In the past decade there has been an exponential growth in the field of herbal medicine and these drugs are gaining popularity both in developing and developed countries because of their natural origin and less side effects. Many traditional medicines in use are derived from medicinal plants, minerals and organic matter.³ A number of medicinal plants, traditionally used for over 1000 years named rasayana are present in herbal preparations of Indian traditional health care systems.⁴ Traditional herbal medicines are naturally occurring; plant derived substances with minimal or no industrial processing that have been used to treat illness within local or regional healing practices. Traditional herbal medicines are getting significant attention in global health debates.⁵

Ficus bengalensis (FB) (Moraceae) is commonly known as Banyan tree or Vata or Vada treen in Ayurveda. There are more than 800 species and 2000 varieties of Ficus species, most of which are native to the old world tropics.⁶ It is endemic to Bangladesh, India and Sri Lanka. It is also known as Bengal fig, Indian fig and East Indian fig, Indian Banyan or simply Banyan (English), also borh, nyagrodha (Sansikrat), Bat, Bargad and Bar (Hindi). The English name Banyan is given by the Britishers to this tree because under the tree Banias that is, the Hindu merchants used to assemble business. The triad Ganges, the Himalayas and the Banyan tree symbolize the images of India, for this reason it is considered as National Tree.

Various parts of Ficus bengalensis are known to possess various pharmacological properties such as Anthelmintic activity, Anti-inflammatory activity, Antibacterial activity, Immunomodulatory activity, Antistress and antiallergic activity, Analgesic and antipyretic activity, Antidiarrhoeal activity, Antiatherogenic activity, Wound healing activity, and Growth promoting activity.⁷ Ficus bengalensis is one of the common plants used in Tribal Belts of Midnapur (West) District of Bengal, for the treatment of diabetes. In the absence of systemic literature, the present study was aimed to evaluate the antidiabetic, antioxidant and antidyslipidemic activity of ethanolic extract of Ficus bengalensis fruits in alloxan induced diabetic rats.

MATERIALS AND METHODS:

Plant material

Ficus bengalensis fruits were collected from a botanical garden in Guindy, Chennai, Tamilnadu, India. The plants were identified and authenticated and a voucher specimen was deposited at the Department of Biochemistry, University of Madras, Chennai.

Preparation of plant extract

The Ficus bengalensis fruits were dried at room temperature and powdered in an electrical grinder, which was then stored in an airtight container at 5°C until further use. The powdered root was delipidated with petroleum ether (60 - 80°C) for overnight. It was then filtered and soxhalation was performed with 95% Ethanol. Ethanol was evaporated in a rotary evaporator at 40 - 50° C under reduced pressure.

Phytochemical screening

The ethanolic extracts of Ficus bengalensis fruit extract were subjected to preliminary phytochemical screening of various plant constituents (Harborne, 1998).

Experimental animals

Male albino Wistar rats (150-180 g) were purchased from TANUVAS, Madavaram, Chennai. The rats were housed in polypropylene cages lined with husk and kept in Animal house, Department of Biochemistry. It was renewed every 24 hours. The rats were fed with commercial pelleted rats chow (VRK Nutritional Solutions, Maharashtra, India) and had free access to water. The experimental rats were maintained in a controlled environment (12:12 hours light/dark cycle) and temperature (30 ± 2°C). The experiments were designed and conducted in accordance with the ethical norms approved by Ministry of Social Justices and Empowerment, Government of India and Institutional Animal Ethics Committee Guidelines for the investigation of experimental pain in conscious rats. The rats were acclimatized for one week before starting the experiments.

Induction of experimental diabetes in rats

Rats were induced diabetes by single intraperitonial injection of alloxan monohydrate dissolved in sterile normal saline at a dose 120 mg/Kg, after 18 hours fasting to induce hyperglycemia.⁸ After 1 hour alloxan administration, the animals were fed on standard pellets and water ad libitum. Rats were supplied with 5% glucose solution for 48 hours after alloxan injection in order to prevent severe hypoglycaemia. After 1 week time for the development and aggravation of diabetes, the rats with moderate diabetes having persistant glycosuria and hyperglycemia (Blood Glucose range of above 250 mg/dL) were considered as diabetic rats and used for the experiment. The treatment was started on the eighth day after alloxan injection and this was considered as first day of treatment.

