Regardless of the type of diabetes, individuals with diabetes are required to control their blood glucose with medications and/or by adhering to an exercise program and a dietary plan. Most of the currently available oral hypoglycaemic drugs possess adverse side effects. Hence search for novel drugs without side effects still continues. Plant drugs and herbal formulations are frequently considered to be less toxic and free from adverse side effects than synthetic one³. Plants have always been an exemplary source of drugs and many of the currently available drugs have been derived either directly or indirectly from them.

Areca Catechu is popularly used in traditional herbal medicines in many parts of the world. The seeds are commonly known in folklore medicine for treatment of various diseases such as dyspepsia, constipation, beriberi and oedema. The seeds contain phenolics and alkaloids such as arecoline, arecaidine and guvacine⁴. A. catechu constituents exert several beneficial effects on skin, suggesting the possible use in cosmetics industries⁵. A. catechu is burned to make charcoal, which is pulverized and added to toothpaste⁶. The betel leaves and areca nuts are used ceremonially in traditional weddings. Traditionally, a groom might offer the bride's parents betel and areca, the leaf and the nut symbolizing the ideal married couple bound together. In Vietnamese the phrase "matters of betel and areca" is synonymous with marriage.

Areca Catechu is found to possess various activities like platelet aggregation activity⁷, anticancer, anti-inflammatory^8,
9,, antidepressant¹⁰, antivenom¹¹ and antioxidant activity¹². In the absence of systemic studies in the literature, the present study was aimed to evaluate the antidiabetic, antioxidant and antidyslipidemic activity of ethanolic extract of Areca Catechu nut in alloxan induced experimental diabetes in rats

MATERIALS AND METHODS:

PLANT MATERIAL

Areca Catechu nuts were collected from a retail shop and authenticated by a qualified taxonomists and a voucher specimen was deposited at the Department of Biochemistry, University of Madras.

PREPARATION OF PLANT EXTRACT

Areca Catechu nuts 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 nuts were 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 extract of Areca Catechu nuts were subjected to preliminary phytochemical screening of various plant constituents¹³.

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 DIABETES MELLITUS

Diabetes was induced by single intraperitonial injection of alloxan monohydrate dissolved in sterile normal saline at a dose 120 mg/Kg, after overnight fasting to induce hyperglycemia. After 1 hour, 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 divided into 4 groups, each comprising of a minimum of six rats as follows:

Group I : Control rats (Water and food ad libitum).

Group II : Alloxan induced diabetic Rats.

Group III : Diabetic rats treated with Areca Catechu nut extract (250 mg/Kg Body weight/day) in aqueous solution orally for 30 days.

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

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

Preparation of tissue homogenate

The pancreatic tissues were excised, rinsed in ice- cold saline. The tissues 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 as tissue homogenate, which was used to assay various parameters.

Blood glucose level was estimated by the method of glucose oxidase/peroxidase as described by Trinde¹⁴and urea by Natelson et al.¹⁵.Plasma was separated and used for insulin assay using ELISA kit for rats. Levels of hemoglobin and glycosylated hemoglobin were estimated according to methods of Drabkin and Austin¹⁶ and Nayak and Pattabiraman¹⁷, respectively. Plasma was used for protein assay ¹⁸ and serum for determination of creatinine¹⁹ and uric acid²⁰. Aspartate transaminase(AST), Alanine transaminase(ALT) and Alkaline phosphatase (ALP) were assayed by the method of King et al.^{21, 22}. For the estimation of glycogen, the extraction was carried out by the method of Morales et al. (1973)²³. The pancreatic tissue homogenate was centrifuged at 5000g to remove cellular debris and supernatant was used for the determination of lipid peroxides and enzymatic antioxidants. Lipid peroxides were eatimated using thiobarbituric acid reactive substances by the method of Ohkawa et al.²⁴ Levels of vitamin C, vitamin E, ceruloplasmin and glutathione (GSH) were determined by the methods of Omaye et al,²⁵ Desai²⁶, Ravin²⁷, Sedlak and Lindsay²⁸, respectively. Enzymatic antioxidants such as superoxide dismutase²⁹, catalase³⁰, glutathione peroxidase³¹ in pancreatic supernatant.

