MEDICINAL CHEMISTRY RESEARCH
Med Chem Res DOI 10.1007/s00044-010-9479-y
ORIGINAL RESEARCH
Acacia catechu hard wood: potential anti-diabetic cum anti-dyslipidemic Swayam Prakash Srivastava • Akansha Mishra • Vikram Bhatia • T. Narender • Arvind K. Srivastava
Received: 15 March 2010 / Accepted: 15 October 2010 Ó Springer Science+Business Media, LLC 2010
Abstract The ethanolic as well as aqueous extracts of the hard wood of Acacia catechu showed improvement on oral glucose tolerance post-sucrose load in normal rats and streptozotocin (STZ)-induced diabetic rats. Around 22 and 27% improvement in glucose tolerance was observed post 7 and 14 days of feeding the ethanolic extracts, respectively, on STZ-induced diabetic rats. Whereas around 17 and 26% improvement on glucose tolerance was observed post 7 and 14 days of feeding the ethanolic extract in the high fructose high fat diet (HFD) fed-low dosed STZ-treated rats. The ethanolic extract of A. catechu hard wood also showed marked anti-dyslipidemic activity on HFD fed Syrian golden hamster as evidenced by around 43 and 26% decline in serum triglycerides and total cholesterol, respectively. The ethanolic and aqueous extracts also showed marked inhibition on eye lens aldose reductase either from normal or STZ-induced diabetic rats. Further studies are warranted to isolate and identify the active ingredients from the ethanolic and aqueous extracts of A. catechu hard wood. Keywords Acacia catechu (A. catechu) hard wood Streptozotocin (STZ) induced diabetic rats High fructose high fat diet (HFD) diabetic rats Type 2 diabetes mellitus (T2DM) Dyslipidemia Aldose reductase (AR) S. P. Srivastava A. Mishra V. Bhatia A. K. Srivastava (&) Division of Biochemistry, Central Drug Research Institute, CSIR, Lucknow 226001, India e-mail:
[email protected] S. P. Srivastava e-mail:
[email protected] T. Narender Division of Medicinal and Process Chemistry, Central Drug Research Institute, CSIR, Lucknow 226001, India
Introduction Type 2 diabetes mellitus (T2DM) is a serious chronic metabolic disorder that has a significant impact on the health, quality of life, and life expectancy of patients, as well as on the health care system. The World Health Organization (WHO) has projected that the number of T2DM subjects will be around 300 million in the world by the year 2025 (Horton, 2008). With the present population of 19.4 million diabetics in India and a projected increase of 300% and thereby leading to approximately 60 million by the year 2025, India would rank first in sharing global burden of diabetes (King et al., 1998). Traditional medicines most often apply to plants, which are being employed as adjutants in the management of diabetes mellitus in many of the Asian countries including India. India has a rich history of using various potent herbs and herbal components for treating diabetes. Medicinal plants or herbs have a variety of metabolites; aliphatic and aromatic compounds have basic skeleton of organic molecule and various functional groups that make them able alter the various metabolic pathways and make them medicinally important. Herbal drugs are prescribed widely because of their effectiveness, less side effects, and relatively low cost (Venkatesh et al., 2003). Therefore, investigation on such agents from traditional medicinal plants has become more important (Suba et al., 2004). A detailed study of such known medicinal plants and search for active molecules might offer natural key to unlock a diabetologist’s pharmacy for the future. During hyperglycemia, cellular levels of glucose greatly increase in tissues, which include eye lens, retina, kidney, and peripheral nerves; this excess glucose is metabolized via polyol pathway (Kinoshita, 1990). Polyol pathway is one of the factors, which has been implicated in the etiology of the secondary complications
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of diabetes (Singh et al., 2000). Aldose reductase (AR; EC 1.1.1.21), a member of the NADPH-dependent aldo–keto reductase family, is a key enzyme in the polyol pathway, which catalyzes the reduction of various aldehydes, including the aldehyde from glucose using NADPH as cofactor. AR converts glucose to sorbitol, which is next converted to fructose by sorbitol dehydrogenase (SDH) using the cofactor NAD?. Acacia catechu belongs to family Leguminosae and is found in various parts of Asia. The flavonoids from the hard wood of A. catechu have been used in many traditional medicine pharmaceutical products, especially in Asia, for variety of purposes including anti-inflammatory, anti-virus, anti-bacterial, anti-cancer, and cardiovascular application (Mahmood et al., 1993; van Loon, 1997; Lee et al., 2000; Shigeta, 2000; Huang et al., 2005). The antiinflammatory properties of these flavonoids are particularly interesting in the management of chronic inflammatory diseases, such as osteoarthritis. The extract of the A. catechu acts as a dual inhibitor of cyclooxygenase and 5-lipooxygenase to reduce inflammation (Burnett et al., 2007). This article reports anti-hyperglycaemic, anti-dyslipidemic, and AR inhibitory activity in ethanolic extract of A. catechu hard wood.
