- Hypoglycemic Activity of the Total Ecdysteroid Extract from Ajuga turkestanica
Hypoglycemic Activity of the Total Ecdysteroid Extract from Ajuga turkestanica
HYPOGLYCEMIC ACTIVITY OF THE TOTAL ECDYSTEROID
EXTRACT FROM Ajuga turkestanica
T. A. Kutepova,1 V. N. Syrov,1 Z. A. Khushbaktova,1 and Z. Saatov1
Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 35, No. 11, pp. 24 – 25, November, 2001.
Original article submitted October 30, 2000.
In recent years, there has been an extensive search for
new effective hypoglycemic agents among natural sub-
stances [1 – 3]. In this respect, a promising source is offered
by phytoecdysteroids. Some compounds of this class pro-
duce, in addition to the anabolic effect, a certain hypoglyce-
mic action [4, 5]. In connection with this, the purpose of our
study was to obtain the total ecdysteroid extract from Ajuga
turkestanica (which is economically more profitable in com-
parison to the isolation of individual ecdysteroids) and to as-
sess the hypoglycemic activity of this extract on the model of
alloxan-induced hyperglycemia and diabetes.
The sum of ecdysteroids (including 22-acetylcyasterone,
cyasterone, ecdysterone, and turkesterone) was obtained
from Ajuga turkestanica (Rgl.) Brig. (Labiatae family) col-
lected in canyons near Derbent (Surkhan Region,
Uzbekistan). The extraction procedure was conducted as de-
scribed in [6 – 10].
The hypoglycemic activity was studied on a group of
white mongrel male rats weighing 160 – 180 g. The
hyperglycemia model was induced by alloxan (150 mg:kg,
s.c.) injected in the form of freshly prepared 5% aqueous so-
lution. The phytoecdysteroid preparation was introduced
once per day in a dose of 5 mg:kg (the most effective dose
determined in preliminary experiments) over a period of
seven days, beginning on the third day after alloxan injec-
tion. In some experiments, on the third day after alloxan in-
jection, the test animals (deprived of food overnight) were
divided into groups with approximately equal blood glucose
index. One group served as control and the other groups were
treated with ecdysteroids, after which all animals were ad-
mitted to the standard vivarium diet and (3 h later) character-
ized with respect to the blood glucose level. In the chronic
diabetes test, the effect of phytoecdysteroids was determined
30 days after alloxan injection.
The reference drug was maninil administered in a daily
dose of 5 mg:kg. Each preparation was studied in eight inde-
pendent tests. the blood for analyses was taken from tail
vein; the blood glucose was determined by the orthotoluidine
technique . The experimental data were statistically pro-
cessed in terms of the Student t-criterion.
RESULTS AND DISCUSSION
On the third day after alloxan injection, all surviving rats
(50%) were characterized by increased blood glucose level
(the secondary hyperglycemia peak according to ). With
respect to the degree of hyperglycemia, the test animals
could be divided into three groups in which the glucose con-
tent in the blood serum fell within 150 mg% (group I),
150 – 250 mg% (II), and 250 – 400 mg%. The alloxan-in-
duced hyperglycemia exhibited a stable character and was re-
tained on the seventh day of observation (see the data for
0091-150X/01/3511-0608$25.00 © 2001 Plenum Publishing Corporation
Pharmaceutical Chemistry Journal Vol. 35, No. 11, 2001
1 Institute of the Chemistry of Plant Substances, Academy of Sciences of
the Republic of Uzbekistan, Tashkent, Uzbekistan.
