Pathophysiology 19 (2012) 3542

Antihyperglycemic, antihyperlipidemic and antioxidant activities of

traditional aqueous extract of Zygophyllum album in streptozotocin
diabetic mice
Jamel El Ghoul a,b,,1 , Moz Smiri b,1 , Saad Ghrab c ,
Naceur A. Boughattas d , Mossadok Ben-Attia a
a Unit de Toxicomtrie & Chronobiomtrie, Laboratoire de Biosurveillance de lEnvironnement (LR01/ES14), Facult des Sciences de Bizerte, Universit de
Carthage, 7021 Zarzouna, Tunisia
b Dpartement des Sciences de la Vie, Facult des Sciences de Bizerte, Universit de Carthage, 7021 Zarzouna, Tunisia
c Laboratoire de Chimie Structurale Organique, Synthses et tudes physicochimique, Facult des Sciences de Tunis, Dpartement de Chimie, Campus

Universitaire El Manar I, 2092 Tunis, Tunisia

d Laboratoire de Pharmacologie (04/UR/09-01), Facult de Mdecine de Monastir, Universit de Monastir, 5019 Monastir, Tunisia

Received 11 October 2011; received in revised form 20 November 2011; accepted 12 December 2011

Abstract
Objective: The aim of this work was to investigate the antihyperglycemic, antioxidant and antihyperlipidemic effects of the aqueous
extract of Zygophyllum album on streptozotocin (STZ)-induced diabetic mice. Methods: Diabetes was induced in Swiss albino mice by
the administration of STZ (45 mg/kg b.w.) intraperitoneally. Aqueous extract of Z. album (100 and 300 mg/kg b.w.) was administered by
oral gavage once a day for a period of 15 days. The effect of the extract on blood glucose, lipids, cholesterol levels in plasma, and also
on enzymatic and non enzymatic antioxidants of defence systems such as superoxide dismutase (SOD), catalase (CAT), glutathione per-
oxidase (GPx) enzyme activities, and vitamin C, vitamin E and glutathione reductase (GSH) levels in liver and pancreas were studied.
Results: Our results showed that Z. album extract reduced the blood glucose, total cholesterol (TC), triglycerides (TG), low-density lipopro-
tein (LDL) and very low-density lipoprotein (VLDL) levels in STZ-diabetic mice. It also significantly abolished the increase in MDA
level, and GPx, SOD and CAT activities in both liver and pancreas. The levels of GSH, vitamin C and high-density lipoprotein (HDL)
were significantly augmented in Z. album treated diabetic mice in comparison with control group. Our findings suggest that Z. album
aqueous extract prevented the diabetic induced MDA levels via the enhancement of the tissue GSH and blood vitamin C levels. Conclu-
sions: These results suggest that Z. album extract exerts the anti-diabetic and antihypercholesterolemic activities through its antioxidant
properties.
2011 Elsevier Ireland Ltd. All rights reserved.

Keywords: Diabetes mellitus; Zygophyllum album; Streptozotocin; Antioxidants; Plasma lipid; Liver; Pancreas; Mice

1. Introduction disease by the year 2025 [1]. It is a chronic metabolic dis-

Diabetes mellitus is increasingly common metabolic dis-
order and one of the five leading causes of death in the
world. It is projected that 300 million people will have the
Corresponding author at: Unit de Toxicomtrie & Chronobiomtrie,
Laboratoire de Biosurveillance de lEnvironnement (LR01/ES14), Facult
des Sciences de Bizerte, Universit de Carthage, 7021 Zarzouna, Tunisia.
E-mail address: jamel.elghoul@yahoo.fr (J.E. Ghoul).
1 These authors contributed equally to this work.
order of multiple aetiologies; and is mainly diagnosed by
blood glucose rise subsequently to insulin deficiency. Type
I, insulin-dependent diabetes mellitus, is characterized when
the body is totally short of the production of insulin. Dia-
betes patients of type I take daily doses of insulin. Type
II, non insulin-dependent diabetes mellitus, is defined by
loosing accuracy to produce enough quantity or appropri-
ately use insulin. This type constitutes the epidemic form
of the disease [2]. Such disorders lead to various profound

