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Journal of Medicinal Plants Research Vol. 5(1), pp. 119-125, 4 January, 2011
Available online at http://www.academicjournals.org/JMPR
ISSN 1996-0875 ©2011 Academic Journals
Full Length Research Paper
Antidiabetic activities of aqueous leaves extract of
Leonotis leonurus in streptozotocin induced diabetic
rats
S. O. Oyedemi*, M. T. Yakubu and A. J. Afolayan
School of Biological Sciences, University of Fort Hare, Alice 5700, South Africa.
Accepted 3 November, 2010
The present study was carried out to investigate the antidiabetic properties of aqueous leaves extract of
Leonotis leonurus in streptozotocin (45 mg/kg intraperitoneal) induced diabetic rats for 15 days. The
induced diabetic rats exhibited high blood glucose level, cholesterol, high density lipoprotein (HDL) and
triglycerides accompanied with weight loss while the level of low density lipoprotein (LDL) was very low.
In addition, the water intake was remarkably high while feed intake was decreased as compared with
normal control group. The continuous oral administration of the extract at the dose of 125, 250 and 500
mg/kg for 15 days was able to lower the blood glucose level, HDL, feed and water intake while that of LDL
was increased. Also, the weight loss of diabetic rats (31 g) after extract treatment was near that of
glibenclamide treated groups. The extract yielded high phenolics content (48 mg/g tannic acid equivalent)
and flavonoids (4.8 mg/g quercetin equivalent). These compounds have been reported to potentiate
insulin secretion. The present study revealed that aqueous extract of L. leonurus possesses
antihyperglycemia and antilipidemic potential and thus could support ethnotherapeutic usage of this
plant.
Key words: Leonotis leonurus, lipids, blood glucose, phenolics, flavonoids.
INTRODUCTION
Diabetes mellitus is a complex chronic disorder that
affects the metabolism of carbohydrates, fats, proteins
and electrolytes due to deficiency of insulin or
insensitivity of target organs to insulin. This disorder is
characterized by chronic hyperglycemia and abnormality
of lipid profile such as cholesterol, low and high density
lipoprotein and triglyceride leading to series of secondary
complications (Rang et al., 1991; Ravi et al., 2005).
These complications include polyuria, polyphagia,
polydypsia, ketosis, retinopathy as well as cardiovascular
disorders (Kumar and Clark, 2002). Presently, the
frequency of diabetes is increasing with a major impact
on the population of developing countries due to the
absence of effective and affordable interventions of
diabetes (Marx, 2002). According to Wild et al. (2004),
*Corresponding author. E-mail: silvanusdemi@gmail.com. Fax:
+27866282295.
about 366 million peoples were projected to be diabetic
by the year 2030. Several hypoglycemic agents have
been used for the treatment of diabetes mellitus but are
reported to produce serious adverse side effect such as
liver problems, lactic acidosis and diarrhea (Rajalakshmi
et al., 2009). In addition, they are not suitable for use
during pregnancy. Therefore, the search for more
effective agents with low cost and low side effect from
plant source has continued to be an important area of
research because of their ready availability, affordability
and low adverse side effect.
In South Africa, L. leonurus (Lamiaceae) is a shrub
indigenous plant found along forest margins, on rocky
hillsides and riverbanks as well as grasslands of the
Eastern and Western Cape, Kwazulu-Natal and
Mpumalanga Provinces of South Africa (Van Wyk et al.,
2000).
The leaves of the plant have a characteristic aromatic-
pungent odour, bright yellow- green colour and rough
texture. It has long been used traditionally for the
120 J. Med. Plant. Res.
treatment of cough, cold, influenza, chest infections,
diabetes mellitus, eczema, epilepsy, delayed
menstruation; intestinal worms, constipation, scorpion
stings, spider and snake bite (Van Wyk et al. 2000;
Ososki et al., 2002; Jager et al., 1996). Our previous
work reported the toxicological effect of sub-chronic
administration of L. leonurus in male Wistar rats
(Oyedemi et al., 2010b). Similarly, we also assessed in
vitro and in vivo antioxidant activities of this plant
(unpublished). Evidences from traditional healers have
shown that L. leonurus may have antidiabetic activity but
have not been proved scientifically (Oyedemi et al.,
2009).
