Diabetes Research and Clinical Practice 67 (2005) 189195

www.elsevier.com/locate/diabres

Potent hypoglycaemic activity of the aqueous extract

of Chamaemelum nobile in normal and
streptozotocin-induced diabetic rats
M. Eddouksa,*, A. Lemhadria, N.A. Zeggwagha, J-B. Michelb,1
a

UFR: PNPE, BP 21, Errachidia, Morocco 52000

Inserm U460, CHU X.Bichat, 16 rue Henri Huchard, Paris 75018, France

Received 5 January 2004; received in revised form 26 May 2004; accepted 13 July 2004

Abstract
The purpose of this study was to investigate the effect of both a single dose and daily oral administration for 15 days of the
aqueous extract of the aerial part of Chamaemelum nobile (C. nobile) at a dose of 20 mg/kg body weight on blood glucose
concentrations and basal insulin levels in normal and streptozotocin-induced diabetic rats (STZ). Single oral administration of C.
nobile aqueous extract reduced blood glucose levels from 6.0  0.3 mmol/l to 4.9  0.09 mmol/l (P < 0.05) 6 h after
administration in normal rats and from 21.1  1.3 mmol/l to 14.5  0.9 mmol/l (P < 0.001) in STZ diabetic rats. Furthermore,
blood glucose levels were decreased from 6.1  0.06 mmol/l to 4.6  0.17 mmol/l (P < 0.01) and from 21.1  1.31 mmol/l to
13.7  0.90 mmol/l (P < 0.01) in normal and STZ diabetic rats, respectively, after 15 days of treatment. Basal plasma insulin
concentrations remain unchanged after treatment in both normal and STZ diabetic rats so the mechanism of this pharmacological activity seems to be independent of insulin secretion.
We conclude that the aqueous extract of C. nobile exhibits a significant hypoglycaemic effect in normal and STZ diabetic rats
without affecting basal plasma insulin concentrations and support, therefore, its traditional use by the Moroccan population.
# 2004 Elsevier Ireland Ltd. All rights reserved.
Keywords: Chamaemelum nobile; Hypoglycaemia; Streptozotocin; Aqueous extract; Oral administration; Blood glucose

1. Introduction
Herbal medicines have been long used for the
treatment of diabetic patients and they are currently
* Corresponding author. Tel.: +212 55 57 44 97;
fax: +212 55 57 44 85.
E-mail address: m.eddouks@caramail.com (M. Eddouks),
U460@bichat.inserm.fr (J. Michel).
1
Tel.: +33 1 44 85 61 60; fax: +33 1 44 85 61 57.

accepted as an alternative therapy for diabetic

treatment. More than 1200 plants have been described
in the scientific and popular literature as hypoglycaemic agents [15]. The streptozotocin-induced
diabetic rat is considered to be a valuable tool for
pathophysiology and pharmacological studies of type 1
diabetes mellitus [6,7].
Chamaemelum nobile (C. nobile) (Asteraceae)
locally known as Babounge is a native shrub widely

0168-8227/$ see front matter # 2004 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.diabres.2004.07.015

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M. Eddouks et al. / Diabetes Research and Clinical Practice 67 (2005) 189195

distributed throughout the south-eastern region of

Morocco (Tafilalet) in which phytotherapy knowledge
has been and continues to be very developed [8]. Dried
flowers of German chamomile, a taxonomically
related species, are largely used to provide sedative
as well as antispasmodic effects [9]; essential oils from
C. nobile possess sedative, anti-inflammatory and
anti-diuretic activities [10] and genotoxic properties
[11]. In diabetes phytotherapy, the effects of aqueous
C. nobile extract have never been demonstrated
experimentally in either clinical or experimental type
1 diabetes mellitus. However, Konig et al. have
previously demonstrated hypoglycaemic activity of
Chamaemeloside, HMG-containing flavonoid glucoside isolated from C. nobile [12].
The object of this study was to investigate the
pharmacological effects of C. nobile on blood glucose
levels in both normal and streptozotocin-induced
diabetic rats (STZ). The effects of C. nobile are
compared to sodium-vanadate used as a reference
hypoglycaemic drug. The effectiveness of this
compound is not a result of stimulation of insulin
secretion. Thus, we have used vanadate as a positive
control to compare with the effect of C. nobile in the
present study. Finally, the effect of C. nobile on basal
plasma insulin concentrations were also analyzed in
order to determine a probable mechanism of action of
this plant.