Experimental design

The rats were grouped into 4 groups, comprising of 6 rats in each group as follows:

Group 1: Control Rats (Water and food ad libitum).

Group 2: Alloxan induced diabetic Rats.

Group 3: Diabetic Rats treated with Ficus bengalensis fruit extract (250 mg/Kg Body weight/day) in aqueous solution orally for 30 days.

Group 4: Diabetic Rats treated with gliclazide (5mg/Kg body weight/day) in aqueous solution orally for 30 days.

During the experimental period, body weight of the rats was determined at regular intervals. At the end of the experimental period, the rats were fasted over night, anaesthetized, and sacrificed by cervical decapitation. The blood was collected with or without anticoagulant for plasma and serum separation respectively.

Blood glucose level was estimated by the method of glucose oxidase/peroxidase as described by Trinder⁹; plasma protein by Lowry’s et al.¹⁰; urea by Natelson et al.¹¹; hemoglobin and glycosylated hemoglobin by the methods of Drabkin and Austin,¹² and Nayak and Pattabiraman,¹³ respectively. Plasma insulin was assayed by using ELISA kit for rats. The levels of creatinine¹⁴ and uric acid,¹⁵ and the activities of AST¹⁶, ALT¹⁷ and ALP¹⁸ in serum were also assayed.

Oral Glucose Tolerance Test (OGTT)

At the end of the experimental period, fasting blood glucose was monitored after overnight fasting of rats. Then rats were orally administered with glucose solution (2 g/kg bw) and the levels of blood glucose in all the group of rats at 30, 60, 90 and 120 minutes after glucose administration was measured using Glucometer.

Assay of oxidative stress markers and antioxidants in pancreas and plasma

The pancreatic tissues were excised, rinsed in ice-cold saline and were homogenized in Tris–HCl buffer (100 mM, pH 7.4) at 4°C, in a Potter– Elvehjem homogenizer with a Teflon pestle at 600 rpm for 3 min. The homogenate was then centrifuged at 12,000g for 30 min at 4°C. The supernatant was collected and used for the determination of lipid peroxides and enzymatic antioxidants. Lipid peroxides were determined by the method of Ohkawa et al.¹⁹ Enzymatic antioxidants such as superoxide dismutase,²⁰ catalase,²¹ and glutathione peroxidase²² in pancreatic supernatant were assayed. Further, the levels of lipid peroxides, and the non-enzymatic antioxidants such as vitamin C,²³ vitamin E,²⁴ ceruloplasmin²⁵ and glutathione (GSH)²⁶ in plasma were determined by the methods of Omaye et al.²⁷; Desai²⁸; Ravin²⁹; Sedlak and Lindsay,³⁰ respectively.

Determination of Liver and muscle glycogen content

The level of glycogen content in liver and muscle was estimated as described by Morales et al. (1973).³¹ Briefly, Glycogen was precipitated from the alkali extract of the tissues by adding 1:3 volume of 95% ethanol and a drop of 1 M ammonium acetate and was kept in a boiling water bath for 5 min. After cooling, the samples were shaken and placed in a freezer overnight. The precipitated glycogen was then collected by centrifugation at 3,000g for 40 min. The precipitate was dissolved in water, then precipitated with alcohol and centrifuged again. The final precipitate was dissolved in water and heated for 5 min in a boiling water bath. Then the samples were cooled in an ice-bath, anthrone reagent was added and heated for 20 min in a boiling water bath. Again the samples were cooled to room temperature and the green colour developed was read at 640 nm in a Shimadzu spectrophotometer. The levels of glycogen were expressed as mg of glucose/g of wet liver tissue.

Assay of plasma lipid profile

Cholesterol content was estimated by the method of Parekh and Jung. Triglyceride was estimated by the method of Rice. HDL Cholesterol fraction was separated by the precipitation techniques of Burstein and Scholnick and the cholesterol content was determined.