Before the commencement of this study, there was
scanty information on the antidiabetic effect of this plant
in male Wistar rats induced with streptozotocin.
Therefore, the objective of this study was aimed to
investigate the antidiabetic and antilipidemic potential of
aqueous leaves extract of L. leonurus in streptozotocin
induced diabetic rats.
MATERIALS AND METHODS
Plant material
The leaves of L. leonurus were collected from rockhill field near
Ntselamanzi location in Nkokonbe Municipality (Eastern Cape,
South Africa) between May and June, 2008. It was authenticated by
Prof. DS. Grierson of the Department of Botany, University of Fort
Hare. Voucher specimen (Sun MED 2) was deposited at the Giffen
herbarium of the University.
Animals used
Male Wistar rats (Rattus novergicus) with average weight of 250.00
± 7.22 g were obtained from the animal house of the Agricultural
and Rural Development Research Institute, University of Fort Hare.
The animals were maintained at a controlled temperature of 28°C
with a 12 h light-dark cycle at room temperature and humidity of 45
to 50%. The animals were allowed free access to food (Balanced
Trusty Chunks (Pioneer Foods (Pty) Ltd, Huguenot, South Africa)
and water for 15 days. The experiment was approved by the Animal
Ethics Committee of the University of Fort Hare.
Assay kits and reagents
The assay kits for triglycerides, cholesterol and high and low
density lipoproteins were obtained from Roche Diagnostic GmbH,
Mannheim, Germany. All other reagents used were of analytical
grade and were supplied by Merck Chemicals (Pty) Ltd., Bellville,
South Africa.
Induction of experimental diabetes in animals
Streptozotocin was freshly prepared in 10 mmol/citrate buffers, pH
4.5, and injected to experimental animals (25 rats) intraperitoneally
at the dosages of 125, 250 and 500 mg/kg body weight (Siddique et
al., 1987). After 48 h of STZ administration, rats with moderate
diabetes having glycosuria and hyperglycemia (blood glucose > 8.1
mmol/L) were taken for the experiment.
Animal grouping and extract administration
Thirty-six male rats were randomized into six groups of six animals
each (30 diabetic surviving rats, 6 normal rats) were used in this
study. The extract was administered orally into the rats using
gavages throughout the experimental period. Group 1: Diabetic rats
received distilled water only (0.5 ml) on daily basis repeatedly for 15
days. Groups 2: Diabetic animals treated daily with 0.5 ml of
glibenclamide (0.6 g/kg body weight). Group 3 to 5 animals were
treated daily with 0.5 ml doses of 125, 250 and 500 mg/kg body
weight of aqueous leaves extract of L. leonurus respectively. The
blood samples were collected every fifth day from the tail vein of the
animals to determine the blood glucose level using glucometer
(Bayer Health Care, Japan). On day 16, the rats were sacrificed by
ether anesthesia.
Preparation of extract
The leaves of the plant were air dried at room temperature for 7
days. The dried leaves were thereafter pulverized using an electric
blender (Waring Products Division, Torrington, USA). The
powdered plant material (200 g) was extracted in distilled water on
a mechanical shaker (Stuart Scientific Orbital Shaker, UK) for 48 h.
The extract was filtered using a Buchner funnel and Whatman No.1
filter paper. The filtrate was freeze-dried using Savant Refrigerated
Vapor Trap (RV T41404, USA) to give a yield of 30 g. The resulting
extract was reconstituted with distilled water to give the required
doses (125, 250 and 500 mg/kg body weight) used in this study.
Preliminary phytochemical screening
The aqueous extract of Strychnos henningsii was tested by
subjecting the extract to phytochemical analysis to determine the
presence of phenols, flavonoids, alkaloids, saponin, glycoside and
tannins using the general chemical test of Zafar and Mujeeb (2002).
Total phenolics
The total phenolics content in the aqueous leaf extract of L.
leonurus was determined spectrophotometrically with Folin
Ciocalteau reagent using the modified method of Wolfe et al.
(2003). An aliquot of the extract (0.5 ml) was mixed with 2.5 ml of
10% Folin-Ciocalteu reagent and 2 ml of Na
2
CO
3
(75% w/v). The
resulting mixture was vortexed for 15 s and incubated at 40°C for
30 min for colour development. The absorbance of the samples
was measured at 765 nm using Hewlett Packard, UV
spectrophotometer. Total phenolics content was expressed as mg/g
tannic acid equivalent from the calibration curve using the equation:
Y = 0.1216x, R
2
= 0.936512, where x was the absorbance and Y
was the tannic acid equivalent (mg/g). The experiment was
conducted in triplicate and the results are reported as mean ± SD
values.