Materials and methods Animals Male albino rats of Sprague Dawley strain (8–10 weeks of age: body weight 120 ± 20 g) and 6–8 weeks old Syrian golden hamsters were procured from the animal colony of Central Drug Research Institute, Lucknow, India. Chemicals Streptozotocin (STZ), metformin, and fenofibrate were obtained from Sigma Chemical Company, St. Louis, USA. Gum acacia, glucose, fructose, sucrose, and cholesterol were obtained from Sisco Research Laboratory (India). Biochemical kits used for the estimation of serum triglycerides and total cholesterol were obtained from the Roche diagnostic kits. All other chemicals used were of highest purity grade. Preparation of ethanolic and aqueous extracts of A. catechu hard wood The hard wood of the plant (1 kg) was chopped, dried in shade, and powdered in disintegrator. The powder was submerged in 10 volumes of 95% ethyl alcohol five times successively. The combined extract was filtered and
concentrated under high vacuum in a rotavapour and termed ethanolic extract. The dried residue after ethanol extraction was collected and powdered in a pulveriser to give a blackish brown power of uniform particle size. The powder was dissolved in distilled water and boiled (4 9 0.8 l). Each extraction was carried out for 4 h. The combined aqueous extract was filtered and concentrated under reduced pressure using rotavapour at 45°C and termed aqueous extracts. Both aqueous and ethanolic extracts were stored at -20°C until used.
Experimental regimen Effect of ethanolic and aqueous extracts of A. catechu on oral glucose tolerance post-sucrose load in normal rats Male albino rats of Sprague Dawley strain were selected for this study. Fasting blood glucose level of each animal was checked by glucometer using glucostrips after an overnight starvation. Animals showing blood glucose level between 60 and 80 mg/dl were finally selected and divided into five groups each consisted of six animals. Rats of experimental groups (2, 3, and 4) were given the suspension of the test extracts (prepared in 1.0% gum acacia at desired dose levels, i.e., 125, 250, and 500 mg/kg body weight. The standard anti-diabetic drug glybenclamide was given at 25.0 mg/kg body weight to animals of group 5. Animals of control group 1 were given an equal amount of 1.0% gum acacia and also termed as sham-treated control. An oral sucrose load of 10 g/kg body weight was given to each animal exactly after 30 min post-administration of the test extract/standard drug/vehicle. Blood glucose profile of each rat was again determined at 0, 30, 60, 90, and 120 min post-administration of sucrose by glucostrips. The average fall in area under curve (AUC) in experimental group compared to control group was termed as % anti-hyperglycaemic activity. Statistical analysis was done by Dunnett’s test. Anti-hyperglycemic activity of ethanolic and aqueous extracts of A. catechu hard wood on STZ-induced diabetic rats Diabetes was induced in rats by intraperitoneal administration of a freshly prepared solution of STZ made in 100 mM citrate buffer (pH 4.5) at 60 mg/kg body weight dose. Fasting blood glucose level was measured post 48 h of STZ administration, and animals having blood glucose level between 270 and 450 mg/dl were considered as diabetic.
