4
7/26/2019 Khoharo Et Al http://slidepdf.com/reader/full/khoharo-et-al 1/4  BLOOD GLUCOSE LOWERING EFFECT OF Nigella sativa IN ALLOXAN INDUCED DIABETIC RATS DIRECT RESEARCH JOURNAL OF HEALTH AND PHARMACOLOGY (DRJHP) Vol.2 (2), pp. 10-13, July 2014 Available online at directresearchpublisher.org/drjhp  ©2014 Direct Research Journals Publisher   Palwasha Abbasi 1 , Sadia Tabassum Abbasi 2 ,Sadia Kazi 1  and Haji Khan Khoharo 3 * 1 Departemnt of Pharmacology, Isra University, Hyderabad, Sindh, Pakistan. 2 Departemnt of Biochemistry,Isra University, Hyderabad, Sindh, Pakistan. 3 Faculty of Medicine and Allied Medical Sciences,Isra University, Hyderabad, Sindh, Pakistan.      . . , 12 . ; : (10), : ( ) (10), :  (10), : (10). ( ) 120/. 0, 7 14. 0.1/ 50/. 21.0. . ≤ 0.05 .   (0.001) , (0.001).   .   . ≥350/ 7 14 (0.0001).   , ,, . *Corresponding Author E-mail [email protected],[email protected]   Nigella sativa  is spicy herb belonging to a family Ranunculaceae and it is commonly as know as black cumin (Arayne et al., 2004). It is cultivated commonly in Europe, Middle East and Asia. In china it is called Hak  jung Chou while in subcontinent, it is commonly called kalonji or kalajeera (Malviya et al., 2010).  Recently, the pharmacological action and potential therapeutic activities of Nigella sativa  have been proved for the management of many disease such as bronchitis, immumne disease , bacterial infection ,hypertension, liver disease, gastrointestinal disease and allergic condition (Zaoui et al., 2002; Kanter, 2007). In Islam it is well said that Nigella sativa  can cure all diseases except the death (Paarakh, 2010). The many beneficial effects of Nigella sativa  have not been satisfactorily scrutinized, but this plant possess many beneficial effects to avert many chonic diseases. Due to insulinotropic action (Farah e al., 2002 ; Rchid et al., 2004) and hepatic gluconeogensis (Farah et all.,2004) , Nigella sativa  acts as antidiabetic agent. By the inhibition of eicosanoid generation and membrane lipid peroxidation Nigella sativa  exhibits its antioxidative properties. The active compound in black cumin is thymoquninone which causes the antidiabtic action of Nigella sativa ( Ilaiyaraja et al., 2010). To confirm the effect of Nigella sativa  on insulin sensitivity and release, many studies have already been conducted (Farah et al.,2004;Ilaiyaraja et al., 2010;Farah et al., 2002;Kanter., 2004).  Recent studies have shown

Khoharo Et Al

Embed Size (px)

Citation preview

Page 1: Khoharo Et Al

7262019 Khoharo Et Al

httpslidepdfcomreaderfullkhoharo-et-al 14

BLOOD GLUCOSE LOWERING EFFECT OF Nigellasativa IN ALLOXAN INDUCED DIABETIC RATS

DIRECT RESEARCH JOURNAL OF HEALTH AND PHARMACOLOGY (DRJHP) Vol2 (2) pp 10-13 July 2014Available online at directresearchpublisherorgdrjhp

copy2014 Direct Research Journals Publisher

983122983141983155983141983137983154983139983144 983120983137983152983141983154

Palwasha Abbasi1 Sadia TabassumAbbasi2Sadia Kazi1 and Haji KhanKhoharo3

1Departemnt of Pharmacology Isra University

Hyderabad Sindh Pakistan2Departemnt of BiochemistryIsra University Hyderabad

Sindh Pakistan3Faculty of Medicine and Allied Medical SciencesIsra

University Hyderabad Sindh Pakistan

983105983106983123983124983122983105983107983124

983109983160983152983141983154983145983149983141983150983156983137983148 983155983156983157983140983161 983159983137983155 983139983137983154983154983145983141983140 983151983157983156 983156983151 983145983150983158983141983155983156983145983143983137983156983141 983156983144983141 983138983148983151983151983140983143983148983157983139983151983155983141 983148983151983159983141983154983145983150983143 983141983142983142983141983139983156 983151983142 983118983145983143983141983148983148983137 983155983137983156983145983158983137 983145983150 983137983148983148983151983160983137983150 983145983150983140983157983139983141983140

983140983145983137983138983141983156983145983139 983154983137983156983155983110983151983154983156983161 983149983137983148983141 983127983145983155983156983137983154 983137983148983138983145983150983151 983154983137983156983155 983159983141983154983141 983155983141983148983141983139983156983141983140

983137983139983139983151983154983140983145983150983143 983156983151 983145983150983139983148983157983155983145983151983150 983137983150983140 983141983160983139983148983157983155983145983151983150 983139983154983145983156983141983154983145983137 983105983150983145983149983137983148983155 983159983141983154983141983147983141983152983156 983145983150 983155983141983152983137983154983137983156983141 983155983156983137983145983150983148983141983155983155 983155983156983141983141983148 983139983137983143983141983155 983137983156 983150983151983154983149983137983148

983156983141983149983152983141983154983137983156983157983154983141 12 983144983151983157983154 983140983137983154983147983085983148983145983143983144983156 983139983161983139983148983141 983137983150983140 983142983154983141983141 983137983139983139983141983155983155 983156983151