Total flavonoids
The method of Ordonez et al. (2006) was used to estimate total
flavonoids contents of the extract solution based on the formation of
a complex flavonoids - aluminums. A volume of 0.5 ml of 2% AlCl
3
ethanol solution was added to 0.5 ml of extract solution. After one
hour of incubation at the room temperature, the absorbance was
measured at 420 nm using UV-VIS spectrophotometer. A yellow
colour indicated the presence of flavonoids at the final
concentration of 0.5 mg/ml. All determinations were done in
triplicate and values were calculated from calibration curve obtained
from quercetin using the equations: Y= 0.0255x, R
2
= 0.9812, where
x was the absorbance and Y the quercetin equivalent (mg/g). The
experiment was conducted in triplicate and the results are reported
as mean ± SD values.
Total proanthocyanidins
Total proanthocyanidins was determined based on the procedure of
Sun et al. (1998). To 0.5 ml of 1 mg/ml extract solution was added 3
ml of vanillin-methanol (4% v/v), and 1.5 ml of hydrochloric acid and
then vortexed. The absorbance of resulting mixture was measured
at 500 nm after 15 min at room temperature. Total proanthocyanidin
content was expressed as catechin equivalents (mg/g) using the
following equation from the calibration curve: Y = 0.5825x, R
2
=
0.9277, where x was the absorbance and Y is the catechin
equivalent (mg/g).
Preparation of serum
The preparation of serum was carried out using the method
described by Yakubu et al. (2005). The blood samples were
collected into clean dry centrifuge tubes. An aliquot (5 ml) of the
blood was collected into sample bottles containing EDTA (BD
Diagnostics, Pre-analytical Systems, Midrand, USA) and was
allowed to clot at room temperature for 10 min. This was
centrifuged at 1282 g × 5 min using Hermle Bench Top Centrifuge
(Model Hermle, Z300, Hamburg, Germany). The sera were later
aspirated with Pasteur pipettes into sample bottles and used within
12 h of preparation for the assay of lipid profiles.
Serum lipids analysis
The levels of low density lipoprotein, high density lipoproteins,
triacylglycerol and cholesterol in the serum of the animals were
determined using the method of Tietz et al. (1994). They were
determined spectrophotometrically using assay kits from Randox
Laboratories Limited, Ardmore, Co Antrim, UK.
Effect of extract on the weight, feed and water intake of the
animals
Feed and water intake were measured everyday at the same hour
during the experimental periods while the body weight of the
animals were measured before the start and every fifth day
throughout the experimental period (15 days).
Statistical analysis
Data were expressed as mean ± SD (standard deviation) of six
replicates and were statistically analyzed using one way analysis of
variance (ANOVA). Means were separated by the Duncan multiple
test using SAS (SAS, 2002). Values were considered significant at
p < 0.05.
RESULTS AND DISCUSSION
The phytochemical screening showed the presence of
flavonoids, tannins, phenolics and saponins (Table 1).
These compounds especially flavonoids and phenolics
have been reported to enhance insulin secretion and
Oyedemi et al. 121
scavenge free radicals that are generated during diabetic
state (Marles and Farnsworth, 1995). The results of
quantitative analysis of polyphenolics compounds
investigated in this study revealed the high phenolics and
flavonoids in the aqueous leaves extract of L. leonurus
phenolics contents (48 mg/g tannic acid equivalent) and
flavonoids (4.8 mg/g quercetin equivalent) as shown in
Table 1. Flavonoids are well known to regenerate the
damaged beta cells in the diabetic rats while phenolics
are found to be effective antihyperglycemic agents
(Chakravarthy et al., 1980; Manickam et al., 1997).
The intraperitoneal injection of streptozotocin at the
dose of 45 mg/kg into rats was characterized by
polydipsia, polyuria, weight loss and hyperglycemia.