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Single dose effect Streptozotocin-induced diabetic male albino rats of Sprague Dawley strain (140 ± 20 g body weight; 8–10 weeks age) were selected for this study. Rats showing almost similar blood glucose level (between 270 and 450 mg/dl) at 0 h were selected and divided into four groups containing six rats in each. Rats of experimental groups (2 and 3) were given suspension of the ethanolic and aqueous extracts prepared in 1% gum acacia orally at a dose of 250 mg/kg body weight, respectively. The biguanide derivative metformin was used as standard anti-diabetic drug and was always given at a dose of 100 mg/kg body weight orally to the experimental group 4. Rats of control group 1 were given an equal amount of 1.0% gum acacia (vehicle), and this group was also termed as sham-treated diabetic control. Blood glucose level of all animals was again monitored at 1, 2, 3, 4, 5, and 24 h, post-administration of test extracts. The average fall in AUC in experimental group compared to control group was termed as % anti-hyperglycaemic activity. Statistical analysis was done by Dunnett’s test. Multiple dose effect The diabetic male albino rats of Sprague Dawley strain having blood glucose level between 270 and 450 mg/dl (140 ± 20 g body weight; 8–10 weeks age) were selected for this study. They were divided into three groups each group consisted of six rats. One group was termed as shamtreated control, whereas the other two groups were termed as experimental groups. Animals of experimental groups (2 and 3) were orally given suspensions of ethanolic extract of A. catechu hard wood and metformin, respectively, for 14 days at a dose of 100 mg/kg body weight. Oral glucose tolerance test of each animal was determined on days 0, 7, and 14 post-treatment. Anti-diabetic and anti-dyslipidemic activity evaluation in ethanolic extract of A. catechu hard wood in high fructose high fat diet (HFD) fed STZ-treated diabetic rats Rats were fed with home made high fructose high fat diet (HFD) for 4 weeks for the development of obesity and dyslipidemia like conditions in them. After 4 weeks, these HFD fed rats were given 40 mg/kg STZ intraperitoneally. STZ was always freshly prepared in sodium citrate buffer (final pH 4.5) and given only to obese rats. The blood glucose level of each rat was checked for three consecutive days with Accu Check glucometer (Germany). The rats were grouped into four on the basis of their blood glucose level ([250 mg/dl). One group was termed as sham-treated
control group which was given 1% gum acacia, whereas the 2nd group was given suspension of the ethanolic extract of the hard wood of A. catechu at 100 mg/kg body weight dose for 14 consecutive days. The third group was treated with metformin at 100 mg/kg dose level. The oral glucose tolerance test and the measurement of total serum cholesterol and triglycerides profiles of each animal were done on days 7 and 14 post-treatment. Anti-dyslipidemic activity evaluation in ethanolic extract of A. catechu hard wood on HFD fed Syrian golden hamsters Male Syrian golden hamsters weighing between 100 and 120 g were initially selected for this experiment. Dyslipidemia was produced by feeding these animals with homemade high fructose high fat diet (60% fructose, 13% fat) for 30–40 days. Dyslipidemic hamsters were divided into groups based on their serum cholesterol and triglycerides profile. The fine suspension of ethanolic extract was given orally to animals of group 2 at a dose of 100 mg/kg for 14 days. The animals of the control group were given vehicle, i.e., 1.0% gum acacia and the animals of standard drug-treated group were given the suspension of fenofibrate at 100 mg/kg and this treatment continued for 14 days. At the end of the experimental period, i.e., on day 15, the blood of each animal was withdrawn from retro-orbital plexus for the lipid profiles in the serum. Serum total cholesterol and triglycerides were measured on semi-autoanalyzer (Dialab) using the assay kits and instructions from the manufacturer. Effect of aqueous and ethanolic extracts of A. catechu hard wood on eye lens AR from normal and STZ-induced diabetic rats Preparation of lens homogenate A 10% homogenate of eye lens from normal and STZinduced diabetic rats was prepared in 0.1 M PBS (pH 7.4) using Potter Elvejhem glass homogenizer with Teflon pestle, filtered with muslin cloth, and centrifuged at 10009g for 10 min. The supernatant was saved and used as enzyme source. Determination of AR activity Lens AR activity was measured according to the method of Hayman and Kinoshita (1965) by following the decrease in the absorption of NADPH at 340 nm over a 3-min period with DL ± Glyceraldehyde as substrate. A quartz cuvette containing 0.7 ml of sodium phosphate buffer (67 mM, pH 6.2), 0.1 ml of lens supernatant (25 9 10-5 M), 0.1 ml of
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lens homogenate, 0.1 ml of DL ± Glyceraldehyde (1 9 10-3 M) (substrate) to a final volume of 1 ml was read against a reference cuvette containing all components but the substrate, DL ± Glyceraldehyde. Inhibitory effect of the ethanolic and aqueous extracts of A. catechu hard wood on AR activity from eye lens To determine the AR inhibiting potential of the ethanolic and aqueous extracts, 10–100 lg of the extracts were added, respectively, to tubes having 1.0 ml reaction mixture and determining the activity with the reference cuvette. The reaction was initiated by the addition of 0.1 ml of substrate, and the rate of reaction was measured as described above. The inhibition percentage (%) was calculated as [(DOD sample/min)/(DOD control/min) 9 100 - 100], where DOD sample/min represents the reduction of absorbance for 3 min with test sample and DOD control/min represents the same, but with 1% DMSO instead of sample.
