An Assessment of Source and dose-dependent Diabetes ...
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Journal of Clinical and Molecular Endocrinology ISSN 2572-5432 2021 Vol. 6 No. 3 :42 1 © Under License of Creative Commons Attribution 3.0 License | This article is available in: http://clinical-and-molecular-endocrinology.imedpub. iMedPub Journals ht tp://www.imedpub.com DOI: 10.36648/2572-5432.6.3.42 Research Article An Assessment of Source and dose- dependent Diabetes Ameliorang acvity of Ethanolic Extract of Nigella sava on Alloxan-Induced Diabec Rat Model Dilruba Akter 1 , Chandni Akter Rokeya 2 , Md. Rafat Tahsin 3 *, Ehfazul Haque 1 , Arifa Sultana 4 , Shaila Kabir 1 , Abu Asad Choudhury 1 , Jakir Ahmed Chowdhury 4 , Md. Shah Amran 1 1 Department of Pharmaceucal Chemistry, Faculty of Pharmacy, University of Dhaka, Dhaka, Bangladesh 2 Department of Pharmacy, University of Asia Pacific, Farmgate, Dhaka, Bangladesh 3 Department of Pharmaceucal Sciences, North South University, Dhaka, Bangladesh 4 Department of Pharmacy, University of Dhaka, Dhaka, Bangladesh Corresponding author: Md. Rafat Tahsin Tel : 01704592755 [email protected] Citation: Akter D, Rokeya CA, Tahsin Md.R, Haque E, Sultana A, et al (2021). An Assessment of Source and dose-dependent Diabetes Ameliorang acvity of Ethanolic Extract of Nigella sava on Alloxan-Induced Diabec Rat Model. J Clin Mol Endocrinol. 2021, 6:3.42 Introducon Type 1 Diabetes mellitus (T1DM), is a chronic autoimmune disease which have stemmed as a leading global health problem and affects people of all ages, genders and races [1]. According to an esmaon, around 5%–10% of adults worldwide are afflicted by this disorder and this will increase 20%–69% in the next 20 years [2,3]. Respecvely, the outbreak of diabetes among those aged between 20 to 79 years may be expected to increase 7.7%, constung 439 million by the year 2030 [4,5]. It is caused by complete or paral insulin deficiency which results in hyperglycaemia [6]. This elevaon in blood glucose levels has smulated the producon of reacve oxygen species (ROS), which cause cellular damage that promote the progression of acute and chronic complicaons including hypoglycemia, ketoacidosis, nonketoc hyperosmolar coma, diabec renopathy, nephropathy, autonomic neuropathy, microangiopathy, various organ failure and infecons [7-10]. Moreover, Diabetes mellitus can also be conjoined with cardiovascular risk factors such as hypertension, dyslipidemia and obesity [11]. Diabetes cannot be migated completely rather it must be kept under ght management [12]. This intricated condion might be controlled by changing diet, sedentary lifestyles and medicaons [13]. The most commonly used medicine to control diabetes include insulin and its derivaves, glucagon-like pepde-1 Abstract Metabolic disorder diabetes results from an alteraon of the secreon or acon of insulin. Nigella sava is a tradionally used specimen since ancient mes. We aimed to invesgate the hypoglycemic potenal of ethanolic extract of Nigella sava seed powder soluon both in a dose and source-dependent manner as well as to fathom out its safety profile so that this plant can be used to ameliorate diabetes. Diabetes was induced in the rat model via intraperitoneal injecon of alloxan (150 mg/kg). Ethanolic extract of T. Nigella sava was administered to rats’ belonged to different groups. Blood glucose levels were assessed periodically and the safety profiles were evaluated through assessment of SGOT, SGPT, creanine, and lipid profiles aſter sacrificing the animals. It has been evidenced that Nigella sava possesses an-diabec acvity. Furthermore, the extract is capable of reversing the disturbed pathological state towards a healthy status. Besides, these therapeuc consequences possess dose-dependent potenality (p>0.05), further a noteworthy source dependent (p> 0.01) response were experienced. It may confer that the inconsistency associated with the remedial impacts between 2 same doses belonged to two disnct sources are due to accuracy of lab-based preparaon, geographic area of culvaon, and also the season of collecon. Apart from that, the visual and stascal inspecons have evidence that the medium and the high dose are imparng almost indisnguishable therapeuc effects. Presumably, the reason lies beneath the receptor saturaon issue. Keywords: Nigella sava, alloxan, hypoglycemic effect, dose dependency, source dependency, safety profile Received: April 16, 2021; Accepted: April 30, 2021; Published: May 07, 2021
Transcript of An Assessment of Source and dose-dependent Diabetes ...