These symptoms agree with the previous findings of
Shenoy and Ramesh (2002). The elevated level of blood
glucose observed after 48 h of streptozotocin induction
confirmed the diabetic state in rats which may be
attributed to the selective cytotoxicity effect of
streptozotocin on the beta cells (Bedoya et al., 1996).
The continued treatment of diabetic rats for 15 days with
the plant extract caused a significant reduction of blood
glucose level (10.5 to 14 mmol/L) comparable to
glibenclamide which is used for the treatment of type II
diabetes (Table 2). Glibenclamide is a standard
hypoglycemic drug that stimulates insulin secretion from
beta cells of islet of Langerhans. The result obtained from
this study was in accordance with that of Ojewole et al.
(2005) who observed antihyperglycemic effect of this
plant in mice. The glucose lowering activity of plant
extract was compared with that of glibenclamide. The
possible mechanism though not investigated in this study
may be attributed to the ability of the extract to potentiate
insulin secretion from pancreatic beta cells or sensitizing
insulin receptors (Ratnasooriya et al., 2004). The
presence of flavonoids and phenolics compounds in the
extract may be responsible for this observation.
The serum cholesterol level in diabetic untreated rats
increased significantly (p< 0.05) above the normal rats
throughout the experimental period (Table 3). The
abnormal high concentration of serum lipids in the
diabetic rats induced by STZ was in agreement with the
findings of Nikkila and Kekki (1973). Similar observation
was made by Bopanna et al. (1997) who linked the rise in
serum lipid to increase mobilization of free fatty acids
from the peripheral fat depots, where free fatty acid
esterification is balanced in lipolysis cycle. In addition,
deficiency of insulin had been reported to be associated
with hypercholesterolemia and hypertriglyceridemia due
to inactivation of lipases to hydrolyze these lipids. In the
present study, the continuous administration of aqueous
leaves extract of L. leonurus and glibenclamide for 15
days reduced the level of cholesterol, triglyceride, HDL
and rise in LDL at certain doses. This observation
corroborates with several studies reported on
antilipidemic effect of plant extract used traditionally in
experimental diabetic animals (Daisy et al., 2009; Marles
122 J. Med. Plant. Res.
Table 1. Phytochemical analysis of aqueous extract of L. leonurus.
Phytochemical compounds Plant extract Total content
Alkaloids + ND
Tannins + ND
Saponin + ND
Flavonoids + 34.16 mg/g
A
Cardiac glycosides + ND
Proanthocyanidins + 25 mg/g
B
Phenolics + 220 mg/g
C
+ = Presence.
A
Tannic acid equivalent.
B
Quercetin equivalent.
C
Catechin equivalent
Table 2. Effect of oral administration of L. leonurus extract on plasma blood glucose levels of STZ induced diabetic rats.
Plasma blood glucose
Treatment
0 (day) 5 (day) 10 (day) 15 (day)
Normal 5.60 ± 0.01 5.60 ± 0.01 5.42 ± 0.02 5.40 ± 0.00
Diabetic control 25.60 ± 0.24 26.30 ± 0.21 31.30 ± 0.16 33.30 ± 0.16
Diabetic + LL (125 mg/kg) 27.47 ± 0.02 20.43 ± 0.05 17.40 ± 0.06 16.97 ± 0. 06
Diabetic + LL (250 mg/kg) 28.50 ± 0.06 18.30 ± 0.04 15.30 ± 0.12 15.23 ± 0.00
Diabetic + LL (500 mg/kg) 27.83 ± 0.05 20.50 ± 0.07 16.30 ± 0.16 13.60 ± 0.04
Diabetic + glibenclamide 27.40 ± 0.02 25.95 ± 0.04 22.30 ± 0.11 18.03 ± 0.02
Values are expressed as means ± SD (n = 6 rats).
Table 3. Effect of aqueous extract of L. leonurus extract at doses investigated on serum lipid profiles in streptozotocin induced
diabetic rats.
