Indian Journal of Pharmaceutical and Biological Research (IJPBR)

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1 Indin J. Phrm. Biol. Res. 216; 4(1):63-73 Originl Reserh Artile Neuroprotetive Effet of Cinmomum zeylnium in streptozotoin indued dietes in Mie Joshi Vndn *, Kumr Arun, Kothiyl Preeti CODEN (USA): IJPB7 ISSN: Indin Journl of Phrmeutil nd Biologil Reserh (IJPBR) Journl homepge: Deprtment of Phrmeutil Sienes, Shri Guru Rm Ri Institute of Tehnology & Sienes, Ptel Ngr, Dehrdun 2481, Uttrkhnd, Indi ARTICLE INFO: ABSTRACT Artile history: Bkground: Dietes is reognized s one of the leding uses of moridity nd mortlity & Reeived: 15 Deemer 215 representing s n emerging glol epidemi worldwide. Dietes nd stroke oth re the onditions Reeived in revised form: whih shre vrious ommon threts. A ptient with Dietes hs higher risk of stroke s ompred to 3 Mrh 216 non Dietis. Dietes nd stroke oth ffets the lood vessels. There re severl iohemil Aepted: 1 Mrh 216 pthwys whih re responsile for the developments of vsulr omplitions due to hyperglyemi. Aville online: 3 Mrh 216 Thus prevention nd tretment of dietes nd stroke n redue the risk of vrious vsulr diseses. Cinnmomum zeylnium hs een used for the tretment of dietes sine long time. Cinnmomum Keywords: zeylnium rih in phenoli ontents (ntioxidnts) hve een identified s mjor tive omponent Dietes mellitus, exhiiting ntioxidnt, nd neuroprotetive effets. The present study evlute the neuroprotetive effet Hyperglyemi, of Cinnmomum zeylnium in streptozotoin indued dietes in mie nd experimentlly indued Oxidtive stress, glol ererl ishemi/reperfusion injury in mie. Mterils nd methods: Swiss lino mie (mle) Cinnmomumzeylnium, weighing 2-3 g were rndomized into eight groups. Dietes ws indued y dministering Streptozotoin streptozotoin (65 mg/kg, i.p).strting from seven dys fter streptozotoin injetion, insulin nd Cinnmomum zeylnium were dministered for 3 weeks. Serum gluose level nd ody weight were mesured weekly. Neuroprotetive tivity ws rried out y glol ererl ishemi on swiss lino mie y rotid rtery olusion for 1 min followed y 24 hr. reperfusion. Mesurement of Triglyerides, Mlondildehyde, ererl infrt size nd glutthione level ws rried out t the end of the study. Results: After 21 dys of tretment with Cinnmomum zeylnium (75 mg/kg, 15 mg/kg nd 3 mg/kg, p.o) signifint inrese in ody weight nd glutthione level nd signifint redution in serum gluose level, triglyerides, MDA levels nd ererl infrt size ws oserved s ompred to dieti ontrol nd dieti+ stroke group. Conlusion: The present study onludes tht Polyphenoli frtion of Cinnmomum zeylnium not only ttenutes the dietes ut lso reverse the ererl infrtion in mie through its neuroprotetive tions nd thus Cinnmomum zeylnium my serves s new therpeuti lterntive for mngement of rin dmge ssoited with type-1 dietes. Introdution Dietes is reognized s one of the leding uses of moridity nd mortlity & representing s n emerging glol epidemi worldwide.[1] It is disorder hrterized y resistne to the tion of insulin, insuffiient insulin seretion, or oth. The linil mnifesttion of these disorders is hyperglyemi. Symptoms of mrked hyperglyemi inlude polyuri, polydipsi, weight loss, sometimes with polyphgi, nd lurred vision. Impirment of growth nd suseptiility to ertin infetions my lso ompny hroni hyperglyemi.[2] Hyperglyemi is key determinnt of vsulr omplitions of dietes nd there is extensive evidene showing tht oth ute nd hroni hyperglyemi hs deleterious effet. Hyperglyemi ontriutes to the development of vsulr omplitions through severl mehnisms: tivtion of the polyol nd hexosmine pthwys, tivtion of protein kinse C, inresed oxidtive stress, inresed prodution of dvned glytion end-produts, inresed synthesis of growth ftors, ytokines nd ngiotensin II.