983139983144983151983159 983137983150983140 983159983137983156983141983154 983110983151983154983156983161 983154983137983156983155 983159983141983154983141 983140983145983158983145983140983141983140 983145983150983156983151 983142983151983157983154 983143983154983151983157983152983155

983137983155 983111983154983151983157983152 983105 983139983151983150983156983154983151983148 (98315098310110) 983111983154983151983157983152 983106 983140983145983137983138983141983156983145983139 (983137983148983148983151983160983137983150983156983154983141983137983156983141983140 983139983151983150983156983154983151983148) (98315098310110) 983111983154983151983157983152 983107 983140983145983137983138983141983156983145983139 983156983154983141983137983156983141983140 983159983145983156983144

983118983145983143983141983148983148983137 983155983137983156983145983158983137 (98315098310110) 983111983154983151983157983152 983108 983140983145983137983138983141983156983145983139983155 983156983154983141983137983156983141983140 983159983145983156983144983111983148983145983149983141983152983145983154983145983140983141 (98315098310110) 983108983145983137983138983141983156983141983155 983149983141983148983148983145983156983157983155 983159983137983155 983145983150983140983157983139983141983140 983138983161

983155983145983150983143983148983141 983145983150983156983154983137983152983141983154983145983156983151983150983141983137983148 983145983150983146983141983139983156983145983151983150 983151983142 983105983148983148983151983160983137983150 (983123983145983143983149983137 983107983151983149983152983137983150983161)

983137983156 983156983144983141 983140983151983155983141 983151983142 120983149983143983147983143 983106983148983151983151983140 983155983137983149983152983148983141983155 983159983141983154983141 983156983137983147983141983150 983151983150

983140983137983161983155 0 7 983137983150983140 14 983111983148983145983149983141983152983145983154983145983140983141 983159983137983155 983143983145983158983141983150 983151983154983137983148983148983161 983137983156 983156983144983141 983140983151983155983141

983151983142 01983149983143983147983143 983137983150983140 983118983145983143983141983148983148983137 983155983137983156983145983158983137 983137983156 983156983144983141 983140983151983155983141 983151983142 50983143983147983143 983108983137983156983137983159983137983155 983137983150983137983148983161983162983141983140 983151983150 983123983120983123983123 983158983141983154983155983145983151983150 210 983124983144983141 983139983151983150983156983145983150983157983151983157983155

983158983137983154983145983137983138983148983141983155 983159983141983154983141 983137983150983137983148983161983162983141983140 983138983161 983105983118983119983126983105 983159983145983156983144 983152983151983155983156 983112983151983139 983124983157983147983141983161

983107983154983137983149983141983154 983124983144983141 983155983145983143983150983145983142983145983139983137983150983156 983152983085983158983137983148983157983141 983159983137983155 983156983137983147983141983150 983137983156 le 005983123983145983143983150983145983142983145983139983137983150983156 983140983145983142983142983141983154983141983150983139983141983155 983159983141983154983141 983151983138983155983141983154983158983141983140 983142983151983154 983138983148983151983151983140 983143983148983157983139983151983155983141

983137983149983151983150983143 983143983154983151983157983152983155 983151983150 983140983145983142983142983141983154983141983150983156 983140983137983161983155 983124983144983141 983138983148983151983151983140 983143983148983157983139983151983155983141 983159983137983155

983148983151983159 983145983150 983118983145983143983141983148983148983137 983155983137983156983145983158983137 983139983151983149983152983137983154983141983140 983159983145983156983144 983137983148983148983151983160983137983150 (9831529831010001)983144983151983159983141983158983141983154 983145983156 983159983137983155 983149983151983154983141 983139983151983149983152983137983154983141983140 983156983151 983143983148983145983149983141983152983145983154983145983140983141 983143983154983151983157983152

(9831529831010001) 983124983144983141 983142983145983150983140983145983150983143 983155983157983143983143983141983155983156983155 983156983144983137983156 983156983144983141 983118983145983143983141983148983148983137 983155983137983156983145983158983137

983148983151983159983141983154983155 983138983148983151983151983140 983143983148983157983139983151983155983141 983124983144983141 983138983148983151983151983140 983143983148983157983139983151983155983141 983148983151983159983141983154983145983150983143 983141983142983142983141983139983156 983151983142

983118983145983143983141983148983148983137 983155983137983156983145983158983137 983159983137983155 983145983150983142983141983154983145983151983154 983156983151 983143983148983145983149983141983152983145983154983145983140983141 983138983157983156 983145983156 983159983137983155983151983138983155983141983154983158983141983140 983124983144983141 983138983148983151983151983140 983143983148983157983139983151983155983141 983137983155 983144983145983143983144 983137983155 ge350983149983143983140983148 983159983137983155

983150983151983156983141983140 983145983150 983105983148983148983151983160983137983150 983143983154983151983157983152 983151983150 983140983137983161983155 7 983137983150983140 14 (98315298310100001)

983115983141983161 983159983151983154983140983155983098 983118983145983143983141983148983148983137 983155983137983156983145983158983137983084 983105983148983148983151983160983137983150 983108983145983137983138983141983156983141983155

983149983141983148983148983145983156983157983155983111983148983145983149983141983152983145983154983145983140983141 983122983137983156983155 983123983145983150983140983144

Corresponding Author E-mail

drhajikhan786gmailcomdrhajikhan123yahoocom

983105983139983139983141983152983156983141983140 983090983095 983114983157983150983141 983090983088983089983092

983113983118983124983122983119983108983125983107983124983113983119983118

Nigella sativa is spicy herb belonging to a familyRanunculaceae and it is commonly as know as blackcumin (Arayne et al 2004) It is cultivated commonly in