Oral Glucose Tolerance Test (OGTT)

At the end of the experimental period, a fasting blood sample was collected from all the groups of rats to perform oral glucose tolerance test. Rats were administered orally with 2 g/kg glucose solution. Blood samples were collected at 30, 60, 90 and 120 minutes after glucose administration and the levels of blood glucose was determined.

Lipid profile

Plasma was used for the estimation of lipid profile. Cholesterol content was estimated by the method of Parekh and Jung³². Triglyceride was estimated by the method of Rice³³. HDL Cholesterol fraction was separated by the precipitation techniques of Burstein and Scholnick³⁴ and the cholesterol content was determined.

RESULTS:

Table 1 shows the qualitative analysis of phytochemicals present in the ethanolic extract of Areca Catechu nut. Phytochemical evaluation revealed the presence of alkaloids, flavanoids, carbohydrates, saponins, tannins, phytosterol, terpenoids and phenols.

Table 1 Phytochemical screening of A. catechu nut extract

PHYTOCONSTITUENTS	INFERENCE
Alkaloids	+
Flavonoids	+
Carbohydrates	+
Glycosides	-
Saponins	+
Tannins	+
Phytosterol	+
Triterpenoids	-
Anthraquinones	+
Phenols	+

Table 2, shows the changes of body weight in control and experimental group of rats. Diabetic rats exhibited reduction in body weight. However, diabetic rats treated with the nut extract as well as gliclazide showed an improvement in body weight.

Table 2: Effect of A. catechu nut extract on changes in body weight of experimental groups of rats after 30 days treatment.

Groups	Body weight (g)
Groups	Initial	Final
Control	166.18 ± 4.04	209.72 ± 5.21
Diabetic	169.36 ± 2.58	147.19 ± 7.35*
Diabetic + A. catechu extract	164.27 ± 3.05	182.56 ± 4.41^@
Diabetic + gliclazide	165.54 ± 4.12	191.16 ± 3.36^@

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.

Table 3 shows the changes in the levels of blood glucose, after oral administration of glucose (2g/ kg) in control and experimental rats. The data of 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 after 120 minutes. In diabetic control rats, the peak increases in blood glucose concentration was observed after 60 minutes and stayed high over the next 60 minutes. Treatment with Areca Catechu showed definite lower peak blood glucose values, 60 minutes after glucose load also elicit lower values almost at the end of 120 minutes.

Table 3. Effect of A. catechu nut extract on the blood glucose level (mg/dl) in the experimental groups of rats receiving an oral glucose load.

Groups	Fasting	30 min	60 min	90 min	120 min
Control	93.25 ± 5.16	134.21 ± 6.44	168.77 ± 9.07	139.06 ± 11.14	99.85 ± 9.25
Diabetic	266.69 ± 17.56*	303.33 ± 23.16*	376.48 ± 30.51*	342.37 ± 25.14*	324.46 ± 21.96*
Diabetic + A. catechu extract	150.61 ± 13.76^@	190.48 ± 19.24^@	243.41 ± 21.93^@	198.67 ± 19.55^@	160.01 ± 14.99^@
Diabetic + gliclazide	141.55 ± 9.25^@	172.52 ± 17.04^@	224.95 ± 18.18^@	176.38 ± 13.89^@	155.07 ± 10.51^@

Table 4 Effect of A. catechu nut 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	99.69 ± 10.05	15.88 ± 2.54	14.96 ± 2.48	6.01 ± 1.42	Nil
Diabetic	283.08 ± 22.56*	5.03 ± 2.02*	10.08 ± 1.67*	13.11 ± 1.92*	+++
Diabetic + A. catechu extract	146.42 ± 11.24^@	11.51 ± 1.95^@	12.47 ± 2.49^@	8.12 ± 1.89^@	Nil
Diabetic + gliclazide	131.20 ± 14.21^@	12.19 ± 1.63^@	13.18 ± 2.09^@	7.06 ± 2.03^@	Nil