[3] These ftors n, in turn, indue diffuse endothelil dysfuntion nd ontriute to the progressive development of miro- nd mrovsulr omplitions.[4] Stroke is long term omplition of dietes. Dietes nd stroke oth re the onditions whih shre vrious ommon threts. A ptient with Dietes hs higher risk of stroke s ompred to non Dietis.[5] Dietes nd stroke oth ffets the lood vessels nd oth re ssoited with other risk ftors suh s hypertension nd dyslipidemi. High lood pressure inreses the risk of stroke.[6] Oxidtive stress plys key role in rin dmge fter ererl ishemi.when n imlne our either y * Corresponding Author: Vndn Joshi, Deprtment of Phrmology, Shri Guru Rm Ri Institute of Tehnology & Sienes, Ptel Ngr, Dehrdun, Indi. 63

2 Joshi et l. / Indin J. Phrm. Biol. Res., 216; 4(1):63-73 inresing free rdils or deresed ntioxidnt defene, the umultion of free rdils is known s the stte of oxidtive stress.[7] After ishemi, n exess of ytosoli free C ++ due to exitotoxiity my overlod the mitohondril proton iruit, whih leds to filure in oxidtion together with inresed ROS prodution.[8] Overprodution of ROS y mitohondri uses the impirment of the ETC, whih leds to deresed ATP prodution, inresed formtion of free rdils. In this study we investigted the ntidieti s well s neuroprotetive effet of Cinnmomum zeylnium in dieti mie. Mny syntheti drugs protet ginst oxidtive dmge, ut they hve side effets. An lterntive solution to the prolem is to onsume nturl ntioxidnts from food supplements nd trditionl mediines. Hene tremendous input is mde worldwide, in serh of the ntioxidnt rih herl plnts to omt diseses. In this study innmon rk extrt ws used s test drug in mie. As per the previous reports it n e onluded tht the extrts of Cinnmon rks exhiited higher ntioxidnt tivity thn other prts of innmon nd ethnol is the est solvent to otin the min ntioxidnt onstituents. All these findings indite tht Cinnmon extrts possess ntioxidnt tivity.[9] Antioxidnt tivity of innmon is due to phenoli ompound suh s hydroxyinnmldehyde, hydroxyinnmi id present in the innmon extrt t s svenger of peroxide rdil nd prevents oxidtive dmge. A pronthoynidine found in Cinnmomum zeylnium i.e innmtnnin B1 exhiit ntioxidnt tivity. It is n tive ompound whih inhiit lipid peroxidtion nd lso n tive svenger of 1,1- diphenyl-2-pirylhydrzyl (DPPH) rdils.[1] Antidieti nd ntioxidnt tivity of innmon ws investigted y the indution of dietes mellitus nd glol ererl ishemi reperfusion injury in mie. Mteril nd methods Prourement of Plnt Cinnmomum zeylnium plnt ws proured from ptnjli hridwr from the month of pril. Brk of the plnt ws olleted from the lol mrket of dehrdun. Plnt smple ws uthentited from Forest Reserh Institute (FRI) Dehrdun. Prourement of drug nd hemils Insulin ws proured from Shri mehent indiresh hospitl, Dehrdun. Prourement of Animls Swiss lino mie (mle) weighing 2-3 g ws proured in the niml house fility of Shri Guru Rm Ri Institute of Tehnology nd Sienes, Ptel Ngr, Dehrdun. Animls will e limtized in the niml house fility of deprtment nd housed in polypropylene ges with husk edding (renewed every 48 h), under 12:12 h light drk yle t 25 C ± 5 C. nd will e fed with stndrd Commeril pellet nd wter d liitum.the Experimentl protool ws pproved y Institutionl Animl Ethil Committee (M.PH/IAEC/1/214/ECC-12 ) nd re of nimls ws s per guidelines of Committee for the purpose of Control nd Supervision of Experiments on Animls (CPCSEA). Extrtion of Polyphenoli frtion of Cinnmomum zeylnium Brk 5 g of dried rk powder ws extrted for 56 hrs with (1ml) ethnol y hot ontinous perlotion method in Soxhlet pprtus. After