Journal of Clinical and Molecular EndocrinologyISSN 2572-5432
2021Vol. 6 No. 3 :42
1© Under License of Creative Commons Attribution 3.0 License | This article is available in: http://clinical-and-molecular-endocrinology.imedpub.
iMedPub Journalshttp://www.imedpub.com
DOI: 10.36648/2572-5432.6.3.42
Research Article
An Assessment of Source and dose-dependent Diabetes Ameliorating activity
of Ethanolic Extract of Nigella sativa on Alloxan-Induced Diabetic Rat Model
Dilruba Akter1, Chandni Akter Rokeya2, Md. Rafat Tahsin3*, Ehfazul Haque1, Arifa Sultana4, Shaila Kabir1, Abu Asad Choudhury1, Jakir Ahmed Chowdhury4, Md. Shah Amran1
1 DepartmentofPharmaceuticalChemistry,FacultyofPharmacy,UniversityofDhaka,Dhaka,Bangladesh
2 Department of Pharmacy, University ofAsiaPacific,Farmgate,Dhaka,Bangladesh
3 DepartmentofPharmaceuticalSciences, North South University, Dhaka, Bangladesh
4 Department of Pharmacy, University of Dhaka,Dhaka,Bangladesh
Corresponding author: Md.RafatTahsin
Tel : 01704592755
Citation:AkterD,RokeyaCA,TahsinMd.R,HaqueE,SultanaA,etal(2021).AnAssessmentofSourceanddose-dependentDiabetesAmelioratingactivityofEthanolicExtractofNigellasativaonAlloxan-InducedDiabeticRatModel.JClinMolEndocrinol.2021,6:3.42
IntroductionType 1 Diabetes mellitus (T1DM), is a chronic autoimmune diseasewhichhavestemmedasaleadingglobalhealthproblemandaffectspeopleofallages,gendersandraces[1].Accordingto an estimation, around 5%–10% of adults worldwide areafflicted by this disorder and this will increase 20%–69% inthenext20years [2,3].Respectively, theoutbreakofdiabetesamongthoseagedbetween20to79yearsmaybeexpectedtoincrease7.7%,constituting439millionbytheyear2030[4,5].Itiscausedbycompleteorpartialinsulindeficiencywhichresultsinhyperglycaemia[6].Thiselevationinbloodglucoselevelshasstimulatedtheproductionofreactiveoxygenspecies(ROS),which cause cellular damage that promote the progression of acute andchroniccomplicationsincludinghypoglycemia,ketoacidosis,nonketotic hyperosmolar coma, diabetic retinopathy,
nephropathy, autonomic neuropathy, microangiopathy, various organfailureandinfections[7-10].Moreover,Diabetesmellituscan also be conjoined with cardiovascular risk factors such ashypertension,dyslipidemiaandobesity[11].
Diabetescannotbemitigatedcompletelyratheritmustbekeptundertightmanagement[12].Thisintricatedconditionmightbecontrolledbychangingdiet,sedentarylifestylesandmedications[13]. The most commonly used medicine to control diabetesinclude insulin and its derivatives, glucagon-like peptide-1
AbstractMetabolicdisorderdiabetesresultsfromanalterationofthesecretionoractionofinsulin.Nigella sativaisatraditionallyusedspecimensinceancienttimes.Weaimed to investigate thehypoglycemicpotentialofethanolic extractofNigella sativaseedpowdersolutionbothinadoseandsource-dependentmanneraswellas to fathomout its safetyprofileso that thisplantcanbeused toamelioratediabetes.Diabeteswasinducedintheratmodelviaintraperitoneal injectionofalloxan(150mg/kg).EthanolicextractofT. Nigella sativawasadministeredtorats’belongedtodifferentgroups.BloodglucoselevelswereassessedperiodicallyandthesafetyprofileswereevaluatedthroughassessmentofSGOT,SGPT,creatinine,andlipidprofilesaftersacrificingtheanimals.IthasbeenevidencedthatNigella sativa possesses anti-diabetic activity. Furthermore, the extract is capable ofreversing the disturbed pathological state towards a healthy status. Besides,these therapeutic consequencespossessdose-dependentpotentiality (p>0.05),furtheranoteworthysourcedependent(p>0.01)responsewereexperienced.Itmayconferthattheinconsistencyassociatedwiththeremedialimpactsbetween2samedosesbelongedtotwodistinctsourcesareduetoaccuracyoflab-basedpreparation, geographic area of cultivation, and also the season of collection.Apart from that, the visual and statistical inspections have evidence that themedium and the high dose are imparting almost indistinguishable therapeuticeffects.Presumably,thereasonliesbeneaththereceptorsaturationissue.
