Antidiabetic and Antihyperlipidemic Activity of
Roots of Matricaria
recutita on Streptozotocin-Induced
Diabetic Rats
Krishna Murti1*, Mayank Panchal1,
Megha Shah1 and Vijay Lambole1
Dept. of Pharmacology, Vidyabharti Trust College of Pharmacy, Umrakh,
India
ABSTRACT:
The present
study was aimed to evaluate the anti diabetic - activity of Matricaria
recutita roots against Streptozotocin (STZ) induced experimental
rats. Ethanolic extract of roots of Matricaria recutita was administered to
streptozotocin induced rats. Glibenclamide was used as a standard drug. Blood
glucose levels were determined after oral administration of a dose of Matricaria
recutita (400 mg/kg b. wt) in diabetic groups. Blood glucose levels
were determined on 0, 7th, 14th and 21st day after oral
administration of ethanolic extracts of Matricaria recutita (400 mg/kg). An ethanolic
extract of
Matricaria recutita was found to reduce blood sugar in
streptozotocin induced diabetic rats. Reduction in blood sugar could be seen
from 7th day after continuous administration of the extract. The effect of
extracts of
Matricaria recutita on serum lipid profile like Total cholesterol,
triglycerides, low density, very low density and high density lipoprotein were
also measured in the diabetic and non diabetic rats. There was significant
reduction in Total cholesterol, LDL cholesterol, VLDL cholesterol and
improvement in HDL cholesterol in diabetic rats. These results indicated that Matricaria
recutita possesses a hypoglycemic and antihyperlipidemic effect.
KEYWORDS: Matricaria recutita, Glibenclamide,
Hypoglycemia, Antihyperlipidemic, Streptozotocin
1. INTRODUCTION:
Diabetes
mellitus is a complex disorder that is characterized by hyperglycemia resulting
from malfunction in insulin secretion and/or insulin action both causing by
impaired metabolism of glucose, lipids and protein1. The chronic
hyperglycemia of diabetes is associated with long term damage, dysfunction and
failure of various organs2. In diabetic rats, the utilization of
impaired carbohydrate leads to accelerate lipolysis, resulted in hyperlipidemia3,
4. Despite the presence of known antidiabetic medicine in the
pharmaceutical market, diabetes and the related complications continued to be a
major medical problem. Recently, some medicinal plants have been reported to be
useful in diabetes worldwide and have been used empirically as antidiabetic and
antihyperlipidemic remedies5-10. Diabetes mellitus is known to cause
hyperlipidemia through various metabolic derangements. Among several metabolic
derangements, insulin deficiency has been known to stimulate lipolysis in the
adipose tissue and gives rise to hyperlipidemia and fatty liver. Thus, in
diabetes hypercholesterolemia and hypertriglyceridemia often occurs11.
More than 400 plant species having hypoglycemic activity have been available in
literature12, 13; however, searching for new antidiabetic drugs from
natural plants is still attractive because they contain substances which take
alternative and safe effect on diabetes mellitus.
Most of
plants contain glycosides, alkaloids, terpenoids, flavonoids, cartenoids, etc.,
that are frequently implicated as having antidiabetic effect14.
Matricaria
recutita
is widely distributed in the tropics and subtropics.
German chamomile is the most commonly used. It grows freely everywhere. Chamomile
is one of the most widely used and well-documented medicinal plants in the world.
