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Phytomedicine 14 (2007) 1522 www.elsevier.de/phymed

CinnamaldehydeA potential antidiabetic agent

P. Subash Babu, S. Prabuseenivasan, S. Ignacimuthu
Division of Ethnopharmacology, Entomology Research Institute, Loyola College, Chennai 600 034, Tamil Nadu, India Received 12 July 2006; accepted 30 October 2006

Abstract
Cinnamonum zeylanicum (cinnamon) is widely used in traditional system of medicine to treat diabetes in India. The present study was carried out to isolate and identify the putative antidiabetic compounds based on bioassay-guided fractionation; the compound identied decreased the plasma glucose levels. The active compound was puried by repeat column and structure of cinnamaldehyde was determined on the basis of chemical and physiochemical evidence. The LD50 value of cinnamaldehyde was determined as 1850737 mg/kg bw. Cinnamaldehyde was administered at different doses (5, 10 and 20 mg/kg bw) for 45 days to streptozotocin (STZ) (60 mg/kg bw)-induced male diabetic wistar rats. It was found that plasma glucose concentration was signicantly (po0.05) decreased in a dose-dependent manner (63.29%) compared to the control. In addition, oral administration of cinnamaldehyde (20 mg/kg bw) signicantly decreased glycosylated hemoglobin (HbA1C), serum total cholesterol, triglyceride levels and at the same time markedly increased plasma insulin, hepatic glycogen and high-density lipoproteincholesterol levels. Also cinnamaldehyde restored the altered plasma enzyme (aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, alkaline phosphatase and acid phosphatase) levels to near normal. Administration of glibenclamide, a reference drug (0.6mg/kg bw) also produced a signicant (po0.05) reduction in blood glucose concentration in STZinduced diabetic rats. The results of this experimental study indicate that cinnamaldehyde possesses hypoglycemic and hypolipidemic effects in STZ-induced diabetic rats. r 2006 Elsevier GmbH. All rights reserved.
Keywords: Cinnamonum zeylanicum; Bioassay-guided isolation; Cinnamaldehyde; Hypoglycemic effect; Streptozotocin

Introduction
Diabetes mellitus is a chronic metabolic disorder affecting approximately 4% population worldwide and is expected to increase by 5.4% in 2025 (Kim et al., 2006). It is characterized by abnormalities in carbohydrate, lipid and lipoprotein metabolism, which not only lead to hyperglycemia but also cause many complications, such hyperlipidemia, hyperinsulinemia, hypertension and atherosclerosis (Chait and Brunzell, 1996). Control of
Corresponding author. Tel.: +44 28178348; fax: +44 28174644.

E-mail address: eri_lc@hotmail.com (S. Ignacimuthu). 0944-7113/$ - see front matter r 2006 Elsevier GmbH. All rights reserved. doi:10.1016/j.phymed.2006.11.005

diabetes mellitus normally involves exercise, diet and chemotheraphy. The conventional pharmacological treatments for type II diabetes have a number of limitations, such as adverse effects and high rates of secondary failure. However, medicinal herbs are expected to have a similar degree of efcacy without the troublesome side effects associated with conventional drug treatment. Presently, there is growing interest in herbal remedies due to the side effects associated with the oral hypoglycemic agents (therapeutic agent) for the treatment of diabetes mellitus (Kim et al., 2006). More than 400 plants with glucose lowering effect are known (Ernst, 1997). Nearly 100 polysaccharides from plants