Keywords: Nigellasativa,alloxan,hypoglycemiceffect,dosedependency,sourcedependency,safetyprofile
Received: April16,2021; Accepted: April30,2021;Published: May 07, 2021
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receptor agonists, thiazolidinediones (TZDs), sulfonylureas,amylin analogues, biguanides, and glucosidase inhibitor [14-17].Currentmedicamentsforthetreatmentoftype2diabetesmellitus have detrimental effects, and sometimes, they arereported for being ineffective in patientwith chronic diabetes[18]. Furthermore, no medication can intensify both insulinsensitivityandsecretionsimultaneously.
Medicinal plants have attained wide attention from scientistsandhavebeendeemedtobeabeneficialadjuvantagentasanoral antidiabetic andhypolipidemic drug,mostly in developingcountries,duetotheirintegratedeffects,rareornosideeffectsand lower cost. [19,20]. Besides that, Nigella sativa has alsobeen thought to be safer among 1000 different antidiabeticmedicinal plants compared to oral antidiabetic drugs [21].Nigellasativaisanannualherbaceousplantspices,belongingtothe familyRanunculaceawhich canbe foundmostly inMiddleEasterncountries includingPakistan, India, Italy, IndonesiaandAfghanistan [22]. It ismost commonly known as “black seed”,“black cumin” or “kalajeera”. Different forms of Nigella sativalikeextract,oil,andpowderhavebeenemployedintraditionalmedicine to treat several illnesses such as fever, diarrhea,bronchitis, cough, hemorrhoids, gastrointestinal, hepatitis andtapeworm disease [23-25]. It is also known as an immunityenhancer. Nigella sativa extract has been demonstrated topossessimmunopotentiating[26],antioxidant[27],antitumoral[28],antidiabetic[32],anti-proliferative[30],antimicrobial[30],antiasthmatic[33],antihypertensive[32],antiparasitic[31],anti-fertility [33], hypolipidemic [29], anti-inflammatory [29], andanti-pyretic [29] activities. Screening for uniquephytochemicalconstituents from Nigella Sativa has earned researcher’sattention because of its ameliorative effects. The ameliorativeeffectsofNigellaSativaaremainlyconferredtothymoquinone,whichisoneofthemajorbioactivecompoundsthatwasunveiledtohaveadefensiveeffectagainstdiabetes[34].PreviousstudiesstatedthatthymoquinoneintroducedamarkeddecreaseinFastingBloodGlucoselevelandanoticeableincreaseininsulinlevelsinrats[35].Besidesthymoquinine,theothercompounds,namelythymol,thymohydroquinone, dithymoquinone, nigellone, alpha-hederin,flavonoids,alkaloids,volatile(0.40%–0.45%)andnon-volatile(32%–40%)oils,carbohydrates(31.0%–33.9%),protein(16.00%–20.85%),fibre (5.50–7.94%), tannins, saponins, minerals such as iron,potassium,magnesium, calcium, zinc and copper (1.79%–3.44%),vitaminAandC,niacin,pyridoxine,thiamine,folateandfattyacidswerealsofoundtohavetherapeuticproperties[36,37].Additionally,kalonjiwaspresentedtohavenocausticsideeffectsortoxicologicaleffectsinbothhumanandanimalmodels[38].
