全 文 ： 2012 年 5 月 第 10 卷 第 3 期 Chin J Nat Med May 2012 Vol. 10 No. 3 185

Chinese Journal of Natural Medicines 2012, 10(3): 0185−0189
doi: 10.3724/SP.J.1009.2012.00185
Chinese
Journal of
Natural
Medicines







β-Cell protective efficacy, hypoglycemic and hypolipidemic
effects of extracts of Achillea millifolium in diabetic rats
Khalid G. Mustafa 1, 2, Bashir A. Ganai 1*, Seema Akbar 2, Mohamad Y. Dar 2, Akbar Masood 1
1Department of Biochemistry, Faculty of Biological Sciences, University of Kashmir, Srinagar 190006 Kashmir, India;
2Drug Standardisation Research Unit, Regional Research Institute of Unani Medicine (CCRUM), Naseem Bagh, University of Kashmir
Campus, Srinagar 190 006 Kashmir, India
Available online 20 May 2012
[ABSTRACT] AIM: To evaluate the therapeutic uses of Achillea millifolium in diabetic rats. METHODS: Diabetes was induced by
single intraperitoneal injection of freshly prepared solution of alloxan monohydrate (150 mg·kg−1 body weight) in Wistar rats of
150−200 g body weight. In this study, the aqueous and methanolic extract of Achillea millifolium was studied for its hypoglycemic and
hypolipidemic properties. The rats were divided into several groups, serving as Normal group, Diabetic Control group, Diabetic
treated with glibenclamide, and extract treated groups. The blood serum collected from the various groups of rats was analysed for its
various biochemical parameters like glucose, cholesterol, triglycerides, VLDL, SGOT, SGPT and ALP. On the 14th day of the experi-
ment the rats were scarified and pancreas was collected for histopathological studies. RESULTS: The extracts at dose levels of 250
and 500 mg·kg−1 body weight showed significant (P ≤ 0.05) decrease in blood glucose level, TGL, VLDL, cholesterol, SGOT, SGPT,
and ALP in diabetic rats. The extracts prevented the β-cells of pancreas from the cytotoxic effects of Alloxan monohydrate.
CONCLUSION: The results indicate that the extracts as mentioned above are effective in hyperglycemia and can effectively protect
against other metabolic aberrations caused by alloxan monohydrate.
[KEY WORDS] Achillea millifolium; Hypoglycemic; Hypolipidemic; Alloxan monohydrate
[CLC Number] R965 [Document code] A [Article ID] 1672-3651(2012)03-0185-05

1 Introduction
Diabetes mellitus is a metabolic disorder characterized
mainly by hyperglycaemia and glycosuria and is mainly due
to lack of insulin secretion in β cells of pancreas and desensi-
tization of insulin receptors for insulin. In diabetic rats, the
utilization of impaired carbohydrate leads to accelerated
lipolysis, resulting in hyperlipidemia. Current anti-diabetic
drugs usually have adverse side effects and, therefore, there is
a need to find safer and more effective anti-diabetic drugs [1].
Nowadays herbal treatments are becoming increasingly
popular as the herbal preparations have no or least side ef-
fects [2]. In developing countries, the World Health Organiza-
tion [3] estimates that about 80% of the population relies on
plant based preparations used in their traditional medicinal
system and as the basic needs for primary human health care.
Plants in traditional medicinal system are future sources of

[Received on] 28-Jun.-2011
[*Corresponding author] Bashir Ahmad Ganai: Associate Prof.,
E-mail: bbcganai@gmail.com, mirkhalid11@yahoo.com
These authors have no any conflict of interest to declare.
new drugs [4]. Anti-hyperglycemic effects of these plants are
attributed to their ability to restore the function of pancreatic
tissues by causing an increase in insulin output or inhibiting
the intestinal absorption of glucose or to the facilitation of
metabolites in insulin dependent processes [5-7]. An attempt
was made to study the beneficial effects of Achillea milli-
folium in alloxan monohydrate-induced diabetic rats.
Achillea millifolium is a flowering plant in the family
Asteraceae, native to the Northern Hemisphere. The herb is
reported to be a diaphoretic, astringent, tonic stimulant and
mild aromatic. It contains isovaleric acid, salicylic acid,
asparagin, sterols, flavonoids, bitters, tannins, and coumarins.
The plant is said to be useful in treating diabetic problems [8]
The aerial parts from various species of the genus Achil-
lea have been used in traditional and modern medicine as
bitter aromatics, astringents, chemostyptics, choleretics and
antiphlogistics [9]. Achillea millifolium, extracts supplied in
polypropylene glycol, is reported to function as a biological
additive in cosmetic products [10]. The extracts of Achillea
millifolium also inhibit the non-enzymatic lipid peroxidation
of rat liver homogenate. The extracts of this plant have shown
to possess antioxidant activity [11] as well as antibacterial
effects against Streptococcus pneumonia, Clostridium per-
Khalid G Mustafa, et al. /Chinese Journal of Natural Medicines 2012, 10(3): 185−189
186 Chin J Nat Med May 2012 Vol. 10 No. 3 2012 年 5 月 第 10 卷 第 3 期

