a review of natural products and plants as anti diabetic (1989)
TRANSCRIPT
Review Paper
A REVIEW OF NATURAL PRODUCTS AND PLANTS AS POTENTIAL ANTIDIABETIC DRUGS
Summary
The present paper reviews the active, natural principles and crude extracts of plants which have been ~Kper~rneuta~~y studied for hypogly~om~~ activity in the last ten years. Phyto~o~stituents with known structures have been classified in appropriate chemical groups and the active crude extracts have been listed alphabetically according to genus. Data are reported on their pharmacological activity, mechanism of action, toxicity and other prop- erties.
Introduction
Diabetes mellitus is a metabolic disease as old as mankind and its incidence is considered to be high 44 - St’loL Treatment of this disorder takes three main forms: i4 diet and exercise, 66;) insulin replacement therapy and G4 the use of oral hypoglycemic agents ~sulfonylureas and biguanidesl. How- ever, since time immemorial, patients with non-insulin requiring diabetes have been treated orally in folk medicine with a variety of plant extracts. The evaluation of these plants and, especially, of their active natural principles is a logical way of searching for new drugs to treat this disease.
We have reviewed the relevant literature on the plants which have been used in folk medicine and for which hypoglycemic activity has been scientifically documented in clinics or by the use of experimental methods.
~~8~~~~~39~~1.~ 0 1939 Elsevier Scientific Publishers Ireland Ltd. Published and Printed in Ireland
TA
BL
E
1
AC
TIV
E
AN
TID
IAB
ET
IC
PRIN
CIP
LE
S IS
OL
AT
ED
FR
OM
PL
AN
TS
:
Act
ive
prin
cipl
e Pl
ant
spec
ies
Part
us
ed
Dat
a on
str
uctu
re
and
actio
n of
pri
ncip
le
Pol
ysac
char
ides
an
d p
rote
ins
Aco
nita
ns
A,
B,
C a
nd
and
D
Arb
oran
s A
and
B
Ane
mar
ans
A,
B,
C
and
D
Atr
acta
ns
A,
B a
nd
C
Coi
xans
A
, B
an
d C
Dio
scor
ans
A,
B,
C,
D,
E a
nd F
Ele
uthe
rans
A
, B
, C
, D
, E
, F
and
G
Aco
nitu
m
carm
icha
elii
D
ebx.
(R
anun
cula
ceae
l
Alo
e ar
bore
scen
s M
ill.
var.
na
tale
nsis
W
ood.
et
E
v.
(Lili
acea
el
Ane
mar
rhen
a as
phod
eloi
des
Bun
ge
(Lili
acea
e)
Atr
acty
loid
es
japo
nica
K
oidz
. (C
ompo
sita
el
Coi
x la
chry
ma-
jobi
L
. va
r.
ma-
yu
en
Stap
f.
(Gra
min
eae)
Dio
scor
ea
japo
nica
T
hunb
. (D
iosc
orea
ceae
)
Ele
uthe
roco
ccus
se
ntic
osus
M
axim
; sy
nony
m:
Aca
ntho
pana
x se
ntic
osus
H
arm
s.
(Ara
liace
ae)
Roo
ts
Lea
ves
Rhi
zom
es
Rhi
zom
es
Seed
s
Tub
ers
Roo
ts
The
se
glyc
ans
exhi
bite
d pr
onou
nced
hy
pogl
ycem
ic
effe
cts
in
norm
al
mic
e.
The
m
ain
glyc
an,
acon
itan
A,
adm
inis
tere
d i.p
. to
aI
loxa
n-pr
o-
duce
d hy
perg
lyce
mic
m
ice,
al
so
exhi
bite
d a
bloo
d su
gar
low
erin
g ac
tion
(Kon
no
et
al.,
1985
d).
The
se
glyc
ans
elic
ited
mar
ked
hypo
glyc
emic
ef
fect
s in
no
rmal
an
d al
loxa
n-in
duce
d hy
perg
lyce
mic
m
ice
(Hik
ino
et a
l., 1
986c
).
The
se
cons
titue
nts
disp
laye
d hy
pogl
ycem
ic
effe
cts
in
norm
al
mic
e an
d th
e m
ain
glyc
an,
anem
aran
C
, ad
min
iste
red
i.p.
to
allo
xan-
in
duce
d hy
perg
lyce
mic
m
ice
redu
ced
plas
ma
gluc
ose
leve
l (T
akah
ashi
et
al.,
198
51
Hyp
ogly
cem
ic
effe
cts
wer
e se
en
in n
orm
al
mic
e an
d th
e m
ain
glyc
an,
atra
ctan
A
, al
so
redu
ced
bloo
d gl
ucos
e w
hen
inje
cted
i.p
. to
al
loxa
n-
indu
ced
hype
rgly
cem
ic
mic
e (K
onno
et
al.,
198
5e).
The
se
com
pone
nts
elic
ited
hypo
glyc
emic
ef
fect
s in
no
rmal
m
ice
and
coix
an
A
show
ed
a hy
pogl
ycem
ic
effe
ct
whe
n ad
min
iste
red
to
allo
xan-
indu
ced
hype
rgly
cem
ic
mic
e (T
akah
ashi
et
al
., 19
86)
All
the
dios
cora
ns
had
a hy
pogl
ycem
ic
effe
ct
whe
n in
ject
ed
i.p.
to
norm
al
mic
e an
d th
e m
ain
glyc
an,
dios
cora
n C
, al
so
exhi
bite
d a
hypo
glyc
emic
ef
fect
in
allo
xan-
indu
ced
hype
rgly
cem
ic
mic
e (H
ikin
o et
al
., 19
86a)
.
Whe
n el
euth
eran
s A
-G
wer
e in
ject
ed
i.p.
to
norm
al
mic
e,
hypo
glyc
emic
ac
tivity
w
as
obse
rved
w
ith
all
the
glyc
ans
exce
pt
eleu
ther
an
E.
1.~.
adm
inis
trat
ion
of
eleu
ther
an
C t
o al
loxa
n-tr
eate
d m
ice
also
low
ered
bl
ood
gluc
ose
leve
l (H
ikin
o et
al.,
198
6d3.
m
w
TA
BL
E
1 (c
ontin
ued)
Act
ive
prin
cipl
e Pl
ant
spec
ies
Part
us
ed
Dat
a on
st
ruct
ure
and
actio
n of
pri
ncip
le
Pana
xans
A
, B
, C
, D
and
E
Qui
nque
fola
ns
A,
B
and
C
Pan
ax
gin
sen
g M
ey.
(Ara
li-
acea
el
Pana
x qu
inqu
efol
ium
L
.
(Ara
liace
ael
Roo
ts
Roo
ts
The
se
glyc
ans
had
a hy
pogl
ycem
ic
actio
n in
no
rmal
m
ice
and
the
i.p.
adm
inis
trat
ion
of
pana
xan
A
and
B i
n al
loxa
n-in
duce
d hy
perg
lyce
mic
mic
e al
so
redu
ced
the
bloo
d gl
ucos
e le
vels
(K
onno
et
al
., 19
841.
Pa
n-
axan
A
ha
s a
mol
ecul
ar
wei
ght
of
14,0
00
and
is
com
pose
d m
ainl
y of
a-1-
6 lin
ked
D-g
~UC
Op
yran
OS
C
resi
dues
w
ith
bran
chin
g at
th
e C
-3
posi
tion;
th
e ra
tio
of
term
inal
s,
bran
chin
g po
sitio
ns
and
inte
rmed
iate
units
is
1:
1:2
(Tom
oda
et
al.,
1984
1.
Pana
xan
B
was
sh
own
to
be
a
pept
idog
lyca
n w
ith
mol
ecul
ar
wei
ght
of
abou
t 1,
800,
OO
O
and
is
com
- pose
d
main
ly
of
a-l-
%
lin
ked
D-g
lUC
Opyra
nO
Se
resi
dues
w
ith
bran
ch-
ing
at
the
C-3
po
sitio
n;
the
ratio
of
te
rmin
als,
br
anch
ing
posi
tions
and
inte
rmed
iate
un
its
is
abou
t 1:
1:1
.8
(Tom
oda
et
al.,
1985
1.
Oth
er
glyc
ans,
pa
naxa
ns
F,
G
and
H
(Hik
ino
et
al.,
1985
c1,
I,
J,
K
and
L
(Osh
ima
et
al.,
1985
1,
Q,
R,
S,
T
and
U
(Kon
no
et
al.,
1985
c1,
M,
N,
0
and
P (K
onno
an
d H
ikin
o,
1987
1 w
ith
hypo
glyc
emic
ef
fect
s w
ere
iso-
late
d fr
om
the
root
s of
P.
gin
sen
g.
The
qu
inqu
efol
ans
show
ed
hypo
glyc
emic
ef
fect
s in
no
rmal
m
ice
and
i.p.
adm
inis
trat
ion
of
quin
quef
olan
A
to
al
loxa
n-in
duce
d hy
per
glyc
emic
m
ice
also
pr
oduc
ed
a hy
pogl
ycem
ic
effe
ct
(Osh
ima
et
al.,
1987
1.
Sacc
hara
ns
A,
B,
C ,
D
, E
an
d F
Sac
char
um
of
fici
nar
um
L
.
(Gra
min
eael
Aer
ial
part
s T
hese
pr
oduc
ts
had
hypo
glyc
emic
an
d an
ti-at
hero
scle
rotic
ac
tivity
in
mic
e an
d ra
ts,
resp
ectiv
ely
(Tak
agi,
1986
1.
The
ac
cum
ulat
ion
of
lipid
pero
xide
s in
duce
d by
a
high
su
gar
diet
w
as
inhi
bite
d by
co
mbi
ned
feed
ing
with
a
poly
sacc
hari
de
frac
tion
of
S.
offi
cin
aru
m
(Hik
ino
et
al.,
1985
dl.
Fla
von
oid
s an
d
rela
ted
pro
ducts
( - l
-Epi
cate
chin
P
tero
carp
us
mars
upiu
m
Rox
b.
Bar
k
(Leg
umin
osae
l
t -
l-E
pica
tech
in
was
re
port
ed
to
prot
ect
rats
fr
om
allo
xani
nduc
ed
diab
etes
w
hen
the
com
poun
d w
as
adm
inis
tere
d (3
0 m
gikg
l tw
ice
daily
for
2 da
ys
prio
r to
al
loxa
n an
d 1
day
afte
r al
loxa
n ad
min
istr
atio
n
Kae
mpf
erol
-~~-
rh
amno
side
Q
uerc
itin-
3.~-
rh
amno
side
~~
i~tin
~~-
rham
~osi
de
Bar
k
(Cha
krav
arth
y et
al
., 19
81al
. M
oreo
ver,
th
is
com
poun
d co
uld
reve
rse
~llo
xan-
indu
ced
hype
rgly
cem
ia
whe
n it
was
ad
min
iste
red
for
2-3
days
(3
0 m
g/kg
tw
ice
daily
) ca
nnin
g 24
h a
fter
al
loxa
n ad
m~n
istr
a-
tion
~~ha
krsv
a~h~
et
al
., 19
81b,
19
81c
and
1982
1. H
owev
er,
othe
r au
thor
s fa
iled
to
conf
irm
th
e an
tidia
betic
ef
fect
of
4 -
~epi
cate
ehi~
in
di
ffer
ent
expe
rim
enta
di
abet
ic
mod
els,
e.
g.
stre
ptoz
otoc
~n-t
reat
ed
C57
BL
/65
mic
e K
olb
et
al.,
1982
1, a
lloxa
n-tr
eate
d W
ista
r ra
ts
(Kol
b et
al
., 19
82;
Shee
han
et
al,,
1983
a,bl
, st
rept
ozot
ocin
-dia
betic
or
spo
nta-
ne
ousl
y di
abet
ic
BB
/E
rats
(B
one
et
al.,
1985
1. (-
l-
Epi
cate
chin
ha
d di
rect
ef
fect
s on
is
lets
of
L
ange
rbau
s fu
nctio
n.
Thi
s co
mpo
und
(1
m&
II i
ncre
ased
in
sulin
se
cret
ion
from
is
olat
ed
rat
isle
ts
in
the
pres
- en
ce
of e
ither
2
or
20 m
lU g
luco
se
in s
tatic
in
cuba
tions
or
in
pe
rfo-
si
on.