The modern drugs used in the management of diabetes isheavily overpriced, andalsoburdenandunreachable formasspopulation. The aim of our current study is to investigate theantidiabeticandhypolipidemiceffectofNigellasativainadoseandsourcedependentmanneraswellasrelativeadverseeffectsand safetyprofile studyon liver andkidney in alloxan-induceddiabeticratmodel.
Method MaterialsWeusedhighestanalyticalgradechemicalsinourcurrentstudy.Dried Nigella sativa seeds were bought from Allahrdan Shop,
Banasree,andDhaka.Humalyzer3000(Semi-AutomatedClinicalChemistry Analyzer of Medigroup Asia limited, Combodia)was employed to measure the blood parameters of rodents.Glucometer of Alere GI of Alere Inc, USA was instituted fromShahbag, Dhaka, Bangladesh. All blood parameter analyzingkitswere received fromPlasmatic Laboratory Product Limited.A chemical agent (alloxan)was purchased fromSigmaAldrich,Germany.
Extraction ProcedureFirstly,Nigellasativaseedswerethoroughlywashedanddriedinsunlightforfewdays.Afterwards,thedriedseedswerecrushedintopowder.Then,thedrypowderedmaterialsweresoakedinmethanolandkeptfor14dayswithoccasionalvigorousstirringand shaking. Subsequently, the extract was filtered by usingWhatmanNo.1Filterpaper.Toreducethevolumefromarotaryevaporator at low temperature andpressure thefiltrate liquidwastakenforthenextstep.
Experimental Design and Animal Handling Wisteralbinothirtyadultmaleratswereobtainedfromtheanimalunit,Jahangirnagar University, Department of Pharmacy, Dhaka, Bangladesh.Theywereincarceratedindividuallyinstainlesssteelcagesat12±1hlight/darkcycleunderthecontrolledtemperature(25◦C) in the Institute of Nutrition & Food Science, UniversityofDhaka. The ratswere givenwith a standard pellet diet andwateradlibitum.Beforeinitiatingtheanalysis,theratswereinhousedthereforacclimatization.Thebodyweightofeachrathasbeenweighedafterward.Theanimalsweredividedinto6groupswhereanevendivisionofrodentsaspertheirbodyweighthasbeentakenplace,andeachgroupincluded5rats.
Group1:NormalControl
Group2:DiabeticControl
Group3:LowDose(100mg/kgbodyweight)
Group4:MediumDose(400mg/kgbodyweight)
Group5:HighDose(750mg/kgbodyweight)
Group6:CommercialPreparation(400mg/kgbodyweight)
The rats were fed normal food and water twice daily in thefirst two weeks without initiating diabetes. A chemical agent,alloxan(150mg/kgbodyweight),wasinjectedintoallgroupsviaintraperitonealroutefordiabeticinductionexceptnormalcontrolgrouponthe14thday.After72hours,thebloodsugarlevelwasscrutinized.Ithasbeenobservedthatdiabeteswasincitedinallratsassociatedtogroups2-5andtreatmentwascommencedonthe18thday,whichwas continued for twenty-eightdays. Thebloodglucoselevelwasexaminedonceineveryweek.Thedosesweregivenbyoralrouteofadministration.
Statistical AnalysisThe discoveries of all study parameters associate to severalgroupsweredelineatedasmean±SD.“OneWayAnovaTest”of SPSS 16” software was used to explore the inter-groupdiscrepancies in results to trace the statistical significance.Here,thestatisticalsignificancelevelwassetata‘p’valueof
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p<0.05. On the other hand, high statistical significance wassetat'p'valueofp<0.01.Intermsofresults,theinter-groupdifferentiabilitywasthoughtstatisticallysignificantandhighlysignificantwhenthep-valuewasseenlessthan0.05and0.01respectively.
ResultsChange in body weightsThepre-treatment&posttreatmentbodyweight(gram)ofratsbelongedtodifferentgroupsareshowninFigure1
Change in blood glucose levelThebloodglucoselevel(mmol/dl)ofalltestgroupfromday1today42areexpressingbelowinmentionedgraphinFigure2.
Safety Profile Study (Liver function test)TheSGOTlevelofallratsbelongedto6groupsaredenotingtheconditionofliverisshowninbelowgraphFigure3.
The levelofSGPTofallratsthatbelongedto6groupsisexpressingtheconditionofliverareexpressingviatheblowshowngraphFigure4.