fringens, Candida albicans, Mycobacterium smegmatics [12].
2 Materials and Methods
2.1 Plant material and extraction
The plant material was collected in July from the local
areas of Kashmir and was identified by the Centre of Tax-
onomy, University of Kashmir. Sample specimen (voucher
specimen No. 710-KASH) was deposited in the herbarium of
Centre of Taxonomy, University of Kashmir. The material
was completely shade dried and coarsely ground. The ex-
tracts were prepared by continuous hot extraction using water
and methanol as solvents. Extracts obtained were concen-
trated, dried and kept in desiccators for further use. The yield
was found to be 7.3 % and 2.6% respectively for methanolic
and aqueous solvents
2.2 Preliminary phytochemical analysis of the extracts
To identify the chemical constituents, the extracts so ob-
tained were subjected to preliminary phytochemical screen-
ing, which was performed using standard procedures [13-14].
2.3 Ash value determination
Two grams of the ground, air dried and accurately
weighed material was taken in a clean and tared crucible.
The crucible was placed in a muffle furnace. The material
was ignited by gradually increasing the heat up to 800 °C
until it is white ash. The crucible was cooled in a desiccator
and weighed. The cooled crucible containing the ash obtained
earlier was moistened with 2 mL of water or HCl (10%) (2
mL), then stirred and filtered. The solution, the residue was
dried on the ashless filter paper and then ignited again in
furnace in order to determine the water insoluble or acid in-
soluble ash value.
2.4 Experimental animals
Wistar rats of 150−200 g of either sex were selected for
the study. They were fed a standard rat pellet and water. Re-
search on animals was conducted in accordance with the
guidelines of the Committee for the Purpose of Control and
Supervision of Experiments on Animals (CPCSEA).
2.5 Acute toxicity study
Acute toxicity study was performed for aqueous and
methanolic extract according to the acute toxic classic
method as per guidelines of Organisation for Economic Co-
operation and Development (OECD). The rats were kept
fasting overnight, being provided only water. Then the extract
was administered orally at different dose levels i.e. 100, 200,
500, 1 000, 1 500, 2 000 mg·kg–1 of body weight. The rats
were observed continuously for 24 h for behavioral and neu-
rological changes and then at 24 and 72 h for any lethality.
2.6 Experimental design
All the animals were randomly divided into five groups
with six animals in each serving as normal, diabetic control,
diabetic treated with 250 mg·kg-1 b.wt of extracts, diabetic
treated with 500 mg·kg–1 b.wt of extracts, reference control
i.e glibenclamide (30 mg).
2.6.1 Oral glucose tolerance test (OGTT)
The oral glucose tolerance test [15] was performed in
overnight fasting (18 h) normal rats. Rats divided into three
groups (n = 6) were administered drinking water, Achillea
millifolium (250 and 500 mg·kg–1 of b. wt) respectively. Glu-
cose (2 g·kg–1) was fed 30 min after the administration of
extracts. Blood was withdrawn from the retro orbital sinus
under ether inhalation at 60, 90, 120 and 150 min of glucose
administration and glucose levels were estimated using the
standard glucose reagent kit.
2.6.2 Assessment of effect of extracts on alloxan-induced
diabetic animals
Rats were made diabetic by a single intraperitoneal in-
jection of alloxan monohydrate 150 mg·kg-1 in normal saline.
Two days after alloxan injection, rats with plasma glucose
levels of > 200 mg·dL–1 were included in the study. Treat-
ment with plant extracts started 72 h after alloxan injection.
The rats were observed for their physiological parameters
like body weight, food intake, fluid intake and urine volume
excreted. Blood samples were drawn at weekly intervals till
the end of study (i.e. 2 weeks). Fasting blood glucose estima-
tion and body weight measurement ware done on days 1, 7,
and 14 of the study. Serum was separated and analyzed for
serum cholesterol, serum triglycerides, serum VLDL, and
serum LDL, serum SGOT/SGPT, and serum ALP estimation.
On the 14th day, all the animals were sacrificed and pancreas
was removed. The sections of pancreas were observed under
microscope for effects of the extracts.
2.6.3 Statistical analysis
All the values of body weight, fasting blood sugar, and
biochemical estimations were expressed as x ± s and ana-
lyzed for ANOVA and post Dunnet’s t-test. Differences be-
tween groups were considered significant at P < 0.05 levels.
3 Results
The preliminary phytochemical screening of the extracts
of Achillea millifolium revealed the presence of tannins, gly-
cosides, terpenoids, flavonoids, and phenolics. The total ash
value of Achillea millifolium root powder was found to be
11.83%. While as the water insoluble ash and acid insoluble
ash value of Achillea millifolium are 7.25% and 5.34%.
The extract treated rats showed an increase in body
weight as compared to the diabetic ones (Table 1) (P ≤ 0.05);
there was decrease in food intake, fluid intake and volume of
urine excreted in extract treated rats compared with the dia-
betic group (Table 2).
The extracts of Achillea millifolium have shown signifi-
cant increase in glucose tolerance. The results are shown in
Table 3. The blood glucose levels were reduced considerably
within 150 min of glucose administration. The methanolic
and aqueous extracts of Achillea millifolium reduced the glu-
cose levels to normal respectively.
Acute toxicity studies revealed the non-toxic nature of
the alcoholic and aqueous extracts of Achillea millifolium up
to a dose level of 2 000 mg·kg-1 body weight in rats. There
was no lethality or toxic reaction found at any of the doses
selected till the end of the study.
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2012 年 5 月 第 10 卷 第 3 期 Chin J Nat Med May 2012 Vol. 10 No. 3 187

