Abou El-Soud et al. Antidiabetic Activities of Foeniculum Vulgare Mill.

Macedonian Journal of Medical Sciences. 2011 Jun 15; 4(2):139-146.

doi:10.3889/MJMS.1857-5773.2011.0173
Basic Science
OPEN  ACCESS

Antidiabetic Activities of Foeniculum Vulgare Mill. Essential Oil

in Streptozotocin-Induced Diabetic Rats
Neveen Abou El-Soud1, Nabila El-Laithy2, Gamila El-Saeed2, Mohamed Salah Wahby3, Mona Khalil4, Fatma Morsy5, Nermeen Shaffie5
1
National Research Center, Complementary Medicine, Cairo, Giza 12311, Egypt; 2National Research Center, Medical Biochemistry, Cairo,
Giza 12311, Egypt; 3National Research Center, Cultivation and Production of Aromatic and Medicinal Plants, Cairo, Giza 12311, Egypt;
4
Gizan University, Medical Applied Science, Medical Chemistry, Gizan, Saudi Arabia; 5National Research Center, Histology and Pathology,
Cairo, Giza 12311, Egypt

Abstract
Citation: Abou El-Soud N, El-Laithy N, El-Saeed Background: Foeniculum vulgare Mill (F. Apiaceae) is an ancient common herb and spice known to
G, Salah Wahby M,Khalil M, Morsy F, Shaffie N.
the ancient Egyptians and Greeks, traditionally used as a carminative, a weak diuretic and lactation
Antidiabetic Activities of Foeniculum Vulgare Mill.
Essential Oil in Streptozotocin-Induced Diabetic stimulant.
Rats. Maced J Med Sci. 2011 Jun 15; 4(2):139-
146. doi.10.3889/MJMS.1957-5773.2011.0173. Aim: To evaluate the essential oil of Foeniculum vulgare Mill for its hypoglycaemic effect and
Key words: diabetes; essential oil; experimen- antioxidant activity in addition to histopathological study in streptozotocin induced diabetic rats.
tal animal; antioxidant; histopathology.
Correspondence: Prof. Neveen Helmy Abou El-
Material and Methods: Rats were divided into 3 groups; normal control, diabetic control, and diabetic
Soud. National Research Center, Complemen- group receiving orally Foeniculum vulgare Mill essential oil (30 mg/kg bw).The dose of essential oil was
tary Medicine, 33-El Bohouth street- Dokki, Cairo, chosen according to its LD50. Serum glucose and whole blood glutathione peroxidase were measured
Giza 12311, Egypt. Phone: 0124359509. E-Mail:
neveenster@gmail.com
in addition to histopathological study of rats kidney and pancreas.
Received: 14-Apr-2011; Revised: 08-May-2011; Results: Ingestion of essential oil of Foeniculum vulgare Mill to diabetic rats corrected the hyperglycemia
Accepted: 09-May-2011; Online first: 16-May-
2011 from (162.5 ± 3.19 mg/dl) to (81.97 ± 1.97 mg/dl) with p<0.05 and the activity of serum glutathione
peroxidase from (59.72 ± 2.78 U/g Hb) to (99.60 ± 6.38 U/g Hb) with p<0.05. Also, improved the
Copyright: © Abou El-Soud N. This is an open-
access article distributed under the terms of the pathological changes noticed in their kidney and pancreas.
Creative Commons Attribution License, which
permits unrestricted use, distribution, and repro- Conclusion: Essential oil of Foeniculum vulgare Mill corrected the hyperglycemia and pathological
duction in any medium, provided the original abnormalities in diabetic induced rats, which could be in part through its antioxidative effect and restoring
author and source are credited.
of redox homeostasis. This makes the possibility of its inclusion in antidiabetic drug industry.
Competing Interests: The author have declared
that no competing interests exist.

