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Journal of Ethnopharmacology 114 (2007) 174–179

Assessment of antidiabetic potential of Cynodon dactylonextract in streptozotocin diabetic rats

Santosh Kumar Singh, Achyut Narayan Kesari,Rajesh Kumar Gupta, Dolly Jaiswal, Geeta Watal ∗

Alternative Therapeutics Unit, Drug Discovery & Development Division, Medicinal Research Laboratory,Department of Chemistry, University of Allahabad, Allahabad 211002, India

Received 18 March 2005; received in revised form 13 July 2007; accepted 27 July 2007Available online 19 August 2007

bstract

This study was undertaken to investigate the hypoglycemic and antidiabetic effect of single and repeated oral administration of the aqueous extractf Cynodon dactylon (Family: Poaceae) in normal and streptozotocin induced diabetic rats, respectively. The effect of repeated oral administrationf aqueous extract on serum lipid profile in diabetic rats was also examined. A range of doses, viz. 250, 500 and 1000 mg/kg bw of aqueous extractf Cynodon dactylon were evaluated and the dose of 500 mg/kg was identified as the most effective dose. It lowers blood glucose level around 31%fter 4 h of administration in normal rats. The same dose of 500 mg/kg produced a fall of 23% in blood glucose level within 1 h during glucoseolerance test (GTT) of mild diabetic rats. This dose has almost similar effect as that of standard drug tolbutamide (250 mg/kg bw). Severelyiabetic rats were also treated daily with 500 mg/kg bw for 14 days and a significant reduction of 59% was observed in fasting blood glucose level.

reduction in the urine sugar level and increase in body weight of severe diabetic rats were additional corroborating factors for its antidiabetic

otential. Total cholesterol (TC), low density lipoprotein (LDL) and triglyceride (TG) levels were decreased by 35, 77 and 29%, respectively, ineverely diabetic rats whereas, cardioprotective, high density lipoprotein (HDL) was increased by 18%. These results clearly indicate that aqueousxtract of Cynodon dactylon has high antidiabetic potential along with significant hypoglycemic and hypolipidemic effects.

2007 Elsevier Ireland Ltd. All rights reserved.

eywords: Cynodon dactylon; Poaceae; Streptozotocin; Antidiabetic; Hypolipidemic

Oterm

. Introduction

Diabetes mellitus is an endocrine disorder that is charac-erized by hyperglycemia (Chandra et al., 2004). A numberf investigations, of oral antihyperglycemic agents from plants

sed in traditional medicine, have been conducted and manyf the plants were found with good activity (Marles andransworth, 1995; Kesari et al., 2006, 2007). The World Health

Abbreviations: C. dactylon, Cynodon dactylon; FBG, fasting blood glucose;TT, glucose tolerance test; BGL, blood glucose level; TC, total cholesterol;G, triglyceride; LDL, low density lipoprotein; HDL, high density lipoprotein;, hours; g, grams; DW, distilled water; STZ, streptozotocin; bw, body weight;D, mild diabetic; SD, severe diabetic; S.D., standard deviation∗ Corresponding author. Tel.: +91 532 2641157/2462125;

ax: +91 532 2462240.E-mail address: geetawatal@rediffmail.com (G. Watal).

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378-8741/$ – see front matter © 2007 Elsevier Ireland Ltd. All rights reserved.oi:10.1016/j.jep.2007.07.039

rganisation (WHO) has also recommended the evaluation ofhe plants’ effectiveness in conditions where we lack safe mod-rn drugs (Day, 1998). This has lead an increasing demand ofesearch on antidiabetic natural products which produces mini-al or no side effects (Rao et al., 1999).Cynodon dactylon (L.) Pers. (Family: Poaceae) commonly

nown as “Doob” in India, is a weed and has been regarded toossess various medicinal properties. The plant posses antimi-robial, and antiviral activity (Dhar et al., 1968) and has alsoeen used to treat urinary tract infection, calculi and prostatitis.he aqueous plant extract is used as anti-inflammatory, diuretic,nti-emetic and purifying agent (Ahmed et al., 1994). It alsoas significant application in treating dysentery, dropsy and sec-

ndary syphilis (Chopra and Handa, 1982). Cynodon dactylonas been used as an antidiabetic agent in traditional system ofedicine in India (Kirtikar and Basu, 1980). The objective of

his investigation was to ascertain the scientific basis of its use

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n treatment of diabetes. The present investigation reports theypoglycemic, hypolipidemic and antihyperglycemic activity ofhe aqueous extract of Cynodon dactylon on which there is norevious data available.