Iaje
etio
n of
ep
iest
echi
n (3
0 m
&kg
tw
ice
daily
fo
r 4
days
) in
to
norm
al
rats
br
ough
t ab
out
an
incr
ease
in
ins
ulin
se
cret
ion
from
is
o-
late
d is
lets
w
hen
expo
sed
to
20 m
M
gluc
ose
and
in i
slet
co
nten
t in
tr
eate
d ra
ts.
Furt
herm
ore,
ad
ult
rat
isle
ts
cultu
red
with
5.
5 m
hI
giu-
eo
se
for
4 da
ys
show
ed
a si
gnif
ican
t in
crea
se
in D
NA
sy
nthe
sis
in t
he
pres
ence
of
0.0
5 m
&I
epi~
tech
in
&Ii
i an
d W
owel
l, 19
84al
. T
he
effe
ct
of
epic
atec
hin
on
insu
lin
rele
ase
couf
d ha
ve
been
br
ough
t ab
out,
at
leas
t in
par
t, by
ch
ange
s in
cyc
lic
AM
P m
etab
olis
m
(epi
cate
chin
at
1
mm
ol~
incr
ease
d cy
clic
A
MP
conc
entr
atio
ns
in i
slet
s,
Hii
and
Ifow
ell,
1984
b3 o
r by
ch
ange
s in
C
a2+
met
abol
ism
(e
pica
tech
in
at
0.8
mm
olll
inhi
bite
d Y
?az’
eff
lux
and
incr
ease
d th
e up
take
of
45C
az+
in
the
pres
- en
ce
of 2
0 m
&I
gluc
ose,
N
ii an
d H
owe&
19
851.
The
se
flav
onoi
ds
are
pres
ent
in
equa
l pr
opor
tions
in
a
frac
tion
iso-
la
ted
from
2.
rz
~gos
a. T
his
frac
tion
prod
uced
hy
~giy
ce~a
in
rab
bits
K
hosa
et
al.,
198
31.
Que
r~et
jn
~uu
~~
n~
~~re
o L
. &
R&
i-
Lea
ves
Ora
l ad
min
istr
atio
n of
thi
s co
mpo
und
(100
mgk
gl
low
ered
th
e bl
ood
Go
varie
gata
L,
vsr,
can
- gl
uco
se
leve
l in
no
rmal
ra
ts
2 h
afte
r gl
ucos
e in
ject
ion
(Abd
-El-
d
ti
Rox
b.
Wah
ab
et
al.,
1987
1. O
n th
e ot
her
hand
, qu
erce
tin
fO.O
I--0
.1
mm
ol/ll
Ileg
umin
osae
l en
hanc
ed
insu
lin
rele
ase
in
isol
ated
ra
t is
lets
of
L
ange
rhan
s;
this
2
com
poun
d (0
.01
mm
ol/lf
al
so
inhi
bite
d se
a**
effl
ux
and
incr
ease
d th
e rJ
up
take
of
q5C
az+
in i
sola
ted
rat
isle
ts
@Ii
i and
H
owel
l, 19
851.
TA
BL
E
(con
tinue
d)
itim
a lg
e.
leve
ls
at
a do
se
of
20 m
g/kg
w
hen
give
n or
ally
to
gl
ucos
e-in
duce
d (C
ompo
sita
e)
hype
rgly
cem
ic
rats
&
War
an
d Pa
y&
1985
1. It
ha
s be
en
dem
onst
rate
d th
at
with
an
ora
l do
se
of 3
0 m
g/kg
th
is
com
poun
d in
crea
sed
the
fast
- in
g pl
asm
a in
sulin
le
vels
in
no
rmog
lyce
mic
ra
ts
and
impr
oved
th
e or
al
gluc
ose
tole
ranc
e te
st
with
a
corr
espo
ndin
g in
crea
se
in g
lueo
se-
indu
ced
insu
lin
secr
etio
n (I
vorr
a et
al
., 19
88al
. H
owev
er,
f3-s
itost
erol
36
-u-g
luco
side
di
d no
t ch
ange
in
sulin
an
d gl
ucos
e le
vels
in
rat
s w
ith
stre
ptoz
otoc
in-i
nduc
ed
seve
re
diab
etes
. T
he
glye
osid
e (0
.1 -
0.
5 m
M1
stim
ulat
ed
insu
lin
rele
ase
from
is
olat
ed
rat
isle
ts
of
Lan
gerh
ans
in
the
pres
ence
of
1.
66 m
M
gluc
ose
but
did
not
incr
ease
th
e in
sulin
- re
leas
ing
capa
city
of
16
.6 m
M
gluc
ose.
T
hese
da
ta
sugg
est
that
6-
si
tost
erol
3+
+gl
ucos
ide
exer
ts
its
actio
n on
int
act
panc
reat
ic
/3-c
ells
by
st
imul
atin
g in
sulin
se
cret
ion.
A
hig
h do
se
of t
hose
co
mpo
und
(600
m
g/kg
i.p
. to
m
ice)
di
d no
t pr
oduc
e an
y sy
mpt
oms
of
toxi
city
an
d no
ne
of
the
mic
e di
ed
duri
ng
the
‘I-d
ay o
bser
vatio
n pe
riod
(I
vorr
a,
M.D
. et
al
., un
publ
ishe
d ob
serv
atio
ns).
Gre
en
bean
s T
his
subs
tanc
e gi
ven
oral
ly
ta
mic
e de
crea
sed
thei
r bl
ood
gluc
ose
leve
ls
(Sam
paio
et
al.,
197
91.
fi-S
itost
erol
C
offe
u ar
abic
a L
. (R
ubia
ceae
l
G~n
seno
side
R
b,
Roo
ts
Rot
h si
ngle
i.p
. ad
min
istr
at~v
n (Y
vkos
awa
et
al.,
1984
1 or
re
peat
ed
adm
inis
trat
ion
of
gi~s
envs
ide
Rb,
(I
O
mg/
rat~
day
for
8 da
ys)
(Yvk
vzaw
a et
al
., 19
85ct
to
stre
ptoz
ot~i
n.di
abet
ie
rats
de
crea
sed
the
elev
ated
se
rum
le
vels
vf
gl
ucos
e,
trig
lyce
ride
s no
n-sh
afte
d fa
tty
acid
s an
d to
tal
chv~
este
rv~
fort
herm
o~e,
th
e Ii
poIy
t~e
activ
ity
of l
ipo-
pr
otei
n Ii
pase
w
as
stim
ulat
ed
with
a
co~c
o~~n
t de
crea
se
in
the
leve
ls
of t
rigl
ycer
ide
and
very
lo
w
dens
ity
lipop
rote
in
in t
he
seru
m
afte
r gi
nsen
vsid
e-R
b,
trea
tmen
t fo
r 6
days
(Y
vkoz
awa
et
al.,
198%
).
In
addi
tion
to
the
hypo
glyc
emic
an
d hy
pvlip
emic
ef
fect
, si
ngle
i.p
. ~m
~n~s
trat
~on
(Yv~
osaw
a et
al
., 19
841
or
repe
ated
ad
min
istr
atio
n (Y
vkoz
awa
et
al.,
198S
c, 1
98%
) of
gin
seno
dde
Rb,
low
ered
th
e se
rum
le
vels
of
~~
ydro
xyb
uty
~~te
an
d ac
e~ac
etat
e in
st
rep~
~toc
i~-
indu
ced
diab
etic
ra
ts.
Thi
s in
dica
tes
au
~m~r
vvem
ent
of
diab
etic
ke
toac
idos
is.
Mor
eove
r, s
ucce
ssiv
e i.p
. ad
min
istr
atio
n of
git
wen
osid
e-
Rb,
re
mar
kabl
y im
prov
ed
diab
etic
sy
mpt
oms
such
as
ov
erea
ting,
po
lyur
ia
and
glye
osur
ia;
on t
he
oth
er h
and,
bo
dy
wei
ght
incr
ease
d in
gi
nsen
os~d
e-R
b~-t
rea~
d di
abet
ic
rats
Q
okoz
awa
et
al.,
1985
a, 1
987a
L
~nrt
herm
ore,
ad
min
istr
atio
n of
~~
seno
s~de
R
b,
in
stre
pto~
ta~n
- di
abet
ic
rats
io
du~e
d a
decr
ease
in
bl
ood
usea
N
le
vel
and
an
incr
ease
in
to
tal
prot
ein
and
seve
ral
amin
o ac
ids
in
seru
m,
but
no
sign
ific
ant
chan
ge
in s
erum
al
bum
in
was
ob
serv
ed.
The
ur
ea
cont
ent
of l
iver
de
crea
sed
with
a
conc
omita
nt
incr
ease
in
RN
A
cont
ent
(Yo-
ko
zaw
a et
al
., 19
87aL
The
hy
pogl
ycem
ic
actio
n of
~~
seno
side
-Rb*
m
ay b
e du
e to
its
ef
fect
s on
gl
ucos
e m
eta~
iism
. T
he
~~~n
osid
e~
Rb,
-tre
ated
gr
oup
show
ed
a de
crea
se
in
the
activ
ity
of h
e~at
ie
glu-
co
se~-
phos
phat
e af
ter
6 da
ys
of t
reat
men
t. In
con
tras
t, th
e he
patic
g~
ucv~
nase
w
as
sign
ific
antly
in
crea
sed
and
the
liver
gl
ycvg
en
con-
te
nt
tend
ed
to
incr
ease
af
ter
6 da
ys
of
gins
envs
ide-
Rb2
tr
eatm
ent
fYok
vsaw
a et
al
., 19
85b)
. G
~nse
nosi
d~R
b~
decr
ease
d gh
xose
in
th
e he
patic
tis
sue
of
diab
etic
ra
ts
whi
le
the
g~uc
ose~
~hos
~~te
le
vel
was
un
chan
ged
and
tke
lact
ate
feve
l te
nded
to
de
crea
se
(Yok
osaw
a et
al
., 19
81b)
. T
he
bloo
d in
sulin
le
vels
re
mai
ned
unch
ange
d th
roug
h-
out
the
Qda
y tr
eatm
ent,
whi
ch
indi
ca~s
tb
at
the
~nse
~osi
d~R
b~-
indu
ced
decr
ease
in
bf
ood
suga
r an
d th
e im
prov
emen
t in
sug
ar
and
lipid
m
etab
olis
m
in
stre
ptoz
otoc
~~
diab
etes
ar
e no
t as
soci
ated
w
ith
an i
ncre
ase
in i
nsul
in
(Kob
ayas
hi
et a
l., 1
985)
. tx
J %
TA
BL
E
1 (c
ontin
ued)
Act
ive
prin
cipl
e
Saud
in
Plan
t sp
ecie
s
Clu
ytiu
&
hard
&a
L.
(Eup
horb
iace
ae)
Part
us
ed
Lea
ves
Dat
a on
st
ruct
ure
and
actio
n of
pr
inci
ple
Thi
s pr
inci
ple,
a
nove
l di
terp
ene,
sh
owed
hy
pogl
ycem
ic
activ
ity
whe
n
it w
as
adm
inis
tere
d to
al
loxa
nize
d m
ice
(40
mgl
kg
i.p.1
(M
ossa
et
al
.,
1985
1.
Tor
men
tic
acid
Urs
olic
ac
id
Ole
anol
ic
acid
Pote
rium
an
cist
roid
es
Des
f.
(Ros
acea
el
Aer
ial
part
s T
his
prin
cipl
e (1
0 m
glkg
l ha
d a
hypo
glyc
emic
ef
fect
in
no
rmal
ra
ts
(Vill
ar
et
al.,
1986
1.
It
was
be
en
dem
onst
rate
d th
at
torm
entic
ac
id
(30
mgl
kgl
had
a hy
pogl
ycem
ic
effe
ct
in
norm
ogly
cem
ic
and
gluc
ose-
indu
ced
hype
rgly
cem
ic
rats
w
ith
a co
rres
pond
ing
incr
ease
in
ci
rcul
at-
ing
insu
lin
leve
ls.
How
ever
, th
e co
mpo
und
(30
mgl
kg)
did
not
chan
ge
the
gluc
ose
and
insu
lin
leve
ls
in
stre
ptoz
otoc
in-i
nduc
ed
diab
etic
ra
ts
(Ivo
rra
et
al.,
1988
b).
On
the
othe
r ha
nd,
torm
entic
ac
id
(0.0
5-0.
5
mM
) in
itiat
ed
insu
lin
secr
etio
n by
is
olat
ed
rat
isle
ts
of
Lan
gerh
ans
in
a do
se-d
epen
dent
fa
shio
n.