the effetive extrtion,solvent were onentrted using rotry flsh evportor nd wter ws removed y evported to dryness on hot wter th to yield soxhlet rude extrt. The presene of polyphenol ws onfirmed y ferri hloride test for tnnins. Addition of ferri hloride solution solution to C.zeylnium extrt gve luish-lk olour, onforming the presene of polyphenol (tnnins) in the extrt. Indution of Type-I Dietes Mellitus with STZ A single dose of streptozotoin (65 mg/kg) prepred in itrte uffer (ph 4.5,.1 M) ws dministered intrperitonilly to overnight fsted mie to indue dietes in ll the group exept ontrol group. All the mie were llowed free ess to wter, pllet diet nd mintined t room temperture in polypropylene ges.stz treted mie were lso fed with gluose solution(1%) for 12 hr to void hypoglyemi. Rts hving serum gluose more thn 25 mg/dl fter 72 hrs of indution were onsidered dieti nd seleted for further study. Experimentl Protool Control nd Dieti mie were rndomly seleted nd divided in to nine groups nd eh group omprises 6 nimls. Group I(Norml Control group) : Norml sline (1 ml/kg, i.p.) ws dministered in mie. Group II(Shm ontrol ): Only surgil proedure ws performed. GroupIII( Dieti ontrol group) : Mie were treted with streptozotoin (65mg/kg, i.p.) for the development of type-1 dietes.. Group IV (dietes + stroke indued group) : 1 min glol ishemi ws indued in dieti mie followed y 24 hr. reperfusion. Group V (Stndrd drug treted group (dietes+stroke indued) : insulin (2 I.U/kg ody weight, s.) ws dministered dily for 15 dys efore the glol ishemi in dieti mie. Originl Reserh Artile 64

3 Joshi et l. / Indin J. Phrm. Biol. Res., 216; 4(1):63-73 Group VI (Test group) :Cinnmomum zeylenium (75 mg/kg ody wt.,p.o.) ws dministered dily for 15 dys efore the glol ishemi in dieti mie. Group VII (Test group) : Cinnmomum zeylenium (15 mg/kg ody wt.) ws dministered dily for 15 dys efore the glol ishemi in dieti mie. Group VIII (Test group) : Cinnmomum zeylenium (3 mg/kg ody wt.) ws dministered dily for 15 dys efore the glol ishemi in dieti mie. Insulin (stndrd) nd Cinnmomum zeylnium (test drug) were dministered for next 15 dys strting from 2 nd week of STZ injetion, efore the glol ishemi in dieti mie. Indution of Glol ererl ishemi: Mie were nesthetized using hlorl hydrte (4 mg/kg, ip). A midline ventrl inision ws mde in the nek to expose the right nd left ommon rotid rteries, whih were isolted from surrounding tissue nd vgus nerve. A otton thred ws pssed elow oth the rotid rteries. Glol ererl ishemi ws indued y oluding the rotid rteries. After 17 min of glol ererl ishemi, reperfusion ws llowed for 24 h. The inision ws sutured k in lyers. The sutured re ws lened with 7% ethnol nd ws spryed with ntisepti dusting powder. The nimls were shifted individully to their home ge nd were llowed to reover overnight.during surgery, the nimls were kept on heting pd in order to mintin the ody temperture, so s to void the effet of temperture vritions on the finl results.[11] Preprtion of post-mitohondril superntnt (PMS). Following depittion, the rin ws removed nd wshed in ooled.9% sline, ws kept on ie nd susequently lotted on filter pper, then weighed nd homogenized in old phosphte uffer (.1 M, ph 7.4) using homogenizer. Homogeniztion proedure ws performed s quikly s possile under ompletely stndrdized onditions. The homogentes ws entrifuged t 1,rpm for 2 min t 4 C nd post-mitohondril superntnt ws kept on ie until ssyed.[12] Anlysis of iohemil prmeters Gluose level: Blood gluose level ws estimted using ommerilly ville kit sed on gluose oxidseperoxidse method.[13] TBAR estimtion: TBAR ws estimted y the method of slter nd swyer(1971).