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have been reported for hypoglycemic activity. Some botanical polysaccharides are considered as important bioactive components responsible for hypoglycemic effect (Wang and Ng, 1999). Also a number of plants have hypolipidemic effect (Sharma et al., 2003). However, there is little information about plants with both hypoglycemic and hypolipidemic effects. Development and utilization of antidiabetic plants have attracted increasing interest. The plant kingdom is a wide eld to search for natural effective oral hypoglycemic or hypolipidemic agent that has slight or no side effects. Hence, compounds with both hypoglycemic and hypolipidemic properties would be useful antidiabetic agents (Luo et al., 2004). A number of investigators have shown that cumarins, avonoids, terpenoids, and a host of other secondary plant metabolites, including arginine and glutamic acid, possess hypoglycemic effect in various experimental models (Marles and Farnsworth, 1995; Ross, 2001). Although the hypoglycemic effect of terpenoids appears to involve stimulation of pancreatic b-cells and subsequent secretion of performed insulin, the metabolism of cumarins probably involves hepatotoxity (Marles and Farnsworth, 1995). In cinnamaldehyde, it undergoes extensive metabolism. The alcohol is rapidly converted to the aldehyde via alcohol dehydrogenase to cinnamaldehyde, which in turn, is converted to cinnamic acid. Thus cinnamic acid is the major intermediate metabolite for both chemicals. The major urinary metabolites are glycine or glucuronic acid conjugates of benzoic acid, which are formed as a result of b-oxidation of cinnamic acid. Glycine and glucuronic acid conjugates of cinnamic acid are formed in small amounts. A minor percentage of cinnamaldehyde undergoes conjugation with glutathione to form mercapturic acid derivatives (JECFA (Joint Expert Committee on Food Additives), 2000). It is well established that cinnamaldehyde really possesses a wide variety of bioactive properties. A number of traditional healers have claimed that cinnamon is effective in the reduction of blood glucose level (Qin et al., 2003; Alam et al., 2003) and promotes hypolipidemic effect (Lee et al., 2003; Kannappan et al., 2006). However, there are no reports available for hypoglycemic and hypolipidemic effects of cinnamaldehyde from Cinnamonum zeylanicum. So the aim of this study was to investigate the hypoglycemic and hypolipedemic effects of cinnamaldehyde (using a bioassay guided separation) in streptozotocin (STZ)-induced diabetic rats.

shade dried. The species was identied and authenticated by Dr. D. Narasimhan, Taxonomist, Department of Botany, Madras Christian College, Chennai and the voucher specimen (MPC-301) was deposited at the Entomology Research Institute, Loyola College, Chennai, Tamil Nadu, India.

Isolation and identication of the active compounds

Fresh bark (1.5 kg) was subjected to hydro-distillation in a Clevenger-type apparatus for 4 h. The yield (v/w) of volatile oil was 0.12%. The volatile oil was dried over anhydrous sodium sulfate and stored in airtight screw capped vials at 10 1C until use. Cinnamon oil (10 gm) was chromatographed on a silica gel column (Merck 70230 mesh, 400 gm, 3.5 i.d. 60 cm) and successively eluted with stepwise gradient of hexane ethyl acetate system (0%, 5%, 10%, 20%, 30%, 50%, 70% and 100%). Twenty-nine fractions were collected and each fraction was spotted on a precoated Silica gel 60 F254, 0.25 mm thick TLC plate (Merck) and eluted in hexane:ethyl acetate (4:1) and fractions with similar Rf values in TLC pattern were pooled together. Fraction-3 (3.5 g) showed signicant plasma glucose lowering effect. For further separation bioactive substance was chromatographed on a silica gel column and eluted with a stepwise gradient of hexaneethyl acetate (8:2) solvent system, and an active isolate of 2.25 g was obtained. This active isolate was subjected to spectral analysis. 1H and 13 C NMR spectra were recorded with a JEOL 300 MHz FT NMR spectrometer (H1) 75, MHz (13C) and chemical shifts were given in ppm. IR spectra were taken on a Perkin Elmer FT-IR (Spectrum One) spectrophotometer and mass spectra on a JEOL JMSDX30 spectrometer.

Experimental animals
Male wistar strain rats weighing about 200250 g bred in the Laboratory of Animal Medicine, Centre for Animal Health Studies, Tamilnadu Veterinary and Animal Sciences University, Madhavaram, Chennai, Tamil Nadu, India were used. All the animals were kept and maintained under laboratory conditions of temperature (2272 1C), humidity (4575%) and 12 h day:12 h night cycle; and were allowed free access to food (standard pellet diet) and water ad libitum. The animals were divided into 7 groups of 8 rats each.

Materials and methods

Induction of diabetes Plant material
C. zeylanicum Blume. (Lauraceae) bark was collected from Kanyakkumari district, Tamil Nadu, India and Diabetes mellitus was induced by single intraperitoneal injection of freshly prepared STZ (60 mg/kg bw) in 0.1 M citrate buffer (pH 4.5) in a volume of

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1 ml/kg bw. Diabetes was developed and stabilized in these STZ treated rats over a period of 7 days (Sarkar et al., 1996). The control animals were treated with citrate buffer (pH 4.5). After 7 days of STZ administration, plasma glucose levels of each rat were determined. Rats with a fasting plasma glucose range of 280350 mg/dl were considered diabetic and included in the study. Blood was collected by sinocular puncture.

glycogen was estimated by the method of Morales et al. (1973).