Fig. 1 Effect of ethanolic, aqueous extracts of A. catechu hard wood and glybenclamide on oral glucose tolerance post-sucrose load in normal rats
Results Effect of the ethanolic and aqueous extracts of A. catechu hard wood on oral glucose tolerance post-sucrose load in normal rats Figure 1 represents the effect of ethanolic and aqueous extracts of A. catechu hard wood on oral glucose tolerance post-sucrose load in normal overnight fasted rats. Both ethanolic as well as aqueous extracts showed inhibition in post-prandial hyperglycemia post-sucrose load. The percent inhibition by ethanolic and aqueous extracts was recorded around 20.8% (P \ 0.05) and 30.2% (P \ 0.01) at 250 mg/kg dose. The standard drug glybenclamide caused around 36.1% (P \ 0.01) inhibition on the rise of post-prandial hyperglycemia at 25 mg/kg dose. The effect of ethanolic was found dose dependant as the inhibition in post-prandial rise in hyperglycemia post-sucrose load by ethanolic extract was calculated 14.6% at 125 mg/kg dose, 20.6% lowering at 250 mg/kg dose, and 37.3% at 500 mg/ kg, respectively. Anti-hyperglycaemic activity evaluation of ethanolic and aqueous extracts of A. catchu in STZ-induced diabetic rat model Effect of ethanolic and aqueous extracts of A. catechu hard wood on STZ-treated diabetic rats It is evident from Fig. 2 that both ethanolic and aqueous extracts caused lowering in blood glucose profile of
Fig. 2 Effect of ethanolic and aqueous extracts of A. catechu and metformin on blood glucose profile of streptozotocin-treated diabetic rats
STZ-induced diabetic rats at 250 mg/kg dose. The lowering in both ethanolic as well as aqueous extract-treated groups started from 1 h and continued till 24 h. The peak lowering in each case was observed at 5 h post-treatment. From the data shown in Fig. 2, the average anti-hyperglycaemic activity was calculated to be around 15.6 (P \ 0.05) and 20.1% (P \ 0.05) during 0–5 h and 17.5 (P \ 0.05) and 18.0% (P \ 0.05) during 0–24 h by ethanolic and aqueous extracts of A. catechu hard wood on STZ-induced diabetic rats. The standard anti-diabetic drug metformin caused much more lowering effect on blood glucose level on STZ-treated diabetic rats even at 100 mg/kg body weight dose. The anti-hyperglycemic activity of metformin was calculated to be around 28.1% (P \ 0.05) during 0–5 h and 32.1% (P \ 0.05) during 0–24 h, respectively. Multiple dose effect of ethanolic extract of A. catechu hard wood on STZ-treated diabetic rats Figures 3 and 4 represent the effect of ethanolic extract of A. catechu on glucose tolerance of STZ-induced diabetic rats. It was evident from the results that ethanolic extract when given to STZ-induced diabetic rats improved glucose
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Fig. 3 Effect of ethanolic extract of A. catechu and metformin on oral glucose tolerance of STZ-induced diabetic rats on day 7 posttreatment
Fig. 4 Effect of ethanolic extract of A. catechu and metformin on oral glucose of STZ-induced diabetic rats on day 14 post-treatment
tolerance maximally around 27.2% on day 14, whereas such effect was observed on day 7 post-treatment by around 22.0% (P \ 0.05) on oral glucose tolerance test (OGTT) in the diabetic rats. On comparison, the standard drug metformin caused around 24.1 and 28.7% improvement on OGTT on days 7 and 14, respectively. Anti-diabetic and anti-dyslipidemic activity evaluation of A. catchu ethanolic extract in high fructose HFD fed STZ-treated diabetic rats Figures 5 and 6 represent the effect of ethanolic extract of A. catechu hard wood on glucose tolerance of high fructose HFD fed STZ-induced diabetic rats. The ethanolic extract improved oral glucose tolerance by 17.0% (P \ 0.05) and 26.2% (P \ 0.05), respectively, when
Fig. 5 Effect of ethanolic extract of A. catechu hard wood and metformin on oral glucose tolerance of high fructose high fat fed STZ-induced diabetic rats on day 7 post-treatment
Fig. 6 Effect of ethanolic extract of A. catechu hard wood on oral glucose tolerance of high fructose high fat fed STZ-induced diabetic rats on day 14 post-treatment
given for 7 and 14 days, respectively. The standard drug metformin showed around 23.2 and 27.4% improvement in glucose tolerance on days 7 and 14, respectively. It was evident from Table 1 that the ethanolic extract of A. catechu hard wood lowered serum triglycerides by around 23.5% and total serum cholesterol by around 17.9%, and serum LDL-cholesterol by around 15.5% when given at 100 mg/kg dose for 14 consecutive days. Mild elevation in serum HDL-cholesterol was also noticed on this day in A. catechu ethanolic extract-treated group. The standard drug metformin did not cause any significant change in serum lipid profile of high fructose high fat fed rats.