Safety Profile Study (Kidney functioning Test)ThebelowmentionedvaluesconcerningthelevelofCreatinine(md/dl)ofratsbelongedto6groupasarequirementofmeasuringthekidneyfunctioningtestarepresentinginFigure5
Safety Profile Study (Lipid Profile)The level of Total Cholesterol Level of all rats belonged to 6groupsareexpressinginbelowFigure6.
Safety Profile Study (Lipid Profile)ThelevelofHDLlevel(mg/dl)ofallratsbelongedto6groupsarepresentinginbelowdrawngraph,Figure7.
Safety Profile Study (Lipid Profile)ThebelowmentionvaluesregardingthelevelofLDLlevel(mg/dl)ofratsbelongedto6groupsarepresentinginbelow,Figure8.
Figure 1 Comparision between the average body weight (mean±standard deviation) of rats belong to 6 groups before starting theexperimentandjustbeforesacrifice.C =Control,A=Alloxan,A+L.D=Alloxan+LowDose,A+M.D=Alloxan+MediumDose,A+H.D=Alloxan+HighDose,A+C.P=Alloxan+Commercialpreparation
Figure 2 Bloodglucoselevelofsixgroupsfromdayzerotodayforty-two.Thedatawereexpressedasmean±standarddeviation.*Expressesthesignificantchange,**Expressingthehighsignificantchange.C=Control,A=Alloxan,A+L.D=Alloxan+LowDose,A+M.D=Alloxan+MediumDose,A+H.D=Alloxan+HighDose,A+C.P=Alloxan+Commercialpreparation
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Figure 3 CamparisionofSGOTlevel(U/L)ofrats,belongedto6groupsatdayforty-twoaftersacrificeC=Control,A=Alloxan,A+L.D=Alloxan+LowDose,A+M.D=Alloxan+MediumDose,A+H.D=Alloxan+HighDose,A+C.P=Alloxan+Commercialpreparation.*Expressesthesignificantchange,**ExpressingtheHighhighsignificantchange.
Figure 4 CamparisionofSGPTlevel(U/L)ofrats,belongedto6groupsatdayforty-twoaftersacrifice.C=Control,A=Alloxan,A+L.D=Alloxan+LowDose,A+M.D=Alloxan+MediumDose,A+H.D=Alloxan+HighDose,A+C.P=Alloxan+Commercialpreparation.*Expressesthesignificantchange,**ExpressingtheHighhighsignificantchange.
Figure 5 CamparisionofCreatininelevel(mg/dl)ofrats,belongedto6groupsatdayforty-twoaftersacrifice.C=Control,A=Alloxan,A+L.D = Alloxan+Low Dose, A+M.D = Alloxan+Medium Dose, A+ H.D =Alloxan+High Dose, A+C.P = Alloxan+Commercialpreparation.*Expressesthesignificantchange,**ExpressingtheHighhighsignificantchange.
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Figure 6 CamparisionofTotalCholesterolLevel(mg/dl)ofrats,belongedto6groupsatdayforty-twoaftersacrifice.C=Control,A=Alloxan,A+L.D=Alloxan+LowDose,A+M.D=Alloxan+MediumDose,A+H.D=Alloxan+HighDose,A+C.P=Alloxan+Commercialpreparation.*Expressesthesignificantchange,**ExpressingtheHighhighsignificantchange.
Figure 7 CamparisionofHDLLevel(mg/dl)ofrats,belongedto6groupsatdayforty-twoaftersacrificeC=Control,A=Alloxan,A+L.D=Alloxan+LowDose,A+M.D=Alloxan+MediumDose,A+H.D=Alloxan+HighDose,A+C.P=Alloxan+Commercialpreparation.*Expressesthesignificantchange,**ExpressingtheHighhighsignificantchange.
Figure 8 ComparisionofLDLLevel(mg/dl)ofratsbelongto6groupsatdayforty-twobeforeaftersacrifice.C=Control,A=Alloxan,A+L.D=Alloxan+LowDose,A+M.D=Alloxan+MediumDose,A+H.D=Alloxan+HighDose,A+C.P=Alloxan+Commercialpreparation.*Expressesthesignificantchange,**ExpressingtheHighhighsignificantchange.