The
co
mpo
und
has
no
effe
ct
on
the
insu
lin-
rele
asin
g ca
paci
ty
of
16.6
m
M
gluc
ose.
T
hese
re
sults
su
gges
t th
at
torm
entic
ac
id
rats
, at
le
ast
in
part
, by
in
crea
sing
in
sulin
se
cret
ion
from
in
tact
pa
ncre
atic
is
lets
of
L
ange
rhan
s (I
vorr
a et
al
., 19
89al
.
Tor
men
tic
acid
w
as
not
toxi
c in
m
ice
in
that
i.p
. ad
min
istr
atio
n of
a
high
do
se
(600
m
glkg
l di
d no
t pr
oduc
e an
y sy
mpt
oms
of
toxi
city
(Ivo
rra,
M
.D.
et
al.,
unpu
blis
hed
obse
rvat
ions
).
Cor
nus
off%
nalis
Si
eb.
et
Zue
c.
Seed
s sy
nony
m:
Mac
roca
rpiu
m
offi
cina
le
Nak
ai
(Cor
nace
ael
Hyp
ogly
cem
ic
activ
ity
was
sh
own
in
rats
w
ith
diab
etes
in
duce
d by
stre
ptoz
otoc
in
(Yam
ahar
a et
al
., 19
81).
Cor
nus
offi
cina
lis
Sieb
. et
Is
olat
ed
toge
ther
w
ith
urso
lic
acid
fr
om
C.
offi
cina
lis,
th
is
com
poun
d
Zuc
c.
Seed
s de
crea
sed
the
amou
nt
of
wat
er
cons
umpt
ion
and
urin
e vo
lum
e in
(C
orna
ceae
l di
abet
ic
rats
(Y
amah
ara
et
al.,
1981
1.
Mom
ordi
ca
coch
inch
inen
sis
Spre
ngel
Se
eds
(Cuc
urbi
tace
ae)
Tw
o gl
ycos
ides
w
ere
isol
ated
, on
e co
ntai
ned
gluc
ose
and
the
othe
r
cont
aine
d gl
ucos
e an
d ar
abin
ose.
B
oth
glyc
osid
es
cont
aine
d ol
eano
lic
acid
as
ag
lyco
ne
and
show
ed
hypo
glyc
emic
ac
tion
in
stre
ptoz
otoc
in-
indu
ced
diab
etic
ra
ts
at
a do
se
of
25
mg/
kg;
i.p.
adm
inis
trat
ion
show
ed
bette
r ac
tivity
th
an
oral
ad
min
ista
tion
(Rez
a-U
l Ja
b1
et
al.,
1986
1.
Ber
beri
ne
~~ps
aici
n
Co@
ch
inen
sis
Fan
cb.
syn-
on
ym:
C.
tect
a W
alt
var.
ci
rine
ns&
Fr
an&
. (~
nun~
n~aE
e~~
Gal
egin
The
a si
nend
s L,
(~
~ea~
eae)
Lat
hpus
japmkus
sic
~~~m
inos
ae)
Aer
ial
part
s ~y
~giy
cern
~c
effe
cts
in
norm
al,
aflo
xan
diab
etic
an
d sp
onta
neou
sly
dia~
tic
KK
m
ice.
A
ntag
oniz
ed
the
hype
rgly
cem
ic
effe
ct
indu
ced
by
i.p.
~adm
in~s
trat
ion
of
gluc
ose
or
adre
nalin
e in
no
rmal
m
ice
and
impr
oved
th
e gl
ucos
e to
lera
nce
of
KK
m
ice
afte
r 15
da
ys
of
~eat
men
t. fu
rthe
rmor
e,
be~~
rine
de
crea
sed
seru
m
~hoI
este
ro1
lev
els
of
mic
e fe
d a
high
ch
oles
tero
l di
et
and
inhi
bite
d th
e pl
atet
et
aggr
egat
ion
of r
abbi
ts
in v
itro
Che
n an
d X
ie,
1986
).
Frui
ts
Cap
saic
in
(14
mg%
t) i
nhib
ited
the
inte
stin
al
gluc
ose
tran
spor
t in
bot
h ra
t an
d th
e ha
mst
er
in v
itro
(~on
sere
e~ns
or~,
19
79;
~ons
eree
nuso
ro
and
G~i
nsok
oo,
1978
, 19
79a)
. T
his
effe
ct
may
be
du
e in
pa
rt
to
a gr
eate
r m
etab
olic
br
eakd
own
of
gluc
ose
into
la
ctic
ac
id
~~on
sere
ennn
usor
n,
1979
1 or
m
ay
be
doe
to
a se
cond
ary
inbi
bi~r
y ef
fect
on
th
e A
TP~
e-de
pend
eat
sodi
um
pum
p (~
onse
reen
usor
n an
d G
~ins
ukon
, 19
79bj
.
Bul
bs
Hyp
og~y
ce~e
ac
tivity
se
en
at
an
oral
do
se
of
10 m
g&g,
in
gb
~cos
e-
indu
ced
hype
rgly
cem
ic
rabb
its.
It
was
a
mor
e po
tent
an
tidia
betic
ag
ent
than
to
~b~t
amid
e 6%
rng
~g~
~Kar
awya
et
al
., 19
841.
Lea
ves
Seed
s T
his
prin
cipl
e is
ci
ted
in
the
revi
ew
of
Gfi
ver
Bev
er
and
Zah
nd
(197
9).
Mor
e re
cent
ly,
the
bypo
~ly~
emic
ef
fect
of
ga
legi
n 63
6 rn
~~g~
in
al
~oxa
n~a~
ti~
rats
ha
s be
en
rem
onst
rate
d.
The
or
al
LD
, of
ga
legi
n su
lfat
e in
mic
e w
as 0
.122
g/k
g ~P
etri
eic
and
Kal
oder
a,
1962
).
Seed
s L
athy
rine
an
d y-
L-g
Iu~m
yl-L
-lat
hyri
ne
show
ed
hypo
glyc
emic
ac
tivity
in
m
ice.
L
atby
rine
(6
6 m
&g
i.v.1
had
a
bypo
~lye
emic
ef
fect
on
al
~oxo
n-in
dn~e
d di
abet
ic
mic
e t~
itsub
ishi
G
hem
, In
d.,
1982
).
TA
BL
E
1 (c
ontin
ued)
Act
ive
prin
cipl
e Pl
ant
spec
ies
Part
us
ed
Dat
a on
st
ruct
ure
and
actio
n of
pr
inci
ple
Lep
idin
e L
epid
ium
ru
dera
le
L.
(Cru
cife
rae)
Aer
ial
part
s H
ypog
lyce
mic
ef
fect
s in
m
ice
and
rabb
its
(Pas
kov
and
Boy
adzh
ieva
,
1981
) in
al
loxa
n-in
duce
d m
ild
chro
nic
diab
etes
(B
oyad
zhie
va,
1981
,
1982
a)
and
in
adre
nalin
e-in
duce
d hy
perg
lyce
mic
ra
ts
(Pas
kov
and
Boy
adzh
ieva
, 19
82).
H
owev
er,
this
pr
inci
ple
faile
d to
af
fect
carb
ohyd
rate
m
etab
olis
m
in
diab
etic
ra
ts
mad
e ab
solu
tely
in
sulin
-
insu
ffic
ient
by
su
rgic
al
panc
reat
ecto
my
(Boy
adzh
ieva
, 19
82b3
).
Furt
herm
ore,
th
is
com
poun
d de
crea
sed
gluc
osur
ia,
poly
dips
ia
and
incr
ease
d gl
ycog
en
in
liver
in
al
loxa
n-in
duce
d m
ild
chro
nic
diab
etes
(Boy
adzh
ieva
, 19
82a)
.
1,2
Subs
titut
ed
pirr
oli-
T
inos
pora
co
rdif
oliu
M
iers
. W
hole
pl
ant
Hyp
ogly
cem
ic
and
cent
ral
nerv
ous
syst
em
depr
essa
nt
activ
ity
in
dine
s (M
enis
perm
acea
e)
rabb
its
(Man
haja
n an
d Jo
lly,
1985
).
253
TA
BL
E
II (
cont
inol
edl
Plan
t sp
ecie
s (F
amily
) Pa
rt
used
(c
ount
ry)
Dat
a on
act
ion
of e
xtra
ct
Bri
de&
u fe
rrug
inea
B
enth
. (~
upho
rbia
ceae
)
Lea
ves
(Afr
ica)
T
he
fast
ing
bloo
d su
gar
leve
ls
of m
atur
ity-o
nset
di
abet
ic
patie
nts
wer
e lo
wer
ed
to
norm
al
by
daily
do
ses
of a
queo
us
extr
acts
; gl
ycos
uria
w
as
elim
inat
ed
afte
r 2
wee
ks
of t
hera
py.
The
aq
ueou
s an
d m
etha
nol
extr
acts
(2
00 m
g/kg
l lo
wer
ed
the
fast
ing
bloo
d su
gar
in n
orm
al
rats
bu
t no
t in
allo
xan-
trea
ted
rats
: ho
wev
er
they
lo
wer
ed
the
hype
rgly
cem
ia
in a
lloxa
n-tr
eate
d ra
ts
whe
n th
ey
wer
e ad
min
iste
red
1 h
prio
r to
al
loxa
n in
ject
ion
(Iw
u,
1983
1. F
lavo
noid
s qu
erce
tin
and
kaem
pfer
ol
and
thei
r gl
ycos
ides
w
ere
isol
ated
fr
om
the
met
hano
l ex
trac
t of
thi
s pl
ant
(Iw
u,
1983
).
Bry
onia
al
ba s
ic
(Cuc
urbi
tace
ael
Bum
elia
sar
toru
m
Mar
t. (S
apot
acea
el
Roo
t ba
rk
(Bra
zil)
Cap
sicu
m
annu
um
L.
(Sol
anac
eael
Met
hano
l ex
trac
ts
(5
mgl
kg)
and
the
frac
tion
cont
aini
ng
trih
ydro
xy-
octa
deca
dien
oic
acid
s (0
.5 m
g/kg
l de
crea
sed
bloo
d su
gar
in r
ats
with
al
loxa
n di
a-
bete
s af
ter
20 d
ays
i.m.
trea
tmen
t (P
anos
yan
et
al.,
1981
1.
An
etha
nol
extr
act
(250
and
50
0 m
glkg
l el
icite
d a
hypo
glyc
emic
ef
fect
in
nor
mal
ra
ts
and
rabb
its.
In
allo
xan-
indu
ced
mild
di
abet
ic
rats
, th
e da
ily
adm
inis
trat
ion
of t
he
etha
nol
extr
act
(500
mg/
kg
per
day
p.o.
1 fo
r 12
day
s lo
wer
ed
the
bloo
d gl
ucos
e le
vels
fr
om
the
8th
day
of
trea
tmen
t. M
oreo
ver,
th
e ex
trac
t im
prov
ed
gluc
ose
tole
ranc
e in
al
loxa
n-in
duce
d di
abet
ic
rats
. In
ad
ditio
n,
the
extr
act
enha
nced
gl
ucos
e up
take
in
ske
leta
l m
uscl
e an
d in
hibi
ted
glye
ogen
olys
is
in
the
liver
. B
esid
es
hypo
glyc
emic
ac
tivity
, th
e et
hano
l ex
trac
t al
so
elic
ited
anti-
in
flam
mat
ory
activ
ity
but
did
not
show
an
y si
gnif
ican
t ef
fect
s on
blo
od
pres
sure
an
d re
spir
atio
n.
LD
,, by
the
p.
o. r
oute
in
mic
e w
as
2580
mgl
kg
and
in r
ats
8670
m
glkg
, an
d by
th
e i.p
. ro
ute
in m
ice
was
12
7 m
glkg
an
d in
rat
s 18
7 m
glkg
(N
o.
breg
a et
al
., 19
85).
Bas
sic
acid
, tr
iterp
enic
ac
id,
was
is
olat
ed
from
th
e et
hano
l ex
trac
t bu
t it
was
no
t es
tabl
ishe
d w
heth
er
bass
ic
acid
is
re
spon
sibl
e fo
r th
e ob
serv
ed
hypo
glyc
emic
ac
tivity
of
the
et
hano
l ex
trac
t (N
obre
ga
et
al.,
1985
).
Frui
ts
(Tro
pica
l re
gion
s)
The
aq
ueou
s ex
trac
t ca
used
a
dose
-dep
ende
nt
decr
ease
in
fas
ting
bloo
d gl
ucos
e le
vels
in
ra
ts
eith
er
by
p.o.
or
i.p
. ro
ute.