0928-4680/$ see front matter 2011 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.pathophys.2011.12.001
36 J.E. Ghoul et al. / Pathophysiology 19 (2012) 3542
secondary complications like as, atherosclerosis, hyperten-
sion, hypercholesterolemia, myocardial infarction, ischemic
attacks, retinopathy and nephropathy [3]. Hyperglycemia can
increase the oxidative stress by several mechanisms, includ-
ing glucose auto-oxidation, non-enzymatic protein glycation
and activation of polyol pathway. The rise in free radical
activity is suggested to play an important role in lipid perox-
idation and protein oxidation of cellular structures resulting
in cell injury and is implicated in the pathogenesis of vas-
cular disease which are the mainly cause of morbidity and
mortality in both type I and type II diabetes [4].
Traditional medicines derived mainly from plants have
played and still plays major role in the management of dia-
betes mellitus [57]. In recent years, the role of alternative
therapeutic approaches has become very popular [8] and since
a single plant may have many pharmacological activities
(anti-diabetic, anti-oxidant and anti-stress activity) they can
be effectively utilized to delay or counter diabetic complica-
tions. Various plant extracts had been evaluated as treatment
against diabetes such as Gongronema latifolium [9], Ricinus
communis [10], Teucrium polium [11], Zygophyllum gaetu-
lum [12] and Zygophyllum coccineum [13]. The decoction of
Zygophyllum album (Zygophyllacae), leaves is widely used
to treat hyperglycemia in folk medicine, in Tunisia; but few
studies had investigated its effects and mechanism of action.
Streptozotocin is frequently used to induce diabetes mel-
litus in experimental animals through its toxic effects on
pancreatic -cells [1417]. STZ has drawn attention as a
potential inducer of oxidative stress and several evidences
indicate that the reactive oxygen species (ROS) generation is
responsible for its wide spectrum of genotoxic effects in vitro
[18]. Although the genotoxic effects of STZ are fairly well
established in vitro, data on its potential to induce mutagenic
alterations in vivo are limited [19]. Disturbances of antiox-
idant defence systems in diabetes have been demonstrated,
including alteration in the activities of antioxidant enzymes
such as superoxide dismutase (SOD), catalase (CAT), glu-
tathione peroxidase (GPx), glutathione reductase (GR) and
impaired glutathione (GSH) metabolism [20]. Implication
of oxidative stress in the pathogenesis of diabetes is sug-
gested not only by oxygen free-radical generation but also
due to nonenzymatic protein glycosylation, auto-oxidation
of glucose [2123], impaired glutathione metabolism [24],
alteration in antioxidant enzymes [25], lipid peroxides for-
mation [26] and decreased ascorbic acid levels [27]. In
addition to GSH [28] there are other defence mechanisms
against free radicals like the enzymes superoxide dismutase
(SOD), glutathione peroxidase (GPx) and catalase (CAT)
whose activities contribute to eliminate superoxide, hydrogen
peroxide and hydroxyl radicals [29].
Since that, the goal of this study was to evaluate the effects
of aqueous extracts of Z. album on the blood glucose level in
streptozotocin-induced diabetic mice. The effect of Z. album
extracts on the levels of malondialdehyde (MDA) and some
oxidative stress scavengers in blood and liver and pancreas
were also determined.
2. Materials and methods
2.1. Preparation of the aqueous extract
Fresh whole Z. album plants were collected from South-
ern Tunisia (Douz/Gbli) between May and July 2007. The
plant was identified by Mr. EL-OUNI botanist and Profes-
sor Emeritus at the University of Carthage (Bizerte, Tunisia).
A voucher specimen was deposited in the herbarium of our
laboratory. The plant material was dried at ambient temper-
ature and stored in a dry place prior to use. The plant was
washed well with water, dried at room temperature in the
dark, and then ground in an electric grinder to give a coarse
powder. A 100 g of the powdered aerial parts were suspended
in 1000 ml distilled water, heated and boiled under reflux for
30 min. The decoction obtained was filtered, and the filtrate
frozen at 20 C and then lyophilised. The average yield
of the lyophylised material (Za-extract) was approximately
18.3%. It was stored at ambient temperature until further use.
2.2. Chemicals and reagents
Reagents were obtained from Sigma Aldrich (Milano,
Italy) and Merck (Darmstadt, Germany), and were of the
highest commercial grade available.
2.3. Experimental induction of type 2 diabetes in mice
The experiments were carried out with 810 weeks-old
adult male Swiss albino mice weighing about 25 (2) g. The
animals were kept in polyacrylic cages (22.5 cm 37.5 cm)
with 5 mice per cage and maintained under standard hous-
ing conditions (room temperature 2427 C and humidity
6065%) with a 12-h light and dark cycle. Food, in the
form of dry pellets, and water were available ad libitum. For
the experimental induction of diabetes, streptozotocin (STZ)
(SigmaAldrich Corp, St. Louis, MO, USA) was freshly pre-
pared by dissolving in citrate buffer (0.01 M, pH 4.5) and ice
cooled, before administration [30]. A single dose of 45 mg/kg
STZ was intraperitoneally injected to mice. One week after
STZ injection, only mice with blood glucose concentration
higher than 250 mg/dl (at fasting state) were considered as
