
e
s hi
gher c
o
m
p
ared
to
the an
drographo
lid
e g
r
ou
p
with th
e d
o
se of
50
m
g
/k
g
bw
with
the
decl
i
n
e ab
o
u
t
32
.3
%. T
hus
,
gi
vi
n
g
AL-
1
w
a
s
m
o
re ef
fect
i
v
e i
n
l
o
weri
ng
bl
o
od
gl
uc
ose
l
e
vel
s
.
Whi
l
e
t
h
e t
e
st
o
f
i
n
su
lin
seru
m
lev
e
ls, AL-1 at do
se
8
0
m
g
/k
g
b
w
in
crease th
e in
su
lin serum
lev
e
ls b
e
tter th
an
an
dro
g
r
a
pho
lide at th
e do
se
of
5
0
m
g
/k
g bw
. Th
e sa
m
e
r
e
su
lts
wer
e
also
sh
own
o
n
p
a
tho
l
ogic and
im
m
unohi
st
oc
hem
i
cal
anal
y
s
i
s
of
m
ouse
p
a
ncreat
i
c
t
e
st
.
In
t
h
at
st
udy
,
Zha
n
g
et al
p
r
ove
d t
h
at
t
h
e
AL-
1
coul
d be
one
o
f
t
h
e ant
i
-
di
ab
et
i
c
agent
s
by
l
o
we
ri
n
g
fa
st
i
n
g gl
ucose l
e
vel
s
as wel
l
as pr
ot
ect
i
on a
g
ai
ns
t
bet
a
cell d
e
structio
n [1
7
]
.
Figure
3. AL
-1 elevated GL
UT-4
t
r
a
n
sl
ocat
i
o
n
t
o
t
h
e
pl
asm
a
m
e
m
b
rane o
f
sol
e
us m
u
scl
e
s [
17]
The s
o
leus
m
u
scles were
isol
ated and
GL
UT-4 conten
t
s
i
n
pl
asm
a
were a
n
al
i
zed
usi
n
g
west
er
n
bl
ot
.
Fi
gu
re 3 e
x
pl
ai
n t
h
e AL
-
1
el
evat
ed G
L
U
T
-4 t
r
a
n
sl
ocat
i
on t
o
t
h
e pl
as
m
a
m
e
m
b
rane of s
o
l
e
us m
u
scl
e
s
.
GLUT-4
p
r
o
t
ein
lev
e
ls in
d
i
ab
etic rats on
ly 4
9
.5% co
m
p
ared
to
n
on-d
i
abetic rats. An
dro
g
rap
h
o
lid
e treat
m
en
t
wi
t
h
t
h
e
d
o
se
of
5
0
m
g
/
kg
b
w
a
nd
AL
-1
t
h
e d
o
se
of
8
0
m
g
/
k
g
bw i
n
crea
ses t
h
e
GL
UT-
4
pr
ot
ei
n l
e
vel
s
u
p
t
o
94.6% a
n
d 84.7%
,
respecti
v
ely. Th
e
m
echani
s
m
of a
n
d
r
og
ra
ph
ol
i
d
e a
n
d L
A
f
o
r
l
o
w
e
ri
n
g
bl
o
o
d
gl
uco
s
e
lev
e
ls was id
en
tified
b
y
m
e
a
s
u
r
i
n
g
th
e in
crease o
f
GLUT
-4 e
x
pression
of protein in m
u
scle
tissue. Hence
,
m
o
re gl
uc
ose
was
bei
n
g
use
d
i
n
m
u
scl
e
t
i
ssue
[1
7]
,[
2
0
]
,
[
2
6]
.
Evaluation Warning : The document was created with Spire.PDF for Python.
I
S
SN
:
2
252
-88
06
IJPHS Vol. 4, No. 4, D
ecem
ber 2015
:
256 – 263
26
2
4.
CO
NCL
USI
O
N
B
a
sed o
n
t
h
e seven
jo
ur
nal
s
t
h
at
were re
vi
e
w
ed
, i
t
can be concl
ude
d t
h
at
Andr
o
g
ra
p
h
i
s
pa
ni
cul
a
t
a
h
a
s an
an
ti-d
i
ab
etic activ
ity.