Europe Middle East and Asia In china it is called Hak jung Chou while in subcontinent it is commonly calledkalonji or kalajeera (Malviya et al 2010)

Recently the

pharmacological action and potential therapeuticactivities of Nigella sativa have been proved for themanagement of many disease such as bronchitisimmumne disease bacterial infection hypertension liverdisease gastrointestinal disease and allergic condition(Zaoui et al 2002 Kanter 2007) In Islam it is well saidthat Nigella sativa can cure all diseases except the death(Paarakh 2010) The many beneficial effects of Nigella

sativa have not been satisfactorily scrutinized but thisplant possess many beneficial effects to avert manychonic diseases Due to insulinotropic action (Farah e

al 2002 Rchid et al 2004) and hepatic gluconeogensis(Farah et all2004) Nigella sativa acts as antidiabeticagent By the inhibition of eicosanoid generation andmembrane lipid peroxidation Nigella sativa exhibits itsantioxidative properties The active compound in blackcumin is thymoquninone which causes the antidiabticaction of Nigella sativa ( Ilaiyaraja et al 2010)

To confirm the effect of Nigella sativa on insulinsensitivity and release many studies have already beenconducted (Farah et al2004Ilaiyaraja et al 2010Farahet al 2002Kanter 2004)

Recent studies have shown

7262019 Khoharo Et Al

httpslidepdfcomreaderfullkhoharo-et-al 24

Khoharo et al 11

Table1 Body weight (grams) in experimental animals (n=40)

MeanplusmnSD

Day 0 Day 7 Day 14

Control 2350plusmn84 2280plusmn23 2280plusmn23Alloxan control 2254plusmn108 2258plusmn42 1722plusmn17Nigella Sativa 2411plusmn1657 23000plusmn1054 19280plusmn2173

Glimepiride 2411plusmn165 2399plusmn24 2235plusmn30p-value pge006 pge007 p=0001

that Nigella sativa prevents intensity of oxidative stressand improves insulin sensitivity (Bloch-Damti andBashan 2005) Nigella sativa increases the insulinsensitivity in peripheral tissues and enhances secretion ofthe β-cells of pancreas because it has been proposedthat in pancreatic β-cells of STZ induced diabetic rats theNigella sativa has ability to restore its structural integrityIt is also observed that in the presence of 83mmolL ofblood glucose the secretion of insulin is increased in thepresence of Nigella sativa as has been checked in in-vitro isolated rat pancreatic islets (Rchid et al2004Kanter etal2004) The reactive oxygen species (ROS) aregenerated by chronic exposure of hyperglycemia and aredirectly neurotoxic and promote neuronal apoptosis as ithas been proposed from previous studies (Farah et al2002) Nigella sativa also have ability to delayed thecomplication related to the diabetes mellitus (Farah et al2010)

The results of previous studies showed that

through different mechanism the Nigella sativa has antidiabetic properties (Kanter et al 2004)

There are two important factors that contribute in thedevelopment of diabetic complication thay are

hyperglycemia and dyslipidemia Nigella sativa in variousanimal studies has shown beneficial effects in correctingboth hyperglycemia and dyslipidemia (Kaleem et al2007) The present study was conducted to evaluateblood glucose lowering effect of Nigella sativa in alloxaninduced diabetic rat model

MATERIALS AND METHODS

Analytical and Experimental studies were conducted on40 male Wistar albino rats at the animal house of IsraUniversity Hyderabad Sindh from May to Novermber

2013 Normal healthy albino rats of 200-300 grams wereselected while female rats sick and moribund animalswere excluded Animals were weighed and tagged keptin separate stainless steel cages at normal temperature12 hour dark-light cycle and free access to chow andwater Forty rats were divided into four groups as GroupA control (n=10) Group B diabetic (alloxan treatedcontrol) (n=10) Group C diabetic treated with Nigellasativa (n=10) Group D diabetic treated with Glimepiride(n=10)

Diabetes mellitus was induced in animals except thecontrol group by single intraperitoneal injection of Alloxan

(Sigma Company) at the dose of 120mgkg dissolved in05ml of acetate buffer About 2-3 ml of blood was drawnfrom the tail of rats collected in vacutainers andcentrifuged at 4000 rpm for 5 minutes to obtain serumBlood samples were taken on days 0 7 and 14 Bodyweight was measured simultaneously The blood glucosetest was performed on HITACHI ANALYZER 902Hyperglycemia was confirmed by measuring randomblood glucose after ten days by spectrophotometerDiabetes mellitus (DM) was defined as random bloodsugar gt200mgdl on three successive days Glimepiride1mg tablet (Amaryl Sanofi Aventis) was purchased fromlocal pharmacy and administered orally at the dose o01mgkg (Shukla et al)

Nigella sativa was administered

orally at the dose of 50gkg (Mansi2006) Data were

analyzed on SPSS version 210 The continuousvariables were analyzed by ANOVA and post Hoc Tukey-Cramer tests The significant p-value was taken at le 005

RESULTS

The results of body weight and blood glucose levels onDays 0 7 and 14 are shown in (Tables 1 and 2)Statistically significant differences were observed on day14 for the body weight as shown in (Table 1) while days0 and 7 were non-significant Significant differences wereobserved for blood glucose among groups on differendays The blood glucose as high as 350mgdl wasobserved in the alloxan treated group on days 7 and 14with significant p-value (p=00001) The blood glucosewas slightly more elevated in Nigella sativa compared toGlimepiride The findings suggest that the Nigella sativaexerts glucose lowering effect however it was lesseffective compared to glimepiride