diabetic and included in the present study.
2.4. Experimental design
A total of 40 mice were divided into five groups in as
follows:
Group I: normal control mice, received only saline solution.
Group II: diabetic control mice, received STZ in single dose
(45 mg/kg, i.p.).
Group III: treated diabetic mice received the aqueous
extract of Z. album extract (100 mg/kg, p.o.).
Group IV: treated diabetic mice received the aqueous extract
of Z. album extract (300 mg/kg, p.o.).
 J.E. Ghoul et al. / Pathophysiology 19 (2012) 3542
Group V: STZ-diabetic mice received gliclazide (25 mg/kg,
i.p.).
Animals were treated by oral gavage once a day for a
period of 15 days.
2.5. Blood and tissue collection
After an overnight fasting, mice were decapitated, and
total arterio-venous blood was collected for glucose and
vitamins analysis. Thereafter, an abdominal incision was
performed, in order to harvest livers and pancreas. The
whole organs were cleaned with chilled normal saline on
the ice. A 10% (w/v) homogenate of organ samples (0.03 M
sodium phosphate buffer, pH 7.4) was prepared by using
an Ultra-Turrax homogenizer at a speed of 9500 rpm. The
homogenized tissue preparation was used to measure MDA,
CAT, SOD, GPx and GSH levels.
2.6. Blood glucose measurement
Blood glucose was measured by O-toluidine method of
Sasaki et al. [31]. Briefly, 0.1 ml of the blood was mixed
1.9 ml of 10% trichloroacetic acid (TCA) solution to precipi-
tate proteins and then centrifuged. 1.0 ml of supernatant was
mixed with 4.0 ml of O-toluidine reagent and was 6 kept in
boiling water bath for 15 min and cooled. The absorbance
was read at 620 nm. Data were expressed as mg/dl.
2.7. Vitamin E determination
Vitamin E was measured by the method of Desai [32]. To
0.25 ml of plasma, 0.25 ml of ethanol was added and thor-
oughly mixed. Then 0.75 ml of petroleum ether was added,
shaken rapidly and centrifuged. 0.5 ml of supernatant was
taken and evaporated to drought. To this 0.05 ml of 0.2%
bathophenanthoraline was added. The assay mixture was pro-
tected from light and 0.05 ml of 0.001 M ferric chloride was
added followed by 0.05 ml of 0.001 M phosphoric acid. The
total volume was made up to 0.75 ml with ethanol. The color
developed was read at 530 nm. The level of vitamin E was
expressed as mg/dl of plasma.
2.8. Vitamin C determination
This assay was based on the method described by Omaye
et al. [33]. To 0.25 ml of plasma, 0.25 ml of water and 0.5 ml
of 5% TCA were added, mixed thoroughly and centrifuged.
To 0.5 ml of the supernatant, 0.1 ml of, 4-dinitrophenyl
hydrazinethioureaCuSO4 (DTC) reagent was added and
incubated at 37.8 C for 3 h. Then 0.75 ml of 65% sulfuric
acid was added mixed well and the solution was allowed
to stand at room temperature for another 30 min. The color
developed was read at 520 nm. The level of vitamin C was
expressed as mg/dl of plasma.
37
2.9. Lipid peroxidation
MDA, as a measure of lipid peroxidation, was mea-
sured spectrophotometrically by the method of Ohkawa et al.
[34], using 1,1,3,3-tetraethoxypropane as standard. MDA is
expressed as n moles per mg protein. To 500 l of liver or
pancreatic homogenates in phosphate buffer (pH 7.4), 300 l
of 30% trichloroacetic acid (TCA), 150 l of 5 N HCl and
300 l of 2% (w/v) 2-thiobarbituric acid (TBA) were added
and then the mixture was heated for 15 min at 90 C. The mix-
ture was centrifuged at 12,000 g for 10 min. Pink colored
supernatant was obtained, which was measured spectropho-
tometrically at 532 nm.
2.10. Reduced glutathione (GSH)
GSH content was estimated by method of Sedlak and
Lindsay [35]. The tissues were homogenized in 0.02 M with
ethylenediaminetetraacetic acid (EDTA). Aliquots of 5 ml
of the homogenates were mixed in test tube with 4 ml of
cold distilled water and 1 ml of 50% TCA. The tubes were
shaken for 10 min using vortex mixer and the centrifuged at
1200 g for 15 min. Following centrifugation 2 ml of super-
natant was mixed with 4 ml of 0.4 M Trisbuffer (pH 8.9).
The whole solution was mixed and 0.1 ml of 0.01 M DTNB
{5,5 -dithiobis (2-nitrobenzoic acid)} was added to it. The
absorbance was read within 5 min of the addition of DTNB
at 412 nm against a reagent blank with no homogenate.
2.11. Glutathione peroxidase (GPx)
GPx was assayed by the method of Rotruck et al. [36]. The
reaction mixture consisted of 0.2 ml of 0.8 mM EDTA, 0.1 ml
of 10 mM sodium azide, 0.1 ml of 2.5 mM hydrogen perox-
ide (H2 O2 ), 0.2 ml of 4 mM reduced glutathione, 0.4 ml of
0.4 M phosphate buffer (pH 7.0), and 0.2 ml homogenate was
incubated at 37.8 C for 10 min. The reaction was arrested
by the addition of 0.5 ml of 10% TCA and the tubes were
centrifuged at 2000 rpm. To the supernatant 3 ml of 0.3 M
disodium hydrogen phosphate and 1.0 ml of 0.04% DTNB
were added and the color developed was read at 420 nm
immediately. The activity of GPx was expressed as moles
of glutathione oxidized/min/mg protein.
2.12. Catalase (CAT)
CAT was assayed by the method of Aebi [37]. To 1.2 ml
of 50 mM phosphate buffer (pH 7.0), 0.2 ml of the tissue
homogenate was added and the enzyme reaction was started
by the addition of 1.0 ml of 30 mM H2 O2 solution. The
decrease in absorbance was measured at 240 nm at 30 s inter-
vals for 3 min. The enzyme blank was run simultaneously
with 1.0 ml of distilled water instead of hydrogen perox-
ide. The enzyme activity was expressed as moles of H2 O2
decomposed/min/mg protein.
38 J.E. Ghoul et al. / Pathophysiology 19 (2012) 3542