Med Chem Res Table 1 Effect of ethanolic extract of A. catechu hard wood and metformin on serum lipid profiles of high fructose high fat fed streptozotocintreated rats Group
Dose (mg/kg)
Serum parameters Triglycerides (mg/dl)
Cholesterol (mg/dl)
HDL-cholesterol (mg/dl)
LDL-cholesterol (mg/dl)
Control
1% gum acacia
503.4 ± 81.1
317.0 ± 51.0
79.5 ± 11.2
254.4 ± 55.0
Ethanolic extract (A. catechu)
100
385.0 ± 46.2 (-23.5)
260.0 ± 28.4 (-17.9)
86.1 ± 9.90 (?8.90)
215.6 ± 32.1 (-15.5)
Metformin
100
427.2 ± 52.4 (-15.1)
304.5 ± 32.4 (-3.94)
85.8 ± 8.30 (?7.93)
232.1 ± 28.8 (-8.76)
Values are mean ± SE. Values given in the parenthesis is the percent change of lipid parameters of extract-treated group as compare to control. Minus sign denotes decrease in value and plus sign denotes increase in value
IC50 were calculated to be around 9.30 and 4.70 lg/ml against normal eye lens and 9.08 and 4.91 lg/ml against the eye lens enzyme from STZ-induced diabetic rats.
Anti-dyslipidemic activity of ethanolic extract of A. catechu on dyslipidaemic Syrian golden hamsters Table 2 represents the anti-dyslipidemic activity profile of the ethanolic extract of A. catechu hard wood on dyslipidaemic Syrian golden hamsters. The ethanolic extract of A. catechu hard wood when given for 14 consecutive days to dyslipidaemic Syrian golden hamsters caused 43.2% lowering in serum triglycerides, 25.8% lowering in serum cholesterol, and 24.0% lowering in LDL-cholesterol levels. Mild elevation in serum HDL-cholesterol was also observed in A. catechu hard wood ethanolic extract-treated group. The standard drug fenofibrate at the same dose level showed 55.2% lowering in TG, 20.8% lowering in cholesterol level, and 49.3% lowering in LDL-cholesterol level, and 14.5% elevation in HDL-cholesterol level was also found. Inhibitory effect of ethanolic and aqueous extracts of A. catechu hard wood on eye lens AR Both the ethanolic and aqueous extracts of A. catechu hard wood showed inhibition on AR from eye lens AR, from normal rats as well as eye lens AR from STZ-induced diabetic rats. Both ethanolic and aqueous extracts caused concentration-dependent effect on eye lens AR from normal as well as STZ-induced diabetic rats (Fig. 7a, b). Their
Discussion Diabetes mellitus is a metabolic disorder caused by either inherited and/or acquired deficiency in production of insulin by the pancreas or by the ineffectiveness of the insulin produced. The therapeutic measures include use of insulin and other agents like amylin analogs, alpha glycosidase inhibitors like acarbose, miglitol and voglibiose, sulphonylureas, biguanides, thiazolidinediones. These drugs also have certain adverse effects like causing hypoglycemia at higher doses, weight gain, lactic acidosis, and oedema (Moller, 2001). Apart from currently available therapeutic options, traditional plant medicines are used throughout the world for the treatment of T2DM. Herbal drugs are prescribed widely because of their effectiveness, less side effects and relatively low cost (Venkatesh et al., 2003). Several phytomolecules including flavonoids (Vessal et al., 2003), alkaloids (Singh et al., 2003), glycosides, saponins (Rao and Gurfinkel, 2000), glycolipids, dietary fibers (Nandini et al., 2003; Mann, 2007), polysaccharides (Quanhong et al., 2005), peptidoglycans, carbohydrates, amino acids and others obtained from various plant sources
Table 2 Effect of ethanolic extract of A. catechu hard wood and fenofibrate on serum lipid profiles of high fructose HFD Syrian golden hamsters Group
Dose (mg/kg)
Serum parameters Triglycerides (mg/dl)
Cholesterol (mg/dl)
HDL-cholesterol (mg/dl)
LDL-cholesterol (mg/dl)
Control
1% gum acacia
453.1 ± 39.2
300.5 ± 27.1