It is included in the pharmacopoeia of 26 countries15
German
chamomile (Matricaria recutita) and Roman chamomile (Chamaemelum
nobile) are the two major types of chamomile used for health conditions and
both are form compositae family. They are believed to have similar effects on
the body, although German chamomile may be slightly stronger. Most research has
used German chamomile, which is more commonly used everywhere except for
England, where Roman chamomile is more common. German chamomile is considered the more potent of the
two, has received more scientific evaluation, and is more widely cultivated
than Roman chamomile; it is believed to possess anti-inflammatory, vulnerary,
deodorant, bacteriostatic, antimicrobial, anticatarrhal, carminative, sedative,
antiseptic, and spasmolytic properties16,17. Roman chamomile is
believed to possess carminative, antiemetic, antispasmodic, and sedative
properties16. Chamomile’s essential oil comprises 0.5% to 1.5% of
the flower head. One hundred Twenty chemical constituents have been identified
in chamomile, including terpenoids, flavonoids, and coumarins15. The
essential oil of both German and Roman chamomile is a light blue color due to
the terpenoid chamazulene. Chamazulene is an artifact formed during
heating and comprises about 5% of the essential oil18.
However, no
simultaneous antidiabetic and antihyperlipidemic activity on the roots of Matricaria
recutita was scientifically
available. Therefore, the present study has been carried out to explore the
antidiabetic and antihyperlipidemic activity of Matricaria
recutita
2. MATERIALS AND
METHODS:
Materials:
The roots of
Matricaria recutita was collected from adjoining areas
of Meerut, in April, 2009, and was authenticated by Associate Professor Dr. M.
K. Saxena, Department of Botany, M. M.P. G. College campus, Modinagar, C.C.S
University, Meerut (Uttar Pradesh), by carrying out macroscopic and microscopic
evaluation.
Animals:
Male Wistar
rats of body wt. 180–200 g were obtained from central Animal House, VBTCP, Umrakh,
India. The animals were fed on standard pellet diet (Hindustan Lever, Mumbai,
India) and water ad libitum. The rats used in the present study were maintained
in accordance with guidelines of the CPCSEA, India and the study approved by
the Institutional ethical committee (VBTCP/IAEC/07/19/10).
Preparation of the root extract:
The shade
dried roots were powdered to get a course granule. About 250 g of dried powder
were extracted with 90% ethanol by continuous hot percolation, using soxhlet
apparatus. The resulted dark – brown extract was concentrated up to 100 ml on
Rota vapour under reduced pressure. The concentrated crude extracts were
lyophilized in to powder and used for the study.
The preliminary phytochemical
analysis:
The
preliminary phytochemical studies were performed for testing different chemical
groups present in ethanolic extract19.
Toxicity studies:
The
animals were divided into six groups separately and were treated orally with
ethanolic extracts of Matricaria recutita at 100, 200 and 400 mg/kg, body weight
doses. The animals were continuously
observed for 1 hr., then frequently for 14 days. The parameters observed were
grooming, hyperactivity, sedation, loss of righting reflex, respiratory rate
and convulsion20.
Streptozotocin-induced diabetic rats:
Streptozotocin
(STZ), obtained from VBTCP, Umrakh was dissolved in ice-cold normal saline
immediately before use. Diabetes was induced in rats by intraperitoneal (i.p)
injection of streptozotocin at a dose of 50 mg/kg21. Forty eight
hours after streptozotocin administration, blood samples were drawn from tail
and glucose levels determined to confirm diabetes. The rats were divided into 4
groups as follows, first group served as normal control, received food and
water. Second group served as diabetic control, received 0.5 ml of 5% Tween 80;
third group served as (diabetic control), received glibenclamide (0.5 mg/kg
p.o.), and fourth groups, (diabetic rats) received 400 mg/kg, b.wt. of
ethanolic extracts of Matricaria recutita.
The treatment was continued daily for 21days. Blood drop was collected from the
tail vein for glucose estimation, just before drug administration on 1st day
and 1 h after sample administration on days 7, 14 and 21 (Table 1).
Biochemical
parameters:
Triglycerides,
cholesterol, HDL-cholesterol, and LDL-cholesterol were estimated from the serum
by using standard kits21, 22, 23.
Statistical evaluation:
All the data
are presented as mean ± SEM. The differences between group were evaluated by
one-way analysis of variance (ANOVA) followed by the Dunnette multiple
comparisons test’s <0.01 was considered to be significant.
3.