RESULTS:

Table 1 shows the presence of different phytochemicals such as alkaloids, flavanoids, glycosides, saponins, tannins, phytosterol, terpenoids, and phenols in the ethanolic extract of Ficus bengalensis fruit.

Table 1 Phytochemical screening of F. bengalensis fruit extract

Phytoconstituents	Inference
Alkaloids	+
Flavonoids	+
Glycosides	+
Saponins	+
Tannins	+
Phytosterol	+
Triterpenoids	+
Anthraquinones	-
Phenols	+

The changes of body weight in control and experimental group of rats were presented in Table 2. Diabetic rats exhibited significant reduction in body weight when compared to normal control rats. Whereas, diabetic rats treated with Ficus bengalensis fruit extract as well as gliclazide showed significant body weight gain.

Table 2. Effect of F. bengalensis fruit extract on changes in body weight of experimental groups of rats after 30 days treatment.

Groups	Body weight (g)
Groups	Initial	Final
Control	170.14 ± 3.74	218.72 ± 5.21
Diabetic	172.32 ± 2.95	145.19 ± 7.35*
Diabetic + F. bengalensis extract	160.29 ± 3.15	181.56 ± 5.71^@
Diabetic + gliclazide	164.34 ± 4.12	185.16 ± 6.36^@

Values are given as mean ± SD for groups of six rats in each. Values are statistically significant at p < 0.05. Statistical significance was compared within the groups as follows: *compared with control, ^@compared with diabetic rats.

Graph 1 represents the levels of blood glucose at different time intervals, after oral administration of glucose (2g/ kg) in control and experimental rats. OGTT revealed that the blood glucose value in control rats reach peak at 60 minutes after the oral glucose load and gradually return backs to normal levels at the end of 120 minutes. In diabetic control rats, the blood glucose concentration was significantly greater than the control values at 30 min and peak 60 minutes, and the curve shift to the right even over the next 60 minutes indicates impaired glucose tolerance. Treatment with fruit extract showed definite lower peak blood glucose values at 60 minutes after glucose load and also a peak returns to the basal level at the end of 120 minutes.

Graph 1. Effect of F. bengalensis fruit extract on the blood glucose level in the experimental groups of rats receiving an oral glucose load.

Table 3. Effect of F. bengalensis fruit extract on the levels of blood glucose, plasma insulin, hemoglobin, glycosylated hemoglobin, and urine sugar in the experimental groups of rats.

Groups	Glucose (mg/dl)	Insulin (µU/ml)	Hemoglobin (g/dl)	Glycosylated hemoglobin (%)	Urine sugar
Control	98.59 ± 10.25	14.98 ± 2.65	14.75 ± 2.46	6.67 ± 1.62	Nil
Diabetic	300.78 ± 22.36*	5.64 ± 1.02*	9.18 ± 1.97*	13.38 ± 2.79*	+++
Diabetic + F. bengalensis extract	145.32 ± 12.44^@	10.41 ± 2.35^@	11.54 ± 2.59^@	8.22 ± 1.91^@	Nil
Diabetic + gliclazide	118.12 ± 16.17^@	12.04 ± 1.98^@	12.19 ± 2.14^@	7.95 ± 2.04^@	Nil

Table 4. Effect of F. bengalensis fruit extract on the levels of protein, urea, creatinine and uric acid in plasma of experimental groups of rats.

Groups	Protein (g/dl)	Urea (mg/dl)	Creatinine (mg/dl)	Uric acid (mg/dl)
Control	8.42 ± 1.15	24.90 ± 1.95	1.15 ± 0.10	2.37 ± 0.92
Diabetic	5.66 ± 0.92*	46.52 ± 4.18*	2.22 ± 0.22*	5.35 ± 1.28*
Diabetic + F. bengalensis extract	6.98 ± 0.88^@	34.06 ± 3.04^@	1.52 ± 0.11^@	3.24 ± 0.96^@
Diabetic + gliclazide	7.44 ± 0.77^@	32.62 ± 2.48^@	1.34 ± 0.10^@	2.75 ± 1.02^@

Table 5. Effect of F. bengalensis fruit extract on the activity of AST, ALT and ALP in the serum of experimental groups of rats.