Introduction Diabetes is an example of a disease that has been

Since ancient times, plants have been an exem-
plary source of medicine [1]. The use of traditional
medicines and medicinal plants in most developing
countries as therapeutic agents for the maintenance of
good health has been widely observed [2]. The World
Health Organization estimated that 80% of the
populations of developing countries rely on traditional
medicines, mostly plant drugs, for their primary health
care needs [3].
treated with plant medicines [4].Research conducted in
last few decades on plants mentioned in ancient litera-
ture or used traditionally for diabetes have shown anti-
diabetic properties [5, 6].
Diabetes mellitus is among the most common
disorders in developed and developing countries. The
disease is increasing rapidly in most parts of the world
[7]. In 1995, the World Health Organization reported that
approximately 150 million persons worldwide had diabe-
tes mellitus, and this number may well be double by 2025

Maced J Med Sci. 2011 Jun 15; 4(2):139-146. 139

Basic Science
[8]. Oxidative stress has been implicated in the develop-
ment of many pathophysiological conditions including
diabetes [9, 10].
Oxidative stress takes place due to the distur-
bance of the balance between the formation of reactive
oxygen species (ROS) and the defense provided by
cellular antioxidants [11]. Reduced glutathione (GSHR),
ubiquitously distributed in all mammalian cells, is a
reducing sulfhydryl (-SH) tripeptide and plays important
roles in the endogenous antioxidant system because it
conjugates toxic substances [12].
Intracellular GSH and its related enzymes, such
as glutathione peroxidase (GSHPx), glutathione-s-trans-
ferase (GSHT), glutathione reductase (GSHR), and
glutamate cysteine ligase (GCL), constitute the cellular
glutathione antioxidant system and represent a crucial
defensive system to protect cells against ROS[13].
Numerous spices and aromatic herbs have been
examined for their antioxidant/antiradical activity,
Foeniculum vulgare Mill (fennel) is one of these herbs.
Fennel is a plant belonging to the Kingdom: Plantae;
Order: Apiales; Family: Apiaceae (Umbelliferae); Ge-
nus: Foeniculum; Species: F. Vulgare; Binomial name:
Foeniculum vulgare Mill. It was known and used by
humans since antiquity [14].
Foeniculum vulgare Mill. (fennel) is a typical aro-
matic plant of the Mediterranean area, long used as a
medicinal and spice herb. Wild fennel was found to
exhibit a radical scavenging activity, as well as a total
phenolic and total flavonoid content, higher than those of
both medicinal and edible fennels. Owing to commercial
importance of its essential oil, fennel oil has been exten-
sively studied for many years [15].
The herb fennel was known to the ancient Chi-
nese, Indian, Egyptian and Greek civilizations [1]. The
name foeniculum is from the Latin word for fragrant hay.
Fennel was in great demand during the middle Ages.
Wealthy people routinely added the seed to fish and
vegetable dishes, while the poor reserved its use for
fasting days as an appetite suppressant. As an herbal
medicine, fennel is reputed to increase milk secretion,
promote menstruation, facilitate birth, ease the male
climacteric, and increase the libido. These supposed
properties led to research on fennel for the development
of synthetic estrogens during the 1930s [16].
There is evidence from two randomized, double-
blind, placebo controlled trials suggesting that fennel is
effective in reducing infantile colic [17]. Fennel has also
140
been studied in human clinical trials for dysmenorrhea
[18], constipation [19] and antihirsutism [20], but addi-
tional research is merited for its effect in diabetes as little
is known about its hypoglycaemic effect and possible
mode of action in diabetes.
The aim of the present study is to evaluate the
essential oil of Foeniculum vulgare Mill for its hypogly-
caemic effect and antioxidant activity in addition to
histopathological study in streptozotocin induced dia-
betic rats.
Methods
Materials
Essential oil of Foeniculum vulgare Mill was
purchased from Kato Aromatic Company-Egypt.
Streptozotocin (STZ) was purchased from Sigma chemi-
cal company, St Louis, Missouri. USA. Chloroform,
Methyl alcohol, ether were purchased from BHD, Eng-
land.
Animals tested
Fifty male albino rats weighing 150-200 g were
supplied by the Animal House of National Research
Center, Cairo-Egypt. Rats were caged under controlled
temperature 20-24°C and 12 h light/dark cycle. They
were fed with standard laboratory chow and water ad
libitum.
Induction of diabetes
Rats were kept on fasting prior to streptozotocin
injection. On the day of administration, STZ was freshly
dissolved in 50 mM sodium citrate (pH 4.5) solution
containing 150 mM NaCl and subcutaneous injection
was given at the dosage of (60 mg/kg bw). Blood glucose
concentration was measured by the spectrophotometric
GOD-PAP method (glucose oxidase-peroxidase) [21].
After 3 days of STZ injection, the animals with glucose
concentration exceeding 200 mg/dl were considered
diabetic.
Rats were divided into 3 groups 10 rats in each
group: group I: normal control rats; group II: diabetic
control rats; and group III: diabetic rats received
Foeniculum vulgare Mill essential oil. (30 mg/kg bw
orally).
The dose of essential oil was chosen according to
its LD50 (the medium 50 lethal doses after acute toxicity)
[22].
http://www.mjms.ukim.edu.mk
 Abou El-Soud et al. Antidiabetic Activities of Foeniculum Vulgare Mill.