2.13. Superoxide dismutase (SOD)

SOD was assayed by the method of Misra and Fridovich

[38]. 0.1 ml of tissue homogenate was added to tubes con-
taining 0.75 ml ethanol and 0.15 ml chloroform (chilled
in ice) and centrifuged. To 0.5 ml of supernatant, added
0.5 ml of 0.6 mM EDTA solution and 1 ml of 0.1 M
carbonatebicarbonate buffer (pH 10.2). The reaction was
initiated by the addition of 0.5 ml of 1.8 mM epinephrine
and the increase in absorbance at 480 nm was measured. The
enzyme activity is expressed as 50% inhibition of epinephrine
autooxidation/min.
2.14. Measurement of lipid prole
Lipid profiles were estimated by the method of Yadav
et al. [39] and were obtained by using commercially avail-
able kits. Total cholesterol, high density lipoprotein (HDL)
cholesterol and triglyceride (TG) levels in serum were
determined according to the instructions of the manufac-
turer (Sigma Diagnostics). For the determination of very
low density lipoprotein (VLDL) and low density lipopro-
tein (LDL), Friedwalds (1972) formula was used which
states: VLDL cholesterol = Triglyceride/5 and LDL choles-
terol = Total cholesterol (VLDL + HDL cholesterol).
2.15. Protein determination
Protein content was determined by the method of Bradford
using assay kit (Sigma Diagnostics).
2.16. Statistical analysis
Results are expressed as the means SD. Students t-test
for unpaired samples was performed using GraphPad Prism
(GraphPad Software, Version 4.0). A value of p < 0.05 was
considered significant.
3. Results
Fig. 1. Effect of aqueous extract of Zygophyllum album on blood glucose
level in STZ-induced diabetic mice. The data are expressed as means S.D.
(n = 8). Values are statistically significant at p < 0.05. a Diabetic control vs.
control. b Diabetic + Zygophyllum album extract 100 mg/kg vs. c diabetic con-
trol. Diabetic + Zygophyllum album extract 300 mg/kg vs. diabetic control.
d Diabetic + gliclazide vs. diabetic control.
3.2. Effect of aqueous extract of Z. album on lipid
peroxidation (Fig. 2)
Thiobarbituric acid reactive substances, as quantified by
MDA, were significantly augmented in diabetic control
group, in comparison with the other groups of mice (I, III,
IV and V), both in liver and pancreas (p < 0.05). MDA level
was also greater in group III in comparison with groups I,
IV and V (p < 0.05), in both pancreas and liver (Fig. 2).
3.3. Effect of aqueous extract of Z. album on serum
vitamin C and E (Fig. 3)
The levels on serum vitamin E and vitamin C level in
STZ-induced diabetic mice are shown in Fig. 3. Diabetic mice
(group II) had low level of vitamin C and the elevation of vita-
min E in serum when compared with control mice (group I).
Diabetic mice (group II) treated with aqueous extract (groups
III and IV) and with glicazide (group V) showed a significant
increase (p < 0.05) in the level of vitamin C and a decrease
(p < 0.05) in the level of vitamin E.
3.4. Effect of aqueous extract of Z. album in liver and
pancreatic activities of GSH, GPx, SOD and CAT
(Tables 1 and 2)