Groups	AST	ALT	ALP
Control	66.22 ± 6.54	19.26 ± 2.49	84.51 ± 10.26
Diabetic	111.89 ± 14.98*	48.18 ± 4.81*	155.36 ± 18.24*
Diabetic + F. bengalensis extract	91.17 ± 10.29^@	23.82 ± 3.96^@	99.90 ± 11.28^@
Diabetic + gliclazide	81.62 ± 8.41^@	22.91 ± 2.98^@	102.50 ± 12.81^@

The enzyme activities are expressed as: AST and ALT µmoles of pyruvate liberated /h/mg of protein; ALP µmoles of phenol liberated/min/mg of protein. Values are given as mean ± SD for groups of six rats in each. Values are statistically significant at p < 0.05. Statistical significance was compared within the groups as follows: *compared with control, ^@compared with diabetic rats.

Table6. Effect of F. bengalensis fruit extract on the level of TBARS in plasma and pancreas of experimental groups of rats.

Groups	TBARS
Groups	Plasma	Pancreas
Control	4.37 ± 0.69	40.41 ± 4.85
Diabetic	8.32 ± 1.61*	78.36 ± 9.54*
Diabetic + F. bengalensis extract	5.45 ± 1.16^@	58.48 ± 6.71^@
Diabetic + gliclazide	5.24 ± 1.02^@	55.45 ± 7.13^@

Units: mM/100 g in tissues; nM/ml in plasma. Values are given as mean ± SD for groups of six rats in each. Values are statistically significant at p < 0.05. Statistical significance was compared within the groups as follows: *compared with control, ^@compared with diabetic rats.

Table 7. Effect of F. bengalensis fruit extract on the activity of SOD, Catalase and GPx, in pancreas of experimental groups of rats.

Groups	SOD	Catalase	GPx
Control	5.35 ± 1.25	15.32 ± 2.09	6.15 ± 1.02
Diabetic	1.48 ± 0.41*	5.93 ± 1.30*	3.19 ± 0.32*
Diabetic + F. bengalensis extract	3.71 ± 0.82^@	12.35 ± 1.77^@	4.56 ± 0.65^@
Diabetic + gliclazide	3.89 ± 0.76^@	13.02 ± 1.88^@	5.30 ± 0.92^@

Activity is expressed as: 50% of inhibition of epinephrine autooxidation/min/mg of protein for SOD; µmoles of hydrogen peroxide decomposed/min/mg of protein for catalase; µmoles of glutathione oxidized/min/mg of protein for GPx. Values are given as mean ± SD for groups of six rats in each. Values are statistically significant at p < 0.05. Statistical significance was compared within the groups as follows: *compared with control, ^@compared with diabetic rats.

Table 8. Effect of F. bengalensis fruit extract on the levels of vitamin C, vitamin E, ceruloplasmin and GSH in plasma of experimental groups of rats.

Groups	Vitamin C	Vitamin E	Ceruloplasmin	GSH
Control	1.45 ± 0.15	0.69 ± 0.10	12.19 ± 1.62	31.74 ± 3.99
Diabetic	0.51 ± 0.08*	0.32 ± 0.14*	5.16 ± 0.89*	15.99 ± 2.45*
Diabetic + F. bengalensis extract	0.99 ± 0.07^@	0.55 ± 0.08^@	9.75 ± 1.46^@	23.86 ± 2.87^@
Diabetic + gliclazide	1.05 ± 0.09^@	0.59 ± 0.06^@	10.21 ± 1.88^@	26.15 ± 3.06^@

Units: mg/dl. Values are given as mean ± SD for groups of six rats in each. Values are statistically significant at p < 0.05. Statistical significance was compared within the groups as follows: *compared with control, ^@compared with diabetic rats.

Table 9. Effect of F. bengalensis fruit extract on the levels of liver and muscle glycogen content in the experimental groups of rats.