Pr
etre
atm
ent
with
50
0 m
glkg
of
th
e ex
trac
t p.
o. o
r i.p
. im
prov
ed
the
oral
gl
ucos
e cu
rves
, an
d th
e p.
o. a
dmin
istr
atio
n of
ex
trac
t re
duce
d th
e in
trac
ardi
ac
gluc
ose
tole
ranc
e cu
rve.
T
he
hypo
glyc
emic
ef
fect
of
C
opsi
cum
m
ay
invo
lve
both
th
e in
hibi
tion
of i
ntes
tinal
gl
ucos
e tr
ans-
po
rt
and
its
actio
n up
on
the
syst
emic
gl
ucos
e m
etab
olis
m
(Mon
sere
enus
orn,
19
801.
Cec
rop
iu ob
tusi
folia
B
ert.
(Mor
a~ea
e~
Lea
ves
(Mex
ico1
Cen
taur
ea
aspe
ra
L.
C,
culc
itrap
a L
. C
. mel
i-
ten&
s L
. C
. ~a~
t~t~
~~
L
.
Aer
ial
part
s (S
pain
)
Cen
taur
ea
c~c~
b~on
ens~
e L
ain2
(C
ompo
sita
el
Lea
ves
and
flow
ers
(Spa
in)
Hyp
ogly
cem
ic
effe
ct
of
an
aque
ous
extr
act
in
allo
xan-
diab
etic
m
ice
was
se
en
whe
n ad
min
iste
red
by p
.0.
or i
.p.
rout
es
(Per
ez
et
al,,
1984
1. A
n aq
ueou
s ex
trac
t (1
5 m
g/m
l iv
.1
exhi
bite
d hy
pogl
ycem
ic
effe
cts
in
norm
al
and
panc
reat
ecto
miz
ed
dogs
; in
bot
h gr
oups
of
ani
mal
s,
an i
ncre
ase
in t
he
conc
entr
atio
n of
tri
glyc
erid
es
was
ob
serv
ed.
In
inta
ct
norm
al
anim
als
ther
e w
as
no c
orre
spon
ding
in
crea
se
in
insu
lin
plas
ma
leve
ls.
The
se
resu
lts
sugg
est
that
th
e ef
fect
of
the
pi
ant
extr
act
may
no
t be
re
late
d to
st
imul
i of
th
e p-
panc
reat
ic
cells
(M
ella
do
and
Lox
oya,
19
841.
Aqu
eous
ex
trac
ts
(20
g/kg
p.
o.1
of t
hese
sp
ecie
s el
icite
d hy
pogl
ycem
ic
effe
cts
in
norm
al
mic
e.
LD
, va
lues
(g
dri
ed
plan
t/kg)
of
aq
ueou
s ex
trac
ts
fi.v
.1 o
f th
ese
spec
ies
wer
e 4.
6 fo
r C
. as
pera
, 14
.6 f
or
C.
ca~
~tr
up~
8.
2 fo
r C
. s~
~t~
t~l~
an
d 4.
1 fo
r C
. m
elite
neis
(M
ass0
et
al
., 19
791.
Tbe
aq
ueou
s ex
trac
t of
C.
aspe
ru
pro-
du
ced
hypo
glyc
emia
in
rat
s an
d m
ice
whi
le
show
ing
no
cent
ral
and
auto
nom
ic
nerv
ous
syst
em
or l
ocal
ane
sthe
tic
activ
ity
in r
ats;
th
e ex
trac
t ca
used
tr
ansi
tory
by
pote
nsio
n in
the
an
esth
etiz
ed
rat
and
cat
and
indu
ced
cont
ract
ions
in
the
is
o la
ted
guin
ea
pig
ileum
. It
sh
owed
no
cho
liner
gic
OF
fi-a
dren
ergi
e ac
tivity
&
lass
o,
1980
1.
Infu
sion
s (5
g/k
g or
ally
) de
crea
sed
bloo
d gl
ucos
e le
vels
in
no
rmog
lyce
mic
an
d gl
ucos
e-in
duce
d hy
perg
lyce
mic
ra
ts,
but
had
no
effe
ct
on
allo
xan-
diab
etic
an
i-
mal
s.
The
re
was
an
inc
reas
e in
cir
cula
ting
insu
lin
leve
ls
in n
orm
ogly
cem
ic
rats
. M
oreo
ver,
a
heav
y re
leas
e of
in
sulin
fr
om
isol
ated
ra
t is
lets
w
as
indu
ced
by
dose
s of
25,
50
and
160
mgl
ml.
The
se
resu
lts
sugg
est
that
th
e ef
fect
of
C.
CO
TC
U-
bion
ensi
s m
ay
be d
ue
to s
timul
atio
n of
ins
ulin
re
leas
e by
the
pa
ncre
as
(Chu
ela
et
al.,
1988
1.
Clu
ytiu
ri
char
dha
sic
Who
le
plan
t (S
audi
A
ra-
(~up
horb
~cea
e~
Ara
bia1
A
dmin
istr
atio
n of
he
xani
e ex
trac
t (1
06
mg/
kg
i.pl
to
norm
al
rabb
its
caus
ed
redu
ctio
n in
the
bl
ood
gluc
ose
(Tilm
isan
y an
d A
jabn
oor,
19
861.
Coc
cini
a in
dica
W
ight
et
A
m.;
syno
mym
: C
. co
rdif
obia
Cog
n.
(Cuc
urbi
~~ea
e~
Lea
ves
and
root
s (I
ndia
1 A
hy
pogl
ycem
ic
effe
ct
and
an
impr
ovem
ent
on
oral
gl
ucos
e to
lera
nce
wer
e ob
serv
ed
in
patie
nts
with
m
atur
ity-o
nset
di
abet
es
mel
litus
tr
eate
d w
ith
the
leav
es
of
this
pl
ant.
The
m
axim
um
effe
ct
was
ob
tain
ed
afte
r th
ree
wee
ks
of
trea
tmen
t (A
zad
Kha
n et
al
., 19
861,
In
anim
als,
th
e ad
min
istr
atio
n of
a
susp
ensi
on
of d
ried
po
wde
red
leav
es
of C
. in
&a
with
m
ilk
caus
ed
a re
duct
ion
in
bloo
d gl
ucos
e le
vels
in
allo
xan
diab
etic
do
gs
but
did
not
indu
ce
hypo
glyc
emia
in
a
norm
al
grou
p of
an
imal
s.
Mor
eove
r,
the
drug
re
duce
d bl
ood
gluc
ose
duri
ng
gluc
ose
tole
ranc
e te
st
cond
ucte
d in
bot
h no
rmal
an
d di
abet
ic
dogs
(S
ingb
et
al
., 19
851.
TA
BL
E
II
(con
tinue
d)
Plan
t sp
ecie
s (F
amily
) Pa
rt
used
(c
ount
ry)
Dat
a on
ac
tion
of
extr
act
Cum
inum
n
igru
m
L.
(Um
belli
fera
e)
Cop
rinu
s co
mat
us
Fr.
(Cop
rina
ceae
)
Seed
s (A
sia)
Frui
ts
(Eur
ope)
Ora
l ad
min
istr
atio
n of
C
. ni
grum
se
eds
(l-4
g/
kg)
as
wel
l as
th
e w
ater
an
d
met
hano
l ex
trac
ts
(4-8
g/
kg)
decr
ease
d bl
ood
gluc
ose
leve
ls
in
norm
al
and
allo
xan-
diab
etic
ra
bbits
. T
otal
bl
ood
lipid
s w
ere
not
infl
uenc
ed
by
this
su
bsta
nce
in
eith
er
norm
al
or
diab
etic
ra
bbits
. A
cute
to
xici
ty
stud
ies
carr
ied
out
in
rabb
its
reve
aled
no
ad
vers
e si
de
effe
cts
of
this
fo
lk
med
icin
e at
th
e do
sage
s us
ed
(2-8
g/kg
p.
o.1
(Akt
har
and
Ali,
19
85).
Plas
ma
gluc
ose
was
so
mew
hat
low
er
10
h af
ter
intr
agas
tric
ad
min
istr
atio
n of
drie
d C
. co
ma&
s (3
.6
g/kg
). C
hron
ic
trea
tmen
t of
no
rmal
m
ice
with
33
.3%
(w
/w)
drie
d C
. co
mat
us
in
the
diet
re
sulte
d in
a
redu
ctio
n in
pl
asm
a gl
ucos
e af
ter
11
days
an
d an
im
prov
emen
t in
i.p
. gl
ucos
e to
lera
nce.
H
owev
er,
body
w
eigh
t ga
in
was
in
terr
upte
d al
thou
gh
ener
gy
inta
ke
was
no
t su
bsta
ntia
lly
redu
ced
(Bai
ley
et
al.,
1984
1.
Cya
mop
sis
tetr
agon
olo-
bu
s L
.
(Leg
umin
osae
)
Dio
scor
ea
dum
etor
um
Pax.
(Dio
scor
eace
ae)
Fibr
e (g
uar
gum
) of
se
eds
(Ind
ia)
Uri
nary
gl
ucos
e ex
cret
ion
decr
ease
d in
9
diab
etic
pa
tient
s w
hen
thei
r di
ets
wer
e
supp
lem
ente
d w
ith
the
diet
ary
fibr
e (g
uar
gum
, 25
g
daily
fo
r 5
or
7 da
ys)
(Jen
-
kins
et
al
., 19
77).
M
oreo
ver,
ad
min
istr
atio
n of
20
g
of
guar
gu
m
to
6 he
alth
y vo
l-
unte
ers
impr
oved
to
lera
nce
to
gluc
ose
by
decr
easi
ng
oral
gl
ucos
e ab
sorp
tion
(Tri
nick
et
al
., 19
86).
T
reat
men
t of
8
type
2
diab
etic
pa
tient
s w
ith
guar
gu
m
impr
oved
pl
asm
a ch
oles
tero
l an
d tr
igly
ceri
de
valu
es
(Bri
ani
et
al.,
1985
).
Frui
ts
and
seed
s (I
ndia
) T
he
who
le
frui
t ex
trac
t (2
0 g/
kg)
show
ed
sign
ific
ant
hypo
glyc
emic
ac
tivity
in
norm
al
rabb
its
and
the
seed
s (2
0 kg
/kg)
ha
d a
hypo
glyc
emic
ef
fect
in
gl
ucos
e-fe
d
fast
ing
rabb
its.
In
allo
xan
diab
etic
an
imal
s,
the
deco
ctio
n w
as
effe
ctiv
e at
40
gi
kg
(Pill
ai
et
al.,
1980
).
Tub
ers
(Nig
eria
) A
hy
droa
lcoh
olic
ex
trac
t ad
min
iste
red
to
fast
ing
norm
al
rabb
its
indu
ced
a
hypo
glyc
emic
ef
fect
ac
com
pani
ed
by
som
e se
riou
s to
xic
reac
tions
(A
kubu
e an
d
Mitt
al,
1982
).
Mor
e re
cent
ly
it w
as
dem
onst
rate
d th
at
the
toxi
c re
actio
ns
coul
d
be
sepa
rate
d fr
om
hypo
glyc
emic
ac
tivity
th
roug
h fr
actio
natio
n of
th
e ex
trac
t by
solv
ent
part
ition
. W
here
as
the
alka
loid
-con
tain
ing
frac
tion
was
hy
perg
lyce
mic
in
fast
ing
norm
al
mic
e,
the
who
le
extr
act
and
the
frac
tions
co
ntai
ning
st
eroi
dal
deri
vativ
es
evid
ence
d si
gnif
ican
t hy
pogl
ycem
ic
activ
ities
in
fa
stin
g no
rmal
m
ice
or
rabb
its
and
in
seve
rely
al
loxa
n di
abet
ic
rabb
its
(Und
ie
and
Aku
bue,
19
86).
Eri
obot
rya
japo
nica
L
ind.
(R
osae
~ae~
L
eave
s &
dial
Eug
enda
j~rn
bo~
~~
L
amk.
; sy
nony
m:
E.
cum
ini
Skee
ls,
Syty
g&
m j
ambo
~~um
D
C.
(Myr
taee
ae~
Seed
s (I
ndia
1
Aer
ial
part
s (I
ndia
)
Fum
aria
pu
rvif
olia
L
amk.