2. Materials and methods

2.1. Plant material
Specimens of C. nobile (Asteraceae) were
collected from the Tafilalet region (semi-arid area)
of Morocco in MayJune 2001, and air-dried at
40 8C. The plant was taxonomically identified and
authenticated by Pr. M. Rejdali (Agronomy and
Veterinary Institute, Rabat) and voucher specimen
(ME 35) was deposited at the herbarium of the
Faculty of Sciences and Techniques, Errachidia [8].
2.2. Preparation of the aqueous extract
Plant material was prepared according to the
traditional method used in Morocco (decoction): 1 g

of powdered aerial part, mixed with 100 ml distilled

water, was boiled for 10 min and then cooled for
15 min. Thereafter, the aqueous extract was filtered
using a Millipore filter (Millipore 0.2 mm, St Quentin
en Yvelines, France) to remove particulate matter. The
dose administered was 20 mg of lyophilized aqueous
extract per kg of body weight and 20 mg of the
lyophilized extract was reconstituted in 1 ml of
distilled water as a vehicle. The aqueous extract
was prepared daily, just before administration. The
dose of 20 mg/kg was used according to Moroccan
traditional phytotherapy.

2.3. Experimental design

Experiments were performed in healthy, adult male
Wistar rats, 68 weeks of age and weighing from 200
to 250 g. Animals were housed under standard
environmental conditions (23  1 8C, 55  5%
humidity and a 12 h light/dark cycle) and maintained
with free access to water and a standard laboratory diet
(carbohydrates; 30%, proteins; 22%, lipids; 12%,
vitamins; 3%) ad libitum.
Diabetes was induced by intravenous injection of
streptozotocin (Sigma, St Louis, Mo, USA) into the
tail vein at a dose of 65 mg/kg body weight [6]. STZ
was dissolved in 0.1 M cold sodium citrate buffer, pH
4.5 immediately before use. After 18 h, animals with
fasting blood glucose levels greater than 16.5 mmol/l
were considered diabetic and then included in this
study.
Normal and diabetic rats were randomly assigned
to three different groups (n = 6 in each group). The
control group received distilled water; treated groups
received aqueous extracts of C. nobile (20 mg/kg) or
the reference drug; sodium-vanadate (Fluka, Chemica,
Switzerland) (0.8 mg/kg). All experiments were
performed in overnight fasted rats. Fasted animals
were deprived of food for at least 16 h but allowed free
access to water.
The drug solutions or vehicle were administered
orally by gavage once daily at 10 h a.m. The effect of
the vehicle, C. nobile aqueous extract or vanadate on
blood glucose were determined in fasted rats, 1, 2, 4
and 6 h after a single oral administration and after 2, 4,
7 and 15 days of treatment.

M. Eddouks et al. / Diabetes Research and Clinical Practice 67 (2005) 189195

2.4. Determination of parameters

Blood samples from rats were collected from the
retro-orbital sinus under ether anesthesia. Blood
glucose levels were determined by the glucose oxidase
method using a reflective glucometer (Model GX,
Ames Miles, Bayer Diagnostics, Genome Biotechnologies, Casablanca, Morocco). Basal plasma insulin
concentrations were determined by radioimmunoassay kit (Pharmacia, Uppsala, Sweden) with a Beta
matic counter (Cronex, Dupont, France). The kit
included human insulin as standard and 125I-labelled
human insulin antibody, which cross reacts with rat
insulin.