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Figure 9 Camparision of Triglyceride Level (mg/dl) of rats, belonged to 6 groups at day forty-two after sacrifice. C = Control, A =Alloxan,A+L.D=Alloxan+LowDose,A+M.D=Alloxan+MediumDose,A+H.D=Alloxan+HighDose,A+C.P=Alloxan+Commercialpreparation.*Expressesthesignificantchange,**ExpressingtheHighhighsignificantchange.
Safety Profile Study (Lipid Profile)ThebelowmentionvaluesregardingthelevelofTriglyceridelevel(mg/dl)ofratsbelongedto6groupsaregivenbelowFigure9.
DiscussionBody Weight MeasurementTheBodyweightofratswasabatedineverysinglegroupwhencompared to negative control. Herein, the reduction of bodyweightwashighest indiabetic control group.On the contrary,intreatmentgroups,withtheaugmentationofdose,depletionwaslessened.Incommercialpreparationtreatedgroups,lowestreductioninbodyweightwasremarked.
Blood Glucose LevelDiabeticinducedratsencountered anincreasedbloodsugarlevelthanallothergroups.Therewasnosignificantreductioninthebloodglucose levelwasseenat lowdose.Whereas, thehighand medium dose produce significantly decline (p<0.05) inbloodglucoselevel.Furthermore,incommercialpreparation,a high statistically significant fall (p<0.01) in blood glucoselevelwasdetected. Yet, all the groupshave thepotentialityto lower the elevated blood sugar level in comparison todiabeticgrouprats.Conversely,thebloodglucoselevelofratsappertain togroup1 (NormalControlgroup)wasauditedtobenormal.
Liver and Kidney Functioning TestThediabeticinducedgroupratsexperiencedhighestlevelofSGOT,SGPTandCreatininethanallothergroups.Thismaybeduetodeleteriouseffectofalloxan.Ontheotherhand,itwasinspectedthat the SGOT, SGPT and Creatinine levels were significantlylowered (p<0.05) at medium and high dose respectively.Contrarily,atlowdoselevelnullsignificancewasobservedwhencomparedwithgroup2(p>0.05).Furthermore,SGOT,SGPTandCreatininelevelsweresharply(p<0.01)decreasedincommercialpreparationincomparisontodiabeticgroup.
Lipid ProfileTheseedsofNigellasativawerefruitfulinloweringtriglycerides,LDL-Candtotalcholesterol intheserumatalldose levels.Thereductionshowedstatisticallysignificantincaseofmediumandhighdoseandincaseofcommercialpreparationhighstatisticalsignificancewasobserved.HDL-Clevelincreasedatalldoselevelswhen compared to the diabetic induced group. There was nosignificantincreaseintheHDL-Clevelwasspottedatlowdose.However,asignificantincreasewasmarkedatmediumandhighdose and high statistical significancewas found in commercialpreparation.
From the above discussion, it can be expressed that thecommercialpreparationcanreducethebloodsugarlevelmoreadroitly than that of experimental lab-based preparations.Several reasonsmay be accountable for the lifted potentialityof commercial preparation for example: the season of seedcollection,orgeologicalareaofcultivationandalsocanbesomeerrors during preparations. Apart from that, the response ofrat’sbelongedtomediumandhighdosesresembletobealmostsimilar fromboth statistical and visual inspection. Itmay ariseduetoreceptorsaturation.
ConclusionEthanolic extract of Nigella sativa exhibit dose and source-dependent activity against diabetes. The commercialpreparation imparted the best effects than that of all othergroups.Mostlikely,severalreasonsfore.g;error-freelab-basedpreparations, geographical area of cultivation, or the seasonof seed collectionmay lie behind this deviation. Furthermore,itwasalso investigated that this seedextract can improve thealtered pathological condition of alloxan-induced diabetic rats.Fromtheviewpointofthesafetystudy,itcanbeterminatedthatthedosesofethanolicextractofNigellasativawerenottoxictotheratsanddidnotsignificantlyalter thepathological state inhealthyindividuals.Hence,ItmightthereforebepresumedthatethanolicextractofNigellasativacouldbeeffectivelyusedasanalternativetherapyinthepreventionandtreatmentofdiabetes
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Reference1. Rabinowe SL, Eisenbarth GS (1984) Type I diabetes mellitus: a
chronic autoimmune disease?. Pediatric Clinics of North America.31:531-43.
