PHYTOTHERAPY RESEARCH

Phytother. Res. 22, 303–307 (2008)

Published online 4 DecemberHYPOGLYCEMIC
2007 in Wiley InterScience
ACTIVITY OF AILANTHUS EXCELSA 303
(www.interscience.wiley.com) DOI: 10.1002/ptr.2311

Hypoglycemic Activity of Ailanthus excelsa

Leaves in Normal and Streptozotocin-induced
Diabetic Rats

W. Cabrera1, S. Genta1, A. Said2, A. Farag3, K. Rashed2 and S. Sánchez1*

1
Departamento de Biología del Desarrollo, Instituto Superior de Investigaciones Biológicas, Consejo Nacional de Investigaciones
Científicas y Técnicas y Universidad Nacional de Tucumán, Chacabuco 461, (4000) San Miguel de Tucumán, Argentina
2
National Research Centre, Pharmacognosy Department, Dokki, Cairo, Egypt
3
Organic Chemistry Department, Faculty of Science, Cairo University, Egypt

The hypoglycemic activity of a 70% methanol extract from the leaves of Ailanthus excelsa Roxb.
(Simaroubaceae) was studied in normal, transiently hyperglycemic and streptozotocin (STZ)-induced diabetic
rats. Oral administration of the extract at doses of 14, 70 and 350 mg/kg body weight caused no significant changes
in fasting blood glucose levels of normal rats. In an oral glucose tolerance test, the extract produced a significant
decrease in glycemia 90 min after the glucose pulse. Daily administration of A. excelsa extract for 60 days
produced a significant hypoglycemic effect in diabetic animals. In addition, this treatment improved the
altered renal function observed in diabetic control rats. This study suggests that Ailanthus leaf extract could
be potentially useful for post-prandial hyperglycemia treatment. Copyright © 2007 John Wiley & Sons, Ltd.

Keywords: Ailanthus excelsa; hypoglycemic effect; streptozotocin-induced diabetes.

1993). Ailanthus is used to cure wounds and skin erup-

INTRODUCTION
Diabetes mellitus is a chronic metabolic disorder
characterized by deregulation in carbohydrate, protein
and fat metabolism (O’Brien and Granner, 1996).
Such alterations result in increased blood glucose,
which causes long-term complications in many organs.
Despite the important progress in the management
of diabetes by using synthetic drugs, many traditional
plant treatments are used throughout the world. The
World Health Organization (WHO) has recommended
that this practice should be encouraged, especially in
developing countries (WHO Expert Committee, 1980).
However, few traditional antidiabetic plants have re-
ceived proper scientific validation.
Ailanthus excelsa Roxb. (natural order: Simaroubaceae),
a large tree originally from China, is known as the ‘tree
of heaven’ (Adamik and Brauns, 1957). Different parts
of this plant are used widely in traditional medicine
for a variety of diseases (British Pharmacopoeia, 1988).
The root bark has been reported to possess cytotoxic
and antitumor activity both in mice and in cell cultures
(Ogura et al., 1977). Stem bark extracts showed potent
antibacterial and antifungal activities (Shrimali et al.,
2001; Joshi et al., 2003). The alcohol extract from leaf
and stem bark exhibits remarkably high antiimplantation
and early abortifacient activity (Dhanasekaran et al.,
tions as mentioned in traditional medicine (Asolkar et al.,
1992). A recent study reveals that ethanol extracts of
A. excelsa leaves have a significant hepatoprotective
effect on experimental liver damage in rats (Hukkeri
et al., 2002). Despite its multiple ethnopharmacological
properties, at present there are no reports in the litera-
ture indicating that any controlled experiment has been
performed to test Ailanthus for antidiabetic activity.
A. excelsa is a rich source of different chemical com-
pounds with a variety of potential biological activities
(Kapoor et al., 1971). Recent investigations have estab-
lished the presence of six flavonoids isolated for the
first time from A. excelsa leaves (Loizzo et al., 2007). Data
indicate that some flavonoids isolated from several
medicinal plants reduce blood glucose levels (Zarzuelo
et al., 1996; Korec et al., 2000). However, at present,
no antidiabetic properties have been determined for
the flavonoids present in Ailanthus extracts.
The purpose of the present study was to examine the
effect of an A. excelsa leaf extract on blood glucose
levels in normal glycemic, transient hyperglycemic and
streptozotocin (STZ)-induced diabetic rats. The effect
of a 60-day administration of the extract to diabetic
rats was also evaluated on several renal parameters in
order to determine its potential antidiabetic use.