Samples collection
After 21 days from the beginning of the experi-
ment, rats were fasted for 12 hours then blood samples
were collected. Blood was collected retro-orbitally from
the inner canthus of the eye under ether anaesthesia
using capillary tubes [23]. Every blood sample was
divided into three tubes, one of them contains EDTA Na
to determine hemoglobin immediately and the other
heparinized whole blood for the determination of glutath-
ione peroxidase immediately, the rest of the sample was
separated in centrifuge at 3000 rpm for 5 minutes to
obtain serum that was used to measure glucose in
different studied groups.
Biochemical measurements
Serum glucose was estimated using kit (glucose
PAP enzymatic oxidase method purchased from Stanbio
Laboratory, Inc. [21].
Glutathione peroxidase activity was determined
in heparinised whole blood by colorimetric method using
Randox Laboratories Kit,UK as described by Ammerman
et al [24].
Table 1: Fasting blood glucose levels and glutathione peroxi-
dase activity in different groups of experimental animals 21 days
after induction of diabetes (N=10).
Values are means ± S.E.M; N = number of animals per group; *p<0.05 compared to diabetic
group.
Table 1 showed also glutathione peroxidise activ-
ity in different groups studied of experimental animals 21
days after induction of diabetes. Glutathione peroxidise
activity were significantly reduced in diabetic group in
comparison to control group. Essential oils of Foeniculum
vulgare Mill significantly corrected this reduction in lev-
els of serum glutathione peroxidase in treated diabetic
rats compared to diabetic control group.
Histological and histochemical results
Kidneys:
The normal histological structure of the kidney
was shown in (Fig. 1, a). The kidney of the diabetic rats
showed vacuolar degeneration in some tubular epithe-

The protocol of the study was reviewed and

approved by Ethical Committee of National Research
Center.

Histopathological and Histochemical

Studies
The kidney and pancreas of different groups were
removed and fixed in 10% formal saline. Paraffin sec-
tions 5 mm thick were stained with haematoxylin and
eosin [25].

Statistical Analysis
The data for various biochemical parameters were
expressed as mean ± SEM and compared using one
way analysis of variance (ANOVA) test. Values were
considered statistically significant at p < 0.05. Statistics
were done using SPSS for windows version 10.