Serum lipids parameter
Normal
control
Diabetes
control
Do D1 D2 D3
Cholesterol (mmol/L) 1.57 ± 0.12 2.33 ± 0.05 1.50 ± 0.16 1.55 ± 0.05 1.60 ± 0.0 1.67 ± 0.12
Triacylglycerol (mmol/L) 2.17 ± 0.34 3.53 ± 0.33 1.10 ± 0.57 1.60 ± 0.30 1.00 ± 0.00 1.60 ±0.22
HDL-C (mmol/L) 1.10 ± 0.08 0.47 ± 0.05 1.30 ± 0.22 1.35 ±0.05 1.30 ±0.00 1.37 ±0.05
LDL-C (mmol/L) 0.92 ± 0.05 3.24 ± 0.02 1.27 ± 0.20 1.30 ± 0.03 1.28 ± 0.01 1.32 ± 0.03
Atherogenic index (LDL-
C/HDL-C)
0.84 6.90 0.97 0.96 0.98 0.96
Values are expressed as means ± SD (n= 6 rats). Do = diabetes+125 mg/kg extract; D1 = diabetes + 250 mg/kg extract; D2 = diabetes +
500 mg/kg extract; D3 = diabetes + glibenclamide (0.6 mg/kg). HDL-C High density lipoprotein-cholesterol. LDL-C =Low density
lipoprotein-cholesterol.
and Farnsworth, 1995; Grover et al., 2002) (Figure 1).
The induction of diabetes into the rats resulted into loss
of body weight between 20 to 31 g in comparison with the
control rats. The feed and water intake of the diseased
animals was significantly increased throughout the study
period. These symptoms are well known marker of
diabetes mellitus in both human and animal models
which is a direct consequence of insulin deficiency
(Shenoy and Ramesh, 2002). Oral administration of plant
extract at the three doses investigated was able to
improve the body weight of the animals. The extract at
the dose of 500 mg/kg significantly decreased the level of
feed and water intake comparable to glibenclamide
treated group while the dose at 250 mg/kg did not have
any significant effect. The result obtained in this study
support the report of Kim et al. (2006) who reported the
effect of Morus alba in controlling the desire for food and
water intake under diabetic condition. The significant
body weight gain observed in diabetic rats was nearly
similar to the control group after oral administration of
plant extract in a dose dependent manner. This result
agrees with other investigators who noticed increase in
body weight gain upon improvement of diabetes status
(Schwechter et al., 2003; Craft and Failla, 1983). The
Oyedemi et al. 123
-50
-40
-30
-20
-10
0
10
20
30
40
50
60
Normal Diabetes Do D1 D2 D3
Animal groups
Body weight gain (g)
Figure 1. The effect of plant extract on body weight gain after 15 days of
experimental periods. Values are expressed as means ± SD (n= 6 rats). Do =
diabetes + 125 mg/kg extract; D1 = diabetes + 250 mg/kg extract; D2 = diabetes
+ 500 mg/kg extract; D3 = diabetes + glibenclamide (0.6 mg/kg).
0
50
100
150
200
250
300
350
Normal Diabetes Do D1 D2 D3
Animal groups
Water intake (ml)
Figure 2. Effect of plant extract on water intake. Values are expressed as means ± SD (n = 6
rats). Do = diabetes+125 mg/kg extract; D1 = diabetes + 250 mg/kg extract; D2 = diabetes + 500
mg/kg extract; D3 = diabetes + glibenclamide (0.6 mg/kg).
mechanisms of action is unknown but suggest a
protective effect of L. leonurus in controlling muscle
wasting (Swanston-Flatt et al., 1990).
In conclusion, the present findings reveal that oral
administration of aqueous extract of L. leonurus leaf has
a beneficial effect in reducing the blood glucose levels as
well as lipids. This study also showed that the plant
extract improves the polydipsia, polyuria and body weight
loss of diabetic rats. Further studies on the
pharmacological and biochemical investigation to
elucidate the mechanism of antidiabetic effect of this
plant will be needed to justify its usage (Figures 2 and 3).
124 J. Med. Plant. Res.
0
10
20
30
40
50
60
70
80
90
Normal Diabetes Do D1 D2 D3
Animal groups
Feed intake (ml)
Figure 3. Effect of aqueous extract of L. leonurus on feed intake in STZ induced diabetic rats.
Values are expressed as means ± SD (n = 6 rats). Do = diabetes + 125 mg/kg extract; D1 =
diabetes + 250 mg/kg extract; D2 = diabetes+500 mg/kg extract; D3 = diabetes + glibenclamide
(0.6 mg/kg)
ACKNOWLEDGEMENT
The authors are grateful to the Govan Mbeki Research
and Development Center, University of Fort Hare, Alice,
South Africa for financial support.
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