2. AlqurashiKA,AljabriKS,BokhariSA (2011)PrevalenceofdiabetesmellitusinaSaudicommunity.AnnalsofSaudimedicine.31:19-23.
3. AlotaibiA,PerryL,GholizadehL,Al-GanmiA(2017) IncidenceandprevalenceratesofdiabetesmellitusinSaudiArabia:Anoverview.Journalofepidemiologyandglobalhealth.7:211-8.
4. Shaw JE, Sicree RA, Zimmet PZ (2010) Global estimates of theprevalenceof diabetes for 2010and2030.Diabetes researchandclinicalpractice.87:4-14.
5. Alberti KG, Zimmet P, Shaw J (2007) International DiabetesFederation: a consensus on Type 2 diabetes prevention. DiabeticMedicine.24:451-63.
6. BastakiA(2005)Diabetesmellitusanditstreatment.InternationaljournalofDiabetesandMetabolism.13:111.
7. VanessaFiorentinoT,PriolettaA,ZuoP,FolliF(2013)Hyperglycemia-induced oxidative stress and its role in diabetes mellitus relatedcardiovascular diseases. Current pharmaceutical design. 19:5695-703.
8. AsmatU, Abad K, Ismail K (2016)Diabetesmellitus and oxidativestress—Aconcisereview.Saudipharmaceuticaljournal.24:547-53.
9. PieroMN.HypoglycemiceffectsofsomeKenyanplantstraditionallyused in management of diabetes mellitus in eastern province(Doctoraldissertation,Mscthesis,KenyattaUniversity).
10.AronsonD.(2008)Hyperglycemiaandthepathobiologyofdiabeticcomplications. Cardiovascular diabetology: Clinical, metabolic andinflammatoryfacets.45:1-6.
11.HamdanA,HajiIdrusR,MokhtarMH(2019)Effectsofnigellasativaon type-2 diabetes mellitus: a systematic review. Internationaljournalofenvironmentalresearchandpublichealth.16:4911.
12.JaberLA,HalapyH,FernetM,TummalapalliS,DiwakaranH.(1996)Evaluationofapharmaceuticalcaremodelondiabetesmanagement.AnnPharmacother,30:238–243.
13.Clement S (1995) Diabetes self-management education. DiabetesCare,18:1204–1214.
14.WolvertonD,BlairMM(2017)Fractureriskassociatedwithcommonmedications used in treating type 2 diabetes mellitus. AmericanJournalofHealth-SystemPharmacy.74:1143-51.
15.Bösenberg LH, Van Zyl DG (2008) The mechanism of action oforal antidiabetic drugs: a review of recent literature. Journal ofEndocrinology,MetabolismandDiabetesofSouthAfrica.13:80-8.
16.QaseemA,HumphreyLL,SweetDE,StarkeyM,ShekelleP. (2012)Oralpharmacologictreatmentoftype2diabetesmellitus:aclinicalpracticeguidelinefromtheAmericanCollegeofPhysicians.Annalsofinternalmedicine.156:218-31.
17. InzucchiSE,BergenstalRM,BuseJB,DiamantM,FerranniniE,etal.(2015)Managementofhyperglycemia in type2diabetes, 2015: apatient-centeredapproach:update toapositionstatementof theAmericanDiabetesAssociationandtheEuropeanAssociationfortheStudyofDiabetes.Diabetescare.38:140-9.
18.Cohen A, Horton ES (2007) Progress in the treatment of type 2diabetes: new pharmacologic approaches to improve glycemiccontrol.Currentmedicalresearchandopinion.23:905-17.
19.Derosa G, Putignano P, Bossi AC, Bonaventura A, Querci F et al.(2011)Exenatideorglimepirideaddedtometforminonmetaboliccontrol and on insulin resistance in type 2 diabetic patients.Europeanjournalofpharmacology.666:251-6.
20.Pan SY, Zhou SF, Gao SH, Yu ZL, Zhang SF et al. (2013) Newperspectives on how to discover drugs from herbal medicines:CAM'soutstandingcontributiontomoderntherapeutics.Evidence-BasedComplementaryandAlternativeMedicine.