Groups	Glycogen (mg glucose/g tissue)
Groups	Liver	Skeletal muscle
Control	40.60 ± 3.32	7.82 ± 0.81
Diabetic	18.55 ± 2.21*	3.77 ± 0.43*
Diabetic + F. bengalensis extract	32.74 ± 3.56^@	5.41 ± 0.64^@
Diabetic + gliclazide	30.75 ± 2.75^@	5.64 ± 0.72^@

Table 10. Effect of F. bengalensis fruit extract on the levels of total cholesterol, triglycerides, LDL-cholesterol and HDL-cholesterol in the plasma of experimental groups of rats.

Groups	Total cholesterol	Triglycerides	LDL	HDL
Control	86.61 ± 10.54	62.39 ± 9.66	51.21 ± 5.52	26.69 ± 2.08
Diabetic	168.25 ± 19.75*	150.87 ± 15.77*	135.35 ± 9.41*	14.54 ± 1.42*
Diabetic + F. bengalensis extract	106.75 ± 15.78^@	89.14 ± 10.45^@	75.79 ± 7.32^@	22.13 ± 1.98^@
Diabetic + gliclazide	95.35 ± 12.52^@	82.46 ± 8.39^@	62.97 ± 6.59^@	26. 51 ± 2.09^@

The altered levels of these parameters were reverted back to near normalcy upon the treatment with the fruit extract.

Table 5 depicts the level of activities of serum enzymes such as AST, ALT and ALP in normal control and experimental group of rats. The increased levels of these enzymes were reverted back to near normalcy upon the treatment with the fruit extract.

The level of TBARS in plasma and pancreas of control and experimental group of rats are presented in Table 6. Diabetic rats showed marked increase in TBARS when compared with control rats. Upon treatment of fruit extract as well as gliclazide to the diabetic rats showed significant decrease in the levels of TBARS when compared with diabetic rats.

Table 7 shows the levels of activities of antioxidant enzymes such as SOD, Catalase, and glutathione peroxidase in pancreatic tissues of normal control and experimental group of rats. A significant decrease in the level of antioxidant enzymes was observed in alloxan induced diabetic rats. Upon treatment with ethanolic extract of Ficus bengalensis fruit as well as gliclazide to alloxan induced diabetic rats restored the level of antioxidant enzymes to normal.

The levels of non enzymatic antioxidant such as Vitamin E, Vitamin C, Ceruloplasmin and reduced glutathione in plasma of control and experimental group of rats are shown in Table 8. The diminished levels of non-enzymatic antioxidants in the diabetic group of rats were significantly improved to near normal values by the oral administration of Ficus bengalensis fruit extract as well as gliclazide, after 30 days of treatment.

Table 9 depicts the level of liver and muscle glycogen content in control and experimental group of rats. The significant decrease in liver and muscle glycogen content were observed in diabetic rats when compared with normal control rats and the level was brought back nearer to normal by oral administration of Ficus bengalensis fruit extract as well as gliclazide.

Table 10 depicts the levels of total cholesterol, triglycerides and lipoproteins (LDL and HDL) cholesterol levels of normal control and experimental group of rats. The elevated levels of total cholesterol, triglycerides and LDL-cholesterol and reduced level of HDL-cholesterol was observed in diabetic rats was restored back nearer to the normal after oral administration of Ficus bengalensis fruit extract as well as gliclazide.

DISCUSSION:

Induction of diabetes with alloxan is associated with the characteristic loss of body weight, which due to increased muscle wasting and loss of tissue proteins.³² The diabetic control group exhibit gradual weight loss as compared with the normal group. Diabetic rats treated with Ficus bengalensis extract as well as gliclazide for 30 days showed a significant improvement in body weight as compared to diabetic animals, which shows beneficial effects of the fruits extract. The capability of Ficus bengalensis to protect body weight loss seems to be as a result of its ability to improve glucose tolerance.

Alloxan induction causes specific damage of β-cells and thus exerts a pronounced increase in blood glucose concentration and decrease in plasma insulin levels. It is well established that gliclazide is used as an antihyperglycemic drug, which increases the insulin secretion from pancreas and it is often used as a standard drug in diabetic models to compare the antidiabetic property of various plant extracts. Oral administration of ficus bengalensis fruits extract to alloxan-induced diabetic rats resulted in significant reduction of blood glucose and increase of plasma insulin levels. This indicates that the ficus bengalensis fruits extract has antidiabetic activity by potentiating the stimulation of insulin release from the remnant pancreatic β-cells.