The antihyperglycemic effect of the extracts on the fast-
ing blood sugar levels of diabetic rats is shown in Table 4.
Administration of alloxan (160 mg·kg-1, i.p.) led to several
fold elevation of fasting blood glucose levels, which was
maintained over a period of 2 weeks. Two weeks of daily
treatment of various extracts (methanolic and aqueous) of
Achillea millifolium led to a dose-dependent fall in blood
sugar levels by 50.70% and 44.25%, respectively. Serum
cholesterol, serum triglycerides, serum LDL, serum VLDL,
serum SGOT, serum SGPT and serum alkaline phosphatise
levels were decreased significantly by glibenclamide and all
the extracts of Achillea millifolium due to 14 days of treat-
ment (Table 5).
Table 1 Effect of extracts of Achillea millifolium on body
weight in Alloxan monohydrate treated diabetic rats ( x ± s, n
= 6)
Body weight /g Groups
0th day 7th day 14th day % Variation
Normal 180 ± 4 184 ± 5 189 ± 5 5.00
Diabetic control 185 ± 3 183 ± 5 181 ± 5 –2.16
Met.ext (A. milli)
(500 mg·kg–1) 165 ± 5 168 ± 4 171 ± 3 3.63
Aq.ext. (A. milli)
(500 mg·kg–1) 170 ± 6 173 ± 4 176 ± 5 3.52
Glibenclamide
(30 mg·kg–1) 165 ± 8 168 ± 6 171 ± 7 3.63
Table 2 Effect of the extracts on food intake, fluid intake and urine excreted by the rats ( x ± s, n = 6)
Normal Diabetic A.milli Met ext (500 mg·kg–1)
A.milli Aq. ext
(500 mg·kg–1)
Glibenclamide
(30 mg·kg–1)
Fluid intake mL/day 30.00 ± 5.35 58.35 ± 5.36 45.86 ± 7.51 43.48 ± 3.67 43.69 ± 3.57
Food intake g/day 23.62 ± 56 33.48 ± 6.57 28.57 ± 6.43 26.58 ± 4.73 27.38 ± 5.86
Urine (wetting of
saw-bedding) + ++++ ++ ++ ++
Table 3 Effect of the extracts of Achillea millifolium on glucose tolerance of rats ( x ± s, n = 6)
Blood glucose level /(mg·dL–1)
Groups
0 min 60 min 90 min 120 min 150 min
Control 82.61 ± 3.4 146.48 ± 5.1 133.30 ± 10.5 125.34 ± 4.3 116.63 ± 3.6
Met.ext (A. Milli) (500 mg·kg–1) 83.49 ± 5.7 119.56 ± 4.4 107.53 ± 3.6 95.06 ± 4.7 82.45 ± 5.5
Aq.ext. (A. Milli) (500 mg·kg–1) 80.76 ± 4.7 121.32 ± 4.3 110.37 ± 4.2 96.59 ± 3.3 84.35 ± 4.0
Glibenclamide (30 mg·kg–1) 82.90 ± 8.8 117.78 ± 6.3 107.92 ± 6.8 97.06 ± 4.5 83.45 ± 5.8
Table 4 Effect of extracts of Achillea millifolium shoots on fasting blood glucose levels of rats ( x ± s, n = 6)
Blood glucose levels /(mg·dL–1)
Groups
0th day 7th day 14th day % Variation
Normal 82.32 ± 2.23 85.43 ± 3.11 83.57 ± 1.97 –1.51
Diabetic control 298.14 ± 7.56* 313.58 ± 7.34* 337.13 ± 5.56* –13.07
Aqueous extract (250 mg·kg–1 b.wt) 301.55 ± 7.29 259.87 ± 6.39 236.57 ± 9.19 21.54
Aqueous extract (500 mg·kg–1 b.wt) 296.47 ± 12.34 232.51 ± 8.52* 165.49 ± 4.49* 44.25
Methanolic extract (250 mg·kg–1 b.wt) 311.35 ± 6.54 275.43 ± 14.39 230.53 ± 6.58 25.95
Methanolic extract (500 mg·kg–1 b.wt) 309.54 ± 7.46 224.65 ± 6.33* 152.59 ± 7.58* 50.70
Glibenclamide (30 mg·kg–1) 305.90 ± 8.85 248.78 ± 9.32 181.92 ± 6.87 40.65
*P < 0.05 (Dunnet t-test), diabetic control vs normal, extract treated groups vs diabetic control
Table 5 Effect of extract of A. millifolium shoots on serum lipid profile of alloxan monohydrate induced diabetic rats ( x ± s, n = 6)
Cholesterol Triglycerides VLDL LDL
Groups
/( mg·dL–1)
Normal 121.00 ± 6.2 86.83 ± 5.5 37.00 ± 1.5 93.23 ± 5.1
Diabetic control 249.33 ± 15.5* 200.83 ± 11.1* 73.00 ± 1.4* 199.16 ± 14.2*
Aq. Ext. (250 mg·kg–1 b.wt) 207.55 ± 7.29 153.87 ± 6.39 51.57 ± 9.19 148.73 ± 6.7
Aq. Ext. (500 mg·kg–1 b.wt) 144.83 ± 4.9** 111.66 ± 7.9* 39.66 ± 1.5* 102.83 ± 5.9*
Met. ext (250 mg·kg–1 b.wt) 193.35 ± 6.54* 145.43 ± 14.39 48.53 ± 6.58 141.85 ± 5.95
Met.Ext.(500 mg·kg–1 b.wt) 138.50 ± 6.5** 95.50 ± 6.1* 47.83 ± 1.9* 94.56 ± 4.8*
Glibenclamide (30 mg·kg–1) 146.83 ± 6.1* 108.00 ± 6.1* 39.50 ± 1.9* 93.73 ± 6.7*
*P < 0.05 (Dunnet t-test), diabetic control vs normal, extract treated groups vs diabetic control
Khalid G Mustafa, et al. /Chinese Journal of Natural Medicines 2012, 10(3): 185−189
188 Chin J Nat Med May 2012 Vol. 10 No. 3 2012 年 5 月 第 10 卷 第 3 期