RESULTS:
Phytochemical screening:
Phytochemical
screening of the plant extract revealed the presence of terpenoids, flavonoids, coumarins and carbohydrates.
Tab 1:
Anti-hyperglycemic activity of extracts of Matricaria
recutita on STZ
induced diabetic rats.
|
Groups Treatment/Dose |
0 day (mg/ml) |
After 7days (mg/ml) |
After 14days
(mg/ml) |
After 21days
(mg/ml) |
|
Normal
control |
62.40 ±5.45 |
96.70 ±5.56 |
85.80 ±4.45 |
79.75 ±5.79 |
|
Diabetic
control |
224.70 ±15.52 |
214.5 ±10.60* |
211.33 ±20.30* |
208.16 ± 17.38* |
|
Glibenclamide
(0.5mg/kg) |
232.33 ±13.9*** |
184.83 ±12.8*** |
129.83 ±19.20
*** |
94.50 ±5.46 *** |
|
Ethanolic
extract (40 mg/kg) |
237.0 ±15.0*** |
190.16 ±16.14*** |
132.66 ±11.01
*** |
98.83 ±10.55
*** |
.The values
are mean ±SEM, n=6, When compared with diabetic control *p<0.05,
**p<0.001, ***p<001 (One way ANOVA followed by Dennett’s, multiple
comparison test.
Tab 2:
Antihyperlipidemic effect of extract of Matricaria
recutita on STZ induced
diabetic rats.
|
Groups Treatment/Dose |
TC |
TG |
HDL-C |
LDL-C |
VLDL-C |
|
Normal
control |
80.50 ±1.35 |
69.33 ±0.75 |
39.83 ±0.69 |
42.00 ±2.79 |
19.83 ±0.75 |
|
Diabetic
control |
135.83 ±1.97* |
139.00 ±1.68* |
28.67 ±1.15* |
89.50 ±2.29* |
29.34 1.67* |
|
Glibenclamide
(0.5mg/kg) |
98.57 ±3.73** |
88.50 ±2.17** |
34.23 ±5.52** |
59.23 ±1.49** |
23.67 ±0.77** |
|
Ethanolic
extract (40 mg/kg) |
99.19 ±2.26** |
89.00 ±2.69** |
35.57 ±1.33** |
58.13 ±1.62** |
24.93 ±0.37** |
The values
are mean ± SEM n= 6, when compared with diabetic control, * = p<0.05, ** = p<0.01,
(One way ANOVA followed by Dennett’s, multiple comparison tests)
Toxicity studies:
In
performing preliminary test for pharmacological activity in rats, ethanolic
extract did not produce any significant changes in the behavioral or
neurological responses upto 400 mg/kg body weight. Acute toxicity studies
revealed the non-toxic nature of the ethanolic extracts of Matricaria recutita. The result obtained from
the LD50 study indicates that ethanolic extract of
Matricaria recutita is safer to use in animals even at a dose of 400
mg/kg p.o.
Antidiabetic
Effects:
Effect of
ethanolic extract of Matricaria recutita on serum glucose levels in diabetic rats
depicted in Table 1. In animals treated with streptozotocin (50 mg/kg i.p)
(Group II), a significant increase in serum glucose level was observed on 7th,
14thand 21st, day when compared with normal rats (Group
I). Group III received Glibenclamide (0.5 mg/kg p.o.) showed decrease in serum
glucose level when compared with diabetic control rats (Group II). After the
oral administration of ethanolic extract of
Matricaria recutita in diabetic control rats, a significant
reduction in blood glucose level was observed on the 7th, 14thand
21st day compared with diabetic control rats (Group II).