Table 5 Effect of A. catechu nut 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	41.42 ± 3.62	7.93 ± 0.82
Diabetic	19.51 ± 2.08*	3.46 ± 0.47*
Diabetic + A. catechu extract	31.71 ± 3.46^@	5.57 ± 0.62^@
Diabetic + gliclazide	34.98 ± 2.75^@	5.90 ± 0.86^@

Table 6 Effect of A. catechu nut 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	8.02 ± 1.09	24.81 ± 2.15	1.17 ± 0.13	2.34 ± 0.90
Diabetic	5.65 ± 0.72*	46.53 ± 4.08*	2.96 ± 0.31*	5.36 ± 1.18*
Diabetic + A. catechu extract	6.65 ± 0.88^@	31.99 ± 3.12^@	1.36 ± 0.18^@	3.24 ± 0.86^@
Diabetic + gliclazide	7.21 ± 0.84^@	29.92 ± 2.98^@	1.21 ± 0.12^@	2.96 ± 1.10^@

Table 7 Effect of A. catechu nut extract on the activity of AST, ALT and ALP in the serum of experimental groups of rats.

Groups	AST	ALT	ALP
Control	65.42 ± 6.34	18.16 ± 2.39	81.91 ± 10.16
Diabetic	111.99 ± 14.98*	46.28 ± 4.71*	153.26 ± 18.64*
Diabetic + A. catechu extract	93.16 ± 10.04^@	24.93 ± 3.62^@	100.05 ± 11.78^@
Diabetic + gliclazide	80.52 ± 8.31^@	20.98 ± 2.02^@	98.64 ± 10.11^@

Table 8 Effect of A. catechu nut extract on the level of TBARS in plasma, pancreas and liver of experimental groups of rats.

Groups	TBARS
Groups	Plasma	Pancreas	Liver
Control	4.17 ± 0.69	40.24 ± 4.75	1.70 ± 0.36
Diabetic	8.12 ± 1.61*	78.26 ± 9.44*	4.37 ± 0.70*
Diabetic + A. catechu extract	5.29 ± 1.16^@	58.29 ± 6.81^@	2.49 ± 0.31^@
Diabetic + gliclazide	5.04 ± 1.02^@	55.99 ± 7.43^@	2.65 ± 0.39^@

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 9 Effect of A. catechu nut extract on the activity of SOD, Catalase and GPx, and the level of GSH in pancreas of experimental groups of rats.

Groups	SOD	Catalase	GPx	GSH
Control	5.05 ± 1.69	15.23 ± 2.10	6.37 ± 1.01	26.09 ± 2.65
Diabetic	1.42 ± 0.40*	5.85 ± 1.42*	3.09 ± 0.31*	12.44 ± 1.61*
Diabetic + A. catechu extract	3.82 ± 0.90^@	12.16 ± 1.47^@	4.73 ± 0.64^@	20.69 ± 2.27^@
Diabetic + gliclazide	3.96 ± 0.87^@	13.10 ± 1.08^@	5.39 ± 0.91^@	22.09 ± 2.74^@

Table 10 Effect of A. catechu nut extract on the activity of SOD, Catalase and GPx, and the level of GSH in liver of experimental groups of rats.

Groups	SOD	Catalase	GPx	GSH
Control	16.04 ± 2.47	70.81 ± 8.31	11.16 ± 1.09	38.19 ± 5.64
Diabetic	5.05 ± 0.71*	30.19 ± 3.54*	3.74 ± 0.69*	21.89 ± 2.82*
Diabetic + A. catechu extract	10.95 ± 1.22^@	61.02 ± 6.09^@	8.16 ± 0.89^@	31.56 ± 4.08^@
Diabetic + gliclazide	12.13 ± 1.50^@	65.45 ± 5.95^@	9.01 ± 1.04^@	32.60 ± 4.59^@

Table 12 depicts the level of total cholesterol, triglycerides and lipoproteins (LDL and HDL) levels of normal control and experimental group of rats. The elevated levels of lipid and lipoproteins (LDL) and reduced level of HDL cholesterol was observed in diabetic rats than normal control and the level was restored back nearer to the normal value was achieved by administration of Areca Catechu nut extract as well as gliclazide.