[14] Redued glutthione: Redued glutthione ws estimted y Ellmn G. method (1959).[15] Estimtion of serum triglyeride level: Triglyeride level ws estimted y using ommerilly ville triglyerides enzymti ssy kit.[16] Estimtion of totl protein: Protein vlues were estimted to express the iohemil prmeters in terms of per mg protein. The quntittive mesurement of the totl protein ws determined y Lowry s method.[17] Assessment of ererl infrt size: At the end of 24 hr. of reperfusion fter glol ishemi rin smples were slied nd slies were inuted in TTC t 37 C.TTC is onverted to red form zone pigment y NAD nd ltte dehydrogense nd thus stined the vile ells deep red. Infrted ells lost the enzyme nd remin unstined dull yellow.[18] Sttistil nlysis: All the dt were expressed s men ± stndrd error men(sem). All the dt were nlyzed y one wy ANOVA followed y tukey s test for signifine, exept ody weight nd gluose level. Dt of Body weight nd gluose level ws nlyzed y two wy ANOVA followed y Bonferroni s multiple omprison test using grph pd prism version 5.3 softwre. Results Effet of Cinnmomum zeylnium on ody weight (g): Administrtion of streptozotoin 7 dys prior to innmomum zeylnium tretment produed signifint derese in ody weight in mie s ompred to norml ontrol. Administrtion of Cinnmomum zeylnium (75, 15, 3 mg/kg p.o) in dieti mie did not hve ny signifint effet on ody wt. till 7 dys of tretment.after 14 dys nd 21 dys tretment of Cinnmomum zeylnium (75, 15, 3 mg/kg p.o) showed signifint (P<.1, P<.1) improvement in ody weight in omprison with dieti ontrol.(fig. 1.1, 1.2) Originl Reserh Artile 65

4 Joshi et l. / Indin J. Phrm. Biol. Res., 216; 4(1): Norml Control Shm ontrol 3 Dieti ontrol Body weight (g) 2 1 Bsl Dy Dy 7 Dy 14 Dy 21 Fig.1.1: Effet of streptozotoin on Body weight of mie 4 Dieti ontrol Dietes+stroke Stndrd(Insulin treted) CZ(low dose) CZ(medium dose) CZ(High dose) 3 Body weight (g) 2 1 Bsl Dy Dy 7 Dy 14 Dy 21 Fig.1.2: Effet of Cinnmomum zeylnium on Body weight of Dieti mie Vlues re expressed s men± SEM, (n=6). represents P<.1 : As ompred to norml ontrol group. represents P<.1 : As ompred to norml ontrol. Effet of Cinnmomum zeylnium on serum gluose level (mg/dl) Administrtion of streptozotoin 7 dys prior to innmomum zeylnium tretment produed signifint inrese in fsting serum gluose level in mie s ompred to norml ontrol. Administrtion of Cinnmomum zeylnium (75, 15, 3 mg/kg p.o) in dieti mie did not hve ny effet on serum gluose level on dy. Administrtion of Cinnmomum zeylnium showed signifint (P<.1, P<.1) lowering of serum gluose level fter 7, 14, 21 dys in omprison with dieti ontrol.(fig. 2.1, 2.2) Originl Reserh Artile 66

5 Joshi et l. / Indin J. Phrm. Biol. Res., 216; 4(1):63-73 Control Shm Control Gluose level(mg/dl) Dieti Control Dy Dy 7 Dy 14 Dy 21 Fig.2.1. Effet of streptozotoin on serum Gluose level in Dieti mie Dieti ontrol 3 Dietes+stroke Stndrd(insulin treted) CZ(low dose) CZ(medium dose) CZ(high dose) Gluose level(mg/dl) 2 1 Dy Dy 7 Dy 14 Dy 21 Fig.2.2. Effet of Cinnmomum zeylnium on Serum Gluose level in Dieti mie Vlues re expressed s men± SEM, (n=6). represents P<.1 : As ompred to norml ontrol group. Effet of Cinnmomum zeylnium on serum triglyerides level(mg/dl) Administrtion of streptozotoin 7 dys prior to innmomum zeylnium tretment produed signifint inrese in serum triglyerides level in mie s ompred to norml ontrol. Administrtion of Cinnmomum zeylnium (75, 15, 3 mg/kg p.o) in dieti mie showed signifint (P<.1) lowering of serum triglyerides level fter 21 dys in omprison with dieti ontrol.(fig.3) Originl Reserh Artile 67