Th
e an
ti-d
i
ab
et
ic activ
ity
o
f
Andr
o
g
r
a
p
h
i
s
p
ani
c
u
l
a
t
a
was foun
d
in
th
e eth
a
no
lic
ext
r
act
an
d i
n
t
h
e fract
i
o
nal
coum
pu
nd
(i
.e
. an
dr
og
ra
ph
ol
i
d
e or i
t
s
anal
og
ue
AL-
1
:
an
dr
o
g
ra
ph
ol
i
d
e
-
l
i
poi
c
acid
)
.
An
ti-d
i
ab
etic activ
ity o
f
And
r
o
g
raphis p
a
n
i
cu
l
a
ta
was
foun
d
t
o
o in
co
m
b
in
ation
with
syn
t
h
e
tic d
r
ug
(i.e. m
e
tform
i
n).
Howe
ver
,
A
ndr
o
g
r
a
p
h
i
s
p
ani
c
u
l
a
t
a
d
e
creased
m
e
tfo
r
min
ab
sorb
tion
b
u
t
no
t sign
ifi
can
tly.
C
o
m
b
i
n
at
i
on of
A
ndr
o
g
ra
p
h
i
s
pa
ni
cul
a
t
a
wi
t
h
ot
her
h
e
rbal
m
e
di
ci
n
e
(i
.e.
Cen
t
ell
a
a
s
ia
tica
,
Cu
r
c
u
m
a
xant
ho
rri
za
and propolis) inc
r
eased
An
drogra
p
h
i
s pan
icu
l
a
t
a
activ
ity. Th
erefore,
A
ndr
ogr
a
phi
s pa
ni
c
u
l
a
t
a
is
p
o
t
en
tially d
e
velo
p
e
d
as an
al
tern
ativ
e an
ti-diab
etic ag
ent
.
Furt
her
st
u
d
y
c
a
n e
xpl
ore t
h
e
m
echani
s
m
of
act
i
on
of
An
dr
o
g
ra
p
h
i
s
pa
ni
cul
a
t
a
as an
ti-d
i
ab
etic in
th
eir ex
tract, fr
action
a
l co
m
p
o
und
and
co
m
b
in
atio
n wit
h
sy
nt
het
i
c
d
r
u
g
or
ot
her
he
rbal
.
REFERE
NC
ES
[1]
World Health O
r
ganization
,
Dep
a
rtement of
Noncommudicab
le
Disease Surveillance, “D
efinitio
n, diagnosis, an
d
classification of
diabetes mellitus
and its complication”,
pp
.
6-13
, 1999.
[2]
American Diabetes Association
,
“Standa
rd of medical car
e
in diabetes 2014”,
Dia
b
etes
car
e
, vol/issue: 1(37), pp. 1
,
2014.
[3]
Interna
tiona
l dia
b
etes fed
e
ra
tion,
“
I
DF
Diabetes
Atlas 5
th
ed”
,
Brussels: international diabetes federation
,
2
0
12.
avai
labl
e at
ww
w.idf.org/d
i
ab
et
es
atl
a
s
.
[4]
Alice, YY., “Canadian
diab
etes
associ
ation 2013
clin
ical pr
actice guidelines
for
the prev
ention
an
d management o
f
diabetes in
Can
a
d: Introdu
ction
”
,
Can J Diabete,
vol/issue: 37(1), pp.
S1-S3,
2013
.
[5]
Eko, V
.
,
“
T
erap
i
diab
etes
m
e
lli
tu
s
”
,
Cermin
dunia kedo
k
teran
, vo
l/issue: 38
(1), pp
. 13-20
, 2011
.
[6]
Karto, “Tingkat
manfaat, k
eamanan, dan
ef
ektivitas tanaman obat dan obat tr
ad
is
ional”, Karang
an
y
a
r
,
Balai Bes
a
r
Penelitian
dan
Pengembangan
Tanaman Obat dan Obat Tr
adisional
(
B
2
P
2T
O-
OT
)
,
B
a
da
n Pe
n
e
l
i
t
i
a
n
d
a
n
Pengembangan Kesehatan
Departemen Keseh
a
tan RI, pp. 5-13, 2
008.
[7]
Elfita, Muharni, Muna
war, Saln
i, Oktasari A.,
“Seny
a
wa
antim
al
ar
ial dari jam
u
r endofik
tumbuhan sambiloto
(
Andrographis paniculata
Nees
)
”
,
J Natur Indon
esia
, vol/issue: 13
(2), pp
. 123-129
, 2011.