The measurement of glycosylated haemoglobin is one of the well established means to identify the average plasma glucose concentration over prolonged periods of time, was first proposed by Koenig et al. (1976).³³ In addition, HbA1c is an important marker in assessing a patient’s risk of vascular complications. Due to persistent elevated blood glucose level under diabetic condition, the circulating level of glycosylated haemoglobin level increased.³⁴ Hence, measurement of both HbA1c and blood glucose levels are now used in the routine management of diabetes.³⁵ There was a significant elevation in the levels of glycosylated haemoglobin, in alloxan-induced diabetic rats compared to normal control rats. Oral administration of Ficus bengalensis fruit extract brought back to near normal as that of standard drug gliclazide treatment.

Liver plays a unique role in regulating carbohydrate metabolism by maintaining glucose concentrations in a normal range over both short and long periods of times. In diabetes, alterations in hepatic glucose metabolism are observed, i.e. increased post absorptive glucose production and impaired suppression of glucose production together with diminished glucose uptake following carbohydrate ingestion. The simultaneous overproduction of glucose and fatty acids in liver further stimulates the secretion of insulin by the pancreatic β-cells, and elicits further peripheral insulin resistance thereby establishing a vicious circle.³⁶ In the present study, a significant decrease in liver and muscle glycogen content were observed in diabetic rats when compared with normal control rats and the level was brought back nearer to normal by oral administration of ficus bengalensis fruits extract as well as gliclazide indicating the improved glucose homeostasis. Besides this Ficus bengalensis fruits extract might involve in extra pancreatic action in alloxan-induced diabetic rats, by stimulating the peripheral glucose utilization and or storage.

The metabolism of proteins is abnormal in diabetes due to deficiency of insulin.³⁷ Earlier studies indicate that serum protein and albumin levels were reduced in diabetic rats.³⁸ Total protein reduction may be due to increased protein catabolism caused by impaired glucose homeostasis.³⁹ A significant decrease in the level of total protein was observed in serum of alloxan induced diabetic rats. This decreased level of total protein were reverted back to near normal by Ficus bengalensis fruit extract as well as gliclazide treated diabetic rats. This is possibly through the increase of insulin secretion, thereby improvement in protein metabolism.

The levels of urea, uric acid and creatinine which are markers of renal dysfunction were found to be increased in the diabetic group of rats.⁴⁰ After treatment with ethanolic extract, the levels of these markers was significantly decreased which confirms the beneficial effect of the fruit extract in diabetes associated renal complications.

The aminotransferases, AST and ALT are located in liver cells and leak out and make their way into the general circulation when liver cells are injured. The ALT is thought to be a more specific indicator of liver inflammation, since the AST may be elevated in diseases of other organs such as the heart or muscle. Alkaline phosphatases act as marker of biliary function and cholestasis. The observed increase in the activities of AST, ALT and ALP in the serum of diabetic rats might be mainly due to the leakage of these enzymes from the liver cells into the blood stream. On the other hand, treatment of the diabetic rats with Ficus bengalensis fruits extract caused reduction in the activity of these enzymes indicating the non toxic as well as tissue protective role of the extract.

Oxidative stress definitely refers to the situation of imbalance between the levels of Reactive oxygen species (ROS) and antioxidant defense. Protection of β-cells against chronic hyperglycemia induced oxidative damage is an important target for the treatment of type 2 diabetes.⁴¹ Diabetic rats showed significant increased levels of oxidative stress marker, lipid peroxides in pancreatic tissues and this is due to increased oxidative stress as a result of persistent elevated supraphysiological glucose concentration. The three major antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (Gpx), and catalase (CAT), differ from each other in structure, tissue distribution, and cofactor requirement. These antioxidant enzymes have got the ability to scavenge ROS relatively at low concentrations. The activities of SOD and Catalase and GPx were lowered in the pancreatic tissue of diabetic rats. Drugs with antioxidant properties were shown to protect pancreatic β-cells against oxidative stress.⁴² Hence, Antioxidant treatment could be a potiential therapeutic procedure for diabetic complications.^43,44 Earlier reports indicate that oral administration of Ficus bengalensis fruits significantly increased the antioxidant enzymes activities.⁴⁵ In the present study, oral administration of Ficus bengalensis fruits extract to diabetic rats restored the levels of lipid peroxides in pancreatic tissues as well as in plasma and activities of the antioxidant enzymes indicating the antioxidant nature of the fruits.