6 Joshi et l. / Indin J. Phrm. Biol. Res., 216; 4(1): Triglyeride level(mg/dl) Norml Control Shm ontrol Dieti Control Dieti+stroke Stndrd(insulin treted) CZ(low dose) CZ(medium dose) CZ(high) Fig.3. Effet of Cinnmomum zeylnium on triglyerides level in dieti mie Vlues re expressed s men± SEM (n=6). represents P<.1 :As ompred to Norml ontrol group. represents P<.1 : As ompred to dieti ontrol group. Effet of Cinnmomum zeylnium on ererl infrt size Glol ererl ishemi of 1 min followed y 24 hr. reperfusion produed signifint inrese in the ererl infrt size in dietes+stroke group s ompred to norml ontrol nd dieti ontrol group. when we ompred ontrol nd shm ontrol group there is no signifint differene when mesured y oth volume nd weight methods. Administrtion of Cinnmomum zeylnium (75, 15, 3 mg/kg p.o) signifintly (P<.1, P<.1) derese the dietes nd I/R indued inrese in the ererl infrt size tht ws mesured y volume nd y weight methods.(fig.4.1, 4.2) 8 % Cererl infrt size d ontrol Shm ontrol Dieti ontrol dietes+stroke stndrd CZ(low) CZ(medium) CZ(high) Fig.4.1. Effet of Cinnmomum zeylnium on glol ererl ishemi I/R injury indued ererl infrt size in mie y weight method. Vlues re expressed s men± SEM, (n=6). represents P<.1 : As ompred to Norml ontrol group. represents P<.1 : As ompred to Dieti ontrol group. represents P<.1 : As ompred to Dietes+ stroke group. d P<.1: As ompred to dietes + stroke group. Originl Reserh Artile 68

7 Joshi et l. / Indin J. Phrm. Biol. Res., 216; 4(1): % Cererl infrt size (y vol) ontrol shm ontrol Dieti ontrol dietes+stroke stndrd CZ(low) CZ(medium) CZ(high) Fig 4.2 Effet of Cinnmomum zeylnium on glol ererl ishemi I/R injury indued ererl infrt size in mie y volume method. Vlues re expressed s men± SEM (n=6). represents P<.1 : As ompred to Norml ontrol group. represents P<.1 : As ompred to Dieti ontrol group. represents P<.1 : As ompred to Dietes+ stroke group. Effet of Cinnmomum zeylnium on Glutthione level(nm/mgprotein) Glol ererl ishemi of 1 min followed y 24 hr. reperfusion nd dietes produed signifint derese in the glutthione level in dieti nd dietes+ stroke group s ompred to norml ontrol group. Tretment with Cinnmomum zeylnium (75, 15, 3 mg/kg p.o) signifintly(p<.1,p<.1) inrese the glutthione level s ompred to dietes+stroke group.(fig.5) 4 Glutthione level(nmol/mgprotein) d Norml Control Shm ontrol Dieti ontrol Dieti + stroke stndrd(insuln treted) CZ(low dose) CZ(medium dose) CZ(high dose) Fig.5. Effet of Cinnmomum zeylnium on glutthione level in Dieti mie. Vlues re expressed s men± SEM (n=6). represents P<.1 : As ompred to Norml ontrol group. represents P<.1 : As ompred to Dieti ontrol group. represents P<.1 : As ompred to Dietes+ stroke group. d represents P<.1: As ompred to dietes + stroke group. Originl Reserh Artile 69

8 Joshi et l. / Indin J. Phrm. Biol. Res., 216; 4(1):63-73 Effet of Cinnmomum zeylnium on Thiorituri id retive sustnes TBAR level (nm/mgprotein) Glol ererl ishemi of 1 min followed y 24 hr. reperfusion nd dietes produed signifint inrese in the TBARS level in dieti nd dietes+ stroke group s ompred to norml ontrol group. when we ompred ontrol nd shm ontrol group there is no signifint differene in TBARS level. Tretment with Cinnmomum zeylnium (75, 15, 3 mg/kg p.o) signifintly(p<.1,p<.1) derese the TBARS level s ompred to dietes+stroke group.(fig.6) 15 TBAR level (nm/mgprotein) 1 5 Norml Control Shm ontrol Dietes Dietes+stroke Stndrd(insulin treted) CZ (low dose) CZ(medium dose) CZ(high dose) Fig.6: Effet of Cinnmomum zeylnium on TBAR level in Dieti mie. Vlues re expressed s men± SEM, (n=6). represents P<.1 : As ompred to Norml ontrol group. represents P<.1 : As ompred to Dieti ontrol group. P<.1 : As ompred to Dietes+ stroke group. A B C Originl Reserh Artile 7