TABLE 1. Effects of the Sum of Ecdysteroids and Maninil on the
Blood Glucose Level in Rats with Alloxan-Induced Hyperglycemia
Glucose level, mg%
initial (3rd day
final (7th day of
Control I 153 � 6.41 159 � 4.8
Phytoecdysteroids 159 � 6.8 93.8 � 5.6* < 0.001
Maninil 152 � 6.9 76.8 � 3.4*,** < 0.001
Control II 242 � 8.6 251 � 16.7
Phytoecdysteroids 236 � 9.2 145 � 6.4* < 0.001
Maninil 245 � 12.0 163 � 9.3* < 0.001
Control III 381 � 12.8 357 � 9.5
Phytoecdysteroids 379 � 19.8 272 � 8.9* < 0.001
Maninil 358 � 21.7 318 � 18.2** < 0.25
Notes. 1 Average blood glucose level before alloxan injection was
85 – 95 mg%. Here and in Tables 2 and 3, differences are reliable for
a confidence level of p < 0.05: * relative to control; ** between
control groups in Table 1). In the animals treated with
phytoecdysteroids, the glycemic index was reduced. In group
I, the blood glucose level on the seventh day of treatment de-
creased by 41.1% to reach a level almost characteristic of in-
tact animals. In group II, the hypoglycemic effect was less
pronounced: a 38.6% decrease relative to the initial level. A
minimum decrease in the glucose level was observed in
group III; nevertheless, even in this group the decrease
(28.2%) was statistically reliable (Table 1).
An additional evidence for the significant hypoglycemic
effect of the total ecdysteroid extract was provided by the ex-
periment on rats with alloxan-induce hyperglycemia, in
which the treatment began after a food load. Table 2 presents
the results of this test for animals with the initial blood glu-
cose level within 200 – 250 mg%. In the control group, the
blood glucose after feeding exhibited a reliable 29.3% in-
crease. In contrast, the level of glucose in rats treated with
ecdysteroids did not increase after the food load; moreover,
the blood glucose at the end of this experiment was 23.1%
lower than the initial level ( p < 0.05) and 43.3% lower as
compared to the corresponding untreated control. In the test
animals with stably expressed chronic alloxan-induced dia-
betes, the hypoglycemic action of phytoecdysteroids was
23.4% (Table 3).
A comparison of the hypoglycemic effect of the sum of
ecdysteroids and the reference drug maninil (widely used in
the treatment of diabetes ) showed that, in animals with a
relatively low excess of glucose in the blood, the action of
phytoecdysteroids was less pronounced as compared to that
of maninil. As the initial blood glucose level increased, the
drug effects exhibited leveling, whereas against a stable
chronic diabetes background, the hypoglycemic effect of the
sum of ecdysteroids was more pronounced than that of
These results are probably explained by a more diversi-
fied mechanism of action of the sum of ecdysteroids. On the
one hand, the effect of the phytopreparation (like that of
steranabols) can be related to a mediated activation of the
glycogen synthesis function of the liver and to an increase in
the resistance of peripheral tissues with respect to insulin.
These mechanisms were repeatedly revealed by investiga-
tions of the effects of individual phytoecdysteroids and
nerobol on the metabolism of hydrocarbons in the animal
[5, 14, 15]. On the other hand, there is evidence that the sum
of phytoecdysteroids can stimulate the synthesis of endogen
insulin by increasing the growth of cells in the insulin-pro-
ducing apparatus of the pancreas . On the contrary, the
hypoglycemic effect of maninil is mostly related to stimula-
tion of the pancreatic �-cells and is not manifested under
conditions of their dysfunction or loss [13, 17].
Thus, the results of our experiments showed that the sum
of phytoecdysteroids extracted from Ajuga turkestanica can
be considered as a promising hypoglycemic preparation.
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Hypoglycemic Activity of the Total Ecdysteroid Extract from Ajuga turkestanica 609
TABLE 2. Effects of the Sum of Ecdysteroids and Maninil on the
Blood Glucose Level after Food Load in Rats with Alloxan-Induced
Glucose level, mg%
initial (3rd day
(3 h after
Control 232 � 14.8 300 � 16.0 < 0.01
Phytoecdysteroids 221 � 13.5 170 � 14.9* < 0.05
Maninil 236 � 16.2 223 � 17.2*,** > 0.5
TABLE 3. Effects of the Sum of Ecdysteroids and Maninil on the
Blood Glucose Level in Rats with Chronic Alloxan-Induced Diabe-
Glucose level, mg%
initial (3rd day
final (7th day of
Control 235 � 17.8 245 � 24.4 > 0.5
Phytoecdysteroids 227 � 15.1 174 � 12.0* < 0.02
Maninil 232 � 11.4 226 � 10.1** > 0.5