Determination of plasma insulin

Plasma insulin concentrations were determined by radioimmunoassay kit (Pharmacia, Uppsala, Sweden) with a beta metric counter (Cronex, Dupont, France). The kit included human insulin as standard and 125Ilabeled human insulin antibody, which cross-reacts similarly with rat insulin.

Experimental design and treatment schedule

In the experiment, a total of 42 rats (12 normal; 30 STZ-diabetic surviving rats) were used. The rats were divided into 7 groups of 6 rats each. Group 1 normal rats treated with vehicle alone (dimethylsulfoxide [DMSO] 0.5%; 1 ml/kg bodyweight); Group 2 normal rats treated with cinnamaldehyde (20 mg/kg bw); Group 3 STZ-treated diabetic rats; Groups 4, 5 and 6 STZtreated diabetic rats treated with cinnamaldehyde 5, 10 and 20 mg/kg bw, respectively. Group 7 STZ-treated diabetic rats treated with glibenclamide (0.6 mg/kg bw) for 45 days. After 45 days of treatment rats were decapitated, their blood was collected and serum for the measurement of cholesterol levels was obtained immediately by centrifugation. Each liver was removed, dried on tissue paper, weighed and stored at 80 1C for the assay of liver glycogen.

Determination of total hemoglobin and glycosylated hemoglobin

Total hemoglobin was estimated by the cyanomethaemoglobin method (Drabkin and Austin, 1932) and glycosylated hemoglobin (HbA1C) was estimated by the method of Sudhakar Nayak and Pattabiraman (1981), as modied by Bannon (1982). Measurement of cholesterol levels Serum total cholesterol, triglycerides and serum HDL-cholesterol were determined using commercial kits (Dialab, Austria).

Plasma enzyme assessments

Alanine aminotransferase (ALT; EC 2.6.1.2) and aspartate aminotransferase (AST; EC 2.6.1.1) activities were assayed by the method of Reitman and Frankel (1957). Lactate dehydrogenase (LDH, EC 1.1.1.27) activity was determined by the method of Cabaud and Wroblewski (1958). Alkaline phosphatase (ALP; EC 3.1.3.1) activity was measured at 405 nm by the formation of paranitrophenol from para-nitrophenylphosphate as a substrate (Principato et al., 1985). Acid phosphatase (ACP; EC 3.1.3.2) activity was measured using the method of Moss (1984). Protein concentration was assayed by the method of Lowry et al. (1951) using bovine serum albumin as a standard.

Acute toxicity testing

A separate experiment was performed to know whether any toxic effects were produced by cinnamaldehyde on liver and kidney. Rats fasted for 12 h were randomly divided into drug-treated test groups and vehicle-treated control group making up 7 groups of 6 rats per cage. Cinnamaldehyde (100, 200, 400, 800 1600 and 3200 mg/kg bw) was separately administered orally to the rats in each of the test groups. Each of the rats in the control groups was treated with vehicle alone (DMSO 0.5%; 1 ml/kg bw). Then the rats in both the test and control groups were allowed access to food and water, and behavioral changes were observed over a period of 24 h for sign of acute toxicity. The mortality number caused by the compound within this period of time was observed. Log doseresponse plots were constructed for the compound, from which the median lethal dose (LD50) of the compound was determined (Lorke, 1983).

Statistical analysis
Statistical analysis was performed using SPSS software package, version 6.0. The values were analyzed by one way analysis of variance (ANOVA) followed by Duncans multiple range test (DMRT) (Duncan, 1957). All the results were expressed as mean7SD for six rats in each group. p-Values o0.05 were considered as signicant.

Estimation of plasma glucose and hepatic glycogen

Fasting plasma glucose was estimated using glucose oxidaseperoxidase method (Trinder, 1969). Hepatic

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Results
Identication of active compound
Using bioassay-guided fractionation one active isolate was obtained. Structural determination of the active isolate was done using different spectral techniques and it was conrmed as trans-cinnamaldehyde. The yield of cinnamaldehyde was 0.225 g per gram of cinnamon. The compound was identied based on the following evidence: C9H8O (MW, 132) EI-MS (70 eV): M+ 132, 103, 77, 63, 51, 39; IR (neat) max/cm: 3029, 1675, 1626, 1123, 747; 1H-NMR (CDCL3, 300 MHz): 6.69, 7.23, 9.70; 13C NMR (CDCL3, 75 MHz): 193.62, 152.71, 133.94, 131.21, 129.03, 128.52, 128.43; the spectral data corroborate with Lee (2002). Oral administration of graded doses of cinnamaldehyde to male wistar rats, in our acute toxicity study produced a median lethal dose value of 1850737 mg/kg bw. Based on this observation the compound is considered to be safe in mammals.