DISCUSSION

Currently obesity is an ever increasing issue of urbanpopulation Obesity is one of the contributing factors othe metabolic disorders like dabetes mellitus hence thereis an urgent need to search into alternative molecules oherbal origin which may prove helpful

The present study compared blood glucose loweringeffects of Nigella sativa and glimepiride and conclusiveresults were observed As reported previously the

7262019 Khoharo Et Al

httpslidepdfcomreaderfullkhoharo-et-al 34

Direct Res J Health Pharm 12

Table 2 Blood glucose level (mgdl) in experimental animals (n=40)

MeanplusmnSD

Day 0 Day 7 Day 14

Control 8870plusmn1280 8870plusmn1280 8240plusmn1450Alloxan control 23390plusmn2797 24810plusmn5388 34000plusmn3853

Nigella Sativa 2113plusmn499 2243plusmn585 2312plusmn594Glimepiride 20920plusmn4948 18280plusmn3736 16700plusmn3138p-value p=0001 p=0001 p=0001

Nigella sativa may improve hyperglycemia anddyslipidemia through different mechanisms similarfindings have been observed in present study (Rchid etal 2004) reported that Nigella sativa stimulates β-cellsof Islets of Langerhans of endocrine pancreas Ali(2004) reported that the Nigella sativa enhances partialregeneration and proliferation of β-cells of Islet ofLangerhans

The findings are consistent with present study as bloodglucose lowering effect is confirmed Another postulatedmechanism of lowering of blood glucose is throughreduced produciton of glucose from the liver amechanism called gluconeogenesis (Farah et al 2002)Le et al (2004) gave the opinion that the Nigella sativareduces intestinal absorption of glucose from the lumenof gut Ali 2004 also reported that the Nigella sativa enhances the insulin effects on the target organs TheNigella sativa has proved of lowering the blood glucosehowever the glimepiride was more effective But againthe findings are of clinical importance as the Nigellasativa is a natural herb The glimepiride is a potent

antidiabetic drug The present study concludes the role ofherbs in lowering blood glucoseThe results of the present study are consistance with

report (Zaoui

et al2002) Study proved the blood

glucose lowering effect of Nigella Sativa and concludedthat the Nigella sativa mediates its glucose loweringeffect through enhancement of peripheral metabolism ofglucose an increase in insulin release andsimultaneously a reduction in glucagon release or may bedue to an intestinal reduction of absorption of glucose The beneficial effects of N sativa on diabetic control hasbeen tested and proved in other animal studies (Altan etal2007Kaleem et al2006)

The finding of blood glucose lowering effect of NigellaSativa are consistent with previously studies asmentioned in literature Kaleem et al (2006) conductedstudy on 32 male Wistar albino rat model to compare theeffects of Nigella sativa with protamine zinc insulin onblood glucose level and lipid peroxidation in Streptozocininduced rats The study reported that the Nigella sativa reduces blood glucose level and exerts antioxidant effectin animal model Thus it is suggested that the Nigellasativa exerts a blood glucose regulating effectscomparable to drug molecule like glimepride in presentstudy

CONCLUSION

The present study concludes that the Nigella sativashows blood glucose lowering effect in alloxan induceddiabetic rat However the effect was less pronouncedcompared to glimepiride Further studies are warranted tobe conducted to elucidate the possible mechanisms oregulating the blood glucose

REFERENCES

Arayne MS Sultana N Mirza AZ Zuberi MH Siddiqui FA (2004) In-vitro hypoglycemic activity of methanolic extract of some indigenousplants Pak J Pharmaceut Sci 20 (4) 268-73

Malviya N Jain S Malviya S (2010) Antidiabetic effect of medicinaplants Pharmaceutica Drug Res 67 (2) 113-8

Zaoui A Cherrah Y Alaoui K Mahassine N Amarouch H Hassar M(2002) Effects of Nigella sativa fixed oil on blood homeostasis in ratJ Ethnopharmacol 79(1) 23-6

Kanter M (2007) Effects of Nigella sativa and its Major ConstituentThymoquinone on Sciatic Nerves in Experimental DiabeticNeuropathy Neuroche Res 23 87-96

Paarakh PM (2010) Nigella sativa Linn- A comprehensive review

Indian J Prod Resour 1 409-29Farah KM Atoji Y Shimizu Y Takewaki T (2002) Isulinotropic

properties of Nigella sativa oil in Streptozotocin plus Nicotinamidediabetic hamster Rec Veter Sci 73 279-82

Rchid H Chevassus H Nmila R Guiral C Petit P Chokairi M (2004)Nigella sativa seed extracts enhance glucose-induced insulin releasefrom rat-isolated Langerhans islets Fundamental Clin Pharmacol 18(5) 525-529

Farah KM Atoji Y Shimizu YShiina T Nikami H Takewaki T (2004)Mechanisms of the hypoglycaemic and immunopotentiating effectsof Nigella sativa L oil in streptozotocin-induced diabetic hamstersRes Veter Sci 77(2) 23-29

Ilaiyaraja N Khanum F(2010) Nigella sativa L A review otherapeutic applications J Herb Med Toxicol 41-8

Farah KM Atoji Y Shimizu Y Takewaki T(2002) Isulinotropicproperties of Nigella sativa oil in Streptozotocin plus Nicotinamidediabetic hamster Rec Veter Science 73 279-282

Kanter M Coskun O Korkmaz A Oter S (2004) Effects of Nigellasativa on oxidative stress and β-cell damage in streptozotocininduced diabetic rats Evolutionary Biol 279(1) 685-691

Bloch-Damti A Bashan N(2005) Proposed mechanisms for theinduction of insulin resistance by oxidative stress J Antioxid RedoxSig 7 1553-1567