Apart from the enzymic antioxidants, non-enzymic antioxidants such as GSH, vitamin C, vitamin E and ceruloplasmin play an excellent role in protecting tissues from oxidative threats. GSH is an intra cellular thiol rich tripeptide, which plays a major role in the protection of tissues.⁴⁶ In the present study, diabetic rats exhibited decreased level of GSH, which might be due to increased utilization of GSH for scavenging free radicals by GPx. Vitamin C is a plasma hydrophilic antioxidant because it disappears faster than other antioxidants when plasma is exposed to ROS.⁴⁷ It functions as a free radical scavenger of active and stable oxyradicals. The observed decrease in plasma vitamin C in diabetic rats might be due to increased utilization as an antioxidant defence against increased ROS or to a decrease in the GSH level, since GSH is required for the recycling of vitamin C.⁴⁸

Vitamin E is a well known physiological antioxidant and membrane stabilizer. It interrupts the chain reaction of lipid peroxy radicals, thus protecting the cell structures against damage.⁴⁹ The decreased level of vitamin E observed in the diabetic rats is compatible with the hypothesis that the plasma vitamin E plays a protective role against increased peroxidation in diabetes. The plasma ceruloplasmin is a powerful free radical scavenger that oxidizes iron from the ferrous to ferric state. Earlier reports suggest that ceruloplasmin level decreases under diabetic conditions leading to the increased generation of superoxide radicals and hydrogen peroxide. The observed decrease in plasma ceruloplasmin in diabetic rats may be due to increased lipid peroxidation and, was reversed by treatment with fruit extract. In the present study, it was found that the levels of non enzymatic antioxidants such as Vitamin E, Vitamin C, ceruloplasmin and reduced glutathione in plasma of alloxan induced diabetic rats gets significantly decreased. Administration of Ficus bengalensis extracts to diabetic rats resulted in a marked increase in the levels of these non enzymatic antioxidants suggesting that the antioxidant potential of Ficus bengalensis fruit.

Dyslipidemia is one of the major risk factors for cardiovascular disease in diabetes mellitus. The characteristic features of diabetic dyslipidemia include high plasma triglyceride concentration, low HDL cholesterol and increased LDL-cholesterol concentrations.⁵⁰ The altered lipid profiles associated with diabetes mellitus are attributed to increased free fatty acid flux secondary to insulin resistance. Type 2 diabetes is associated with significant cardiovascular morbidity and mortality. Lowering of cholesterol with statins reduces cardiovascular risk in diabetes. But, most people with diabetes mellitus are often need treatment with multiple agents to achieve therapeutic goals. Oral administration of Ficus bengalensis fruit extract to diabetic rats significantly decrease the levels of triglyceride, total cholesterol, LDL-cholesterol while at the same time increase the HDL-cholesterol levels.

CONCLUSION:

The results of the present study indicate that the Ficus bengalensis fruits extract possess significant antidiabetic activity. The observed pharmacological properties might be due to the presence of biologically active ingredients present in Ficus bengalensis fruits. Also, the study provides a scientific rationale for the use of Ficus bengalensis fruits in the traditional medicine for the treatment of diabetes mellitus. However, further studies to isolate the active principle responsible for the observed pharmacological properties are warranted to explore the possible mechanism by which the fruits extract aids in maintaining glucose and lipid homeostasis.

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Received on 02.01.2013

Modified on 15.01.2013

Accepted on 20.01.2013

Research J. Pharmacology and Pharmacodynamics. 5(2): March –April 2013, 110-118

Antidiabetic potential of Ficus bengalensis fruit extract studied in alloxan-induced experimental diabetes in rats

Alkaloids

Glycosides