Results
Biochemical results
The characteristic abnormalities observed in the
diabetic rats were shown in Table 1 where the blood
glucose was significantly increased when compared to
control animals. A reduction was observed in blood
glucose in diabetic rats treated with the tested essential
oil of Foeniculum vulgare Mill.
Figure 1: Section of the kidney of a rat (a): normal control (Hx. & E. X
200). (b): Section of the kidney of streptozotocin diabetic rat showing
massive cellular infiltration (arrow) and areas of hemorrhage in inter-
stitial tissue (star). (Hx. & E. X 50) (c): Another field of the kidney of the
same group showing some completely degenerated glomeruli with
thickening of Bowman’s capsule (curved arrow), while others showed
lobulation with wide urinary space (arrow head). (d): Another section
of the same group showing vacuolar degeneration in some tubular
epithelial cells (arrow), and cell debris scattered in tubular lumina
(arrow head). (Hx. & E. X 100).

Maced J Med Sci. 2011 Jun 15; 4(2):139-146. 141

Basic Science

lial cells and cell debris scattered in tubular lumina,

increase in thickness of tubular epithelial cells with
narrowing of lumen, signs of degeneration in the form of
karyolysis and karyorrhexis. Massive cellular infiltration,
areas of hemorrhage in interstitial tissue and deformed
renal tissue architecture were seen. Some glomeruli
showed complete degeneration with thickening of Bow-
man’s capsule, while others showed lobulation with wide
urinary space (Fig. 1, b, c & d).
The kidney of diabetic rats treated with Foeniculum
vulgare essential oil showed more protective effects as
compared to diabetic rats not treated with Foeniculum
vulgare essential oil in the form of diminution of cellular
infiltration, hemorrhage in interstitial tissue, glomerular
degeneration and cell debris in tubular lumina, while
vacuolar degeneration in some tubular epithelial cells
Figure 3: Section of pancreas of a rat (a): normal control. (Hx. & E. X
still could be noticed (Fig. 2, c). 100). (b): Section of pancreatic tissue of streptozotocin diabetic rat
showing marked increase in the connective tissue component of the
gland (interlobular and intralobular) (star)., blood vessels are markedly
dilated and congested (arrow). (Hx. & E. X 50) (c): Higher magnifica-
tion of the previous group shows vacuolar degeneration in the cells of
islets of Langerhan specially in the center (arrow), while the nuclei of
the serous acini cells appeared flattened and pushed towards the
bottom of the cells (arrow head). (Hx. & E. X 100).

nucleus and in some places residue of destructed cells

were visible. The relative reduction of the size of islets,
dilatation and congestion of large vessel and marked
increase in connective tissue component at the expense
of functioning tissue were obvious. The exocrine part of
the gland (serous acini) showed flattening of their nuclei
that were pushed to the bottom of the cells (Fig. 3, b &c).

Figure 2: (c): Section of the kidney of streptozotocin diabetic rat treated

with Foeniculum vulgare Mill showing lobulation of some glomeruli
(arrow head) and vacuolar degeneration in some tubular epithelial
cells (arrow). (Hx. & E. X 100).

Pancreas:
The normal architecture of pancreatic tissue was
shown in (Fig. 3,a). Pancreatic sections stained with Hx
& E showed that streptozotocin caused severe necrotic
changes of pancreatic islets, especially in the center of Figure 4: (e) is a section of pancreatic tissue of streptozotocin diabetic
the islets. Nuclear changes, karyolysis, disappearing of rat treated with Foeniculum vulgare Mill showing normalization of the
pancreatic tissue. (Hx. & E. X 100).