(F
umar
iace
ael
Aer
ial
part
s (I
ndia
)
Gan
oder
ma
ldd
um
K
ar-
&en
(P
olyp
orac
eae)
Fung
us
(Chi
na,
Japa
n1
An
alco
holic
ex
trac
t (1
00-2
00
mgl
kg,
oral
ly)
exer
ted
a si
gnif
ican
t hy
pogl
ycem
ic
effe
ct
in n
orm
al
rabb
its
but
had
no e
ffec
t on
allo
xan-
trea
ted
rabb
its.
Tbi
s su
g-
gest
s th
at
the
extr
act
acts
by
ini
tiatin
g th
e re
leas
e of
ins
ulin
fr
om
panc
reat
ic
fi*
cells
of
nor
mal
ra
bbits
. T
he
dose
us
ed
did
not
prod
uce
acut
e to
xici
ty
(Nor
een
et
al.,
1988
1.
It
was
de
mon
stra
ted
that
or
al
adm
inis
trat
ion
of
the
seed
s to
ra
ts
for
15 d
ays
caus
ed
a lo
wer
ing
of b
lood
gl
ucos
e ac
com
pani
ed
by a
sig
nifi
cant
in
crea
se
in p
an-
crea
tic
cath
epsi
n B
act
ivity
. T
hese
ef
fect
s w
ere
com
para
ble
to
thos
e of
ch
loro
- pr
opam
ide
(Ban
sal
et
al.,
1981
).
Ora
l ad
min
istr
atio
n of
pow
dere
d pl
ant
(l-2
g/
kg1
or
the
met
hano
l ex
trac
t (5
gl
kg1
decr
ease
d th
e b
loo
d
gluc
ose
leve
l of
no
rmal
ra
bbits
bu
t ha
d no
ef
fect
on
al
loxa
n.tr
eate
d ra
bbits
. T
his
sugg
ests
th
at
this
pl
ant
acts
pr
obab
ly
by i
nitia
ting
the
rele
ase
of i
nsul
in
from
th
e pa
ncre
atic
@
ells
of
no
rmal
ra
bbits
. A
cute
to
xi-
city
st
udie
s an
d re
cord
s of
be
havi
oral
pa
ttern
s ca
rrie
d ou
t in
ra
bbits
an
d ra
ts
resp
ectiv
ely
show
ed
no a
dver
se
effe
cts
at t
he
dosa
ges
test
ed
(3-6
g/
kg1
(Akh
tar
et
al.,
1984
1,
A
hypo
glyc
emic
ef
fect
w
as
seen
fo
r th
e po
wde
red
plan
t (l
-3
g/kg
, p.
o.1
in
nor.
m
a1 r
abbi
ts.
In
allo
xan-
diab
etic
ra
bbits
, th
e pl
ant
did
not
prod
uce
this
ef
fect
, w
hich
su
gges
ts
that
it
may
ac
t by
st
imul
atin
g pa
ncre
atic
/l-
cells
in
no
rmal
an
i-
mal
s.
The
ac
ute
toxi
city
st
udie
s an
d be
havi
oral
pa
ttern
re
cord
s in
dica
te
that
th
e pl
ant
was
qu
ite
safe
at
the
do
sage
s em
ploy
ed
(3-6
g/
kg1
sinc
e no
vis
ible
si
gns
of
toxi
city
or
adv
erse
ef
fect
s w
ere
obse
rved
1A
khta
r et
al
,, 19
841.
An
aque
ous
extr
act
(50
mgi
rat
wei
ghin
g 20
0-25
0 gl
red
uced
bl
ood
gluc
ose
and
insu
lin
leve
ls
10 m
in a
fter
or
al
gluc
ose
infu
sion
an
d in
crea
sed
bloo
d in
sulin
w
ith-
out
affe
ctin
g bl
ood
gluc
ose
30 a
nd
60 m
in
afte
r or
al
giuc
ose
infu
sion
. G
luco
se
abso
rptio
n fr
om
the
smal
l in
test
ine
was
no
t in
hibi
ted
by
the
wat
er
extr
act
(200
K
g/m
l).
In a
dditi
on,
the
wat
er
extr
act
150
m&
at)
inbi
bite
d th
e el
evat
ion
of b
lood
gl
ucos
e in
duee
d by
in
trav
enou
s in
fusi
on
of
adre
nalin
e w
ithou
t el
evat
ing
the
bloo
d in
sulin
le
vel.
Thi
s ex
trac
t in
hibi
ted
adre
nalin
e-in
duce
d lip
olys
is
in
rat
adip
oeyt
es
whi
le
it fa
iled
to a
ffec
t lip
ogen
esis
fr
om
gluc
ose
(Kim
ura
et
al.,
1988
1.
Plan
t sp
ecie
s (F
amily
) Pa
rt
used
(c
ount
ry)
Dat
a on
act
ion
of e
xtra
ct
Gyn
mem
a sy
lves
tre
R.
Br.
(A
scle
piad
acea
el
Lea
ves
(Ind
ia1
Ora
l ad
min
istr
atio
n of
th
e po
wde
red
leav
es
decr
ease
d bl
ood
gluc
ose
and
incr
ease
d th
e ci
rcul
atin
g in
sulin
le
vels
in
allo
xan
diab
etic
ra
bbits
an
d in
a s
ingl
e m
atur
ity-o
nset
di
abet
ic
patie
nt.
Thi
s ef
fect
w
as
asso
ciat
ed
with
a
redu
ctio
n in
th
e se
rum
lip
id
leve
ls
(Sha
nmug
asun
dara
m
et
al.,
1981
). M
oreo
ver,
or
al
trea
t-
men
t of
allo
xan-
diab
etic
ra
ts
for
a pe
riod
of
tw
o w
eeks
w
ith
an a
queo
us
extr
act
corr
ecte
d th
e hy
perg
lyce
mia
in
mod
erat
ely
diab
etic
an
imal
s bu
t di
d no
t re
duce
bl
ood
suga
r le
vels
in
sev
ere
and
toxi
c gr
oups
of
dia
betic
ra
ts;
how
ever
, in
the
se
grou
ps
the
drug
pr
olon
ged
thei
r su
rviv
al
time
(Sri
vast
ava
et
al.,
1985
, 19
861.
R
athi
et
al
. (1
9811
dem
onst
rate
d th
at
the
leve
ls
of s
ome
prot
ein-
boun
d po
lysa
e-
ehar
ides
(h
exur
onic
ac
id,
hexo
ses,
he
xosa
m~n
es,
non~
amin
opol
ysae
char
ides
an
d si
alie
ac
id)
and
som
e gl
yeos
amin
o~ly
cans
(h
yalu
roni
c ac
id
and
hepa
rin
sulf
ate)
ar
e in
crea
sed
in a
lloxa
n-in
duce
d di
abet
ic
rats
. T
he
depo
sitio
n an
d ac
cum
ulat
ion
of
thes
e m
acro
mol
ecul
es
in
tissu
es
is
rela
ted
to
the
vasc
ular
co
mpl
icat
ions
of
di
abet
es
mel
litus
. T
hese
au
thor
s al
so
show
ed
that
tr
eatm
ent
of d
iabe
tic
anim
als
with
a
hydr
oalc
ohol
ic
extr
a&
of
G.
sylu
estr
e (2
00 m
g/kg
da
ily
for
a m
onth
) br
ough
t th
ese
elev
ated
le
vels
ba
ck
to
near
no
rmal
va
lues
, M
oreo
ver,
th
e le
vels
of
the
3e
hond
roiti
n su
lfat
es
and
the
sulf
ated
to
no
n-su
lfat
ed
glyc
osam
inog
lyca
n ra
tio,
whi
ch
show
ed
a de
crea
se
in d
iabe
tic
anim
als,
w
ere
rest
ored
to
no
rmal
or
ne
ar
norm
al
by G
ymne
ma
trea
tmen
t (R
athi
et
al
., 19
811.
Whe
n dr
ied
leaf
po
wde
r of
G.
sylv
estr
e (2
50 m
g/kg
fo
r 12
or
24 w
eeks
) w
as
adm
inis
tere
d to
al
loxa
n di
a-
betic
ra
bbits
, it
not
only
pr
oduc
ed
a de
crea
se
in
bloo
d gl
ucos
e le
vels
, bu
t al
so
corr
ecte
d ce
rtai
n m
etab
olic
di
sord
ers
in
liver
, ki
dney
an
d m
uscl
e of
di
abet
ic
anim
als.
In
thi
s w
ay,
the
glye
ogen
an
d pr
otei
n de
plet
ion
and
lipid
ac
cum
ulat
ion
in t
he
diab
etic
an
imal
w
ere
reve
rsed
by
G.
sylw
estr
e tr
eatm
ent.
The
up
take
an
d in
corp
orat
ion
of
f’%
]glu
cose
in
to
glyc
ogen
an
d pr
otei
n w
ere
incr
ease
d in
th
e liv
er,
kidn
ey
and
mus
cle
in d
iabe
tic
anim
als
give
n G
. sy
lwes
tre
and
path
olog
ical
ch
ange
s in
itiat
ed
in
the
liver
du
ring
th
e hy
perg
lyce
mic
ph
ase
appe
ared
to
be
re
vers
ed
whe
n G
. sy
lves
tre
was
us
ed
to
cont
rol
hype
rgly
cem
ia.
Mor
eove
r,
the
activ
ities
of
th
e in
sulin
-dep
ende
nt
enzy
mes
(h
exok
inas
e,
glyc
ogen
sy
nthe
tase
, gl
ycer
alde
hyde
~3~p
hosp
hate
de
hydr
ogen
ase
and
gluc
ose-
g-ph
osph
ate
dehy
drog
e-
nase
l th
at
are
low
ered
in
th
e di
abet
ic
tissu
es,
wer
e in
crea
sed
by
G.
sylv
estr
e ad
min
istr
atio
n w
hile
th
ere
was
a
decr
ease
in
the
el
evat
ed
activ
ities
of
enz
ymes
ca
taly
sing
in
sulin
-ind
epen
dent
pa
thw
ays
(gly
coge
n ph
osph
oryl
ase,
gl
ucon
eoge
nic
enzy
mes
, gl
ucos
e-@
phos
phat
ase,
fr
ucto
se
1-6
diph
osph
atas
e an
d so
rbito
l de
hy-
drog
enas
e)
duri
ng
the
adm
inis
trat
ion
of
the
herb
(S
hanm
ugas
unda
ram
et
al
.,
Ham
mad
o sa
licor
nica
R
, B
r.
Khe
nopo
diac
eae)
Hed
yotk
bi
flor
a R
oth.
sy
nony
m:
GId
enla
ndio
co
rgm
bosa
L
.
(R~b
ia~e
ae~
Leu
caen
a le
ucoc
ephu
lu
sic
(Le~
min
o~e~
Lup
ine:
al
bus
L.
(Leg
umin
osae
l
Lyt
hrum
oa
&at
i L
. Fl
ower
s,
leav
es
and
(Lyt
hrae
eael
st
ems
(Spa
in1
1983
1. M
ore
rece
ntly
, it
has
been
de
mon
stra
ted
that
gy
mne
mie
ac
id,
isol
ated
fr
om
the
leav
es
of G
. s~
lve~
tTe
(0.2
g/k
g p.
o.1
inhi
bite
d th
e su
cros
e-in
duce
d et
eva-
tio
n of
the
bl
ood
gluc
ose
leve
l in
rat
s (Y
oshi
oka
et
al.,
1985
1. G
ymne
mie
ac
id
was
fo
und
to
be
a co
mpl
ex
mix
ture
of
at
leas
t ni
ne
clos
ely-
rela
ted
acid
ic
glye
osid
es
(Sin
shei
mer
et
al.,
197
0; S
insh
eim
er
and
Rao
, 19
701.
Who
le
plan
t (S
audi
A
ra-
Ara
bia)
A
n et
hano
l ex
trac
t (Z
OO
-400
m
g/kg
l pr
oduc
ed
a de
crea
se
in b
lood
su
gar
leve
ls
in a
lloxa
n-tr
eate
d m
ice
but
had
no e
ffec
t on
nor
mal
an
imal
s.
The
ex
trac
t ha
d no
ap
pare
nt
adve
rse
toxi
c ef
fect
s.
Phyt
oche
mic
al
anal
ysis
sh
owed
th
e pr
esen
ce
of
alka
loid
s,
card
iac
glyc
osid
es,
flav
onoi
ds,
ster
ols,
vo
latil
e oi
l an
d ba
ses,
ta
nnin
s,
eoum
arin
s an
d sa
poni
ns
(Aja
bnoo
r et
al.,
198
4al.