[8]
A
h
m
a
d, I., A
q
i
l
, F
., O
w
a
is
, M
., “
M
odern ph
y
t
om
edi
c
in
e:
Turning medicinal plan
ts
into
drugs”, W
e
inhe
im
:
WILEY-VCH Verlag
GmbH &
Co. KGaA, pp
. 2
73, 2006
.
[9]
Band
y
o
p
a
dh
ya
y,
SS., Dutta
, RP.,
Mistr
y
, H., “
H
e
r
bal th
erap
y for
diabe
t
es: Ph
ytoc
onstituent
and t
h
eir m
ech
anism
of action”,
Int J Interdiscipl
inary
Research
, vo
l/is
sue: 1(6), pp
. 4
,
2014.
[10]
Chao, WW., Lin, BF., “Isolation and id
entif
i
cation of b
i
oactiv
e compounds in
Andrographis panicula
ta
Chuanxinlian
”,
Chin Med
,
vo
l/is
sue: 13(5), pp
. 1
7
, 2010
.
[11]
Nugroho, AE.,
Andrie, M., Warditian
i
,
NK., Siswanto, E
., Pram
ono, S., Luki
t
a
ningsih,
E., “Antidiab
e
ti
c an
d
antihip
erl
i
pidem
i
c eff
ect of
Andrographis paniculata
(Burm. f.)
Nees and androg
ra
pholid
e in hig
h
-fructose-fat-fed
rats”,
Indian
J Pharmacol
, vol/is
sue: 44(3), pp
. 3
77-381, 2012
.
[12]
J
a
y
a
kum
ar
, T.
,
H
s
ieh, CY
., Le
e, J
J
., S
h
eu, J
R
.,
“Experimen
t
al and clinical pharmacolog
y
of
Andrographis
paniculata
and
i
t
s m
a
y
o
r b
i
oa
cti
v
e ph
yto
c
onstitu
ent
andrographo
lide
”
,
Evid
Based Complement
Alternat M
e
d
, vol.
846730,
pp. 1-9
,
2013
.
[13]
Ar
y
a
ni, T., “Pengujian validasi analisis
kadar and
r
ografolid secara kromatogr
afi cair kinerja tinggi
(KCKT) dengan
eluas
i
gr
adi
e
n te
rhadap
eks
t
rak h
e
rba s
a
m
b
iloto
(
Andrographis paniculata
Nees
)”
,
Berk
. Pan
e
l.
Hayati
, vol. 11, pp
.
73-76, 2005
.
[14]
Departemen
kes
e
hatan, “Far
makope herb
al Indon
esia 1
st
ed”, Jakarta, Depkes RI
, p
p
. 122-4
,
2009
.
[15]
Zhang, XF., Tan, BK.,
“Anti-diabetic prop
erty
of eth
a
nolic
extr
act of
Andrographis panicu
lata
in
strep
t
ozotosin
-
diabe
tic
ra
ts”,
A
c
ta Pharmacol
S
i
n
, vo
l/issue: 21(
12), pp
. 1157-11
64, 2000
.
[16]
G
a
yathri
, V
., L
e
ks
hm
i, P
., P
a
dmanabhan
,
RN
., “
A
nti-diab
etes a
c
tivit
y of
ethanol extract of
Cent
ella asiati
ca
(L.)
Urban (whole plant) in Strepto
z
o
t
ocin-i
ndu
ced di
abet
ic ra
ts
, is
ola
tion of an ac
tiv
e
fraction
and tox
i
cit
y
evalu
a
tion
of the
ex
trac
t”
,
I
n
t J Med
Arom
Plants
, vol/issue: 1(3), pp. 278-2
86, 2011
.
[17]
Zhang, Z., Jiang
,
J., Yu, P
.,
Zen
g
, X., Larrick, JW., Wang, Y., “H
y
poglicem
ic and beta cell pr
otective effects
o
f
andrographolide analogu
e
fo
r diabetes tr
eatment”,
J Translation Med
, vol. 7, pp
. 62
, 2009. doi:10.1
186/1479-5876-
7-62.