MATERIALS AND METHODS

* Correspondence to: Sara S. Sánchez, Departamento de Biología del
Desarrollo, Instituto Superior de Investigaciones Biológicas, Consejo Plant material. Leaves of A. excelsa were collected
Nacional de Investigaciones Científicas y Técnicas y Universidad Nacional in April from the Zoo Garden, Giza, Egypt and air-
de Tucumán, Chacabuco 461, (4000) San Miguel de Tucumán, Tucumán, dried. The plant material was botanically authenticated
Argentina.
E-mail: ssanchez@fbqf.unt.edu.ar
by Dr Kamal El-Batanony and a voucher specimen
Contract/grant sponsor: Research Council of the Universidad Nacional (N° 142904) was deposited at the Herbarium of the
de Tucumán (CIUNT). Faculty of Science, Cairo University, Egypt.
Copyright © 2007 John Wiley & Sons, Ltd. Received
Phytother. Res. 9 April(2008)
22, 303–307 2007
Revised
DOI:2110.1002/ptr
June 2007
Copyright © 2007 John Wiley & Sons, Ltd. Accepted 10 July 2007
304 W. CABRERA ET AL.
Preparation of the methanol extract of A. excelsa leaves.
Three hundred grams of dried powdered leaves of
A. excelsa was extracted with 3 L of 70% methanol
in a continuous extraction apparatus (Soxhlet) until
exhaustion. The extract was concentrated under reduced
pressure. The residue was dissolved in 100 mL of dis-
tilled water and subjected to freeze drying. The extract
yield after freeze drying was 32.0 g.
Experimental animals. Male adult Wistar rats (weight
250–300 g) from the colony bred at the Biology Insti-
tute of the National University of Tucumán, Tucumán,
Argentina, were used. The animals were housed in
plastic cages in an air conditioned animal room. They
were fed with a standard laboratory diet, given tap water
ad libitum and kept under controlled temperature
(23 ± 1 °C), humidity (approximately 60%) and a dark-
light cycle (12 h) until experiments were carried out.
All animals were maintained and handled according
to International Ethical Guidelines for the Care of
Laboratory Animals (United States Food and Drug
Administration).
Effects of A. excelsa extract on blood glucose levels
in normal rats. Fasted male Wistar rats were divided
into four groups of ten animals each. One group was
used as the control and received only water, while the
other groups received leaf extract orally in doses of
14, 70 or 350 mg/kg body weight. Blood samples were
obtained by amputation of the tail tip at different times
during the above treatments. Glycemia was measured
by using an Accu-chek Active® (Roche Diagnostics
GmbH D-68298 Mannheim, Germany), based on glucose
dye oxidoreductase mediator reaction.
Glucose tolerance test in normal rats. The glucose
tolerance test was carried out in fasted rats, which were
divided into five groups of ten animals each. One group
received orally distilled water and was kept as a con-
trol. The other groups were given orally the following:
(i) a reference drug (glymepiride, 5 mg/kg body weight);
(ii) leaf extract, 14 mg/kg body weight (low dose);
(iii) leaf extract, 70 mg/kg body weight, (iv) leaf extract,
350 mg/kg body weight (high dose). Thirty minutes later
a 50% (w/v) glucose solution was administered orally
(2 g/kg body weight) to each rat. Blood samples were
taken from the tail vein at 0 min (just before glucose
administration) and at 15, 30, 45, 60, 75, 90, 120 and
180 min for the determination of blood glucose, as
described above.
Determination of fasting blood glucose and plasma
insulin levels in diabetic rats. Stable diabetes was in-
duced by intraperitoneal administration to male Wistar
rats of streptozotocin (STZ, Sigma Chemical Company,
St Louis, MO, USA) dissolved in 10 mM sodium citrate
buffer (pH 4.5), at a dose of 45 mg/kg body weight.
Control rats received only citrate buffer. Diabetes was
achieved within 24 h in the majority of the animals, as
determined by the blood glucose levels and glucosuria.
Only the animals with glycemia of >350 mg/dL 2 days
after STZ treatment were included in the study.
Diabetic rats were divided into five groups (n = 10
per group): a control group without treatment, three