Plasma glucose levels measured in normal and experimental rats after a single day and at the end of 7, 15, 30 and 45 days of treatment are given in Table 1. STZ-treated diabetic rats showed signicant increase in the levels of blood glucose as compared to normal rats. Oral administration of cinnamaldehyde 20 mg/kg bw showed highly signicant (po0.05) effect than 5 and 10 mg/kg bw doses. As the effect of cinnamaldehyde at a dose of 20 mg/kg bw was more effective in 45 days treatment, this dose was selected for further biochemical studies. Table 2 presents the effect of cinnamaldehyde on changes in body weight, food uptake, plasma insulin, total hemoglobin, HbA1C and liver glycogen in normal and diabetic rats. In diabetic rats, there was a signicant (po0.05) decrease in body weight, liver glycogen, plasma insulin and total hemoglobin and an increase in food uptake and HbA1C as compared to normal rats. Oral administration of cinnamaldehyde signicantly (po0.05) increased the body weight, plasma insulin, liver glycogen and total hemoglobin and decreased food

Table 1. Groups

Effect of cinnamaldehyde on plasma glucose levels in normal and streptozotocin-induced diabetic male wistar rats Plasma glucose levels (mg/dl) Diabetic 7th day 98.874.69b 87.474.72a 382.1719.3f 291.375.05d 306.279.1e 274.376.3c 281.677.2cd 15th day 89.276.22a 88.573.81a 398.5712.4e 271.977.58d 280.677.9d 197.578.3c 173.977.6b 30th day 94.0374.08a 95.377.38a 415.3715.20f 263.279.25e 238.379.8d 163.3711.2c 148.377.2b 45th day 83.976.14a 87.677.47a 431.0717.31e 256.9711.38d 189.478.6c 127.476.3b 119.679.4b

Normal Normal+cinnamaldehyde (20 mg/kg bw) Diabetic control Diabetic+cinnamaldehyde (5 mg/kg bw) Diabetic+cinnamaldehyde (10 mg/kg bw) Diabetic+cinnamaldehyde (20 mg/kg bw) Diabetic+glibenclamide (0.6 mg/kg bw

85.675.3 98.374.2 341.9712.8 317.779.7 328.777.4 346.4711.7 305.3714.9

Each value is mean7SD for six rats in each group. Values not sharing a common superscript differ signicantly at po0.05 (DMRT).

Table 2. Effect of cinnamaldehyde on body weight, hemoglobin, glycosylated hemoglobin, hepatic glycogen and plasma insulin in normal and streptozotocin-induced diabetic male wistar rats
Groups Body weight (g/day) Initial Final Food intake (g/day) Total hemoglobin (mg/dl) 14.0370.83c 14.2670.72c Glycosylated Hepatic hemoglobin glycogen (% total Hb) (g/100 g wet tissue 0.5270.07ab 0.4970.04a 4.0970.37c 4.4470.39d 1.9470.21a 3.8770.28c 3.1670.33b Plasma insulin (mU/ml) 14.070.65c 15.470.79d 8.2070.42a 13.470.57c 12.770.58b

Normal Normal+cinnamaldehyde (20 mg/kg bw) Diabetic control Diabetic+cinnamaldehyde (20 mg/kg bw) Diabetic+glibenclamide (0.6 mg/ kg bw)

195.8715.6 190.675.6 195.278.3 193.7713.4 198.675.7

205.4710.7c 198.678.6bc 165.776.5a 190.675.4b 193.479.2b

45.373.6 48.874.7 61.275.1 46.873.5 49.772.9

7.470.49a 0.9770.11d 12.5670.78b 0.5870.04bc 11.770.69b 0.6170.03c

Each value is mean7SD for six rats in each group. Values not sharing a common superscript differ signicantly at po0.05 (DMRT).

