Hypoglycemic Effect of Foeniculum vulgare Mill. Fruit on Dexamethasone Induced Insulin Resistance Rats

 

 

VR Dongare1*, AU Arvindekar2 and CS Magadum3

1Appasaheb Birnale College of Pharmacy, Sangli

2Department of Biochemistry,  Shivaji University, Kolhapur.

3Ashokrao   Mane College of Pharmacy, Pethvadgaon. (M.S) India

 

 

ABSTRACT:

Aim: - To assess the hypoglycemic effect of Foeniculum vulgare Mill. Fruit on dexamethasone induced insulin resistance rats.

Method: - Wistar male rats (n=5) were made insulin resistance by administering dexamethasone injection subcutaneously to the overnight fasted rats and continue till the end of the experiment along with methanolic extract of Foeniculum vulgare Mill. Fruit for test and pioglitazone for std. At the end of the experimental period i.e. on day 11th the animals anesthetize with ether, blood was collected by retroobital puncture and serum separated for the estimation of glucose, triglycerides, cholesterol, insulin. The animals were weighed at the beginning and at the end of experimental period. The liver and muscle glycogen was also measured.

Results: - Methanolic extract of Foeniculum vulgare Mill. Fruit lowers blood glucose, triglycerides, cholesterol and increase liver and muscle glycogen in dexamethasone induced insulin resistance rats.

Conclusion: The present study was indicating that   Foeniculum vulgare Mill. Fruit showed significant glucose and triglyceride lowering activities as compared with diabetic control. In comparison with standard pioglitazone, Foeniculum vulgare Mill. Fruit showed comparable serum glucose lowering and better triglyceride lowering activity.

 

 

KEYWORDS: Insulin resistance, Foeniculum vulgare, Dexamethasone, Blood glucose,

 

 

INTRODUCTION:

Diabetes mellitus is disorder of carbohydrate, fat, protein metabolism attributed to diminished production of insulin or insulin resistance.1

 

Diabetes is a global disease with a huge adverse impact on health and mortality, particularly from cardiovascular disorders. It occurs at any time of life from infancy to old age. Type 2 diabetes is primarily a life style disorder, which accounts for around 90% of diabetes cases and increasing at an astonishing rate, particularly in developing countries like India. In 1995, it has been estimated that around 135 million people had this condition, and this may increase to as many as 300 million by the year 2025.2

 

It is characterized by abnormalities in carbohydrate, lipid and lipoprotein metabolism which not only lead to hyperglycemia but also cause many complications, such as hyperlipidemia, hyperinsulinemia, hypertension and atherosclerosis.3

 

Coronary, cerebrovascular and peripheral vascular diseases are the principal causes of morbidity and the mortality in type 2 diabetes mellitus. The accelerated macro vascular disease in type2 diabetes mellitus is due to partly in increased incidence of cardiovascular risk factor such as hypertension, obesity and dyslipidemia. Type 2 diabetes mellitus is associated with an increased incidence of micro and macroangiopathy and hypertension.


These disorders may, together with other risk factors, such as hyperlipidemia, oxidant stress and insulin resistance state alters endothelial function and consequently triggers the start of atherosclerosis in type 2 diabetes mellitus.

 

Endothelial function is more altered in type 2 diabetic patient than in type1 diabetic patient, even though the blood glucose control may not be significantly different. A longer period of undetected blood abnormalities, lipid alterations or decreased insulin sensitivity could be involved. Biochemical changes are activated by high blood glucose concentration and can explain the adverse effects of hypoglycemia on the retina, lens, nerves and also on endothelium.4

 

Increasing evidence from both experimental and clinical studies suggests that oxidative stress plays a major role in the pathogenesis of diabetes mellitus. Free radicals are formed disproportionately in diabetes by glucose oxidation, non enzymatic glycation of proteins and the subsequent oxidative degradation of glycated proteins. Recent experimental and clinical studies have uncovered new insights in to the role of oxidative stress in diabetic complications, suggesting a different and innovative approach to a possible “causal” antioxidant therapy e.g. flavonoids.5

 

MATERIALS AND METHODS:-

1] Preparation of extract-

The air dried powdered Foeniculum vulgare Mill. Fruit extracted in soxhlet extraction assemblyby using methanol.6

 

2] Acute oral toxicity study-

The acute oral toxicity study was studied as per the OECD guideline 425 in Wistar rats maintained under standard conditions. Acute toxicity for methanolic extract of Foeniculum vulgare Mill. Fruit was carried out using groups of three wistar rats by administering a dose 2000 mg/kg, in normal saline orally while the control received only the vehicle.7

 

3] Antidiabetic activity:-

Animals:-

Wistar rats weighed between150-250 which was bred in the Department of pharmacology A.B.C.P. Sangli. The animals were housed under well ventilated natural conditions in large cage. The animals were made insulin resistance by administering dexamethasone subcutaneously and hypoglycemic activity of methanolic extract of Foeniculum vulgare Mill. Fruit was assessed.

 

Dexamethasone induced insulin resistance model-

Animals were divided in to following manner- for Dexamethasone induced insulin resistance model-

 

1]    Normal control

Oral saline

2]   Dexamethasone         control

Dexamethasone sodium phosphate 10mg/kg once daily, s.c.

3]       Test

Dexamethasone sodium phosphate + methanolic extract (200mg/kg b.w., p.o.)

4]      Std.