groups with different doses, 14, 70 and 350 mg leaf
extract/kg body weight per day, and a group that
Copyright © 2007 John Wiley & Sons, Ltd.
received glymepiride (5 mg/kg body weight/day). All
samples were administered daily using an intragastric
tube for a period of 60 days. Fasting blood glucose
levels were determined throughout the experimental
period as described above. Plasma insulin level was
assayed with an enzyme immunoassay (ELISA) using
a monoclonal anti-insulin antibody (Boehringer-
Mannheim, Mannheim, Germany).
Creatinine clearance. Diabetic rats treated with the
leaf extract at a dose of 70 mg/kg body weight/day for
60 days, diabetic untreated rats and control normal
rats were placed in individual metabolic cages for 48 h.
The first 24 h comprised an acclimatization period,
after which a 24 h urine sample was collected. At the end
of the collection period, blood samples were obtained
by amputation of the tail tip. Serum and urinary crea-
tinine were determined using an Alcyon Analyzer ISE
(Abbott). Creatinine clearance, a measure of glomerular
filtration, was calculated using standard formulae.
Urinary albumin excretion. Diabetic rats treated with
leaf extract for 60 days, diabetic untreated rats and
control normal rats were housed in metabolic cages for
urine collection as described above. Urinary albumin
concentration was determined using an ALCYON
Analyzer ISE (Abbott).
Statistical analysis. Results were expressed as mean ±
SD. The significance of the differences between the
mean of the test and control studies was established
by Student’s t test. Values of p < 0.05 were considered
to be significant.
RESULTS AND DISCUSSION
This study was carried out in order to elucidate the
effect of a leaf extract of A. excelsa on blood glucose
levels in normal and STZ-diabetic rats. To the best of
our knowledge, this is the first report addressing the
hypoglycemic activity of an Ailanthus extract.
The results show that a single oral administration of
a methanol leaf extract at doses of 70 mg/kg body weight
(Fig. 1), 14 mg/kg body weight or 350 mg/kg body weight
Figure 1. Effect of the administration of A. excelsa leaf extract
on the fasting blood glucose levels in normal rats. (䊏) Normal
control rats. (䊊) Leaf extract-treated rats (70 mg/kg body weight).
Data are the mean ± SD from three different experiments. Each
experiment was performed with groups of ten rats.
Phytother. Res. 22, 303–307 (2008)
DOI: 10.1002/ptr
 HYPOGLYCEMIC ACTIVITY OF AILANTHUS EXCELSA
Figure 2. Effect of A. excelsa leaf extract on blood glucose
levels during glucose tolerance test in normal rats. (䊏) Normal
control rats. (䉱) Leaf extract-treated rats (14 mg/kg body weight).
(䊐) Leaf extract-treated rats (70 mg/kg body weight). (䊊) Leaf
extract-treated rats (350 mg/kg body weight). (䊉) Glymepiride
(5 mg/kg body weight) treated rats. Data are the mean ± SD
from three different experiments. Each experiment was per-
formed with groups of ten rats.
(data not shown) had no effect on blood glucose levels
in fasted normal rats compared with that of control rats,
which received water. Evidence from the literature sug-
gests that some plants act like biguanides and do not
affect the blood glucose basal state (Bailey et al., 1985;
Hermann et al., 1994). In our case, it is possible that the
Ailanthus extract could act by a similar mechanism.
In the present work, it was demonstrated that the
oral administration of a leaf extract caused a rapid
decrease in the hyperglycemic peak after glucose
loading in normal rats (glucose tolerance test). As shown
in Fig. 2, a dose of 70 mg/kg body weight caused a
significant decrease in the blood glucose levels 90 min
after the glucose pulse. A high dose of the extract
(350 mg/kg body weight) led to a slight reduction in
glycemia compared with the strong effect of the 70 mg/
kg body weight dose, while a low dose (14 mg/kg body
weight) did not cause any effect on the blood glucose
levels. These facts demonstrate a dose-dependent
activity of the leaf extract in the glucose tolerance test.