Who
le
plan
t (I
ndia
1 A
w
ater
ex
trac
t sh
owed
a
hypo
glyc
emic
ef
fect
in
al
loxa
n-di
a~tic
ra
bbits
. O
n co
lum
n ch
rom
atog
raph
y,
this
ex
trac
t ga
ve
a hy
pogl
ycem
ic
frac
tion
com
pose
d of
13
fre
e am
ino
acid
s,
pept
ides
or
pr
otei
ns,
K’,
Na+
and
C
l- (
Dec
hatiw
ongs
e et
al
., 19
831.
Seed
s (I
ndia
1 Po
wde
red
seed
s ha
ve
hypo
glyc
emic
an
d hy
poch
oles
tero
lem
ic
effe
cts
in
diab
etic
an
d hy
perc
hole
ster
olem
ie
rats
. T
he
seed
s co
ntai
n m
imos
ine,
a
toxi
c am
ino
acid
(S
ingh
al
et a
l., 1
9821
.
Seed
s (I
ndia
) A
n ac
tive
frac
tion
(4 m
glkg
p.
o.1
exhi
bite
d a
hypo
glyc
emic
ef
fect
on
nor
mal
ra
b-
bits
K
abo
et
al.,
1983
1 an
d in
gl
ucos
e-
or
diaz
oxid
e-in
duce
d hy
perg
lyce
mic
ra
b-
bits
bu
t ha
d no
ef
fect
in
al
loxa
n-
or
stre
ptoz
otoe
in-h
yper
glyc
emic
ra
ts,
whi
ch
sugg
ests
th
at
the
pres
enee
of
@pa
ncre
atic
ce
lls
is r
equi
red
for
activ
ity
(Cab
0 et
al
., 19
841.
Seve
ral
extr
acts
of
fl
ower
s,
leav
es
and
stem
(1
0 g/
kg
p.o.
1 po
sses
sed
hypo
glyc
emic
ac
tivity
in
no
rmal
an
d in
gl
ucos
e-in
duce
d hy
perg
lyce
mic
ra
bbits
; th
ere
was
an
in
crea
se
in c
ircu
latin
g in
sulin
in
nor
mog
lyce
mic
ra
bbits
. T
he
root
w
as
inac
tive
(Cad
avid
an
d C
alle
ja,
1980
1. T
he
ethe
r ex
trac
t w
as
the
mos
t ac
tive
extr
act
and
it ca
used
a
sign
ific
ant
redu
ctia
n in
blo
od
gluc
ose
in n
orm
al
rats
an
d a
corr
espo
ndin
g in
crea
se
of c
ircu
latin
g in
sulin
; m
oreo
ver,
th
e et
her
extr
act
(50
mgl
mll
incr
ease
d in
sulin
se
cret
ion
in i
sola
ted
rat
isfe
ts
of L
ange
rhan
s (L
amel
a et
al
., 19
851.
Eth
er
extr
act
(10
g/kg
, p.
o.1
also
ex
hibi
ted
hypo
glyc
emic
ac
tivity
in
ra
ts
with
gl
ucos
e-
and
epin
ephr
ine-
indu
ced
hype
rgly
cem
ia
and
in a
lloxa
n-di
abet
ic
mic
e.
In a
lloxa
n-
and
stre
ptoz
otoc
in-d
iabe
tic
rats
, th
e da
ily
adm
inis
trat
ion
of t
his
extr
act
(10
g/kg
/day
fo
r 8
days
) in
duce
d a
part
ial
reve
rsal
of
th
e di
abet
ic-l
ike
8
Plan
t sp
ecie
s (F
amily
) Pa
rt
used
(c
ount
ry)
Dat
a on
act
ion
of e
xtra
ct
Mom
ordi
ca
~ha
ran~
~
L.
(Cuc
urbi
taee
ael
stat
e.
Mor
eove
r,
both
st
em
and
flow
er
extr
acts
re
duce
d th
e el
evat
ed
r-gl
utam
yl
tran
spep
tidas
e ac
tivity
in
duce
d by
str
epto
zoto
cin
in r
ats
whi
le
the
stem
ex
trac
ts
redu
ced
the
elev
ated
la
ctic
de
hydr
ogen
ase
activ
ity.
The
fl
ower
ex
trac
t cl
earl
y ac
cent
uate
d th
e el
evat
ed
leve
ls
of a
spar
tate
am
inot
rans
fera
se
indu
ced
by s
trep
- to
zoto
cin
(Lam
ela
et
al.,
1986
1. O
n th
e ot
her
hand
, th
e et
her
extr
act
(10
g/kg
, p.
o.1
indu
ced
an e
nhan
cem
ent
of g
lyco
gen
cont
ent
in t
he
liver
bu
t ha
d no
eff
ect
on m
uscu
lar
glyc
ogen
co
nten
t an
d,
in a
dditi
on,
the
extr
act
low
ered
se
rum
le
vels
of
tri
glyc
erid
es
whi
le
incr
easi
ng
free
fa
tty
acid
s le
vels
. N
o ef
fect
on
ser
um
cho-
le
ster
ol
leve
ls
was
ob
serv
ed
(Lam
ela
et a
l., 1
9851
.
Frui
ts
(Asi
a,
Cen
tral
an
d So
uth
Am
eric
a1
Aqu
eous
ex
trac
ts
of M
. ch
aran
t&
frui
t re
duce
d bl
ood
gluc
ose
leve
ls
in
norm
al
rats
an
d im
prov
ed
gluc
ose
tole
ranc
e in
rat
s (L
eath
erda
le
et a
l., 1
981;
Kar
unan
ay-
ake
et
al.,
1984
1. P
owde
red
frui
t (0
.5-1
,5
g/kg
) pr
oduc
ed
a hy
pogl
ycem
ic
effe
ct
in
norm
al
and
allo
xan-
indu
ced
diab
etic
ra
bbits
(A
khta
r et
al
., 19
811.
An
aque
ous
extr
act
of “
cera
see”
, a
wild
va
riet
y of
M.
char
untia
, im
prov
ed
gluc
ose
tole
ranc
e in
nor
mal
m
ice
and
redu
ced
hype
rgly
cem
ia
in s
trep
tozo
toei
n-di
abet
ic
mic
e.
Thi
s ef
fect
w
as
not
asso
ciat
ed
with
in
crea
sed
circ
ulat
ing
insu
lin,
whi
ch
sugg
ests
th
at
“cer
asee
” m
ay
exer
t an
ex
trap
ancr
eatic
ef
fect
(B
aile
y et
al
., 19
851.
Mor
eove
r,
oral
ad
min
istr
atio
n of
M
. ch
aran
tiu
juic
e im
prov
ed
gluc
ose
tole
ranc
e in
no
n-
insu
lin
depe
nden
t di
abet
ics
(Lea
ther
dale
et
al
., 19
81;
Wel
ihin
da
et
al.,
1986
1. It
w
as
hypo
thes
ized
th
at
M.
char
untia
fr
uit
cont
ains
m
ore
than
on
e ty
pe
of h
ypog
ly
cem
ic
com
pone
nt.
The
se
may
in
clud
e a
prin
cipl
e ca
lled
“cha
rant
in”,
a
hom
oge-
ne
ous
mix
ture
of
p-s
itost
erol
fl
+glu
eosi
de
and
5,25
-stig
mat
adie
n-3.
~-ol
-glu
cosi
de
(Sue
row
, 19
651
that
ca
n pr
oduc
e a
hypo
glyc
emic
ef
fect
in
no
rmal
ra
bbits
(L
otli-
ka
r an
d B
ajar
ama-
Rao
, 19
663.
The
re
is e
vide
nce
for
the
exis
tenc
e of
ins
ulin
-lik
e co
mpo
unds
. A
pep
tide,
po
lype
ptid
e-p,
ha
s be
en
isol
ated
fr
om
frui
t, se
eds
and
tis-
sue
of M
. ck
arun
tia
and
caus
ed
hypo
glyc
emic
ef
fect
s w
hen
it w
as
adm
inis
tere
d su
bcut
aneo
usly
in
pa
tient
s w
ith
juve
nile
di
abet
es
(Kha
nna
et
al.,
1981
1. O
ther
po
lype
ptid
es
decr
easi
ng
bloo
d su
gar
leve
ls
in
norm
al
and
diab
etic
m
ice
wer
e al
so
isol
ated
fr
om
the
frui
t of
M.
chur
untio
(L
ei e
t al
., 19
851.
Mor
eove
r,
diff
eren
t fr
actio
ns
(Ng
et
al.,
1986
bl
and
a ga
lact
ose-
bind
ing
lect
in
with
a
mol
ecul
ar
wei
ght
of 1
24,0
00 (
Ng
et
al.,
1986
al c
apab
le
of a
ntili
poly
tic
and
lipog
enic
ae
tivi-
tie
s in
is
olat
ed
rat
adip
ocyt
es
have
be
en
isol
ated
fr
om
M.
char
antiu
se
eds.
A
lthou
gh
som
e au
thor
s ha
ve
indi
cate
d th
at
the
effe
ct
of
M.
char
antia
is
no
t as
soci
ated
w
ith
an i
ncre
ase
in c
ircu
latin
g in
sulin
(L
eath
erda
le
et a
l., 1
981;
Bai
ley
Myr
tus
com
mvn
is
L.
Lea
ves
and
bran
chle
ts
(Myr
tace
ael
(Lib
ya1
et
al.,
1985
1, W
elih
inda
et
al
. (1
9821
dem
onst
rate
d th
at
an
aque
ous
extr
act
from
th
e fr
uit
of M
. c~
uru~
~~
was
a
pote
nt
stiiu
lato
r of
ins
ulin
re
leas
e fr
om
@-c
ell-
ri
ch
panc
reat
ic
isle
ts
isol
ated
fr
om
obes
e-hy
perg
lyce
mic
m
ice.
T
his
actio
n m
ay
invo
lve
inte
ract
ion
with
th
e m
embr
ane
lipid
s in
a
way
w
hich
di
ffer
s fr
om
the
phys
iolo
gica
l ac
tivat
ion
of s
ecre
tion.
T
he
insu
lin-r
elea
sing
ef
fect
of
M.
chm
antiu
ca
n no
t be
attr
ibut
ed
to
“eha
rant
in”.
M
, ch
aTan
t& s
eeds
(l
-3
glda
y pe
r ra
bbit)
in
duce
d a
hypo
glyc
emic
ef
fect
an
d im
prov
ed
gluc
ose
tole
ranc
e in
mild
ly
stre
pto-
zo
toci
n-di
abet
ic
rabb
its.
Thi
s ef
fect
w
as
asso
ciat
ed
with
an
inc
reas
e in
liv
er
gly
coge
n an
d a
decr
ease
in
ele
vate
d le
vels
of
ser
um
chol
este
rol,
free
fa
tty
acid
s an
d tr
igly
ceri
des.
H
owev
er,
the
seed
s di
d no
t im
prov
e im
pair
ed
rena
l fu
nctio
n ca
used
by
str
epto
zoto
cin,
no
r di
d th
ey
decr
ease
th
e el
evat
ed
leve
ls
of u
rea
and
seru
m
erea
tinin
e (K
edar
an
d ~b
akra
bart
i, 19
821.
M.
c~a~
a~~~
ju
ice
(1 m
l/l00
gf
st
imul
ated
gl
ucos
e up
take
by
dia
phra
gm
tissu
e in
vit
ro.
Ora
l tr
eatm
ent
with
th
e ju
ice
prio
r to
a
gluc
ose
load
w
as
foun
d to
in
crea
se
the
glyc
ogen
co
nten
t of
liv
er
and
mus
de
whi
le
it ba
d no
ef
fect
on
th
e tr
igly
ceri
de
cont
ent
of a
dipo
se
tissu
e (W
elih
inda
an
d ~r
unan
ayak
e,
1986
1.
A
hydr
oalc
obol
ic
extr
act
(2 g
/kg)
in
hibi
ted
the
acut
e ph
ase
of
hype
rgly
cem
ia
indu
ced
by s
trep
tozo
toci
n w
hen
a si
ngle
do
se
was
gi
ven
intr
agas
tric
ally
to
mic
e 30
min
be
fore
st
rept
ozot
~in.
W
hen
Myr
tus
extr
act
was
gi
ven
48 h
aft
er
stre
p-
tozo
toci
n,
it re
duce
d th
e hy
perg
lyce
mia
an
d th
is
effe
ct
coul
d be
m
aint
aine
d by
re
peat
ed
adm
inis
trat
ion.