Dexamethasone sodium phosphate +   Pioglitazone (30mg/kg, p.o.)

 

 

Method: Dexamethasone induced insulin resistance model-

In groups 2-4, dexamethasone was injected subcutaneously to the overnight fasted rats and continues till the end of the experiment along with methanolic extract for test and pioglitazone for std. At the experimental period i.e. on day 11th the animals anesthetize with ether, blood was collected by retroorbital puncture and serum separated for the estimation of glucose, triglyceride, cholesterol, insulin. The animals were weighed at the beginning and at the end of the experimental period. The liver and muscle glycogen was also measured. Serum insulin was estimated by ELISA method using ELISA kit.8

 

Statistical Analysis:

All the results were expressed as mean SEM and the data were analyzed using one–way ANOVA followed by Dunnett’s multiple comparison post hock test P-values <0.01were considered significant9

 

RESULTS:

Acute toxicity study:-

The groups were observed mortality and behavioral changes during 48hrs. The LD50 of methanolic   extract of Foeniculum vulgare in rats by oral route was found to be 200mg/Kg.

 

Antidiabetic activity:-

Biochemical parameters

Normal Control

Diabetic Control

Test

Std

Blood glucose

90.2±

2.57**

202.2±

3.39*

98±

1.4

100.2

±1.28

Cholesterol

72.3±

0.64**

108.4±

1.03*

88.7

±0.46

85.76

±0.45

Triglycerides

100.9±

2.33**

201.72

±2.55*

149.12±1.3

133.5

±0.51

HDL Cholesterol

38.7±

0.60**

21.79±

0.27*

35.27

±0.28

33.47

±0.21

LDL

13.42±

0.68**

50.46±

2.08*

26.60

±0.28

25.75

±0.74

VLDL

20.18±

0.46**

40.34±

0.51*

29.82

±0.27

26.71

±0.10

Insulin

25.67±

0.36**

42.51±

0.70*

28.78

±0.54

27.92

±0.39

Liver glycogen

35.64±

0.77**

22.284

±1.35*

32.9±

1.47

36.5

±0.50

Muscle glycogen

6.12±

0.23**

3.296±

0.34*

5.8±

0.43

6.2

±0.24

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table showing Foeniculum vulgare significantly lowers blood glucoseand triglycerides.

Values are mean ±SEM; n=5 in each group *p<0.01 when compared with control. **p<0.01 when compared with normal.

 

 

DISCUSSION:-

The results of this study demonstrated that dexamethasone increases triglyceride levels, causing an imbalance in lipid metabolism leading to hyperlipidemia and increase in glucose levels leading to hyperglycemia.10

 

The use of medicinal plants has a long folk for the treatment of diabetes mellitus, (11) currently available synthetic antidiabetic agent produce serious side effects like hypoglycemic coma. Thus it is possible to develop newer drugs, lesser side effects, and better efficiency at lowered cost.

 

 

In summary, the present study demonstrated that type II diabetes mellitus leads to insulin resistance and elevated level of cholesterol, triglycerides and LDL, which can be significantly managed by methanolic extract of Foeniculum vulgare mill. Fruit.

 

ACKNOWLEDGEMENT:

The author is thankful to Principal shri D. D. Chougule, Appasaheb Birnale College of Pharmacy , Sangli for providing facilities.

 

REFERENCES:

1.       Claudia E.N. et al. Antidiabetic and hypoglycemic effect of Laportea ovalifolia in alloxan induced diabetes rats. Afr. J. Trad CAM ISSN   2006  36, 0189-6016.

2.       B.R. Prashanta Kumar, et al. Serum glucose and triglyceride lowering activity of some novel glitazones against dexamethasone induced hyperlipidemia and insulin resistance. Indian Journal of Pharmacology, 2007; 39,299-302.

3.       P. Subash Babu, et al. Cinamaldehyde- A potential antidiabetic agent. Phytomedicine 2007; 14, 15-22.

4.       B.Guerci, et al Endothelial dysfunction and type 2 diabetes. Diabetes Metab (Paris), 2001. 27, 436-447.

5.       A.lukacinova, et al. Preventive effect of flavonoids on alloxan induced diabetes mellitus in rats. AcTAVET. 2008;77, 175-182.

6.       Kokate C.K., Ar. Purohit, S.B. Gokhale 2004 “ Pharmacognosy” 27th edition, Pune , Nirali Prakashan, 106.

7.       OECD Guidelines for Testing Chemicals, Guidelines 423, Acute oral toxicity – acute toxic class method. Paris 1996.

8.       Md. Shalam, M.S.Harish, S.A Farhana. Prevention of dexamethasone and fructose induced insulin resistance in rats by SH-01D, a herbal preparation. 2006 ;38,419-422.

9.       D.G. Langade, et al. (2006) In vitro prevention by ACE inhibitors of cataract induced by glucose. 38,107-110.

10.    Md. Shalam, M.S.Harish, S.A Farhana. Prevention of dexamethasone and fructose induced insulin resistance in rats by SH-01D, a herbal preparation. . 2006; 38,419-422.

11.    Noreen Wadood, et al.Effect of a compound recipe ( medicinal plants) on serum insulin levels of alloxan induced diabetic rabbits.

 

 

Received on 07.07.2009

Accepted on 10.09.2009     

© A&V Publication all right reserved

Research Journal of Pharmacognosy  and Phytochemistry. 2(2): March -April 2010, 163-165