9 Joshi et l. / Indin J. Phrm. Biol. Res., 216; 4(1):63-73 D E F G H Figure 1: Neuroprotetive effet of Cinnmomum zeylnium extrt ginst Glol ererl ishemi reperfusion dmge in dieti mie evluted y 2,3,5-triphenyltetrzolium hloride (TTC) stining. Brin oronl setions were prepred nd then eh setion ws stined with TTC. (A) Norml ontrol, (B) shm ontrol, (C) Dieti ontrol, (D) Dietes +stroke, (E) Stndrd (insulin treted), (F) CZ(75 mg/kg), (G) CZ(15 mg/kg), (H) CZ(3 mg/kg). The infrtion ws mrkedly redued in the mie rin treted with CZ(15 mg/kg),cz(3 mg/kg) nd Stndrd(insulin treted). Disussion In the present study n ttempt ws mde to evlute the neuroprotetive effet of Cinnmomum zeylnium in streptozotoin indued nd glol ererl ishemi/reperfusion injury indued mie. It is well known tht Dietes mellitus (DM), is most ommon prolem round the world & ontriutes to the development of different types of omplitions due to vrious pthologil hnges like hnge in thikening of pillry sement memrne, inrese in vessel wll mtrix nd ellulr prolifertion. Dietes mellitus lso represents strong independent risk ftor for stroke.[2] Different types of moleulr signling mehnism tivted y hyperglyemi re Protein kinse C, polyol pthwy flux, Hexosmine pthwy flux nd Advned glytion end produts (AGEs) formtion whih n further leds to stroke.[19] Oxidtive stress plys key role in rin dmge fter ererl ishemi.when n imlne our either y inresing free rdils or deresed ntioxidnt defene, the umultion of free rdils is known s the stte of oxidtive stress.[2] ROS re smll oxygen-derived moleules, inluding the superoxide nion rdil (O2ï-), hydroxyl rdil (OH. ), nd ertin non-rdils tht re either oxidizing gents or esily onverted into rdils, suh s hydrogen peroxide (H 2O 2) nd the oxygen singlet (1O2).[8] The primry soure of free rdil genertion in ells during ererl ishemi is due to derese in mitohondril redox potentil using ROS prodution from the Endothelil ell, minly t the level of ytohrome III (Rmssmy C.,26). After ishemi, n exess of ytosoli free C ++ due to exitotoxiity my overlod the mitohondril proton iruit, whih leds to filure in oxidtion together with inresed ROS prodution. 7 Overprodution of ROS y mitohondri uses the impirment of the ETC, whih leds to deresed ATP prodution, inresed formtion of free rdils, ltered lium homeostsis nd mitohondril dysfuntion.[21] Trnsient middle ererl rtery olusion (MCAO) in rts indues ROS prodution nd mitohondril dysfuntion, inluding the intivity of ETC enzymes.[22] In this study we investigted the ntidieti s well s neuroprotetive effet of Cinnmomum zeylnium in dieti mie. Mny syntheti drugs protet ginst oxidtive dmge, ut they hve side effets. An lterntive solution to the prolem is to onsume nturl ntioxidnts from food supplements nd trditionl mediines. Hene tremendous Originl Reserh Artile 71

10 input is mde worldwide, in serh of the ntioxidnt rih herl plnts to omt diseses.[23] In this study innmon rk extrt ws used s test drug in mie. As per the previous reports it n e onluded tht the extrts of Cinnmon rks exhiited higher ntioxidnt tivity thn other prts of innmon nd ethnol is the est solvent to otin the min ntioxidnt onstituents. All these findings indite tht Cinnmon extrts possess ntioxidnt tivity.[9] Antioxidnt tivity of innmon is due to phenoli ompound suh s hydroxyinnmldehyde, hydroxyinnmi id present in the innmon extrt t s svenger of peroxide rdil nd prevents oxidtive dmge.[24] A pronthoynidine found in Cinnmomum zeylnium i.e innmtnnin B1 exhiit ntioxidnt tivity. It is n tive ompound whih inhiit lipid peroxidtion nd lso n tive svenger of 1,1-diphenyl-2-pirylhydrzyl (DPPH) rdils.