Tables 1 and 2 show the levels of the oxidative stress

3.1. Effect of aqueous extract of Z. album on blood
enzymes activities, respectively, in liver and pancreas. GPx,
glucose (Fig. 1)
SOD and CAT activity levels were significantly increased in
diabetic control mice than in other groups (p < 0.05). How-
Induction of diabetes in the experimental mice was con-
ever, the GSH level was significantly diminished in diabetic
firmed of a high fasting blood glucose level. A significant
mice when compared to shame, and diabetic treated mice
(p < 0.05) increase in the level of blood glucose (group
with either Z. album extracts or glicazide.
II) was observed in diabetic mice when compared to con-
trols (group I). Administration of aqueous extract of Z. 3.5. Effect of ethanolic extract of Z. album on serum
album at a dose of 100 mg/kg (group III) and 300 mg/kg lipid proles
(group IV) to diabetic mice significantly (p < 0.05) decreased
the level of blood glucose again to near normal level Serum TC, TG, LDL, VLDL and HDL levels of the exper-
(Fig. 1). imental groups of animals are shown in Table 3. Serum TC,
 J.E. Ghoul et al. / Pathophysiology 19 (2012) 3542 39

Table 1
Effect of traditional aqueous extract of Zygophyllum album on anti-oxidative enzymes activities in the liver in STZ-induced diabetic mice.
Groups I II III IV V
GSH 6.83 0.23 1.94 0.19a 3.24 0.16b 6.01 0.09c 6.02 0.14d
GPx 11.94 0.17 18.74 0.27a 15.04 0.13b 13.56 0.6c 9.85 1.32d
SOD 4.02 0.3 8.91 0.15a 6.39 0.2b 3.98 0.24c 3.88 0.36d
CAT 18.69 0.48 27.33 0.39a 24.1 0.09b 21.05 0.27c 16.89 1.2d
The data are expressed as means S.D. (n = 8). Values are statistically significant at p < 0.05.
Nanomoles per milligram of protein for GSH.
Micromoles of glutathione oxidized per minute per milligram of protein for GPx.
Activity is expressed as: 50% of inhibition of epinephrine auto-oxidation per minute for SOD; Micromoles of hydrogen peroxide decomposed per minute per
milligram of protein for CAT.
a Diabetic control vs. control.
b Diabetic + Zygophyllum album extract 100 mg/kg vs. diabetic control.
c Diabetic + Zygophyllum album extract 300 mg/kg vs. diabetic control.
d Diabetic + gliclazide vs. diabetic control.