Kaleem M Kirimani D Asif M Ahmed Q Bilqees B(2007) Biochemicaeffect of Nigella sativa L seed in diabetic Rats Turk J Biol 3 95102

Shukla N Joshi A Dubey BK (2012) Antidiabetic Activity of EthenolicExtract of Albizzia Leebeck In Alloxan-Induced Diabetic Rats WorldJ Pharmaceutical Res 1 1350-1360

Mansi KMS(2006) Effects of Oral administration of water extract oNigella sativa on the Hypothalamus pituitary adrenal Axis in

7262019 Khoharo Et Al

httpslidepdfcomreaderfullkhoharo-et-al 44

Khoharo et al 13

Experimental Diabetes Int`l J Pharmacol2 104-109Ali BH(2004) The effects of Nigella Sativa oil on Gentamycin

Nephrotoxicity in rats Am J Chin Med 32(1) 49-55Le PM Benhaddou-Andaloussi A Elimadi A Settaf A Cherrah Y

Haddad PS(2004) The petroleum ether extract of Nigella sativaexerts lipid-lowering and insulin-sensitizing actions in the rat Journalof Ethnopharmacology 94(2-3) 251-259

Zaoui A Cherrah Y Alaoui K Mahassine N Amarouch H Hassar M

(2002) Effects of Nigella sativa fixed oil on blood homeostasis in ratJ Ethnopharmacol 79(1)23-26

Altan MF Kanter M Donmez S Kartal ME Buyukbas S (2007)Combination therapy of Nigella sativa and human parathyroidhormone on bone mass biomechanical behavior and structure instreptozotocin-induced diabetic rats Acta Histochemica-Elsevier109(4)304-314

Kaleem M Kirimani D Asif M Ahmed Q Bilqees B (2006) Biochemicaleffects of Nigella sativa L seeds in diabetic rats Indian J Exp Biol44(9)745-748

Page 2: Khoharo Et Al

7262019 Khoharo Et Al

httpslidepdfcomreaderfullkhoharo-et-al 24

Khoharo et al 11

Table1 Body weight (grams) in experimental animals (n=40)

MeanplusmnSD

Day 0 Day 7 Day 14

Control 2350plusmn84 2280plusmn23 2280plusmn23Alloxan control 2254plusmn108 2258plusmn42 1722plusmn17Nigella Sativa 2411plusmn1657 23000plusmn1054 19280plusmn2173

Glimepiride 2411plusmn165 2399plusmn24 2235plusmn30p-value pge006 pge007 p=0001

that Nigella sativa prevents intensity of oxidative stressand improves insulin sensitivity (Bloch-Damti andBashan 2005) Nigella sativa increases the insulinsensitivity in peripheral tissues and enhances secretion ofthe β-cells of pancreas because it has been proposedthat in pancreatic β-cells of STZ induced diabetic rats theNigella sativa has ability to restore its structural integrityIt is also observed that in the presence of 83mmolL ofblood glucose the secretion of insulin is increased in thepresence of Nigella sativa as has been checked in in-vitro isolated rat pancreatic islets (Rchid et al2004Kanter etal2004) The reactive oxygen species (ROS) aregenerated by chronic exposure of hyperglycemia and aredirectly neurotoxic and promote neuronal apoptosis as ithas been proposed from previous studies (Farah et al2002) Nigella sativa also have ability to delayed thecomplication related to the diabetes mellitus (Farah et al2010)

The results of previous studies showed that

through different mechanism the Nigella sativa has antidiabetic properties (Kanter et al 2004)

There are two important factors that contribute in thedevelopment of diabetic complication thay are

hyperglycemia and dyslipidemia Nigella sativa in variousanimal studies has shown beneficial effects in correctingboth hyperglycemia and dyslipidemia (Kaleem et al2007) The present study was conducted to evaluateblood glucose lowering effect of Nigella sativa in alloxaninduced diabetic rat model

MATERIALS AND METHODS

Analytical and Experimental studies were conducted on40 male Wistar albino rats at the animal house of IsraUniversity Hyderabad Sindh from May to Novermber

2013 Normal healthy albino rats of 200-300 grams wereselected while female rats sick and moribund animalswere excluded Animals were weighed and tagged keptin separate stainless steel cages at normal temperature12 hour dark-light cycle and free access to chow andwater Forty rats were divided into four groups as GroupA control (n=10) Group B diabetic (alloxan treatedcontrol) (n=10) Group C diabetic treated with Nigellasativa (n=10) Group D diabetic treated with Glimepiride(n=10)

Diabetes mellitus was induced in animals except thecontrol group by single intraperitoneal injection of Alloxan

(Sigma Company) at the dose of 120mgkg dissolved in05ml of acetate buffer About 2-3 ml of blood was drawnfrom the tail of rats collected in vacutainers andcentrifuged at 4000 rpm for 5 minutes to obtain serumBlood samples were taken on days 0 7 and 14 Bodyweight was measured simultaneously The blood glucosetest was performed on HITACHI ANALYZER 902Hyperglycemia was confirmed by measuring randomblood glucose after ten days by spectrophotometerDiabetes mellitus (DM) was defined as random bloodsugar gt200mgdl on three successive days Glimepiride1mg tablet (Amaryl Sanofi Aventis) was purchased fromlocal pharmacy and administered orally at the dose o01mgkg (Shukla et al)

Nigella sativa was administered

orally at the dose of 50gkg (Mansi2006) Data were

analyzed on SPSS version 210 The continuousvariables were analyzed by ANOVA and post Hoc Tukey-Cramer tests The significant p-value was taken at le 005