. Materials and methods

.1. Preparation of the aqueous extract

Cynodon dactylon were collected from the campus of Uni-ersity of Allahabad, Allahabad, India. It was identified anduthenticated by Botanical Survey of India, Allahabad branchnd Prof. B.D. Singh, taxonomist, Allahabad Agriculture Insti-ute, Naini, Allahabad. The green plant up to 500 g was extractedith boiling water for 48 h. The resulting extract was filtered and

oncentrated in rotavapour under reduced pressure. The con-entrated extract was lyophilized to get a powder (yield 15.8%,/w).

.2. Experimental animals

Male albino Wistar rats of body weight 180–220 g wereelected for all the experiments. Animals were kept in our animalouse at an ambient temperature of 25–30 ◦C and 45–55% rela-ive humidity with a 12 h each of dark and light cycle. Animalsere fed pellet diet (Pashu aahar, Varanasi) and water ad libitum.

.3. Induction of diabetes in rats

Diabetes was induced by a single intraperitoneal injection ofreshly prepared streptozotocin (45 mg/kg bw) in 0.1 M citrateuffer (pH 4.5) to overnight fasted rats. After 3 days of STZdministration rats were divided according to their FBG levelsnto two groups: mild diabetic rats (FBG 120–250 mg/dl) andevere diabetic (FBG > 250 mg/dl).

.4. Estimation

Blood glucose level (BGL), total cholesterol (TC), high den-ity lipoprotein (HDL) cholesterol and triglycerides (TG) werestimated using standard kits of Bayers Diagnostic Ltd., India.DL cholesterol was calculated from the above measurement byriedwald et al. (1972) formula. Body weight was determinedravimetrically and urine sugar was detected by reagent-basedristrix from Bayer.

.5. Experimental design

.5.1. Assessment of hypoglycemic activity in normalealthy rats

Twenty-four normal healthy male rats were fasted overnight.he fasted animals were divided equally into four groups of six

ats each. Pretreatment FBG levels of each group were evalu-

ted. Group I served as untreated control given vehicle (waternly), whereas the other three groups II, III and IV were givenyophilized aqueous extract suspended in distilled water orallyn doses of 250, 500 and 1000 mg/kg bw, respectively. Blood

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rmacology 114 (2007) 174–179 175

amples were collected from the tail vein after 2, 4 and 6 h andhe percentage change in blood glucose were calculated for eachroup.

.5.2. Assessment of antidiabetic activity on glucoseolerance in mild-diabetic rats

The antidiabetic effect of aqueous extract was assessed inild-diabetic rats using a glucose tolerance test. The overnight

asted rats were divided into five groups (V, VI, VII, VIII andX) of six rats each. Pretreatment FBG levels of each group werevaluated. Group V (diabetic control) received vehicle (waternly) whereas doses of 250, 500 and 1000 mg/kg bw of aqueousxtract and a dose of 250 mg/kg bw of tolbutamide were givenrally to groups VI, VII, VIII and IX, respectively. BGL of eachroup was further evaluated after 90 min of the treatment consid-red as 0 h value. Two grams per kilogram bw glucose solutionas given to all the groups and their BGL were estimated afterand 2 h of glucose administration.

.5.3. Assessment of antidiabetic and hypolipidemicotential in severely diabetic rats

A study was carried on three groups (X, XI and XII) of six ratsach. Group X served as normal control, group XI as diabeticontrol and group XII as diabetic treated groups. Control ratsgroup X and XI) were given vehicle (distilled water) only whileroup XII was orally treated with a single dose of 500 mg/kg bwf aqueous extract suspended in distilled water daily for 2 weeks.asting blood glucose, total cholesterol, HDL cholesterol, urineugar and triglycerides levels were estimated, before and afterhe treatment, weekly up to 2 weeks and LDL cholesterol wasalculated by using Friedwald formula.