DISCUSSION:

The therapeutic values of plants lie in phytochemical constituents that exert distinct physiological activities in the human body. Highly coloured vegetables and fruits found to be highest in phytoconstituents, but tea, chocolate, nuts, flax nuts, and olive oil are excellent sources as well. Phytochemical analysis of A. catechu nut extract revealed the presence of alkaloids, flavanoids, carbohydrates, saponins, tannins, phytosterol, terpenoids and phenols. These phytochemicals were speculated to account for the observed pharmacological effects of the extract.

Alloxan acts as a cytotoxin for beta-cells of the islet of langerhans, causes diabetes by inducing β cell necrosis³⁵. The reactive oxygen species mediates the cytotoxic action with the increase in cytosolic calcium concentration, leading to rapid beta-cells destruction³⁶. Diabetic rats exhibit gradual weight loss as compared with the normal group. This process is due to muscle wasting and depletion of protein in tissues. A decrease in body weight was observed in diabetic group indicating the increased proteolysis. Diabetic rats treated with Areca Catechu nut extract and gliclazide for 30 days showed a significant improvement in body weight as compared to diabetic animals, which shows the beneficial effects of the extract in controlling the muscular wasting. The results of the present study are in agreement with those of previous reports³⁷.

Diabetes mellitus is characterized by decreased glucose tolerance due to low secretion of insulin or its action. Oral glucose tolerance test (OGTT) is a test of immense value in favour of using fasting plasma glucose concentration to facilitate the diagnosis of diabetes mellitus. OGTT revealed that the blood glucose levels in control rats reach peak at 60 minutes after the oral glucose load and gradually return backs to normal levels after 120 minutes. In diabetic control rats, the peak increases in blood glucose concentration was observed after 60 minutes and remained high over the next 60 minutes. However, oral treatment with Areca Catechu showed definite lower peak blood glucose values, 60 minutes after glucose load also gives lower values almost at the end of 120 minutes indicating the improved glucose tolerance

Blood glucose estimation provides valuable information about the severity and therapeutic control of diabetes mellitus. In diabetes, the blood glucose levels are drastically elevated which results from reduced glucose utilization by various tissues. Alloxan induction causes specific damage in β cells and thus exerts a pronounced increase in blood glucose concentration. 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 alloxan induced diabetic models to compare the antidiabetic property of various plant extracts. Oral administration of Areca Catechu nut extract to alloxan induced diabetic rats resulted in reduction in blood glucose level indicating the hypoglycemic nature of the nut extract.

Insulin is the key hormone responsible for metabolizing sugar and preventing the accumulation of glucose in blood stream. In diabetic rats, there is decreased insulin level when compared to control rats. The decreased insulin level depends upon the degree of β cells destruction. Administration of Areca Catechu nut extract as well as gliclazide to alloxan induced diabetic rats shows improved insulin level. This indicates that the Areca Catechu extract has antidiabetic activity by potentiating the stimulation of insulin release from the bound form or from the remnant pancreatic β cell.

Glycosylated haemoglobin (HbA1c) is a standard biochemical marker in assessment of diabetes. Glycated haemoglobin is a unique form of haemoglobin used primarily to identify the average plasma glucose concentration over prolonged periods of time. It is formed in non-enzymatic pathway by hemoglobin’s normal exposure to persistent high plasma levels of glucose³⁸. The studies show that HbA1c is an important marker in assessing a patient’s risk of microvascular complications and hypoglycaemia. Hence, measurement of both HbA1c and blood glucose levels are now used in the routine management of diabetic individuals³⁹ .Diabetic rats showed higher levels of glycated hemoglobin indicating their poor glycemic control. There was a significant elevation in the levels of glycosylated haemoglobin, while the level of total haemoglobin decreased during diabetes compared to normal control rats. Oral administration of Areca Catechu extract brought back to near normal indicating the improved glycemic control. Urine sugar which was present in the diabetic groups of rats was found to be absent in the rats treated with extract indicating the improved glucose homeostasis.