RESULTS

The results of body weight and blood glucose levels onDays 0 7 and 14 are shown in (Tables 1 and 2)Statistically significant differences were observed on day14 for the body weight as shown in (Table 1) while days0 and 7 were non-significant Significant differences wereobserved for blood glucose among groups on differendays The blood glucose as high as 350mgdl wasobserved in the alloxan treated group on days 7 and 14with significant p-value (p=00001) The blood glucosewas slightly more elevated in Nigella sativa compared toGlimepiride The findings suggest that the Nigella sativaexerts glucose lowering effect however it was lesseffective compared to glimepiride

DISCUSSION

Currently obesity is an ever increasing issue of urbanpopulation Obesity is one of the contributing factors othe metabolic disorders like dabetes mellitus hence thereis an urgent need to search into alternative molecules oherbal origin which may prove helpful

The present study compared blood glucose loweringeffects of Nigella sativa and glimepiride and conclusiveresults were observed As reported previously the

7262019 Khoharo Et Al

httpslidepdfcomreaderfullkhoharo-et-al 34

Direct Res J Health Pharm 12

Table 2 Blood glucose level (mgdl) in experimental animals (n=40)

MeanplusmnSD

Day 0 Day 7 Day 14

Control 8870plusmn1280 8870plusmn1280 8240plusmn1450Alloxan control 23390plusmn2797 24810plusmn5388 34000plusmn3853

Nigella Sativa 2113plusmn499 2243plusmn585 2312plusmn594Glimepiride 20920plusmn4948 18280plusmn3736 16700plusmn3138p-value p=0001 p=0001 p=0001

Nigella sativa may improve hyperglycemia anddyslipidemia through different mechanisms similarfindings have been observed in present study (Rchid etal 2004) reported that Nigella sativa stimulates β-cellsof Islets of Langerhans of endocrine pancreas Ali(2004) reported that the Nigella sativa enhances partialregeneration and proliferation of β-cells of Islet ofLangerhans

The findings are consistent with present study as bloodglucose lowering effect is confirmed Another postulatedmechanism of lowering of blood glucose is throughreduced produciton of glucose from the liver amechanism called gluconeogenesis (Farah et al 2002)Le et al (2004) gave the opinion that the Nigella sativareduces intestinal absorption of glucose from the lumenof gut Ali 2004 also reported that the Nigella sativa enhances the insulin effects on the target organs TheNigella sativa has proved of lowering the blood glucosehowever the glimepiride was more effective But againthe findings are of clinical importance as the Nigellasativa is a natural herb The glimepiride is a potent

antidiabetic drug The present study concludes the role ofherbs in lowering blood glucoseThe results of the present study are consistance with

report (Zaoui

et al2002) Study proved the blood

glucose lowering effect of Nigella Sativa and concludedthat the Nigella sativa mediates its glucose loweringeffect through enhancement of peripheral metabolism ofglucose an increase in insulin release andsimultaneously a reduction in glucagon release or may bedue to an intestinal reduction of absorption of glucose The beneficial effects of N sativa on diabetic control hasbeen tested and proved in other animal studies (Altan etal2007Kaleem et al2006)

The finding of blood glucose lowering effect of NigellaSativa are consistent with previously studies asmentioned in literature Kaleem et al (2006) conductedstudy on 32 male Wistar albino rat model to compare theeffects of Nigella sativa with protamine zinc insulin onblood glucose level and lipid peroxidation in Streptozocininduced rats The study reported that the Nigella sativa reduces blood glucose level and exerts antioxidant effectin animal model Thus it is suggested that the Nigellasativa exerts a blood glucose regulating effectscomparable to drug molecule like glimepride in presentstudy

CONCLUSION

The present study concludes that the Nigella sativashows blood glucose lowering effect in alloxan induceddiabetic rat However the effect was less pronouncedcompared to glimepiride Further studies are warranted tobe conducted to elucidate the possible mechanisms oregulating the blood glucose

REFERENCES

Arayne MS Sultana N Mirza AZ Zuberi MH Siddiqui FA (2004) In-vitro hypoglycemic activity of methanolic extract of some indigenousplants Pak J Pharmaceut Sci 20 (4) 268-73

Malviya N Jain S Malviya S (2010) Antidiabetic effect of medicinaplants Pharmaceutica Drug Res 67 (2) 113-8

Zaoui A Cherrah Y Alaoui K Mahassine N Amarouch H Hassar M(2002) Effects of Nigella sativa fixed oil on blood homeostasis in ratJ Ethnopharmacol 79(1) 23-6

Kanter M (2007) Effects of Nigella sativa and its Major ConstituentThymoquinone on Sciatic Nerves in Experimental DiabeticNeuropathy Neuroche Res 23 87-96

Paarakh PM (2010) Nigella sativa Linn- A comprehensive review

Indian J Prod Resour 1 409-29Farah KM Atoji Y Shimizu Y Takewaki T (2002) Isulinotropic

properties of Nigella sativa oil in Streptozotocin plus Nicotinamidediabetic hamster Rec Veter Sci 73 279-82

Rchid H Chevassus H Nmila R Guiral C Petit P Chokairi M (2004)Nigella sativa seed extracts enhance glucose-induced insulin releasefrom rat-isolated Langerhans islets Fundamental Clin Pharmacol 18(5) 525-529

Farah KM Atoji Y Shimizu YShiina T Nikami H Takewaki T (2004)Mechanisms of the hypoglycaemic and immunopotentiating effectsof Nigella sativa L oil in streptozotocin-induced diabetic hamstersRes Veter Sci 77(2) 23-29