Table 6 Effect of extract of A. millifolium shoots on SGOT, SGPT and ALP of alloxan monohydrate induced diabetic rats ( x ± s,
n = 6)
SGOT SGPTT ALP
Groups
/( U·L–1)
Normal 21.00 ± 5.58 26.67 ± 6.53 96.67 ± 10.42
Diabetic control 44.17 ± 4.49* 47.69 ± 5.16* 169.17 ± 17.55*
Aqueous extract (250 mg·kg–1 b.wt ) 29.00 ± 7.32 35.60 ± 5.94 136.56 ± 6.10
Aqueous extract (500 mg·kg–1 b.wt) 24.83 ± 6.47* 27.66 ± 6.79* 98.66 ± 7.75*
Methanolic extract (250 mg·kg–1 b.wt) 27.35 ± 6.47 33.43 ± 4.69 129.53 ± 6.88
Methanolic extract (500 mg·kg–1 b.wt) 22.46 ± 5.57* 25.50 ± 7.81* 96.83 ± 7.95*
Glibenclamide (30 mg·kg–1) 22.83 ± 5.64* 26.07 ± 5.15* 98.50 ± 5.96*
*P < 0.05 (Dunnet t-test), diabetic control vs normal, extract treated groups vs diabetic control

Fig. 1 shows normal acini, and normal cellular popula-
tion in the islets of langerhans in pancreas of vehicle-treated
rats (A). Extensive damage to the islets of langerhans and
reduced dimensions of islets (B), restoration of normal cellu-
lar population size of islets with hyperplasia by Glibencla-
mide (C) is also shown. The partial restoration of normal
cellular population and enlarged size of β-cells with hyper-
plasia is shown by methanol and aqueous extracts. (Fig. 1.
D–E).