86.3 ± 4.80
97.4 ± 8.70
Ethanolic extract (A. catechu)
100
257.0 ± 19.2* (-43.2)
223.2 ± 18.7 (-25.8)
94.4 ± 4.60 (?9.40)
73.9 ± 6.90* (-24.0)
Fenofibrate
100
203.2 ± 10.1** (-55.2)
237.9 ± 24.8 (-20.8)
98.8 ± 6.78 (?14.5)
49.4 ± 4.21** (-49.3)
Values are mean ± SE. Values given in the parenthesis is the percent change of lipid parameters of extract-treated group as compare to control Minus sign denotes decrease in value and plus sign denotes increase in value. Statistical significance * \0.50, ** \0.01
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possibility of possessing insulin sensitizing activity. The ethanolic extract showed improves glucose tolerance after multiple dose post-feeding in STZ-treated diabetic rats at a relatively lower dose. Further anti-hyperglycaemic and anti-dyslipidaemic activities were evaluated in high fructose high fat fed STZ-treated diabetic rats, shares some common features of type 2 diabetes, i.e., dyslipidemia, hyperglycemia, and usually the secondary complications, as the ethanolic extract of A. catechu hard wood was found to have anti-hyperglycemic as well as anti-dyslipidemic activities. Further the anti-dyslipidemic activity of the ethanolic extract was confirmed in HFD fed dyslipidemic Syrian golden hamsters. The ethanolic and aqueous extracts of A. catechu hard wood showed AR inhibitory action against normal rat eye lens and diabetic rat eye lens AR. Since elevated level of AR is responsible for the development of diabetic cataract, one of the secondary complications, the ethanolic as well as aqueous extracts of A. catechu, may have the potential to prevent secondary complications of T2DM. The studies are though not very mature at the definitely but definitely a conclusion may be drawn at the moment that the ethanolic and aqueous extracts of the hard wood of A. catechu have confirmed anti-hyperglycemic, anti-dyslipidemic, and AR inhibiting activities; therefore it offers the possibility of identifying the anti-diabetic molecules that could be utilized in the design and synthesis of new plant based anti-diabetic agents. Fig. 7 a, b Concentration-dependent effect ethanolic and aqueous extracts of A. catechu hard wood on rat eye lenses aldose reductase from normal (a) and STZ-induced diabetic (b) rats (% inhibition are shown at the top of the bar)
have been reported as potent hypoglycemic agents. In the present study, anti-diabetic and anti-dyslipidemic activities of the ethanolic and aqueous extracts of A. catechu hard wood were validated in few animal models of T2DM. In sucrose-loaded rat model, the aqueous as well as ethanolic extracts of A. catechu hard wood have marked ability to improve oral glucose tolerance comparable to standard anti-diabetic drug glybenclamide. Glybenclamide have insulin secretaceous activity (Krentz et al., 1994), it may be presumed that the ethanolic as well as aqueous extracts may also have insulin secretaceous activity that lower down the blood glucose level. The ethanolic extract of A. catechu hard wood lowers the blood glucose in dosedependent manner in the sucrose-loaded rat model. Ethanolic as well as aqueous also showed the anti-hyperglycaemic activity in single dose STZ-treated diabetic rats, it was compared with that of metformin. As metformin is already known to be an insulin sensitizer (Scarpello and Howlett, 2008), therefore it is assumed that the aqueous and ethanolic extracts of A. catechu hard wood might have
Acknowledgment Financial assistance in the form of Senior Research Fellowship to one of the authors (Swayam Prakash Srivastava) from CSIR, New Delhi (India) to carry out this work is highly acknowledged.
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