Liver plays a unique role in controlling carbohydrate metabolism by maintaining glucose concentrations in a normal range over both short and long periods of times. Liver produces glucose by breaking down glycogen (glycogenolysis) and by de novo synthesis of glucose (gluconeogenesis) from non-carbohydrate precursors such as lactate, amino acids and glycerol. In the present study the experimental diabetic rats treated with Areca Catechu nut extract as well as gliclazide treated groups restored the level of hepatic glycogen by means of decreasing the activity of glycogen phosphorylase and increasing the activity of glycogen synthase. It indicates that the defective glycogen storage of the diabetic state was corrected by Areca Catechu which might be due to the improved glucose homeostasis

A variety of proteins are subjected to non-enzymatic glycation and contributes to the long-term complications of diabetes⁴⁰ . The observed decrease in total protein content in diabetic rats may be ascribed to (i) decreased amino acid uptake; (ii) greatly decreased concentration of variety of essential amino acids; (iii) increased conversion rate of glycogenic amino acids to carbon dioxide and water; and (iv) reduction in protein synthesis secondary to a decreased amount and availability of mRNA⁴¹ .

Urea is the main end product of protein catabolism in the body. Accumulation of urea nitrogen in experimental diabetes may due to the enhanced breakdown of both liver and plasma proteins⁴². Diabetes causes disturbance in renal function and blood urea level was significantly increased in diabetic rats. Oral administration of Areca Catechu nut extracts reduced the level of urea in alloxan induced diabetic rats indicating the prophylactic role of the extract in protein metabolism. Our results are in concordance with the recent reports⁴³.

Uric acid is one of the main antioxidant present in the body and diabetes causes reduced levels of uric acid⁴⁴. The extract reflects the antioxidant potential as it reduced the oxidative stress and increase in uric acid level. Diabetic rats exhibited higher uric acid levels indicating the increased oxidative stress. However, oral administration of Areca Catechu nut extract normalized the levels of uric acid indicating the free radical scavenging action of the extract.

Creatinine is a byproduct of the breakdown of creatine and phosphocreatine, which are considered as an energy storage compounds in muscle. The serum creatinine concentration may vary based on a number of factors including diet composition, muscle mass and gender. Serum creatinine values also depend on the ability of the kidney to excrete creatinine. An elevation in creatinine usually occurs simultaneously with an increase in blood urea nitrogen. In the present study, the oral treatment with extract significantly reduced the serum creatinine level. Therefore, it may be concluded that the early renal changes occurred in the diabetic rats were significantly improved by the oral administration of the nut extract.

Aminotransferases, such as alanine aminotransferase and aspartate aminotransferase measure the concentration of intracellular hepatic enzymes that have leaked into the circulation and serve as a marker of hepatocyte injury. Alkaline phosphatises act as markers of biliary function and cholestasis. It is hypothesized that elevation in ALT, AST and ALP are considered as predictors of diabetes. The elevation of these pathophysiological enzymes may also reflect the damage of the hepatic cells. Kim et al. concluded that the elevation in AST and ALT levels may be due to the destructive changes in the hepatic cells as a result of toxaemia⁴⁵. On the other hand, other investigators have postulated that diabetes could induce defects in sarcolemmal enzymatic activities⁴⁶ which leads finally to such effects. Diabetic rats exhibited higher levels of these serum enzymes indicating the liver damage. Oral administration of Areca Catechu extract to alloxan induced diabetic rats resulted in gradual normalization of the activities of AST, ALT and ALP suggesting the non toxic nature as well as organ protective role of the extract.

Free radicals are generated as by-products of normal cellular metabolism; however, several conditions are known to disturb the balance between ROS production and cellular defense mechanisms. This imbalance can result in cell dysfunction and destruction resulting in tissue injury. The intensified free radical production during experimental diabetes resulted in the elevated levels of lipid peroxides and hydroperoxides by oxidative degradation of polyunsaturated fatty acids. Diabetic rats showed marked increase in TBARS when compared with normal rats. Treatment of Areca Catechu nut extracts as well as gliclazide to the diabetic rats showed significant decrease in the levels of TBARS when compared with diabetic rats indicating the free radical scavenging potential of the extract

The increase in the level of ROS in diabetes could be due to their increased production and/ or decreased destruction by nonenzymic and enzymic catalase (CAT), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD)] antioxidants ⁴⁷. The level of these antioxidant enzymes critically influences the susceptibility of various tissues to oxidative stress and is associated with the development of complications in diabetes. Also this is particularly relevant and harmful for the β cells, which is among those tissues that have the lowest levels of intrinsic antioxidant defenses⁴⁸. Enzymatic antioxidant activities such as superoxide dismutase, catalase and glutathione peroxidise decrease in liver, kidney and heart tissues of patients with diabetes mellitus⁴⁹. Oral administration of ethanolic extract of Areca Catechu nut restored the activities of enzymatic antioxidants which reflects the antioxidant potential of the extract.