.6. LD50

Two groups of rats of both sex (6 animals per group) weredministered orally by a single dose of and 10 times of the effec-ive dose of the aqueous extract of Cynodon dactylon. The ratsere observed for gross behavioural, neurologic, autonomic and

oxic effect at regular intervals. Food consumption, faeces andrine were also examined at 2 h and then at 6 h intervals for 24 h.

.7. Statistical analysis

The data are expressed as mean ± S.D. Statistical com-arisons were performed by one-way analysis of varianceANOVA) followed by Duncan’s multiple range test (DMRT).he results were considered statistically significant if the P-alues were 0.05 or less.

. Results

.1. Effect of extract on FBG in normoglycemic rats

Results of the effect of aqueous extract of Cynodon dactylonn blood glucose levels of normal rats are presented in Table 1.ll the three doses of the extract produced significant hypo-lycemic effect after 4 h oral administration. The animals treated

176 S.K. Singh et al. / Journal of Ethnopharmacology 114 (2007) 174–179

Table 1Hypoglycemic effect of graded doses of aqueous extract of Cynodon dactylon in normal rats (mean ± S.D.)

Experimental animals (normal) Treatment (aqueous extract) Blood glucose levels (mg/dl)

Pretreatment level Post-treatment levels

FBG 2 h 4 h 6 h

Control Distilled water 81.8 ± 2.8 82.2 ± 4.3 80.6 ± 2.8 78.8 ± 4.1Treated 250 mg/kg 75.2 ± 2.3 60.3 ± 3.1 54.7 ± 3.8* 63.5 ± 5.8*

Treated 500 mg/kg 77.5 ± 7.1 58.9 ± 2.8 53.4 ± 3.9* 65.2 ± 5.6*

Treated 1000 mg/kg 78.8 ± 7.1 62.2 ± 4.9 55.9 ± 4.2* 69.4 ± 4.5*

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ith dose of 250 and 1000 mg/kg produce a fall of 27.2 and9%, respectively, after 4 h of extract administration. However,t was more marked as 31% in the animals treated with a dosef 500 mg/kg bw after 4 h of administration. The hypoglycemicffect was moderate after 2 h of the extract administration withll the three doses. However, increased BGL was observed afterh of treatment.

.2. Effect of extract on GTT in mild-diabetic rats

In order to choose the optimum dose for the diabetic animals,ifferent doses of aqueous extract (250, 500 and 1000 mg/kgw) were evaluated on glucose tolerance in mild diabetic ratslong with the standard drug tolbutamide (250 mg/kg bw). Fig. 1epicts the effect of the above mentioned doses of Cynodon

actylon aqueous extract and tolbutamide on glucose tolerancep to 2 h in mild-diabetic rats. A reduction of 12.5% in BGL wasbserved within 1 h of GTT by the dose of 250 mg/kg bw, and thisall increased further to 23% with 500 mg/kg bw of the extract.

ig. 1. Antidiabetic effect of graded doses of aqueous extract of Cynodon dacty-on on glucose tolerance in mild diabetic rats. *P < 0.01 as compared to control.

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owever, the same doses decreased the BGL only about 10–20%fter 2 h of glucose administration. Moreover, the higher dose of000 mg/kg bw had similar effect as that of 250 mg/kg bw of thextract. A dose of 250 mg/kg bw of tolbutamide reduced BGLy 26 and 20% at 1 and 2 h, respectively, during GTT. The fallroduced by 500 mg/kg bw of the aqueous extract of Cynodonactylon and 250 mg/kg bw of the standard drug tolbutamide arelmost similar and therefore comparable. It, therefore appearshat 500 mg/kg bw of the aqueous extract of Cynodon dactylons the most effective dose on GTT of STZ induced mild diabeticats and hence it was selected for evaluation in severe diabeticats.