Ilaiyaraja N Khanum F(2010) Nigella sativa L A review otherapeutic applications J Herb Med Toxicol 41-8

Farah KM Atoji Y Shimizu Y Takewaki T(2002) Isulinotropicproperties of Nigella sativa oil in Streptozotocin plus Nicotinamidediabetic hamster Rec Veter Science 73 279-282

Kanter M Coskun O Korkmaz A Oter S (2004) Effects of Nigellasativa on oxidative stress and β-cell damage in streptozotocininduced diabetic rats Evolutionary Biol 279(1) 685-691

Bloch-Damti A Bashan N(2005) Proposed mechanisms for theinduction of insulin resistance by oxidative stress J Antioxid RedoxSig 7 1553-1567

Kaleem M Kirimani D Asif M Ahmed Q Bilqees B(2007) Biochemicaeffect of Nigella sativa L seed in diabetic Rats Turk J Biol 3 95102

Shukla N Joshi A Dubey BK (2012) Antidiabetic Activity of EthenolicExtract of Albizzia Leebeck In Alloxan-Induced Diabetic Rats WorldJ Pharmaceutical Res 1 1350-1360

Mansi KMS(2006) Effects of Oral administration of water extract oNigella sativa on the Hypothalamus pituitary adrenal Axis in

7262019 Khoharo Et Al

httpslidepdfcomreaderfullkhoharo-et-al 44

Khoharo et al 13

Experimental Diabetes Int`l J Pharmacol2 104-109Ali BH(2004) The effects of Nigella Sativa oil on Gentamycin

Nephrotoxicity in rats Am J Chin Med 32(1) 49-55Le PM Benhaddou-Andaloussi A Elimadi A Settaf A Cherrah Y

Haddad PS(2004) The petroleum ether extract of Nigella sativaexerts lipid-lowering and insulin-sensitizing actions in the rat Journalof Ethnopharmacology 94(2-3) 251-259

Zaoui A Cherrah Y Alaoui K Mahassine N Amarouch H Hassar M

(2002) Effects of Nigella sativa fixed oil on blood homeostasis in ratJ Ethnopharmacol 79(1)23-26

Altan MF Kanter M Donmez S Kartal ME Buyukbas S (2007)Combination therapy of Nigella sativa and human parathyroidhormone on bone mass biomechanical behavior and structure instreptozotocin-induced diabetic rats Acta Histochemica-Elsevier109(4)304-314

Kaleem M Kirimani D Asif M Ahmed Q Bilqees B (2006) Biochemicaleffects of Nigella sativa L seeds in diabetic rats Indian J Exp Biol44(9)745-748

Page 3: Khoharo Et Al

7262019 Khoharo Et Al

httpslidepdfcomreaderfullkhoharo-et-al 34

Direct Res J Health Pharm 12

Table 2 Blood glucose level (mgdl) in experimental animals (n=40)

MeanplusmnSD

Day 0 Day 7 Day 14

Control 8870plusmn1280 8870plusmn1280 8240plusmn1450Alloxan control 23390plusmn2797 24810plusmn5388 34000plusmn3853

Nigella Sativa 2113plusmn499 2243plusmn585 2312plusmn594Glimepiride 20920plusmn4948 18280plusmn3736 16700plusmn3138p-value p=0001 p=0001 p=0001

Nigella sativa may improve hyperglycemia anddyslipidemia through different mechanisms similarfindings have been observed in present study (Rchid etal 2004) reported that Nigella sativa stimulates β-cellsof Islets of Langerhans of endocrine pancreas Ali(2004) reported that the Nigella sativa enhances partialregeneration and proliferation of β-cells of Islet ofLangerhans

The findings are consistent with present study as bloodglucose lowering effect is confirmed Another postulatedmechanism of lowering of blood glucose is throughreduced produciton of glucose from the liver amechanism called gluconeogenesis (Farah et al 2002)Le et al (2004) gave the opinion that the Nigella sativareduces intestinal absorption of glucose from the lumenof gut Ali 2004 also reported that the Nigella sativa enhances the insulin effects on the target organs TheNigella sativa has proved of lowering the blood glucosehowever the glimepiride was more effective But againthe findings are of clinical importance as the Nigellasativa is a natural herb The glimepiride is a potent

antidiabetic drug The present study concludes the role ofherbs in lowering blood glucoseThe results of the present study are consistance with

report (Zaoui

et al2002) Study proved the blood

glucose lowering effect of Nigella Sativa and concludedthat the Nigella sativa mediates its glucose loweringeffect through enhancement of peripheral metabolism ofglucose an increase in insulin release andsimultaneously a reduction in glucagon release or may bedue to an intestinal reduction of absorption of glucose The beneficial effects of N sativa on diabetic control hasbeen tested and proved in other animal studies (Altan etal2007Kaleem et al2006)

The finding of blood glucose lowering effect of NigellaSativa are consistent with previously studies asmentioned in literature Kaleem et al (2006) conductedstudy on 32 male Wistar albino rat model to compare theeffects of Nigella sativa with protamine zinc insulin onblood glucose level and lipid peroxidation in Streptozocininduced rats The study reported that the Nigella sativa reduces blood glucose level and exerts antioxidant effectin animal model Thus it is suggested that the Nigellasativa exerts a blood glucose regulating effectscomparable to drug molecule like glimepride in presentstudy

CONCLUSION

The present study concludes that the Nigella sativashows blood glucose lowering effect in alloxan induceddiabetic rat However the effect was less pronouncedcompared to glimepiride Further studies are warranted tobe conducted to elucidate the possible mechanisms oregulating the blood glucose