Anti-hyperlipidaemic activity
The lipid
profiles in control and experimental rats are depicted in Table 2 in STZ
induced diabetic rats. The diabetic control rats (Group II) showed significant
increase in serum triglycerides, Total cholesterol, very low density
lipoproteins (VLDL), low density lipoproteins (LDL), and High density
lipoproteins (HDL) when compared with normal (Group I). Standard Glibenclamide
(Group III) also reduced triglycerides, Total cholesterol, very low density
lipoproteins (VLDL), low density lipoproteins (LDL), and increased High density
lipoproteins (HDL) when compared with normal (Group I).The ethanolic extract
showed significant decrease (p<0.001) in Total cholesterol, LDL, VLDL,
Triglycerides and significant increase (p<0.001) in HDL when compared with diabetic control group (Group II). All these
effects were observed on day 14thand 21st .The present
experimental result indicated that ethanolic extract exhibited a potent blood
glucose lowering properties and hypolipidemic effect in STZ diabetic rats.
4.
DISCUSSION:
Diabetes mellitus is one of the leading
causes of death, illness and economic loss all over the world.
Insulin-dependent (Type I, IDDM) diabetes is characterized by juvenile onset
and by absolute insulin deficiency. Non-insulin-dependent (Type II, NIDDM)
diabetes is characterized by mature onset, by varying basal insulin levels and
a frequent association with obesity.
We found an elevated blood glucose
concentration accompanied by increase in total cholesterol, triglycerides,
LDL,VLDL and decrease in HDL cholesterol in streptozotocin induced diabetic
rats as compared to normal control animals. Oral administration of ethanolic
extract of Matricaria recutita normalized
the levels of blood glucose. The potent antidiabetic effect of the plant extract
suggests the presence of potent antidiabetic active principles, which produced
antihyperglycemic effect in diabetic rats.
In recent years, considerable interest has
been directed towards the investigation of plasma lipids and lipoproteins
pattern in diabetes mellitus due to the fact that abnormal lipid level leads to
the development of coronary artery disease in diabetic patients24.
Reduced insulin secretion and defect in insulin function results in enhanced
metabolism of lipids from adipose tissue to the plasma. Impairment in insulin
sensitivity due to high concentration of lipids in the cells is responsible for
the elevated cardiovascular risk in diabetes mellitus25. Thus, the
altered lipid and lipoprotein pattern observed in diabetic rats could be due to
defect in insulin secretion and/or action. Hypercholesterolemia and
hypertriglyceridemia have been reported to occur in alloxan-induced diabetic
rats. Accumulation of cholesterol and phospholipids in liver due to elevated
plasma free fatty acids has been reported in diabetic
rats. In the present study, ethanolic extract of Matricaria recutita had significantly decreased Total
Cholesterol, Triglycerides, VLDL, and LDL with increase in HDL which is having
a protective function for the heart compared with diabetic control group26.
5. ACKNOWLEDGEMENTS:
This research was carried out in the college
campus of Vidyabharti Trust College of Pharmacy, Umrakh, India. The authors are
grateful to Principal and Management Trustee for constant support.
6.
REFERENCES:
1. Babu
V, Gangagadevi T and Subramaniam A. Diabetes induced by
STZ in rats. Ind J of Pharmacology.
35;
2007: 290-96.
2. Bajpay A, editor. Ecological
Studies of Boerhaavia verticillata
poir with special reference to
phytochemical and therapeutic
importance. Ph.D. Thesis, Banaras Hindu University, Varanasi,
India, 1993.
3. Bhattaram
VA, Ceraefe M, Kohlest C, et al. Pharmacokinetics
and bioavailability of herbal medicinal products. Phytomed. 9; 2002: 1-36.
4. Chopra RN, Ghosh S, Dey P, et al. Pharmacology and therapeutics of Boerhaavia diffusa (punarnava). Indian Medical Gazette. 68;
1923:203-208.
5. Dhar ML, Dhar MM, Dhawan BN, et al.
Screening of
Indian plants for biological activity. Indian Journal of Experimental
Biology. 6; 1968: 232-247.
6. EL-Hazmi MAF, Warsy
AS. Obesity, over weight and type II diabetes in Saudi adult patients. Saudi Med J., 20; 1999: 167-172.