191

(P < 0.01), 4 h (P < 0.001) and 6 h (P < 0.001) of a

single oral administration in STZ rats (Fig. 1b).
3.2. Repeated oral administration

3. Results

The effects of once daily repeated oral administration of C. nobile (20 mg/kg) and vanadate (0.8 mg/
kg) in normal and STZ diabetic rats are shown in
Fig. 2. In normal rats treated with C. nobile extract,
blood glucose levels were decreased on the second
(P < 0.01), fourth (P < 0.001) and fifteenth day (P <
0.01) (Fig. 2a) of treatment. However, the blood
glucose levels showed a slight increase 7 days after the
start of C. nobile treatment (Fig. 2a). Repeated
vanadate administration did not cause any change of
blood glucose levels (Fig. 2a).
In STZ diabetic rats, once daily repeated oral
administration of the aqueous C. nobile extract
(20 mg/kg) produced a significant decrease of blood
glucose levels from the second day (P < 0.05) to the
fifteenth day (P < 0.01) (Fig. 2b). Finally, vanadate
treatment caused a significant decrease of blood
glucose levels from the second day (P < 0.05) to the
fifteenthth day (P < 0.001) of repeated oral administration (0.8 mg/kg) (Fig. 2b).

3.1. Single oral administration

3.3. Basal plasma insulin concentrations

Fig. 1 depicts the blood glucose lowering effect of

a single oral administration of the aqueous extract of
C. nobile aerial part (20 mg/kg) and vanadate (0.8 mg/
kg) in normal (Fig. 1a) and STZ diabetic rats (Fig. 1b).
In normal rats, the blood glucose levels dropped
significantly from the second hour (P < 0.01) to the
sixth hour (P < 0.05) after a single oral administration
of aqueous C. nobile extract (20 mg/kg) (Fig. 1a).
Vanadate treatment at a dose of 0.8 mg/kg) produced
a slight decrease in blood glucose levels 2 h after
treatment (P < 0.05) (Fig. 1a). In STZ rats, a
significant progressive decrease of blood glucose
levels was noted in both C. nobile and vanadate treated
groups (Fig. 1b). Pre-treatment blood glucose levels in
diabetic rats dropped from the first (P < 0.05) to the
sixth hour (P < 0.001) after a single oral administration of aqueous C. nobile extract (20 mg/kg)
(Fig. 1b). Vanadate at a dose of 0.8 mg/kg caused a
significant decrease in blood glucose levels after 2 h

Basal plasma insulin concentrations did not differ

significantly in the C. nobile treated group (20 mg/kg)
when compared to untreated group in both normal
and diabetic rats 15 days after C. nobile treatment
(Table 1). In addition, vanadate treatment did not
affect insulin secretion in both normal and STZ rats
(Table 1).

2.5. Statistical analysis

Data were expressed as mean  S.E.M. Statistical
analysis were performed using the analysis of variance
(ANOVA) followed by Bonferroni post tests. Differences were considered to be significant when P <
0.05.

4. Discussion
The present study was undertaken to investigate the
anti-hyperglycaemic activity of C. nobile aerial part
extract in STZ induced diabetic rats, a type 1 diabetes
animal model. Vanadate, a potent inhibitor of tyrosine
phosphatases [13], was used as a reference drug. It is
known that vanadate mimics several insulin actions in
vivo: the stimulation of hexose uptake, the stimulation
of lipogenesis and the inhibition of lipolysis [14].

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M. Eddouks et al. / Diabetes Research and Clinical Practice 67 (2005) 189195

Fig. 1. Plasma glucose levels over 6 h after single oral administration of the aqueous C. nobile extract (20 mg/kg) in normal (Panel a) and
diabetic rats (Panel b). Data are expressed as means  S.E.M., n = 6 rats per group. *P < 0.05; **P < 0.01; ***P < 0.001, when compared to
baseline values; (&): Control; (~): C. nobile; (*): Vanadate.

Administration of this compound to STZ diabetic rats,

normalizes plasma levels of glucose, lipids, creatinine
and thyroid hormones [15,16].
Our results demonstrate that C. nobile significantly
improves glucose homeostasis. Single oral administration of a dose of 20 mg/kg produces a potent and
strong hypoglycaemic effect in both normal and STZ
diabetic rats. However, when studying a chronic
disease such as diabetes, it is more pertinent to test the

maintenance of lower blood glucose levels with longterm treatment rather than the acute hypoglycaemic
effect after a single dose. In this study, we have
measured fasting blood glucose on second, fourth,
seventh and fifteenth days after treatment. Like the
short-term treatment, we found that C. nobile
progressively reduced blood glucose levels in both
normal and STZ diabetic rats. In normal rats, the
hypoglycaemic activity may be due to inhibition of