Table 2
Effect of aqueous extract of Zygophyllum album on anti-oxidative enzymes activities in pancreas in STZ-induced diabetic mice.
Groups I II III IV V
GSH 2.23 0.08 0.63 0.06a 0.97 0.025b 2.08 0.012c 2.02 0.006d
GPx 7.03 0.19 13.01 0.2a 11.23 0.21b 7.13 0.3c 8.05 0.17d
SOD 2.35 0.2 6.2 0.12a 4.31 0.06b 2.95 0.07c 2.65 0.17d
CAT 15.63 0.53 26.22 0.48a 22.07 0.31b 17.63 0.43c 16.02 0.35d
The data are expressed as means S.D. (n = 8). Values are statistically significant at p < 0.05.
Nanomoles per milligram of protein for GSH.
Micromoles of glutathione oxidized per minute per milligram of protein for GPx.
Activity is expressed as: 50% of inhibition of epinephrine auto-oxidation per minute for SOD; Micromoles of hydrogen peroxide decomposed per minute per
milligram of protein for CAT.
a Diabetic control vs. control.
b Diabetic +Zygophyllum album extract 100 mg/kg vs. diabetic control.
c Diabetic + Zygophyllum album extract 300 mg/kg vs. diabetic control.
d Diabetic + gliclazide vs. diabetic control.

TG, LDL and VLDL were significantly higher (p < 0.05) in
STZ-induced diabetic mice (group II) than those in normal
controls (group I). Decreased levels of HDL were observed
in STZ induced diabetic mice compared to normal untreated
mice.
Treatment with aqueous extract of Z. album and gliclazide
resulted in a significant decrease (p < 0.05) in TC, TG, LDL
and VLDL levels compared to those in STZ-induced dia-
betic mice. Serum HDL levels were significantly increased
(p < 0.05) in the diabetic treated group.
4. Discussion
Recently, a growing concern has brought back to
traditional and alternative medicines, both for their phar-
macological properties and their economical interest. As
mentioned above, various phyto-therapeutic products are
already used; and convey satisfactory results. In essence,
Zygophyllum sp., Mediterranean Zygophyllacea plants, are
widely used in traditional medicine for their anti-diabetic,
antiseptic, antispasmodic, anti eczema [40] anti-diarrheal