7. Frayn
KN, editor. Insulin resistance, impaired postprandial lipid metabolism and
abdominal obesity. Med Princ Pract. 11; 2002: 31-40.
8. Ghosh M, Razmovski
V. Fundamentals of Experimental pharmacology, Scientific book agency Kolkatta.
1999; 2nd Ed: 159-158.
9. Granner DK, Granner
RK, Mayes PA., et al. Hormones of the
Pancreas and Gastrointestinal Tract. In: Murray. Harper’s Biochemistry,
Appleton and Lange, Connecticut, USA, 24; 1996: 586-587.
10. Hardman JG and
Limberd LE. Insulin, oral hypoglycem-ic agents and the pharmacology of the
endocrine pancreas. In Good- man and Gilman's: The Pharma-cological basis of
Therapeutics. Mcgraw-Hill Company Limited, USA, 10; 2001: 1383-1399.
11. Hou, Z, Zhang Z, Wu
H, et al. Effect of Sanguis
draxonis (a Chinese traditional herb) on the formation of insulin
resistance in rats. Diabetes Res Clin Practice. 68: 2005: 3-11.
12. Huang TH, Kota BP,
Razmovski V, et al. Herbal or natural medicines as modulators of
peroxisome proliferator-activated receptors and related nuclear receptors for
therapy of metabolic syndrome. Basic
Clin Pharmacol Toxicology. 96;
2005: 3-14.
13. Lopes-Virella,
Maria F, Stone P. Cholesterol determination in HDLs separated by three different
methods. Clin Chem. 23; 1977: 882-4.
14. Lowry OH,
Rosenborough NT, Farr AL, et al. Protein measurements with the folin phenol
reagent. J Biol Chem. 193; 1951: 265-75.
15. Salamon I.
Chamomile. A medicinal plant. The Herb, Spice, and Medicinal Plant Digest. 10;
1992: 1-4.
16. Newall CA, Anderson
LA, Phillipson JD. Herbal medicines: a guide for health-care professionals.
London: Pharmaceutical Press. 9;
1996: 296.
17. Blumenthal M. The
complete German Commission E monographs: therapeutic guide to herbal medicines.
Austin: American Botanical Council, 1998.
18. Anonymous.
Chamomile. In: Dombek C, ed. Lawerence Review of Natural Products. St. Louis:
Facts and Comparisons, 1991.
19. McGowan MW, Joseph
DA, Strandbergh DR. A peroxidase coupled method for the colorimetric de termination of serum triglycerides. Clin
Chem. 29; 1983: 538-42.
20. Mitra SK,
Gopumadhavan S, Muralidhar TS. Effect of a herbomineral preparation D-400 in
streptozotocin induced diabetic rats. J
Ethnopharmacol. 54; 1996: 41-46.
21. Morel DW, Chisolm
GM. Antioxidant treatment of diabetic
rats inhibits lipoprotein oxidation and cytotoxicity. J
Lipid Res. 30; 1989: 1827-1834.
22. Oliver-Bever B.
Oral hypoglycemic action of medicinal plants in tropical West Africa. Cambridge University Press, London, 1986:
245-267.
23. Rai MK,
editor. A review on some antidiabetic
plants of India. Ancient Science of Life, 14: 1995: 42-54.
24. Scheen, JA, editor.
Drug treatment of non-insulin dependent diabetes mellitus in the 1990s. Achievement and future development drugs.
54; 1997: 355-368.
25. Shukla R, Sharma
SB, Puri D. Medicinal plants for treatment of diabetes mellitus. Indian
J Clinical Biochem. 15: 2006:
169-177.
26. Trease GE, Evans
WC. A Text book of Pharmacognosy. ELSB
Baillere Tindal, Oxford, 1987; 1055.
Received on 28.03.2011
Accepted on 10.04.2011
© A&V Publication all right reserved
Research J. Pharmacology and
Pharmacodynamics. 3(4): July –August, 2011, 180-183