.3. Effect of extract on FBG and lipid profile in severeiabetic rats

The effect of repeated oral administration of Cynodon dacty-on aqueous extract in severe diabetic rats is shown in Table 2. Inormal control rats, fasting blood glucose (FBG) levels observedt 7th and 14th days after treatment with vehicle was almostimilar to that of pretreatment levels. In diabetic control ratshe FBG rises gradually in 14 days. However, administrationf the most effective dose (500 mg/kg bw) of the extract pro-uced a marked antihyperglycemic effect in treated diabetic rats.he FBG decreases from 309.5 to 125.8 mg/dl after 2 weeks

reatment. The post-treatment levels of total cholesterol, LDLholesterol and triglyceride of the treated group were signifi-antly lesser than the pretreatment levels. A fall of 35% in TC,7% in LDL cholesterol and 29% in TG levels was observed inevere diabetic rats after 14 days of extract treatment. There wasn increase of 18%in HDL cholesterol in the treated diabeticroups.

.4. Effect of extract on urine sugar and body weight inevere diabetic rats

Table 3 depicts the effect of 500 mg/kg bw of Cynodon dacty-on aqueous extract on urine sugar levels and body weights of

evere diabetic rats. The urine sugar in treated diabetic groupsecreased by 75% after 14 days of treatment. The body weightf treated diabetic groups increased continuously as comparedo diabetic control.

S.K. Singh et al. / Journal of Ethnopharmacology 114 (2007) 174–179 177

Table 2Effect of oral administration of the aqueous extract of Cynodon dactylon on FBG and serum lipid profile in severe diabetic (SD) rats (mean ± S.D.)

Experimental animals Treatment (aqueous extract) Pretreatment level Post-treatment levels

7 day 14 day

FBG (mg/dl)Normal (control) Distilled water 82.2 ± 3.5 85.6 ± 2.6* 84.6 ± 4.3*

SD (control) Distilled water 300.8 ± 5.7 310.8 ± 3.5* 319.8 ± 3.6*

SD (treated) 500 mg/kg 309.6 ± 7.2 190.5 ± 4.2* 125.8 ± 4.1*

Total cholesterol (mg/dl)Normal (control) Distilled water 55.8 ± 6.45 7.2 ± 6.6* 59.7 ± 6.8*

SD (control) Distilled water 104.4 ± 4.4 114.0 ± 4.9* 118.5 ± 5.4*

SD (treated) 500 mg/kg 106.7 ± 5.8 80.2 ± 4.6* 69.7 ± 7.2*

HDL cholesterol (mg/dl)Normal (control) Distilled water 28.5 ± 4.2 29.8 ± 6.1** 30.5 ± 2.4**

SD (control) Distilled water 38.6 ± 2.8 29.8 ± 3.4** 25.8 ± 8.1**

SD (treated) 500 mg/kg 32.5 ± 3.5 37.4 ± 6.6** 39.4 ± 6.2**

Triglycerides (mg/dl)Normal (control) Distilled water 75.8 ± 3.5 81.2 ± 7.8* 86.5 ± 4.4*

SD (control) Distilled water 135.5 ± 3.2 143.1 ± 6.5* 150.8 ± 4.3*

SD (treated) 500 mg/kg 137.8 ± 2.7 101.5 ± 3.2* 98.5 ± 4.6*

LDL cholesterol (mg/dl)Normal (control) Distilled water 11.9 ± 4.8 11.1 ± 4.7* 11.9 ± 5.2*

SD (control) Distilled water 38.7 ± 5.2 55.3 ± 4.5* 58.6 ± 5.5*

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* P < 0.001 as compared to pretreatment level.** P < 0.05 as compared to pretreatment level.

.5. LD50

Experiment was carried out on normal healthy rats. Theehaviour of the treated rats appeared normal. No toxic effectas reported up to 5 and 10 times of the effective dose of the

queous extract and there were no death in any of these groups.

. Discussion

The findings of this study indicate that an aqueous extractf Cynodon dactylon had a significant hypoglycemic effect inormal rats, up to 6 h. The effect was dose-dependent up to00 mg/kg bw. However, the response decreased at higher dose

f 1000 mg/kg bw dose. Such a phenomenon of less hypo-lycemic response at higher doses is common in indigenouslants and has already been observed in Aegle marmelose (Raot al., 1995; Sharma et al., 1996a), Murraya koenigii (Kesari et

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able 3ffect of the most effective dose of Cynodon dactylon aqueous extract on urine sugar

xperimental animals Treatment (aqueous extract)

rine sugarNormal (control) Distilled waterSD (control) Distilled waterSD (treated) 500 mg/kg

ody weight (g)Normal (control) Distilled waterSD (control) Distilled waterSD (treated) 500 mg/kg

46.6 ± 3.2 22.5 ± 4.3 10.6 ± 4.8

l., 2005), Vinca rosea (Chattopadhyay et al., 1991) and Cin-amomum tamala (Sharma et al., 1996b).