Table 3
Effects of aqueous extract of Zygophyllum album on serum lipids content in STZ-induced diabetic mice.
Groups I II III IV V
TC 2.18 0.19 4.88 0.13 3.26 0.09 2.65 0.08 2.14 0.18
HDL 0.96 0.09 0.51 0.08a 0.73 0.06b 1.05 0.1c 0.88 0.12d
VLDL 0.326 0.035 0.916 0.09a 0.64 0.015b 0.376 0.1c 0.35 0.081d
LDL 0.894 0.1 3.73 0.21a 1.614 0.35b 1.224 0.12c 0.91 0.13d
TG 1.63 0.13 3.02 0.15a 2.75 0.18b 1.88 0.21c 1.75 0.19d
Plasma total cholesterol (TC), high-density lipoprotein (HDL), very low-density lipoprotein (VLDL), low-density lipoprotein (LDL) and triglycerides (TG)
were measured by kits. Values are expressed as mmol/l and are given as mean SD for five groups of 8 animals each. Values are statistically significant at
p < 0.05.
a Diabetic control vs. control.
b Diabetic + Zygophyllum album extract 100 mg/kg vs. diabetic control.
c Diabetic + Zygophyllum album extract 300 mg/kg vs. diabetic control.
d Diabetic + gliclazide vs. diabetic control.
40 J.E. Ghoul et al. / Pathophysiology 19 (2012) 3542
Fig. 2. Effect of aqueous extract of Zygophyllum album on lipid peroxida-
tion (MDA) in liver (A) and pancreas (B) in STZ-induced diabetic mice. The
data are expressed as means S.D. (n = 8). Values are statistically significant
at p < 0.05. a Diabetic control vs. control. b Diabetic + Zygophyllum album
extract 100 mg/kg vs. c diabetic control. Diabetic + Zygophyllum album
extract 300 mg/kg vs. diabetic control. d Diabetic + gliclazide vs. diabetic
control.
[41] and anti inflammatory [42] effects. In this paper, we
had experimentally investigated the anti-diabetic effect of Z.
album aqueous extracts, with special focus on their impact
on the oxidative/anti-oxidative system.
Our results showed that the daily injection of the aque-
ous extract of Z. album during 15 days abolished the blood
sugar increase in the STZ induced diabetic mice. This effect
was dose dependent. These results were well corroborated
those reported by other authors using various Zygophyllacea
plants [40,43]. The mainly proposed mechanism of such gly-
caemia decrease may be bypassed through enhancement of
the peripheral sugar uptake and metabolism and insulin secre-
tion [44].
Because of the misbalanced oxidative/anti oxidative
system in diabetes mellitus and its involvement in the
mechanism of various pathological complications, the effect
of the aqueous extract of this plant on the oxidative stress,
was investigated. In accordance to results reported by Kakkar
Fig. 3. Effect of aqueous extract of Zygophyllum album on serum vitamin
C (A) and vitamin E (B) level in STZ-induced diabetic mice. The data
are expressed as means S.D. (n = 8). Values are statistically significant
at p < 0.05. a Diabetic control vs. control. b Diabetic + Zygophyllum album
extract 100 mg/kg vs. diabetic control. c Diabetic + Zygophyllum album
extract 300 mg/kg vs. diabetic control. d Diabetic + gliclazide vs. diabetic
control.
et al. [45], we had found that streptozotocin increased both
the lipid peroxidation (MDA) and the anti-oxidant enzyme
(SOD, GPx and CAT) activities, in diabetic control mice. The
authors delineated that the increase in antioxidant enzyme
activities could primarily be a response to the diabetic
state; whereas STZ appears to not exert any direct effects
on these activities [45]. Interestingly, the administered Z.
album aqueous extract potentially prevented the liver and
pancreatic MDA increase observed in diabetic mice, in a
dose dependent manner. Such diminution in the lipid perox-
idation may be a consequence of the observed enhancement
of the enzymatic (GSH) and non enzymatic (vitamin C)
anti oxidative scavengers. According to Evans and Halliwell
[46] the antioxidant defences consist of low molecular
mass antioxidants, intracellular enzymes, sequestration of
transition metal ions and repair mechanisms. Particularly
important low molecular mass antioxidants are glutathione,
vitamin E, ubiquinone, -carotene, vitamins C and A. GSH
 J.E. Ghoul et al. / Pathophysiology 19 (2012) 3542
and vitamin C strongly prevent the lipid peroxidation and
DNA damages induced by the hydroxyl radical [47].
Currently used drugs against diabetes are essentially
focused on controlling and lowering blood glucose to a
normal level, via different pathways, while diabetic com-
plications require other treatments. Somewhat, undesirable
side-effect such as hypoglyceamia, lactic acid intoxication
and gastrointestinal upset appear after patients took these
medicines [2]. To disclose the wonder, alternative medicines
are looked as an adequate solution. The reported results,
herein, suggest that Z. album aqueous extract is able to
re-establish both the blood glucose level and the oxidative
stress status, which are determinants of diabetic secondary
complications. The actions of the extract need to be fur-
ther studied to clarify which compounds are active and
to establish their mechanisms of action in the therapeutic
effects.
The levels of serum lipids are usually elevated in dia-
betes mellitus and such an elevation represents a risk factor
for coronary heart disease [48]. Marked increase in total
cholesterol, triglycerides, VLDL, LDL and decreased HDL
cholesterol are observed in untreated diabetic mice.
Several authors have reported anti-hyperlipedimic activ-
ity of medicinal plants [4951]. Diabetes mellitus is related
to a hyperlipidemia and leads to serious anomalies in lipids
composition and concentration [52]. These anomalies can
induce cardiovascular diseases [53]. It is known that the
increase in serum lipids in STZ-induced diabetic rats played
an important role in such pathology [54]. In our study, we
recorded a significant increase in the serum concentration
of total cholesterol and triglyceride levels at STZ-induced
diabetic mice (p < 0.001). The high level of total choles-
terol in the blood could be seen as a major risk factor
generating coronary heart disease [55]. These results agree
with those found by Eddouks et al. [56], Ravi et al. [57]
who suggest that the abnormal high concentration of serum
lipids observed in diabetic subjects is mainly due to the
increase in the mobilization of fatty acids from fat tissue
[57]. Indeed, Betterridge [58] have indicated that the defi-
ciency in insulin or the insulin resistance may be responsible
for hyperlipidaemia due to the insulin inhibiting action on
the 3-hydroxy-3-methyl-methylglutaryl coenzyme-A a key
enzyme in the cholesterol biosynthesis. During diabetes, the
hyperlipidemia may be regarded as a result of the non-
inhibiting action of the lipolytic hormones on adipose tissues
[59].
5. Conclusion
The present study showed that increased oxidative stress
is apparent in STZ-induced diabetic animals. The traditional
aqueous extract of Z. album exhibited a significant antihy-
perglycemic as well as antioxidant activity in experimentally
diabetic mice.
41
Conict of interest statement
No conflicts of interest.
Acknowledgment
We are grateful to the Tunisian Ministry of Superior Edu-
cation and Scientific Research for financial support.
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