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Table 3. Effect of cinnamaldehyde on serum total cholesterol, triglyceride, HDL cholesterol levels in normal and streptozotocininduced diabetic male wistar rats Groups Normal Normal+cinnamaldehyde (20 mg/kg bw) Diabetic control Diabetic+cinnamaldehyde (20 mg/kg bw) Diabetic+glibenclamide (0.6 mg/kg bw) Total cholesterol (mg/dl) 94.573.32 97.773.69a 246.7713.2d 113.574.80b 127.374.24c
a

Triglycerides (mg/dl) 14.670.80 13.571.08a 38.072.00d 17.570.65c 15.270.47b

ab

HDL-cholesterol (mg/dl) 57.273.01c 54.372.81b 38.571.33a 54.372.42b 52.772.15b

Each value is mean7SD for six rats in each group. Values not sharing a common superscript differ signicantly at po0.05 (DMRT).

Table 4. Effect of cinnamaldehyde on plasma AST, ALT, LDH, ALP and ACP levels in normal and streptozotocin-induced diabetic male wistar rats Groups Normal Normal+cinnamaldehyde (20 mg/kg bw) Diabetic control Diabetic+cinnamaldehyde (20 mg/kg bw) Diabetic+glibenclamide (0.6 mg/kg bw) AST (U/dl) 37.371.13a 42.271.26b 63.772.19e 45.571.25c 47.571.84d ALT (U/dl) 54.573.24a 52.174.16a 89.474.85c 62.873.07b 67.473.42b LDH (U/l) 1167.5768.2a 1092.7773.8a 1563.5793.4c 1291.2753.8b 1327.9767.3b ALP (U/l) 53.772.82a 57.873.16b 82.773.48e 65.972.35c 72.172.82d ACP (U/l) 13.770.65a 14.370.82a 21.670.58d 15.870.45b 17.370.50c

Each value is mean7SD for six rats in each group. Values not sharing a common superscript differ signicantly at po0.05 (DMRT).

uptake and HbA1C (40.2%) when compared to untreated diabetic rats. Table 3 shows the levels of serum lipids in normal and experimental rats. There was a signicant decrease in the level of serum HDL-cholesterol and a signicant increase in the levels of total cholesterol and triglycerides in diabetic rats when compared to normal rats. Administration of cinnamaldehyde brought back the levels of serum lipids to near normal. Table 4 shows that the activities of plasma enzymes AST, ALT, LDH, ALP and ACP signicantly (po0.05) increased in diabetic rats compared to controls. Oral administration of cinnamaldehyde for 45 days signicantly restores the enzyme levels to near normal in diabetic rats.

Discussion
The aim of the present study was to evaluate the antihyperglycemic and hypolipidemic effects of cinnamaldehyde in STZ-induced diabetic rats. Diabetes mellitus causes a disturbance in the uptake of glucose as well as glucose metabolism. The use of a lower dose of STZ (60 mg/kg) produced an incomplete destruction of pancreatic b-cells even though the rats become permanently diabetic (Aybar et al., 2002). After treatment with a low dose of STZ there should be many surviving b-cells, and regeneration is also possible

(Gomes et al., 2001). Hyperglycemia generates abnormally high levels of free radicals by autoxidation of glucose and protein glycation, and oxidative stress has been reported to be a causal factor of cardiovascular complications in STZ-induced diabetes mellitus (Okutan et al., 2005). Hyperglycemia is associated with the generation of reactive oxygen species (ROS) causing oxidative damage particularly to heart, kidney, eyes, nerves, liver, small and large vessels and gastrointestinal system (Tunali and Yanardag, 2006). The increased levels of plasma glucose in STZ-induced diabetic rats were lowered by cinnamaldehyde administration. The antihyperglycemic action of cinnamaldehyde results from the potentiation of insulin from existing b-cells of the islets of Langerhans. The plasma glucose lowering activity was compared with glibenclamide, a standard hypoglycemic drug. Glibenclamide has been used for many years to treat diabetes, to stimulate insulin secretion from pancreatic b-cells (Tian et al., 1998). From the results of the present study, it appears that still insulin producing cells are functioning and the stimulation of insulin release could be responsible for most of the metabolic effects. It may be suggested that the mechanism of action of cinnamaldehyde is similar to glibenclamide. Although a number of active principles have also been observed with antidiabetic activity (Villasenor et al., 2004; Sheehan and Zemaitis, 1983), this is the rst report that demonstrates antidiabetic properties for cinnamaldehyde.