Vitamin C and vitamin E, often referred to as “antioxidant vitamins” that have been suggested to limit oxidative damage in humans and lower the risk of certain chronic diseases such as diabetes mellitus. Vitamin C is a key antioxidant that particularly protects the lipids from peroxidative damage by aqueous solution. Ceruloplasmin is a free radical scavenger as well as a late acute phase reactant protein. It is involved in iron metabolism⁵⁰. Further, it has also been suggested that the levels of trace elements, especially copper, might be increased in the diabetic state. 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 was significantly decreased. Oral administration of Areca Catechu nut extracts as well as gliclazide to alloxan induced diabetic rats resulted in a marked increased in the levels of these non enzymatic antioxidants suggesting the free radicals scavenging potential of Areca Catechu nut extract which in turn may be responsible for its anti hyperglycemic property.

Diabetes mellitus is associated with higher incidence of dyslipidemia⁵¹. DM is associated with a cluster of interrelated plasma lipid and lipoprotein (LP) abnormalities that are all recognized as predictors for coronary heart disease, including reduced plasma levels of high density lipoprotein cholesterol particles and elevated plasma levels of TG ⁵². The total cholesterol, triglycerides and lipoprotein levels were brought back to normal in Areca Catechu extract given rats when compared to diabetic rats. In the present study, the altered lipid profile was normalized upon treatment with Areca Catechu nut extract exemplifying the hypolipidemic role of the extract.

CONCLUSION:

The present study also warrants further studies to isolate and characterising potent molecules for diabetes and its lipids associated complications. In conclusion, the secondary metabolites present in the extract may synergistically act to improve the complications observed in the experimental diabetes. The results of the present study support the use of Areca Catechu nut extract for the treatment of diabetes mellitus. It indicates that the extract possess antidiabetic activity which is evident from Oral glucose tolerance test and other clinically significant biochemical parameters. The antioxidant property of the extract is well established from the improved levels of enzymatic and non enzymatic antioxidants. The hypolipidemic property of the extract is evident from the normalized levels of lipid profile. The data also provides a scientific rationale for the use of Areca nuts in the traditional medicine for the treatment of various ailments.

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Received on 02.01.2013

Modified on 15.01.2013

Accepted on 20.01.2013

Research Journal of Pharmacognosy and Phytochemistry. 5(2): March-April 2013, 100-108

Groups	Vitamin C	Vitamin E	Ceruloplasmin	GSH
Control	1.49 ± 0.15	0.69 ± 0.09	12.29 ± 1.62	30.74 ± 3.99
Diabetic	0.50 ± 0.09*	0.32 ± 0.04*	5.06 ± 0.89*	14.99 ± 2.45*
Diabetic + A. catechu extract	0.98 ± 0.12^@	0.55 ± 0.07^@	9.95 ± 1.46^@	22.86 ± 2.87^@
Diabetic + gliclazide	1.02 ± 0.14^@	0.59 ± 0.05^@	10.41 ± 1.88^@	25.15 ± 3.06^@

Groups	Total cholesterol	Triglycerides	LDL	HDL
Control	92.51 ± 11.84	62.29 ± 8.46	50.05 ± 6.12	28.95 ± 2.08
Diabetic	169.12 ± 18.65*	152.07 ± 14.07*	124.45 ± 9.61*	14.64 ± 1.62*
Diabetic + A. catechu extract	103.87 ± 14.18@	90.15 ± 10.05@	72.69 ± 7.49@	22.03 ± 1.78@
Diabetic + gliclazide	97.18 ± 11.92@	84.46 ± 8.09@	60.17 ± 6.59@	23.91 ± 2.11@

Alkaloids

Glycosides