The GTT studies of the mild diabetic animals reveal a max-mum fall of 23% in 1 h by the dose of 500 mg/kg bw whereas,he doses of 250 and 1000 mg/kg bw produced almost similarall of about 12% only in BGL. Moreover, the dose of 500 mg/kgw of the aqueous extract showed similar effect as that of syn-hetic drug tolbutamide (250 mg/kg bw). The GTT studies alsoonfirm 500 mg/kg bw to be the most effective dose as foundn the case of normal animals. This dose was therefore, selectedor further studies in the case of severely diabetic animals and aall of 38 and 59% was observed in FBG after 7 and 14 days ofreatment, respectively.

Hyperlipidemia has been reported to accompany hyper-lycemia states (Randle et al., 1963; Taskinen, 1993). Highevels of TC and more importantly LDL cholesterol are majororonary risk factors (National Cholesterol Education Program

and body weight in severe diabetic rats (SD) (mean ± S.D.)

Pretreatment level Post-treatment levels

0 day 7 day 14 day

Nil Nil Nil++++ ++++ ++++++++ ++ +

220.5 ± 2.5 224.9 ± 5.7 251.3 ± 4.5150.4 ± 4.3 144.3 ± 5.1 139.6 ± 4.7154.2 ± 4.5 159.3 ± 6.7 174.8 ± 5.4

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78 S.K. Singh et al. / Journal of Eth

xpert Panel, 1994; Temme et al., 2002), whereas several stud-es showed that an increase in HDL cholesterol is associatedith a decrease in coronary risk. Most of the drugs that decrease

otal cholesterol also decrease HDL cholesterol (Wilson, 1990).owever, it is interesting to find that in the present study theose of 500 mg/kg bw of the aqueous extract not only loweredhe TC, TG, and LDL levels by 35, 29 and 77%, respectively,ut also enhanced the cardio protective lipid HDL by 18% after4 days treatment. This would definitely reduce the incidencef coronary events (Lipid Research Clinics Programs, 1984),hich is the major cause of morbidity and deaths in diabetic

ubjects (Huse et al., 1988; Baynes, 1991).A decrease in body weight was registered in the case of STZ

iabetic control group rats while in the treated group the weightoss was reversed. The ability of the aqueous extract to protectody weight loss seems to be as a result of its ability to reduceyperglycemia. A fall of 75% in urine sugar was also observedfter 14 days of treatment.

Phytochemical investigation of Cynodon dactylon reveals theresences of flavonoids and sterols (Aishah et al., 1997; Patilt al., 2005). These principles are known to be bioactive forhe management of diabetes (Shammas, 1987; Rhemann andaman, 1989). It is well known that certain flavonoids exhibitypoglycemic activity (Pathak et al., 1991; Ahmad et al., 2000)nd are also known for their ability of beta cell regenerationf pancreas (Chakravarti et al., 1980, 1981). Sterols have alsohown to decrease blood sugar in experimental animal modelsSuba et al., 2004). Thus, the significant antidiabetic effect ofqueous extract of Cynodon dactylon may be due to the pres-nce of more than one antihyperglycemic principle and theirynergistic properties.

From this study we can conclusively state that Cynodonactylon aqueous extract has shown remarkable effects on bloodlucose level and marked improvement on hyperlipidemia due toiabetes. Its specific effect on HDL has additional advantage inhecking coronary risks. The extract seems to have no toxicity aso death is reported upto 10 times of effective dose. Further phar-acological and biochemical investigations are underway to

lucidate the mechanism of the antidiabetic and hypolipidemicffect in Cynodon dactylon.

cknowledgement

The authors are thankful to National Medicinal Plant Board,ew Delhi, India, for providing financial assistance.

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