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Decrease in body weight of diabetic rats is possible due to catabolism of fats and protein, even though the food intake is more in diabetic rats than control. Due to insulin deciency protein content is decreased in muscular tissue by proteolysis (Vats et al., 2004). Oral administration of cinnamaldehyde partially improves body weight in diabetic rats. Lower levels of total hemoglobin observed in diabetic rats might be due to the increased formation of HbA1C. In uncontrolled or poorly controlled diabetes, there is an increased glycosylation of a number of proteins including hemoglobin and a-crystallin of lens (Alberti and Press, 1982). HbA1C was found to increase in patients with diabetes mellitus to approximately 16% and the amount of increase was directly proportional to the fasting blood glucose levels (Pari and Saravanan, 2002). Oral administration of cinnamaldehyde decreases hyperglycemia and therefore levels of HbA1C decreased (40.2%). Insulin is a stimulator of glycogen synthase system and when insulin is lacking this enzyme is not activated. On the other hand insulin inhibits glycogenolysis and, if there is a lack of insulin glycogenolysis, it is not under inhibition of insulin and, therefore, glycogen content of the liver decreases (Vats et al., 2004). Oral administration of cinnamaldehyde signicantly increases hepatic glycogen levels in STZ-diabetic rats, possibly because of the reactivation of the glycogen synthase system as a result of increased insulin secretion. Lipids play a vital role in the pathogenesis of diabetes mellitus. The most common lipid abnormalities in diabetes are hypertriglyceridemia and hypercholesterolemia. In our study, we have noticed elevated levels of serum lipids such as cholesterol and triglycerides in diabetic rats. The levels of increased serum lipids in diabetes represent a risk factor for coronary heart disease (Al-Shamaony et al., 1994). Under normal circumstances, insulin activates lipoprotein lipase and hydrolyzes triglycerides (Shirwaikar et al., 2004). Insulin increases uptake of fatty acids into adipose tissue and increases triglyceride synthesis. Moreover, insulin inhibits lipolysis. In case of insulin deciency, lipolysis is not inhibited and we have increased lipolysis which nally leads to hyperlipidemia. In insulin-decient diabetes, the concentration of serum free fatty acids is elevated as a result of free fatty acid outow from fat depots, where the balance of the free fatty acid estericationtriglyceride lipolysis cycle is displaced in favor of lipolysis (Shirwaikar et al., 2004). HDL is an antiatherogenic lipoprotein. It transports cholesterol from peripheral tissues into the liver and thereby acts as a protective factor against coronary heart disease. The level of HDL-cholesterol, which increased after cinnamaldehyde administration, might be due to the increase in the activity of lecithin cholesterol acyl transferase (LCAT), which may contribute to the regulation of

blood lipids (Patil et al., 2004). Administration of cinnamaldehyde lowers serum lipids, and also increases the serum HDL-cholesterol level in diabetic rats. The increase in the activities of plasma AST, ALT, LDH, ALP and ACP indicated that diabetes may be induced due to liver dysfunction. Ohaeri (2001) also found that liver was necrotized in STZ-induced diabetic rats. Therefore, increase in the activities of AST, ALT, LDH, ALP and ACP in plasma may be mainly due to the leakage of these enzymes from the liver cytosol into the blood stream (Navarro et al., 1993), which gives an indication on the hepatotoxic effect of STZ. On the other hand, treatment of the diabetic rats with cinnamaldehyde caused reduction in the activity of these enzymes in plasma compared to the mean values of diabetic group and consequently may alleviate liver damage caused by STZ-induced diabetes. These results are in agreement with those obtained by El-Demerdash et al. (2005) in rats. Our nding shows that oral administration of cinnamaldehyde produces signicant antihyperglycemic effect, lowers both total cholesterol and triglyceride levels and, at the same time, increases HDL-cholesterol in STZ-induced diabetic rats. This investigation reveals the potential of cinnamaldehyde for use as a natural oral agent, with both hypoglycemic and hypolipidemic effects.

Acknowledgments
The authors are grateful to Indian Council of Medical Research, New Delhi for providing Research Grant. They also thank the Director, Dr. ALM. Post Graduate Institute of Basic Medical Sciences, University of Madras for permission to undertake part of the studies at PGIBMS.

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