[18]
Szkudelski,
T., “The mechan
ism of
allox
a
n and streptozo
t
ocin
action
in B cell of th
e rat p
a
ncr
eas”,
Physiol
.
Re
,
vol.
50, pp
. 536-546
, 2001.
[19]
Adriawan, IR
.,
Andrie, M., Susilowa
ti, R
.
, Pramono, S., Nugr
oho, AE., “E
valuasi ef
ek an
ti-d
i
abetes mellitus
ekstrak terpurif
ikasi
Andrographis panicula
ta
(
B
urm. f.) Ness dan androgr
ap
holide d
e
ngan
parameter
indek
s
HOMA-IR”,
Tra
d
.
Me
d.
J
,
vol/is
sue: 19(1), pp
. 1
9
-23, 2014
.
[20]
S
y
amsul, ES., N
ugroho, AE., Pr
amono, S.,
“Aktivitas antidiabetes kombinasi ek
strak terpurif
ikasi herba sambiloto
(
Andrographis paniculata
(Burm. f.) Nees.) dan
metformin pada
tikus DM tipe 2
resistensi insulin
”,
Maja
lah Obat
Tradisional,
vol/issue: 16(3), pp.
124-131, 2011
.
[21]
Nugroho, AE.,
Kusumaramdani, G., Wid
y
an
ig
gar, A.,
Anggoro, DP., Pramono, S., “Antidiabetic eff
e
ct of
combination of
n-hexane insolu
ble
fraction of ethanolic extr
act of
Andrographis paniculata
with
other tradi
tion
a
l
medicines”,
In
t Food
Research J
, vol/issue: 21(2)
, pp
. 785-789
, 2
014.
Evaluation Warning : The document was created with Spire.PDF for Python.
I
J
PH
S I
S
SN
:
225
2-8
8
0
6
A Review o
f
t
h
e An
ti-d
i
ab
etic Activity o
f
And
r
og
rap
h
i
s
pan
icu
l
a
t
a
(Bu
r
m. f.)
Nees b
a
s
ed .... (Titi Ko
ma
l
a
sari)
26
3
[22]
Nugroho, AE., Lindawati, NY.,
He
rly
a
nti, K., W
i
d
y
astuti, L.,
Pramono, S., “Antid
iabetic
e
ffect of
a combination o
f
andrographolide-enrich
ed extract of
Androgpraphis panicula
ta
(B
urm
F
.
) Nees
an
d as
iat
i
cos
i
d
e
-en
r
iched
extr
ac
t o
f
Centel
la asia
tica
L. in
high
fructo
s
e-fat f
e
d r
a
ts”,
I
ndian J Exp Biol
, vol 51, pp. 110
1-1108, 2013
.
[23]
S
hulm
a
n, GI.,
“
C
ellul
a
r m
e
chan
is
m
of ins
u
lin
re
s
i
s
t
ance
”,
J
Clin
Investiga
tion,
vo
l/issue: 10
6(2), p
p
171-3, 2000.
[24]
W
illiam
s
on, E.,
Driver, S., B
a
xte
r
, K.,
“
S
tockle
y
’
s: Herbal Medic
i
nes Intera
ctions”
,
London: Pharm
aceu
tic
al Press,
pp. 2
,
2009
.
[25]
Birandar
,
SR.,
Rachetti, BD.,
“Ext
raction of
some secondar
y
metabolite
s
& thin
lay
e
r ch
ro
matograph
y
from
differen
t
p
a
rts of
Cent
ella
asiati
c
a
L. (URB)”,
American J Life S
c
i
, vol/issue: 1(6
)
, pp
. 243-247
, 2
013.
[26]
K
onrad, D
., S
o
m
w
ar, R., S
w
ee
ne
y, G
., Y
a
w
o
rs
k
y
, K
., H
a
yas
h
i
,
M
., Ram
l
al
, T.
,
K
lip, A
., “
T
he
antih
yp
ergl
yc
em
ic
drug
α
-lipoi
c aci
d s
tim
ulates
glucose uptake via b
o
th GLUT4 translocati
on and G
L
UT4 act
ivat
ion
:
Potentia
l role o
f
p38 mitogen-activated
protein k
i
n
a
se in
GLUT4
activ
ation
”
,
Diab
etes
,
vol. 1464-1
471, 2001
.
Evaluation Warning : The document was created with Spire.PDF for Python.