[1] Antidieti nd ntioxidnt tivity of innmon ws investigted y the indution of dietes mellitus nd glol ererl ishemi reperfusion injury in mie. Dietes mellitus(type I) ws hemilly indued in mie y dministering single dose of streptozotoin (STZ, 65 mg/kg, i.p), whih produes ytotoxiity to β ells of islets of lngerhns y inresing the tivity of xnthine oxidse nd poly ADP-riose polymerse (PARP), whih onsequently use poptoti nd neroti ell deth in pnreti β ells. STZ ws used in this study euse of its properties suh s seletive β ell toxiity nd miniml toxi to other orgns. Hlf life of streptozotoin is lso high s ompred to lloxn.[25] Glol ererl ishemi ws indued y oth ommon rotid rtery olusion for 1 min nd reperfusion for 24 hr[11], s indited y the formtion of ererl infrtion, inrese in the mlondildehyde level, nd derese in the glutthione level. Pretretment with Cinnmomum zeylnium 21 dys prior to ishemi insult signifintly inhiited the mlondildehyde level nd ererl infrtion. In this study ntidieti effets of Cinnmomum zeylnium ws lso evluted euse dietes is the leding use of rin dmge due to severl mehnism.[26] There ws signifint inrese in the mrkers of dietes i.e serum gluose level, Serum triglyerides level, deresed ody weight nd lso inrese in the mrkers of rin dmge i.e perent ererl infrtion, TBARS level, glutthione level fter the dministrtion of STZ s ompred to non dieti group. Cinnmomum zeylnium (75 mg/kg, 15 mg/kg nd 3 mg/kg, p.o) showed redution in the serum gluose level, serum triglyeride level, MDA (Mlondildehyde), ererl infrt size nd inrese in ody weight nd glutthione level s ompred to dieti ontrol nd dietes+ stroke group. Low dose shows less effet s ompred to medium dose nd high dose. Cinnmomum zeylnium (75 mg/kg, 15 mg/kg nd 3 mg/kg, p.o) did not showed ny effet on ody weight on dy nd dy 7, ut it showed signifint inrese in ody weight on dy 14 nd dy 21.Dieti ontrol group showed signifint differene s ompred to norml ontrol Joshi et l. / Indin J. Phrm. Biol. Res., 216; 4(1):63-73 nd shm ontrol group when the inresed level of mrkers of oxidtive stress(rin dmge) ws oserved nd this finding of the present study strongly suggest the dietes mellitus plys key role in the pthogenesis of oxidtive stress nd rin stroke.results indites tht Cinnmomum zeylnium is good neuroprotetive nd ould e used s therpeuti tretment in rin stroke.the phenoli onstituents of CZ re likely to e responsile for the nti-oxidnt nd free rdil svenging tivity oserved. Conlusion From the ove disussion nd results it n e onluded tht: Cinnmomum zeylnium rk extrt shows neuroprotetive s well s ntidieti effet in streptozotoin indued dietes in mie. Tretment with innmomum zeylnium (75 mg/kg, 15 mg/kg nd 3 mg/kg) seems to lower lood gluose nd triglyerides level nd lso it hs ntioxidnt nd free rdil svenging properties. Out of the results there ws signifint derese in MDA level nd inrese in glutthione level whih re the min mrkers of rin dmge. In onlusion this study is the min evidene for the therpeuti potentil of Cinnmomum zeylnium in glol ererl ishemi reperfusion injury.the study supports n importnt onept tht the onset of neurodegenertion due to dietes my e delyed or mitigted with use of dietry ntioxidnts nd ntidieti drugs tht protet ginst oxidtive stress nd neurodegenertion. Conflit of interest sttement We delre tht we hve no onflit of interest. Aknowledgement The uthor re thnkful to uthorities of Shri Guru Rm Ri Institute of Tehnology nd siene for providing support to the study nd other filities like internet, lirry, nd other tehnil support to perform this study. Referenes 1. Konstntinos, P., Miej, B., Mihel, E., Nikolos, P., Dimitrios, P., 215 Complitions of dietes, Journl of Dietes Reserh, Artile ID , pp Crig, ME., Httersly, A., Donghul, KC., 29, Definition, epidemiology nd lssifition of dietes in hildrens nd dolesents, Interntionl soiety for peditris & dolesent dietes, Vol.1, Issue 12, pp Chirelli, F., Mrovehio, ML., 213, The moleulr mehnism underlying dieti omplitions, Interntionl journl of peditri endorinology, suppl-1, pp Mihel, JF., 28, Mirovsulr nd mrovsulr omplitions of dietes, Clinil dietes, Vol 26, Issue 2, pp Originl Reserh Artile 72