REFERENCES

Arayne MS Sultana N Mirza AZ Zuberi MH Siddiqui FA (2004) In-vitro hypoglycemic activity of methanolic extract of some indigenousplants Pak J Pharmaceut Sci 20 (4) 268-73

Malviya N Jain S Malviya S (2010) Antidiabetic effect of medicinaplants Pharmaceutica Drug Res 67 (2) 113-8

Zaoui A Cherrah Y Alaoui K Mahassine N Amarouch H Hassar M(2002) Effects of Nigella sativa fixed oil on blood homeostasis in ratJ Ethnopharmacol 79(1) 23-6

Kanter M (2007) Effects of Nigella sativa and its Major ConstituentThymoquinone on Sciatic Nerves in Experimental DiabeticNeuropathy Neuroche Res 23 87-96

Paarakh PM (2010) Nigella sativa Linn- A comprehensive review

Indian J Prod Resour 1 409-29Farah KM Atoji Y Shimizu Y Takewaki T (2002) Isulinotropic

properties of Nigella sativa oil in Streptozotocin plus Nicotinamidediabetic hamster Rec Veter Sci 73 279-82

Rchid H Chevassus H Nmila R Guiral C Petit P Chokairi M (2004)Nigella sativa seed extracts enhance glucose-induced insulin releasefrom rat-isolated Langerhans islets Fundamental Clin Pharmacol 18(5) 525-529

Farah KM Atoji Y Shimizu YShiina T Nikami H Takewaki T (2004)Mechanisms of the hypoglycaemic and immunopotentiating effectsof Nigella sativa L oil in streptozotocin-induced diabetic hamstersRes Veter Sci 77(2) 23-29

Ilaiyaraja N Khanum F(2010) Nigella sativa L A review otherapeutic applications J Herb Med Toxicol 41-8

Farah KM Atoji Y Shimizu Y Takewaki T(2002) Isulinotropicproperties of Nigella sativa oil in Streptozotocin plus Nicotinamidediabetic hamster Rec Veter Science 73 279-282

Kanter M Coskun O Korkmaz A Oter S (2004) Effects of Nigellasativa on oxidative stress and β-cell damage in streptozotocininduced diabetic rats Evolutionary Biol 279(1) 685-691

Bloch-Damti A Bashan N(2005) Proposed mechanisms for theinduction of insulin resistance by oxidative stress J Antioxid RedoxSig 7 1553-1567

Kaleem M Kirimani D Asif M Ahmed Q Bilqees B(2007) Biochemicaeffect of Nigella sativa L seed in diabetic Rats Turk J Biol 3 95102

Shukla N Joshi A Dubey BK (2012) Antidiabetic Activity of EthenolicExtract of Albizzia Leebeck In Alloxan-Induced Diabetic Rats WorldJ Pharmaceutical Res 1 1350-1360

Mansi KMS(2006) Effects of Oral administration of water extract oNigella sativa on the Hypothalamus pituitary adrenal Axis in

7262019 Khoharo Et Al

httpslidepdfcomreaderfullkhoharo-et-al 44

Khoharo et al 13

Experimental Diabetes Int`l J Pharmacol2 104-109Ali BH(2004) The effects of Nigella Sativa oil on Gentamycin

Nephrotoxicity in rats Am J Chin Med 32(1) 49-55Le PM Benhaddou-Andaloussi A Elimadi A Settaf A Cherrah Y

Haddad PS(2004) The petroleum ether extract of Nigella sativaexerts lipid-lowering and insulin-sensitizing actions in the rat Journalof Ethnopharmacology 94(2-3) 251-259

Zaoui A Cherrah Y Alaoui K Mahassine N Amarouch H Hassar M

(2002) Effects of Nigella sativa fixed oil on blood homeostasis in ratJ Ethnopharmacol 79(1)23-26

Altan MF Kanter M Donmez S Kartal ME Buyukbas S (2007)Combination therapy of Nigella sativa and human parathyroidhormone on bone mass biomechanical behavior and structure instreptozotocin-induced diabetic rats Acta Histochemica-Elsevier109(4)304-314

Kaleem M Kirimani D Asif M Ahmed Q Bilqees B (2006) Biochemicaleffects of Nigella sativa L seeds in diabetic rats Indian J Exp Biol44(9)745-748

Page 4: Khoharo Et Al

7262019 Khoharo Et Al

httpslidepdfcomreaderfullkhoharo-et-al 44

Khoharo et al 13

Experimental Diabetes Int`l J Pharmacol2 104-109Ali BH(2004) The effects of Nigella Sativa oil on Gentamycin

Nephrotoxicity in rats Am J Chin Med 32(1) 49-55Le PM Benhaddou-Andaloussi A Elimadi A Settaf A Cherrah Y

Haddad PS(2004) The petroleum ether extract of Nigella sativaexerts lipid-lowering and insulin-sensitizing actions in the rat Journalof Ethnopharmacology 94(2-3) 251-259

Zaoui A Cherrah Y Alaoui K Mahassine N Amarouch H Hassar M

(2002) Effects of Nigella sativa fixed oil on blood homeostasis in ratJ Ethnopharmacol 79(1)23-26

Altan MF Kanter M Donmez S Kartal ME Buyukbas S (2007)Combination therapy of Nigella sativa and human parathyroidhormone on bone mass biomechanical behavior and structure instreptozotocin-induced diabetic rats Acta Histochemica-Elsevier109(4)304-314

Kaleem M Kirimani D Asif M Ahmed Q Bilqees B (2006) Biochemicaleffects of Nigella sativa L seeds in diabetic rats Indian J Exp Biol44(9)745-748