M. Eddouks et al. / Diabetes Research and Clinical Practice 67 (2005) 189195

193

Fig. 2. Plasma glucose levels over once daily repeated oral administration of the aqueous C. nobile extract (20 mg/kg) for 15 days in normal
(Panel a) and diabetic rats (Panel b). Data are expressed as means  S.E.M., n= 6 rats per group. *P < 0.05; **P < 0.01; ***P < 0.001, when
compared to baseline values.(&): Control; (~): C. nobile; (*): Vanadate.

key enzymes involved in the gluconeogenesis and

glycogenolysis pathways. A similar mechanism was
proposed to explain the hypoglycaemic effect of
Coriandrum sativum in normal rats [17]. This hypoglycaemic activity was very potent because, in spite of
counter regulatory factors, which combat the fall in
blood glucose by stimulating glucose production and
limiting glucose utilization, hypoglycaemia was
maintained [1819]. On other hand, in control STZ

diabetic rats, blood glucose levels were increased

significantly from the second day. This increment
could be due to reduced glucose clearance apparently
arising from a defect in glucose transport [20] and/or
to the early appearance in insulin resistance in adult
STZ diabetic rats [21].
The extract of C. nobile aerial part had no effect on
basal plasma insulin concentrations in both normal
and STZ diabetic rats. It appears that the observed

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M. Eddouks et al. / Diabetes Research and Clinical Practice 67 (2005) 189195

Table 1
Basal plasma insulin concentrations (mU/ml) after repeated oral
administration of the aqueous C. nobile extract at a dose of 20 mg/kg
in normal and diabetic rats
Experimental groups

Plasma insulin concentrations (mU/ml)

Day 0

Day 15

Normal rats
Control
C. nobile
Vanadate

35.4  2.17
34.95  0.33
31.81 3.15

36.45  4.12 NS
32.77  0.94 NS
32.71  3.00 NS

Diabetic rats
Control
C. nobile
Vanadate

7.08  0.39
5.64  0.73
6.05  0.52

6.75  0.15 NS
4.49  0.35 NS
5.72  0.82 NS

Data are expressed as means S.E.M., n = 6 rats in each group. NS:

Not significant compared to baseline values (day 0 of repeated oral
administration).

hypoglycaemic activity was mediated by an extrapancreatic effect independently of insulin secretion.

The underlying mechanism(s) of this blood glucose
lowering activity may be due to stimulation of
peripheral glucose utilisation, especially in muscle
and adipose tissue. In this context, several medicinal
plants have been reported to restore activity of key
enzymes of glucose and glycogen metabolism which
are strongly disturbed in STZ diabetic rats [2223].
Recently, we have demonstrated that the hypoglycaemic activity of Spergularia purpurea arises from
inhibition of hepatic glucose production [24]. Since
STZ induced diabetes was accompanied by insulin
resistance, C. nobile may act by improving insulin
sensitivity. Several medicinal plants have been
reported to possess an insulin sensitizing activity in
STZ diabetic rats [2527]. However, whether the C.
nobile extract may improve glucose homeostasis by
restoring normal insulin sensitivity in STZ diabetic
rats awaits further studies. On other hand, it is well
known that insulin signalling is very important for
glucose metabolism. Recently, Bolin et al. (2003) have
reported that a traditional herbal medicine improves in
vivo insulin action in STZ diabetic rats via enhancing
insulin signalling [28,29]. A similar mechanism may
operate in the C. nobile treated group to improve
glucose homeostasis in STZ diabetic rats. Another
possible site of action of C. nobile to exert its
hypoglycaemic effect is the gastrointestinal tract;
C. nobile may slow the digestion of food and decrease
the rate of carbohydrate absorption.

In conclusion, this is the first report demonstrating

that C. nobile can be used to treat type 1 diabetes. This
finding represents an experimental confirmation of the
Moroccan traditional use of this plant for the treatment
of diabetes mellitus. Consequently, consumption of C.
nobile aerial part could prevent the complications of
hyperglycaemia associated with diabetes. Finally, the
precise mechanism(s) and site(s) of this activity and
the active constituent(s) of C. nobile are still to be
determined in addition to toxicological studies in
further experiments.

Acknowledgements
The authors thank the Comite Inter Universitaire
Maroco-Francais, Action integre e N8 MA/03/83
for supporting this work.

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