142 http://www.mjms.ukim.edu.mk

A protective effect was obtained by using
Foeniculum vulgare Mill essential oil to diabetic rats.
Examination of pancreas sections of this group showed
that the pancreatic tissue retained its normal architec-
ture (Fig. 4, e).
Discussion
Diabetes mellitus, an endocrine and metabolic dis-
order characterized by chronic hyperglycemia produces
multiple biochemical impairments and oxidative stress
especially an increased susceptibility to lipid peroxidation
that play role in the progression of the symptoms of
diabetes [26]. Several hypotheses have been postu-
lated to explain the development of free radicals in
diabetes which include auto oxidation of glucose,
enzymatic and non-enzymatic glycation of proteins with
increased formation of glucose derived advanced
glycosylation end products (AGEs), enhanced glucose
flux through polyol pathway [27] and reduction of anti-
oxidant defence [28].
Despite progress in the management of diabetes
mellitus by synthetic drugs most of these drugs have
side effects in the long run. So, the search for improved
and safe natural antidiabetic agents is ongoing and
World Health Organization has also recommended the
development of herbal medicine in this concern [3].
Spices are dried herbs they are known to exert
several beneficial physiological effects including the
antidiabetic influence [29]. Among the spices, fenugreek
seeds (Trigonella foenumgraecum), garlic (Allium
sativum), onion (Allium cepa), and turmeric (Curcuma
longa) have been experimentally documented to pos-
sess antidiabetic potential. In a limited number of stud-
ies, cumin seeds (Cuminum cyminum), ginger (Zingiber
officinale), mustard (Brassica nigra), curry leaves
(Murraya koenigii) and coriander (Coriandrum sativum)
have been reported to be hypoglycaemic [30].
Most bioactive spices constituents are collec-
tively called phytochemicals. The large majority of these
phytochemicals are redox active molecules and there-
fore defined as antioxidants [14].
Foeniculum vulgare Mill (Fennel) is another spice
that has been used for centuries in the Mediterranean
area as an aromatic herb and also in folk medicine, due
to the pharmacological properties of its essential oil.
Typically, fennel and its preparations are used to cure
various disorders, acting as a carminative, digestive,
Maced J Med Sci. 2011 Jun 15; 4(2):139-146.
Abou El-Soud et al. Antidiabetic Activities of Foeniculum Vulgare Mill.
lactogoge and diuretic agent [31].
Fennel seeds contain between 3% and 6% of an
essential oil and approximately 20% of a fixed oil com-
posed of petroselinic acid, oleic acid, and tocopherols.
The essential oils of sweet and bitter fennel contain up
to 90% trans-anethole, up to 20% fenchone and small
amounts of limonene, camphor, alpha-pinene, and about
6 additional minor volatile compounds [32]. It was re-
ported that fennel oil possessed antiinflamatory , antioxi-
dant and pro-oxidant activities [33].
In this study we used streptozotocin (STZ) to
induce diabetes in rats. STZ is well known for its selec-
tive pancreatic B- cell toxicity and has been extensively
used in induction of diabetes mellitus in animals [34].
Experimental evidence has demonstrated that some of
its deleterious effects are attributable to induction of
metabolic processes, which lead on to an increase in the
generation of reactive oxygen species (ROS) [35]. Apart
from production of ROS, STZ also inhibits free radical
scavenger-enzymes [36].
Antioxidant defense mechanisms are important
for the protection of cells and tissues against oxidative
damage. The major endogenous antioxidant enzyme-
systems in mammalian body include superoxide
dismutase (SOD), catalase (CAT), selenium-dependent
glutathione peroxidase (GSHPx-Se), glutathione per-
oxidase (GSHPx), and glutathione reductase (GSHR).
The major non-enzymatic endogenous antioxidants in-
clude glutathione (GSH) and vitamin E [37].Reduced
antioxidant levels, as a result of increased free radical
production in experimental diabetes, have been previ-
ously reported [38, 39].
In this study we noticed the reduction of glutath-
ione peroxidase (GSHPx) activity in the diabetic induced
rats which can be due to the oxidative stress as part of
diabetes pathogenesis. Cytosolic GSHPx is an enzyme
containing four selenium-cofactors that protects tissues
from damage by catalyzing the breakdown of hydrogen
peroxide and organic hydroperoxides [13]. The current
results showed that GSHPx activity largely decreased in
diabetic induced rats compared to non-diabetic control
rats, and this decrease was reversed by administration