T
he
extr
act
had
no e
ffec
t on
the
bl
ood
gluc
ose
leve
l of
no
rmal
m
ice
(Elf
ella
h et
al
., 19
841.
N~
u~~
~
b&at
a R
. B
r.
(Com
posi
te)
Opu
ntia
st
rept
acan
tha
Lem
aire
(~
a~ce
ae~
Lea
ves
(Cen
tral
A
mer
ica)
Stem
s iM
exic
o
An
etha
nolic
ex
trac
t (5
00 m
g/kg
l po
sses
sed
hypo
glyc
emic
ac
tivity
bo
th
in n
orm
al
and
alio
xa~h
y~er
gly~
emie
m
ice
(Gup
ta
et
al.,
1984
1,
Ora
l ad
min
istr
atio
n of
sa
p (5
m
l/kg)
ob
tain
ed
from
O
punt
ia
stem
s pr
oduc
ed
hypo
glyc
emic
ef
fect
s in
no
rmal
do
gs,
in g
luco
se-i
nduc
ed
hype
rgly
cem
ic
rats
an
d ra
bbits
an
d in
pa
n~ea
tec~
miz
ed
rabb
its
(Iba
flez
~~am
acho
an
d O
man
-Ram
os,
1979
; Ib
a~ez
-Cam
acho
et
al
., 19
831,
but
th
ere
was
no
eff
ect
in p
aner
eate
etom
ized
ra
bbits
tr
eate
d w
ith
allo
xan.
T
his
indi
cate
s th
at
in o
rder
to
ob
tain
th
e O
pmti
a hy
pogl
ycem
ic
effe
ct
the
pres
ence
of
int
act
panc
reat
ic
tissu
e is
req
uire
d (I
bane
z-
Cam
acho
et
al
., 19
831.
Mor
eove
r,
com
plem
enta
ry
daily
ad
min
istr
atio
n of
Opu
ntiu
sa
p to
di
abet
ic
volu
ntee
rs
unde
r ch
lorp
ropa
mid
e tr
eatm
ent
impr
oved
th
e ge
n-
eral
sy
mpt
omat
olog
y of
the
pa
tient
s as
w
ell
as
thei
r in
sulin
an
d gl
ucos
e bl
ood
leve
ls
(Mec
kes-
Loz
oya
and
Rom
an-R
amos
, 19
861.
The
hy
perg
lyce
mic
ho
rmon
es,
g gl
ucag
on,
cort
isol
an
d gr
owth
ho
rmon
e ap
pear
ed
not
to
be
invo
lved
in
th
e
TA
BL
E
II
(con
tinue
d)
Plan
t sp
ecie
s (F
amily
) Pa
rt
used
(c
ount
ry)
Dat
a on
ac
tion
of
extr
act
Pan
ax g
inse
ng
Mey
. R
oots
(C
hina
, Ja
pan
and
(Ara
liace
ael
Kor
ea)
hypo
glyc
emic
ef
fect
of
O
punt
io.
In
an
oral
gl
ucos
e to
lera
nce
test
ru
n on
he
alth
y
volu
ntee
rs,
the
leve
ls
of
thes
e ho
rmon
es
wer
e no
t m
odif
ied
by
Opu
nti
a ad
min
is-
trat
ion
(Fer
nand
ez
et
al.,
1984
1.
Mor
e re
cent
ly,
it ha
s be
en
sugg
este
d th
at
Opu
n-
tia
prob
ably
ac
ts
by
inte
rfer
ing
with
in
test
inal
de
xtro
se
abso
rptio
n be
caus
e
Opu
nti
a in
take
in
he
alth
y vo
lunt
eers
(1
00
gl
dim
inis
hed
bloo
d gl
ucos
e in
an
or
al
gluc
ose
tole
ranc
e te
st
but
had
no
effe
ct
in
an
intr
aven
ous
gluc
ose
tole
ranc
e te
st
and
no
effe
ct
on
basa
l gl
ucos
e le
vels
(F
rati-
Mur
ani
et
al.,
1987
).
Dif
fere
nt
hypo
glyc
emic
an
d in
sulin
-lik
e pr
inci
ples
ha
ve
been
is
olat
ed
from
th
e
root
s an
d in
clud
e va
riou
s gl
ycan
s,
desi
gnat
ed
pana
xans
A
to
P
and
gins
enos
ide
Rb,
(s
ee
Tab
le
11.
Som
e co
mpo
unds
ar
e re
port
ed
with
an
tilip
olyt
ic
activ
ity:
aden
-
osin
e,
a ca
rbox
ilic
acid
an
d a
pept
ide
with
a
mol
ecul
ar
wei
ght
of
1400
th
at
can
inhi
bit
cate
chol
amin
e-in
duce
d lip
olys
is
in
rat
epid
idym
al
fat
pads
(N
g an
d Y
eung
,
1985
1.
Fina
lly,
two
frac
tions
fr
om
wat
er
and
met
hano
lic
extr
acts
ha
ve
been
is
o-
late
d fr
om
P.
pan
ax,
DPG
-3-2
an
d E
PG-3
-2,
resp
ectiv
ely,
fo
r w
hich
th
e ch
emic
al
stru
ctur
es
have
ye
t to
be
de
term
ined
bu
t w
hich
po
sses
s hy
pogl
ycem
ic
activ
ity.
A
hypo
glyc
emic
co
mpo
nent
w
as
part
ially
pu
rifi
ed
from
gi
nsen
g ro
ots
by
vari
ous
met
hods
of
fr
actio
natio
n ba
sed
on
an
assa
y sy
stem
to
ev
alua
te
hypo
glyc
emic
effe
cts
in
allo
xan
diab
etic
m
ice.
So
me
gins
eng
frac
tions
in
hibi
ted
epin
ephr
ine-
indu
ced
tran
sien
t hy
perg
lyce
mia
in
m
ice,
in
crea
sed
glyc
ogen
co
nten
t in
ra
t liv
er,
decr
ease
d th
e bl
ood
leve
ls
of
acet
one
bodi
es
in
allo
xan
diab
etic
m
ice
and
inhi
b-
ited
the
rele
ase
of
free
fa
tty
acid
s fr
om
rat
epid
idym
al
fat
pads
(K
imur
a et
al
.,
1981
al.
Kim
ura
et
al.
(198
1b)
isol
ated
tw
o hy
pogl
ycem
ic
frac
tions
, D
PG-3
-2
and
EPG
-3-2
, fr
om
P.
gin
sen
g an
d de
mon
stra
ted
that
th
e hy
pogl
ycem
ic
effe
ct
of
EPG
-3-2
on
al
loxa
n di
abet
ic
mic
e w
as
abol
ishe
d by
i.v
. in
ject
ion
of
antis
era
agai
nst
bovi
ne
insu
lin.
Thi
s in
dica
ted
a st
imul
ator
y ac
tion
of
the
frac
tion
on
bloo
d in
sulin
le
vels
. M
oreo
ver,
th
e sa
me
dose
of
E
PG-3
-2
(lo-
50
mgl
kgl
incr
ease
d bl
ood
insu
lin
leve
ls
in
allo
xan
diab
etic
m
ice
and
in
norm
al
mic
e lo
aded
i.p.
with
gl
ucos
e bu
t ha
d no
ef
fect
in
no
rmal
m
ice.
O
n th
e ot
her
hand
, D
PG-3
-2
(0.2
m
glm
ll st
imul
ated
in
sulin
re
leas
e fr
om
perf
used
ra
t pa
ncre
as
and
enha
nced
gluc
ose-
stim
ulat
ed
insu
lin
rele
ase
from
th
e pa
ncre
as
of
both
no
rmal
an
d di
abet
ic
rats
. T
his
effe
ct
was
al
so
obse
rved
in
th
e pr
esen
ce
of
cycl
ohex
amid
e,
whi
ch
sug-
gest
s th
at
the
insu
lin
rele
ase
from
th
e pa
ncre
as
indu
ced
by
DPG
-3-2
w
as
inde
-
pend
ent
of
insu
lin
bios
ynth
esis
. W
aki
et
al.
(198
2)
dem
onst
rate
d th
at
DPG
-3-2
Ph
ylla
ntu
s n
kuri
L
.; sy
n-
onym
: P
. xn
k2a~
ia
Wal
l, (E
upho
rbia
ceae
}
Lea
ves
(Ind
ia)
P~
~ta
go
~sy
lliu
m
L.
(~la
~ta~
na~e
ae~
Muc
ilage
(M
exic
o)
Pou
part
ia
birr
ea
Aub
r.;
syno
nym
: Sc
~Toe
ar~o
bi
rrea
H
oehs
t. (A
na~a
rdia
ceae
~
Lea
ves
(Afr
ica1
(0.2
mgi
mll
incr
ease
d in
corp
orat
ion
of 1
4C-I
euci
ne in
to
a pr
otei
n fr
actio
n ob
tain
ed
by
perf
usin
g th
e pa
ncre
as
of d
iabe
tic
and
norm
al
rats
. G
luco
se
incr
ease
d in
cor-
po
ratio
n of
13H
Jleu
eine
int
o in
sulin
in
isl
ets
from
no
rmog
lyce
mic
m
ice
fKK
1 an
d hy
perg
lyce
mic
m
ice
&K
-CA
Y)
whe
reas
D
PG-3
-2
had
this
ef
fect
on
y in
K
K-C
AY
m
ice.
In
add
ition
, lo
ng-t
erm
tr
eatm
ent
with
R
PG-3
-2
10.5
mg/
mll
stim
ulat
ed
insu
- lin
bi
osyn
thes
is
in
isle
ts
from
K
K-C
AY
mic
e (W
aki
et
al.,
1982
1. K
imur
a an
d Su
zuki
41
9811
ana
lyze
d th
e gl
ucos
e to
lera
nce
curv
es
of
KK
-CA
Y
mic
e ph
arm
acok
inet
ical
ly
by t
he
use
of a
mat
hem
atic
al
mod
el
(Com
part
men
t-H
m
odel
).
The
cu
rves
w
ere
clas
sifi
ed
into
se
vera
l pa
ttern
s by
an
alys
is
of
the
hum
ping
ef
fect
(t
he
tran
sien
t ri
se
in
bloo
d gl
ucos
e le
vel
afte
r a
prec
ipito
us
fall)
. T
he
hum
ping
ef
fect
w
as
enha
nced
by
th
ose
hypo
gIyc
emic
s w
hich
pr
omot
e in
sulin
se
cret
ion
from
pa
ncre
atic
is
lets
(s
ulfo
nylu
reas
~ an
d w
as
decr
ease
d by
th
ose
hypo
glyc
emic
s w
hich
pr
omot
e gl
ucos
e ut
iliza
tion
in
peri
pher
al
tissu
es
Cbi
guan
- id
es).
It
ha
s be
en
dem
onst
rate
d th
at
DPG
3-2
inhi
bite
d th
e hu
mpi
ng
effe
ct
in a
do
se-d
epen
dent
m
anne
r;
this
ef
fect
w
as
clea
rly
dist
in~i
shab
Ie
from
th
at
of t
ol-
buta
mid
e.
How
ever
, bo
th
DPG
-3-2
an
d to
lbut
amid
e ha
ve
an
insu
lin-r
elea
sing
ef
fect
in
pan
crea
tic
isle
ts.
An
aque
ous
extr
act
low
ered
bl
ood
suga
r le
veis
in
no
rmal
an
d al
loxa
n-di
abet
ic
rabb
its
(~am
akri
shna
n et
al
., 19
821.
Mor
e re
eent
ly,
two
flav
onoi
ds
isol
ated
fr
om
the
wat
er-s
olub
le
frac
tion
of t
he
etha
nol
extr
act
show
ed
hypo
glyc
emic
ac
tivity
in
allo
xan-
trea
ted
albi
no
rats
w
hen
they
w
ere
adm
inis
tere
d at
a
dose
of
100
mg/
kg
p.o
., bu
t ha
d no
eff
ect
in n
orm
al
rats
(H
uker
i et
al
., 19
881.
Car
ranz
a et
al
. (1
9851
indi
cate
d th
at
this
pl
ant
can
be
usef
ul
for
met
abol
ic
eon-
tr
ol
of d
iabe
tic
patie
nts.
Fr
ati-
Mun
ari
et
al.