The 70 mg/kg body weight dose had a significantly
stronger effect than that of the other two doses. The
results obtained led us to suppose that the effect of the
Ailanthus extract could take place through a sulfonylurea-
like mechanism, since it caused a decrease in blood
glucose levels during the glucose tolerance test in a
similar manner to glymepiride. Moreover, the failure
to inhibit the hyperglycemic peak suggests that the
Ailanthus extract had no effect on the transit and
absorption of glucose in the digestive tract. The above
findings suggest that this extract may have therapeutic
potential in post-prandial hyperglycemia.
STZ-induced diabetes has been described as a useful
experimental model to study the antidiabetic activity of
several agents (Junod et al., 1969; Fisher, 1985). In the
present study, the STZ dose (45 mg/kg body weight)
was selected in order to partially destroy the pancreatic
β-cells. Under these conditions, insulin was secreted,
but not in sufficient amounts to regulate blood glucose
levels and, consequently, the rats became permanently
diabetic.
In the above experimental model of diabetes, blood
glucose levels were significantly higher than those in
Copyright © 2007 John Wiley & Sons, Ltd.
305
Figure 3. Effect of a 60-day oral administration of A. excelsa
leaf extract on blood glucose levels of diabetic rats. (䊏)
Diabetic control group. (䊐) Leaf extract-treated rats (70 mg/kg
body weight). (䊉) Leaf extract-treated rats (350 mg/kg body
weight). (䉫) Glymepiride (5 mg/kg body weight) treated rats.
Data are the mean ± SD from three different experiments. Each
experiment was performed with groups of ten rats.
normal rats. A. excelsa extract at a dose of 70 mg/kg
body weight per day was orally administered to diabetic
rats for 60 days and fasted blood glucose and insulin
plasma levels were determined. This treatment produced
a significant decrease in the blood glucose level and an
increase in plasma insulin level compared with untreated
diabetic animals. As shown in Fig. 3, this effect was
observed from the beginning of the treatment, the
maximal effect being observed at day 15 in treated
diabetic rats. At this time, glycemia was approximately
79% lower than that before treatment. The same effect
was observed using a high dose (350 mg/kg body weight
per day) of leaf extract for 60 days. On the contrary, a
low dose of 14 mg/kg body weight per day showed no
hypoglycemic effect in diabetic rats (data not shown).
Given the dose-dependent activity of the extract in these
assays, it is concluded that 70 mg/kg body weight per
day is an effective hypoglycemic dose for diabetic rats.
The possible mechanism by which the leaf extract from
A. excelsa brings about its hypoglycemic effect may be
by stimulation of insulin secretion from the remaining
pancreatic β -cells, as evidenced by the significant in-
crease in the plasma insulin levels following adminis-
tration of the extract (Fig. 4).
The results indicate that a chronic hyperglycemia in
STZ-diabetic rats induced renal alterations character-
ized by increased urinary albumin excretion (Table 1).
This effect is considered as a significant marker of renal
dysfunction (Almdal and Vilstrup, 1988; Gomes et al.,
1997). Many reports have demonstrated that therapeu-
tic intervention can delay the development of diabetic
renal disease (Mathiesen et al., 1994). It was demon-
strated that after a 60 day treatment with leaf extract at
a dose of 70 mg/kg body weight per day, the urinary
albumin excretion was significantly decreased compared
with the values of the diabetic group (Table 1). These
results are in agreement with the increase in creatinine
clearance and the improvement in the general con-
dition of diabetic rats. These results provide a scientific
basis for the potential use of A. excelsa leaves for the
treatment of renal complications in diabetes.
Several medicinal plant extracts are valuable anti-
diabetic agents and may involve one or more active
Phytother. Res. 22, 303–307 (2008)
DOI: 10.1002/ptr
306 W. CABRERA ET AL.