of fennel essential oil.
Glutathione peroxidase (GSHPx) is reported to
have a broader protective spectrum than other enzymes
as catalaze for example because in addition to H2O2, it
also metabolizes other hydroperoxides including lipid
hydroperoxides [40]. The accumulation of H2O2 and
other hydroperoxides might have induced the activity of
143
Basic Science
GSHPx leading to its up-regulation in the diabetic rats.
The observation that rodent and human islets
have reduced expression of GSHPx has led to the
conclusion that a normal approach for protection of B-
cells against oxidative stress would involve over-expres-
sion of GSHPx [41]. Thus, the over-expression of GSHPx
could be a protective mechanism against oxidative stress.
Administration of fennel oil down-regulated the
activity of GSHPx, thus indicating that fennel oil attenu-
ated the changes in the pancreatic antioxidant enzymes
in response to generation of oxidants. The antioxidant
properties of this oil have been recognized in previous
studies [42, 43] which could be attributed to the rich
content of phenolic compounds [44].
The current results indicated that the pathological
effects in rats kidney and pancreas tissues induced by
diabetes due to oxidative stress were reversible and
corrected by ingestion of fennel oil this could be attrib-
uted to its antioxidative effects.
The kidney histopathology data of STZ induced
diabetic rats showed marked tubular degeneration, haem-
orrhage, thickening in the Bowman’s space due to
glomerular damage. The results indicated a primary and
a secondary effect of the diabetic state on the kidney of
the rat. The primary effect, the diabetes factor was
associated with hyperglycaemia and was responsible
for dilatation of proximal and distal tubules in the cortex.
The secondary effect, named the individual response
factor, was associated with inflammatory processes
[45].Diuresis is a common feature associated with dia-
betes which may be the reason for structural changes
observed with glomerulus [46].
The recovery of renal function with treatment of
fennel oil can be explained by the regenerative capability
of the renal tubules. Similar results have been observed
with the treatment of STZ induced diabetic rats with other
herbal extracts as fenugreek alkaloid extract [5] and
onion oil [6]. The role of fennel oil in reversing the diabetic
state at the cellular level besides the metabolic normali-
zation further proves its potential as an antidiabetic
assert.
The present study revealed that the immediate
action of STZ induced diabetes on pancreatic tissue was
severe necrotic changes of pancreatic islets, especially
in the center of the islets as well as nuclear changes,
karyolysis, disappearing of nucleus and in some places
residue of destructed cells. The ultra structure of STZ
diabetic pancreas showed considerable reduction in the
144
islet langerhans and depleted islets. These are in agree-
ment with earlier reports using other herbal extracts [5,
6]. The diabetic rats treated with fennel oil showed
pancreatic islet regeneration. The excellent recovery of
pancreatic tissue with treatment of fennel oil can be
explained by the regenerative effect of exocrine cells of
pancreas which may enlighten the positive effects of this
agent on the production of insulin.
Fennel was traditionally reported to be highly
recommended for diabetics. Our results demonstrated
the marked improvements of hyperglycemia and patho-
logical changes induced by streptozotocin after fennel
ingestion which can prove its effect as antidiabetic in folk
medicine. Research studies on effect of fennel oil on
blood glucose are not numerous. A single study by
Barros et al [44] reported that fennel can improve rat
glucose tolerance obviously.
The antioxidant potential of this herb , might
explain some of its empirical uses in folk medicine for
diabetes. This can be true as in diabetic subjects, altered
glycaemia and lipaemia are closely correlated with mark-
ers of systemic oxidative stress [47]. In addition, fennel
reported to suppress the nuclear factor-kappaB activa-
tion pathway which is linked to several inflammatory
diseases as diabetes [48].
Based on our findings, we conclude that ingestion
of essential oil of Foeniculum vulgare Mill to diabetic
induced rats corrected the hyperglycemia and patho-
logical abnormalities which could be in part through its
antioxidative effect and restoring of redox homeostasis.
This makes the possibility of its inclusion in antidiabetic
drug industry.
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