21.AhmadA,HusainA,MujeebM,KhanSA,NajmiAK,etal.(2013)Areview on therapeutic potential of Nigella sativa: Amiracle herb.AsianPacificjournaloftropicalbiomedicine.3:337-52.
22.Mathur ML, Gaur J, Sharma R, Haldiya KR (2011) AntidiabeticpropertiesofaspiceplantNigellasativa. JournalofEndocrinologyandMetabolism.1:1-8.
23.Ramadan,M.F. (2007)Nutritionalvalue, functionalpropertiesandnutraceutical applications of black cumin (Nigella sativa L.): Anoverview.Int.J.FoodSci.Technol.,42,1208–1218.
24.Ali, B.H, Blunden, G. (2003) Pharmacological and toxicologicalpropertiesofNigellasativa.Phytother.Res.17,299–305.
25.HoucherZ, BoudiafK, Benboubetra M, HoucherB. (2007) Effectsof methanolic extracts and commercial oil of Nigella sativa L. onbloodglucoseandantioxidantcapacity inalloxan-induceddiabeticrats. Pteridines. 18: 8–18.
26.Haq A, Lobo PI, Al-Tufail M, Rama NR, Al-Sedairy ST. (1999) Immunomodulatory effect of Nigella sativa proteinsfractionated by ion exchange chromatography. Int JImmunopharmacol. 21: 283–95.
27.Burits M, Bucar F. (2000). Antioxidant activity of Nigella sativaessentialoil.Phytotherapyresearch.14:323-8.
28.WorthenDR,GhoshehOA,CrooksPA.(1998)Theinvitroanti-tumoractivityofsomecrudeandpurifiedcomponentsofblackseed,NigellasativaL.Anticancerresearch.18:1527-32.
29.MeralI,YenerZ,KahramanT,MertN.(2001)EffectofNigellasativaon glucose concentration, lipid peroxidation, anti-oxidant defencesystemandliverdamageinexperimentally-induceddiabeticrabbits.JournalofVeterinaryMedicineSeriesA.48:593-9.
30.HannanA,SaleemS,ChaudharyS,BarkaatM,ArshadMU. (2008)Anti-bacterial activity of Nigella sativa against clinical isolatesof methicillin resistant Staphylococcus aureus. J Ayub Med CollAbbottabad.20:72-4.
31.Houghton PJ, Zarka R, de las Heras B, Hoult JR. (1995) Fixed oilof Nigella sativa and derived thymoquinone inhibit eicosanoidgeneration in leukocytesandmembrane lipidperoxidation.Plantamedica.61:33-6.
32.Farkhondeh T, Samarghandian S, Borji A. (2017) An overview oncardioprotective and anti-diabetic effects of thymoquinone. AsianPacificjournaloftropicalmedicine.10:849-54.
33.Keshri G, Singh MM, Lakshmi V, Kamboj VP (1995) Post-coitalcontraceptiveefficacyof theseedsofNigella sativa in rats. IndianJournalofPhysiologyandPharmacology.39:59.
34.KhaderM,EcklPM(2014)Thymoquinone:anemergingnaturaldrugwithawiderangeofmedicalapplications. Iranian journalofbasicmedicalsciences.7:950.
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35. Abdelrazek H, Kilany OE, Muhammad MA, Tag HM, Abdelazim AM(2018)Blackseedthymoquinoneimprovedinsulinsecretion,hepaticglycogen storage, and oxidative stress in streptozotocin-induceddiabeticmalewistarrats.Oxidativemedicineandcellularlongevity.
36.Daryabeygi-Khotbehsara R, Golzarand M, Ghaffari MP, DjafarianK (2017) Nigella sativa improves glucose homeostasis and serumlipids in type 2 diabetes: A systematic review andmeta-analysis.Complementarytherapiesinmedicine.35:6-13.
37.Monnier L, Colette C, Dunseath GJ, Owens DR (2007) The loss ofpostprandial glycemic control precedes stepwise deterioration offastingwithworseningdiabetes.Diabetescare.30:263-9.
38.Yimer EM, Tuem KB, Karim A, Ur-Rehman N, Anwar F (2019)Nigella sativa L.(black cumin): a promising natural remedy forwide range of illnesses. Evidence-Based Complementary andAlternativeMedicine.