11 Joshi et l. / Indin J. Phrm. Biol. Res., 216; 4(1): Berndette, BA., 2, Lifestyle ftors nd stroke risk : exerise, lohol, diet, oesity, smoking, drug use & stress, urrent theroslerosis ftors, vol.2, Issue 2, pp Ptel, CA., 211, Crdiovsulr omplitions of dietes mellitus, Journl of pplied phrmeutil sienes, Vol. 1, Issue 4, pp Pintdosi, CA., Zhng, J., 1996, Mitohondril genertion of retive oxygen speies fter rin ishemi in the rt, Stroke 27: pp Lin, MT., Bel, MF., 26, Mitohondril dysfuntion nd oxidtive stress in neurodegenertive diseses. Nture 443, pp Chng, HY., et l., 212, ntioxidnt tivity of vrious prts of innmomum ssi extrted with different extrtion methods, Moleules, Vol. 17, pp Ds, M., Mndl, S., Mllik, B., Hzr, J., 213, Ethnootnil, phytohemil & phrmologil spets of innmomum zeylnium lume, Interntionl reserh journl of phrmy, Vol. 4, Issue 4, pp Rehni, AK., et l., 28, Phrmologil preonditioning of the rin: possile interply etween opioid nd litonin gene relted peptide trnsdution systems.phrmologil Reports, 6, pp Poonm, K. et l., 1992, Oxidtive hnges in rin of niline exposed rts Arh Environ ConTox, 23, pp Trinder, P., 1969, gluose oxidse method, Ann linbiohem, Slter TF & Swyer BC, the stimultory effet of ron tetrhloride nd other hlogen lknes on peroxidtive retion in rts liver funtion in vitro, iohem J., 123, PP Ellmn GL, tissue sulphydryl groups, rhives of iohemistry & iophysis, 1959;82: Mx Disovery TM,21, triglyerides enzymti ssy kit mnul, io sientifi orp. 17. Lowry, OH., et l., Protein mesurement with folin phenol regent, J Biol Chem, 193, pp Dhyni, P., Kumr A., & Kothiyl P.,, Neuroprotetive tivity of Asophyllum Nodosum on experimentlly indued glol ererl ishemi/reperfusion injury in mie, INTERNATIONAL JOURNAL OF PHARMACOGNOSY,213; 1(2), PP Joshi, V., Kumr, A., Kothiyl, P.,215, Dietes: A risk ftor for mortlity from rin stroke, Indin journl of phrmeutil nd iologil reserh, vol. 3(2), pp Niizum, K., Endo, H., Chn, PH., 29, Oxidtive stress nd mitohondril dysfuntion s determinnts of ishemi neuronl deth nd survivl. Journl of Neurosiene, 19 (Suppl. 1), pp Andreyev, AY., Kushnrev, YE., Strkov, AA., 215, Mitohondril metolism of retive oxygen speies. Biohemistry 7, pp Rmón RB, Julio Césr GR, Exitotoxiity nd Oxidtive Stress in Aute Ishemi Stroke, Deprtment of Physiology & Immunology, University of Brelon, pp Blekr, N.,et l. 214, Modultory tivity of polyphenoli frtion of Cinnmomum zeylnium L. rk on multiple rms of immunity in norml nd immunoompromised mie, Journl of Applied Phrmeutil Siene, Vol. 4 (7), pp Psupuleti VR., Siew HG., 214, Cinnmon: A multifeted mediinl plnt, Hindwi Pulishing Corportion, pp Akrzdeh, A., et l. 27, Indution of dietes y streptozotoin in rts, Indin Journl of Clinil Biohemistry, Vol.22 (2), pp Kmil, D., et l, 214, Stroke pthophysiology nd retive oxygen speies, systems iology of free rdil nd ntioxidnt, pp Cite this rtile s: Joshi Vndn, Kumr Arun, Kothiyl Preeti. Neuroprotetive Effet of Cinmomum zeylnium in streptozotoin indued dietes in Mie. Indin J. Phrm. Biol. Res.216; 4(1): All 216 re reserved y Indin Journl of Phrmeutil nd Biologil Reserh This Journl is liensed under Cretive Commons Attriution-Non Commeril -Shre Alike 3. Unported Liense. This rtile n e downloded to ANDROID OS sed moile. Originl Reserh Artile 73