Fig. 1 Micrographs of rat pancreas stained by haematoxy-
lin and eosin of, (A) untreated; (B) alloxan induced diabetic
rats i.e. diabetic control; (C) glibenclamide; (D) methanolic
extract of A. millifolium 500 mg·kg–1 of body weight; (E)
aqueous extract of A. millifolium 500 mg·kg–1 of body weight
4 Discussion
The present study investigates the hypoglycaemic and
hypolipidemic effect of Achillea millifolium on al-
loxan-monohydrate induced diabetic rats. The fundamental
mechanism underlying hyperglycemia in diabetes mellitus
involves over-production (excessive hepatic glycogenolysis
and gluconeogenesis) and decreased utilization of glucose by
the tissues [16]. Fourteen days administration of aqueous and
methanolic solution of Achillea millifolium resulted in sig-
nificant reduction in the fasting blood glucose level compared
to diabetic rats. The difference observed between the initial
and final fasting plasma glucose levels of different groups
revealed a significant elevation in blood glucose in diabetic
control group compared to normal. Medicinal plants could be
considered as potential sources for providing a reasonable
amount of the required elements other than diet to the pa-
tients of diabetes mellitus [17]. In alloxan monohydrate in-
duced diabetic rats there was a significant increase in lipids,
total cholesterol, triglycerides (P < 0.05). In Achillea milli-
folium treated rats, there was a reduction in cholesterol,
triglycerides, lipids, which shows the hypolipidemic effect of
this plant. The hypolipidemic effect may be due to the inhibi-
tion of fatty acid synthesis. Intraperitoneal injection of 160
mg·kg–1 bw/d of alloxan monohydrate to fasting rats resulted
in sustained hyperglycemia starting about 72 h post-injection.
Alloxan is a toxic glucose analogue, which selectively de-
stroys insulin-producing cells in the pancreas (that is β cells)
when administered to rodents and many other animal species
[18]. This causes an insulin-dependent diabetes mellitus
(called Alloxan Diabetes) in these animals, with character-
istics similar to Type I diabetes in humans. Alloxan is selec-
tively toxic to insulin-producing pancreatic β cells because it
preferentially accumulates in β cells through uptake via the
GLUT2 glucose transporter. Alloxan, in the presence of in-
tracellular thiols, generates reactive oxygen species (ROS) in
a cyclic reaction with its reduction product, dialuric acid. The
β cell toxic action of alloxan is initiated by free radicals
formed in this redox reaction. One study suggests that alloxan
does not cause diabetes in humans [19]. Others found a sig-
nificant difference in alloxan plasma levels in children with
and without Type I diabetes [20]. Histopathological examina-
tion of the pancreatic islets showed extensive necrosis that
was most noticeable in the central parts of the islets in the
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2012 年 5 月 第 10 卷 第 3 期 Chin J Nat Med May 2012 Vol. 10 No. 3 189

diabetic. Histopathological assessment of the pancreatic tis-
sues of extract treated diabetic rats showed improved islet
morphology (Fig. 1). From the study it could be said that the
medicinal plants could be considered as potential sources for
providing a reasonable amount of the required elements other
than diet to the patients of diabetes mellitus.
5 Conclusions
Methanolic and aqueous extracts of Achillea millifolium
extracts exhibited significant anti-hyperglycemic and anti-
hyperlipidemic activities in alloxan-induced diabetic rats.
The methanolic extract showed the maximum activity and
reduced blood glucose level by 50.70%. There was a protec-
tive effect against the destructive effects of alloxan monohy-
drate in diabetic rats.
Acknowledgement
We are grateful to the Central Council for Research in
Unani Medicine, New Delhi, India for financial assistance.
We are also highly thankful to Mr Showkat Ahmad Teli, Mr.
Mohammad Maqbool Mir, Mr Bashir Ahmad and Mr Ashiq
Ahmad Bhat for their valuable contribution to plant collec-
tion and allocation of animals.
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