Table 1. Effect of 60 day administration of A. excelsa extract on diabetic rats

Body weight Blood glucose Plasma insulin Creatinine clearance Urinary albumin
Animal group (g) (mg/dL) (μIU/mL) (mL/min/100 g body weight) excretion (mg/24 h)

Control 352.3 ± 20.7 107.3 ± 13.8 14.73 ± 0.99 0.23 ± 0.04 ND

Diabetic 277.4 ± 34.1a 423.7 ± 31.4a 4.50 ± 0.36a 0.12 ± 0.02a 68.3 ± 10.1a
Diabetic + leaf extract 360.3 ± 27.4 113.0 ± 14.7 13.89 ± 1.02 0.21 ± 0.02 12.1 ± 11.3

The values are the mean ± SD of 10 animals (male Wistar rats) in each group. a Probability values <0.05 were considered significant
compared with control group. ND, not detected. Dose of leaf extract is 70 mg/kg body weight.

1998; Kim et al., 2004). In a recent work, Loizzo et al.

Figure 4. Effect of a 60-day oral administration of A. excelsa
leaf extract on plasma insulin levels of diabetic rats. (䊏)
Diabetic control group. (䊐) Leaf extract-treated rats (70 mg/kg
body weight). (䊉) Leaf extract-treated rats (350 mg/kg body
weight). (䉬) Glymepiride (5 mg/kg body weight) treated rats.
Data are the mean ± SD from three different experiments. Each
experiment was performed with groups of ten rats.
(2007) reported that a methanol extract of Ailanthus
excelsa leaves contains six flavonoids isolated for the
first time from this species, namely apigenin, luteolin,
kaempferol-3-O-α-arabinopyranoside, kaempferol-3-O-
β-galactopyranoside, quercetin-3-O-α-arabinopyrano-
side and luteolin-7-O-β-glucopyranoside (Loizzo et al.,
2007). Taking the above into account, it is believed that
one or more of these chemical compounds present
in the leaf extract of A. excelsa are likely to contribute
to the observed hypoglycemic activity. The active
constituent(s) of leaves involved and the precise mecha-
nism of this activity are being studied.
The findings reveal that the leaf extract from A. excelsa
has an important hypoglycemic effect on transiently
hyperglycemic and STZ-induced diabetic rats, but not
on fasted normal rats. Moreover, these results suggest
that the Ailanthus extract might have therapeutic
potential in post-prandial hyperglycemia and could
ameliorate the impaired renal function associated with
diabetes.

components responsible for blood glucose reduction

(Marles and Farnsworth, 1995; Grover et al., 2002).
Flavonoids of different plant origin showed a promis-
ing antidiabetic activity, as demonstrated in diabetic
animal models (Zarzuelo et al., 1996; Nojima et al.,
Acknowledgements
This research was supported by Research Council of the Universidad
Nacional de Tucumán (CIUNT) grant to S. S. Sánchez. We wish to
thank Virginia Méndez for proofreading.

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