(198
51 su
gges
ted
that
th
e m
ucila
ge
inte
rfer
red
with
in
test
inal
gl
ucos
e ab
sorp
tion
sinc
e m
ucila
ge
adm
inis
trat
ion
(10
gl m
ixed
w
ith
glue
ose
in h
ealth
y vo
lunt
eers
lo
wer
ed
gluc
ose
leve
ls,
and
this
di
d no
t O
CC
UF w
hen
the
muc
ilage
w
as
give
n pr
ior
to g
luco
se.
Ora
l ad
min
istr
atio
n of
an
aq
ueou
s or
et
hyl
acet
ate
extr
act
~250
-100
0 m
g/kg
l de
crea
sed
the
gluc
ose
leve
ls
in g
luco
se-i
udu~
ed
bype
rgly
~em
ic
rats
; th
e aq
ueou
s ex
trac
t w
as
also
ef
fect
ive
in a
lloxa
n-di
abet
ic
rats
bu
t no
t in
nor
mog
lyce
mie
ra
ts.
The
L
D,,
of a
queo
us
extr
act
was
fo
und
to
be
1.9
g/kg
(i
.p.
in m
ice1
(L
aure
ns
et
al.,
1984
1. M
oreo
ver,
in
vitr
o st
udie
s w
ith
puri
fied
al
dose
-red
ucta
se
(enz
yme
that
co
nver
ts
gluc
ose
into
so
rbito
ll sh
owed
th
at
the
aque
ous
and
ethy
l ac
etat
e ex
trac
t ex
hibi
ted
enzy
me-
in
hibi
ting
activ
ity
with
an
IC
,, (5
0%
inhi
bito
ry
con-
ce
ntra
tion)
of
1.3
5 rg
iml
and
0.81
pgi
ml,
resp
ectiv
ely.
T
hes
e re
sults
in
dica
te
that
TA
BL
E
II (
cont
inue
d1
Plan
t sp
ecie
s (F
amily
1 Pa
rt
used
(c
ount
ry)
Dat
a on
act
ion
of e
xtra
ct
E
this
pl
ant
has
a po
ssib
le
antid
iabe
tic
effe
ct
in r
espe
ct
to
cata
ract
an
d po
st-d
ia-
betic
ne
urop
athi
es,
sinc
e th
e ac
cum
ulat
ion
of s
orbi
tol
is r
espo
nsib
le,
at
leas
t in
pa
rt,
for
thes
e di
abet
es
com
plic
atio
ns
(Lau
fens
et
al
., 19
851.
Psi
dhn
gaajava L
.
(~yr
ta~e
ae~
Salv
ia l
avan
duli
foli
a V
ahl.
(Lab
iata
ef
Frui
ts
(Chi
na1
Lea
ves
(Jap
an1
Lea
ves
(Spa
in1
Aer
ial
part
s (S
pain
)
Aeu
te
i.p.
trea
tmen
t w
ith
I g/
kg
frui
t ju
ice
prod
uced
a
hypo
glyc
emic
ef
fect
in
no
rmal
an
d al
loxa
n-tr
eate
d di
abet
ic
mic
e.
Ora
l ad
min
istr
atio
n in
mat
urity
-ons
et
diab
etic
an
d he
alth
y vo
lunt
eers
al
so
low
ered
bl
ood
gluc
ose
(Che
ng
and
Yan
g,
1983
1.
An
etha
nolic
ex
trac
t fr
om
leav
es
(200
mglkg, p.o.
1 an
d a
n-B
uOH
so
lubl
e ex
trac
t pr
epar
ed
from
an
et
hano
lic
extr
act
125
or
100
mgl
kgl
wer
e fo
und
to
inhi
bit
the
incr
ease
in
pl
asm
a gl
ucos
e le
vel
in
allo
xan-
indu
ced
diab
etic
ra
ts
and
also
im
prov
e gl
ucos
e to
lera
nce
in d
iabe
tic
rats
. T
he
etha
nbol
ic
extr
act,
the
n-B
uOH
- so
lubl
e fr
actio
n an
d w
ater
-sol
uble
fr
actio
n w
ere
foun
d to
su
ppre
ss
adre
nalin
e-
indu
ced
lipol
ysis
in
fa
t ce
lls
from
ra
t ep
idid
ymal
ad
ipos
e tis
sues
(M
aruy
ama
et
al.,
1985
1.
Ora
l ad
min
istr
atio
n of
an
infu
sion
an
d an
et
hyl
ethe
r fr
actio
n (5
g/k
g! e
xhib
ited
kypo
gly~
emic
ac
tivity
in
n~
~o~l
y~er
nie
and
in
gluc
ose-
indu
&ed
ky
per~
ly~e
mic
ra
bbits
. In
allo
xan-
diab
etic
ra
bbits
, th
e da
ily
adm
inis
trat
ion
of 5
g/k
g of
the
in
fu-
sion
re
sulte
d in
a
decr
ease
in
th
e bl
ood
gluc
ose
leve
ls,
Adm
inis
trat
ion
of
the
ethy
l et
her
frac
tion
prod
uced
an
inc
reas
e in
cir
cula
ting
insu
lin
in n
orm
ogly
cem
~c
anim
als.
T
his
sugg
ests
th
at
the
hypo
glyc
emic
ac
tivity
m
ay
be d
ue
to
in p
art
to
stim
ulat
ion
of i
nsul
in
secr
etio
n fr
om
isle
ts
of L
ange
rhan
s (A
lons
o et
al.,
198
01.
An
infu
sion
an
d a
susp
ensi
on
(0.2
5 g/
kg
p.o.
1 sh
owed
hy
pogl
ycem
ic
effe
cts
in n
or
mog
lyce
mic
ra
bbits
w
here
as
no c
hang
e w
as
seen
in
ins
ulin
le
vels
. In
allo
xan-
dia-
be
tic
rabb
its,
daily
ad
min
istr
atio
n of
0.
25
g/kg
of
in
fusi
on
decr
ease
d bl
ood
gluc
ose
leve
ls.
Abs
orpt
ion
of g
luco
se
by t
he
inte
stin
e m
ay
be a
sig
nifi
cant
fa
ctor
si
nce
ther
e w
as
an h
ypog
lyce
mic
ef
fect
in
glu
cose
-ind
uced
hy
perg
lyce
mic
ra
bbits
w
hen
the
plan
t in
fusi
on
was
ad
min
iste
red
sim
ulta
neou
sly
with
gl
ucos
e bu
t th
is
effe
ct
was
no
t ob
serv
ed
wke
n tk
e pl
ant
infu
sion
w
as
adm
inis
tere
d 60
min
be
fore
gl
ucos
e (J
imen
ez
et
al.,
1936
1.
d
TA
BL
E
II (
cont
inue
d1
Plan
t sp
ecie
s (F
amily
) Pa
rt
used
(c
ount
ry)
Dat
a on
act
ion
of e
xtra
ct
Tri
gose
llu
foen
um
cum
IA
.
(Leg
umin
osae
l
grae
- Se
eds
(Isr
ael)
H
ypog
lyce
mic
ac
tivity
ha
s be
en
repo
rted
in
th
e re
view
of
O
liver
B
ever
an
d Z
ahnd
(1
9791
. Sha
m
et
al.
(197
41 re
port
ed
that
~~
~go~
e~~
seed
s an
d th
e m
ajor
al
kalo
id
com
pone
nt,
trig
onel
line,
ex
erte
d a
mild
hy
pogl
ycem
ic
effe
ct;
othe
r eo
m-
pone
nts,
ni
cotin
ie
acid
an
d eo
umar
in,
disp
laye
d a
mor
e pr
ofou
nd
but
shor
ter
hypo
glyc
emic
ac
tivity
in
al
loxa
n-di
abet
ic
rats
. M
ore
rece
ntly
it
has
been
de
mon
stra
ted
that
th
e an
tidia
betic
ac
tion
of
Xri
gone
lla
can
be
asso
ciat
ed
with
th
e de
fatte
d se
ed
mat
eria
l w
hich
co
ntai
ns
fibe
rs,
sapo
nins
, an
d pr
otei
ns
(Rib
es
et
al.,
1984
; V
alet
te
et
al.,
1984
1 an
d m
ore
spec
ific
ally
w
ith
subf
ract
ion
a w
hich
co
ntai
ns
the
test
a an
d en
dosp
erm
an
d is
ric
h in
fib
ers
(Rib
es
et
al.,
1986
1. T
he
defa
tted
frac
tion
caus
ed
a de
crea
se
in h
yper
glyc
emia
an
d hy
poeh
oles
tero
lem
ia
in
allo
xan-
diab
etic
do
gs
whi
le
the
lipid
ex
trac
t pr
oved
to
be
in
effe
ctiv
e (R
ibes
et
al
., 19
84);
Val
ette
et
al
., 19
841.
Chr
onic
ad
min
istr
atio
n of
su
bfra
ctio
n a
(mix
ed
with
tw
o da
ily
mea
ls,
in a
dditi
on
to i
nsul
in
trea
tmen
t fo
r a
peri
od
of 2
1 da
ys)
in
allo
xan-
diab
etic
do
gs
resu
lted
in
a de
crea
se
of
hype
rgly
cem
ia
and
glye
osur
ia
acco
mpa
nied
by
a r
educ
tion
of t
he
high
pl
asm
a gl
ucag
on
and
som
atos
tatin
le
vels
in
dia
betic
do
gs;
ther
e w
as
also
a d
ecre
ase
in t
he
hype
rgly
cem
ic
resp
onse
to
ora
l gl
ucos
e to
lera
nce.
In
co
ntra
st,
chro
nic
adm
inis
trat
ion
of
subf
ract
ion
b,
whi
ch
cont
ains
th
e co
tyle
dons
an
d ax
es
and
is
rich
in
sa
poni
ns
and
prot
eins
, ha
d no
ef
fect
on
hyp
ergl
ycem
ia
or
on t
he
leve
ls
of p
ancr
eatic
ho
rmon
es
in d
iabe
tic
dogs
(R
ibes
et
al
., 19
86).
Am
in
Riy
ad
et
al.
(198
81 d
emon
stra
ted
that
tr
eatm
ent
of
stre
ptoz
otoc
in
diab
etic
ra
ts
with
di
ets
cont
aini
ng
20%
fe
nugr
eek
seed
s fo
r a
peri
od
of
10
wee
ks
did
not
impr
ove
the
diab
etic
st
ate:
on
th
e ot
her
hand
, di
abet
ic
anim
als
pret
reat
ed
for
5 w
eeks
w
ith
fenu
gree
k an
d fo
llow
ed
by 6
wee
ks
of
feed
ing
with
th
e sa
me
diet
, sh
owed
a
gene
ral
impr
ovem
ent
in
thei
r cl
inic
al
stat
us
in t
hat
hype
rgly
cem
ia,
free
fa
tty
acid
s,
chol
este
rol
and
trig
lyce
ride
le
vels
w
ere
redu
ced.
267
Our report covers the literature published during the last ten-year period (1979-19881 because there is an earlier review that Covers the literature up to 1978 (Oliver Bever and Zahnd, 19791.
The present information has been organized in two different ways. The first classifies according to general chemical structure those hypoglycemic natural products which have been isolated from plants (Table 11. The second approach is devoted to those plants whose hypoglycemic action has been studied experimentally but whose active principles have not yet been isolated. We have listed these different plants alphabetically according to their botanical genus (Table 21. In both instances we give information about the pharmacological data, mechanisms of action, toxicity and other proper- ties.
Discussion
Since ancient times, plants have been used in the treatment of diabetes mellitus. In the present work we describe the plants whose activities have been studied in the 1979-1988 decade. In general, we can say that there are a great many hypoglycemic plants and the chemical structure of their active principles varies widely. Therefore, there must also be considerable diver- sity in the mechanisms of action. Some act by in&easing the release of insu- lin and require a minimum of fi-cells to exert their action. Other plant extracts or constituents act by modifying glucose metabolism and finally there are some that appear to correct the complications of diabetes. All are important since they potentially can be used to treat the different aspects of diabetes mellitus. They are a fertile source for new hypoglycemic agents.
For the study of antidiabetic plants, we consider glucose-induced hyperglycemic rats and streptozotocin-induced diabetic rats as good preliminary models for hypoglycemic screening. It is important to do a toxicity study because, as is known, hepatotoxic agents can influence the activity of certain hepatie enzymes involved in gluconeogenesis. This can lead to a reduction in the amount of glucose that reaches the blood resulting in false-positive results. As is the case with any ethnopharma~ologi~ study, careful collection of plant material and proper identification/verification is of primary importance.
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