Effects of Cinnamomum zeylanicum (Ceylon cinnamon) on blood glucose and lipids in a diabetic and healthy rat model

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PHCOG RES. ORIGINAL ARTICLE Effects of Cinnmomum zeylnicum (Ceylon cinnmon) on lood glucose nd lipids in dietic nd helthy rt model Priyng Rnsinghe, Snj Perer, Mngl Guntilke 1, Erng Aeywrdene, Nuwn Gunpl, Siriml Premkumr 3, Kml Perer, Dilni Lokuhetty 2, Prsd Ktulnd Deprtments of Clinicl Medicine, 1 Physiology nd 2 Pthology, Fculty of Medicine, University of Colomo, Sri Lnk, 3 Herl Technology Division, Industril Technology Institute, Sri Lnk Sumitted: 31-07-2011 Revised: 07-09-2011 Pulished: 07-04-2012 ABSTRACT Ojectives: To evlute short- nd long-term effects of Cinnmomum zeylnicum on food consumption, ody weight, glycemic control, nd lipids in helthy nd dietes-induced rts. Mterils nd Methods: The study ws conducted in two phses (Phse I nd Phse II), using Sprgue-Dwley rts in four groups. Phse I evluted cute effects on fsting lood glucose (FBG) (Groups 1 nd 2) nd on post-orl glucose (Groups 3 nd 4) lood glucose. Groups 1 nd 3 received distilled-wter nd Groups 2 nd 4 received cinnmon-extrcts. Phse II evluted effects on food consumption, ody weight, lood glucose, nd lipids over 1 month. Group A (n = 8, distilled-wter) nd Group B (n = 8, cinnmon-extrcts) were helthy rts, while Group C (n = 5, distilled-wter) nd Group D (n = 5, cinnmon-extrcts) were dietes-induced rts. Serum lipid profile nd HA1c were mesured on D-0 nd D-30. FBG, 2-h post-prndil lood glucose, ody weight, nd food consumption were mesured on every fifth dy. Results: Phse I: There ws no significnt difference in seril lood glucose vlues in cinnmon-treted group from time 0 (P > 0.05). Following orl glucose, the cinnmon group demonstrted fster decline in lood glucose compred to controls (P < 0.05). Phse II: Between D0 nd D30, the difference in food consumption ws shown only in dietes-induced rts (P < 0.001). Similrly, the significnt difference following cinnmon-extrcts in FBG nd 2-h post-prndil lood glucose from D0 to D30 ws shown only in dietes-induced rts. In cinnmon-extrcts dministered groups, totl nd LDL cholesterol levels were lower on D30 in oth helthy nd dietes-induced nimls (P < 0.001). Conclusions: C. zeylnicum lowered lood glucose, reduced food intke, nd improved lipid prmeters in dietes-induced rts. Access this rticle online Wesite: www.phcogres.com DOI: 10.4103/0974-8490.94719 Quick Response Code: Key words: Blood glucose, Ceylon cinnmon, Cinnmomum zeylnicum, dietes mellitus, lipids, Sprgue-Dwley rts INTRODUCTION Dietes mellitus is leding cuse of moridity nd mortlity worldwide, with n estimted 80% of the world popultion with dietes living in developing countries. [1] Most ptients with the disese hve type 2 dietes to which the South Asins re known to hve n incresed predisposition. [2] The cuses of type 2 dietes re multi-fctoril, nd the diet plys n importnt role on its incidence, severity, nd mngement. [3] Hence, studies hve Address for correspondence: Dr. P. Rnsinghe, Dietes Reserch Unit, Deprtment of Clinicl Medicine, Fculty of Medicine, University of Colomo, Colomo, Sri Lnk. E-mil: rn90210@yhoo.com frequently focused on dietry components eneficil in the prevention nd tretment of dietes. Recent studies hve demonstrted tht herl products hve eneficil effects in ptients with dietes y improving glucose nd lipid metolism, ntioxidnt sttus, nd cpillry function. [4] Cinnmon is one such dietry component tht hs shown to hve iologiclly ctive sustnces with insulin-mimetic properties. In vitro [5,6] nd in vivo [7,8] studies hve shown tht cinnmon enhnces glucose uptke y ctivting the insulin receptor kinse ctivity, uto-phosphoryltion of the insulin receptor, nd glycogen synthse ctivity. Cinnmon, the inner rk of tropicl evergreen tree hs two min types, Ceylon cinnmon (Cinnmomum zeylnicum Phrmcognosy Reserch April-June 2012 Vol 4 Issue 2 73

Rnsinghe, et l.: Effects of C. zeylnicum on lood glucose nd lipids Blume) nd Chinese Cssi (Cinnmomum romticum Ness) nd which when dried, rolls into tuulr form known s quill. Cinnmon is ville in either its whole quill form (cinnmon sticks) or s ground powder. In ntive Ayurvedic medicine, cinnmon is considered remedy for respirtory, digestive, nd gynecologicl ilments. Recent studies emerging from western countries hve shown mny potentilly eneficil helth effects of cinnmon such s nti-inflmmtory properties, nti-microil ctivity, lood glucose control, reducing crdiovsculr disese, oosting cognitive function, nd reducing risk of colonic cncer. [9-11] Sri Lnk is middle-income country in the South Asin region produces the lrgest quntity of C. zeylnicum nd the est qulity cinnmon. C. zeylnicum, lso known s Ceylon cinnmon (the source of its Ltin nme, zeylnicum) or true cinnmon, is indigenous to Sri Lnk. One importnt difference etween true cinnmon nd the cssi cinnmon is their coumrin content. [12] Coumrins re nturlly occurring plnt compounds with strong nticogulnt properties. The coumrin content in Ceylon cinnmon ppers to e very smll to cuse helth risks, wheres the coumrin level in C. romticum ppers to e much higher nd my pose helth risks if consumed in higher quntity on regulr sis. [12] In ddition, coumrins lso hve potentilly toxic effects on the liver. [13] Previous studies hve explored the nti-dietic effects of Cinnmon cssi (C. romticum) extrct in vivo nd in vitro. [5-8] However, there is reltive lck of knowledge regrding the effects of the indigenous species of Sri Lnkn Cinnmon (C. zeylnicum) on lood glucose nd lipids. The im of this study ws to evlute the short- nd medium-term effects of C. zeylnicum extrcts on food consumption, ody weight, lood glucose nd glycemic control, nd lipids in oth helthy nd dietes-induced rts s n niml model. MATERIALS AND METHODS The study ws conducted in two phses from June to August 2010. Ethicl pprovl ws otined from the Ethics Review Committee of the Fculty of Medicine, University of Colomo, Sri Lnk. Preprtion of cinnmon extrct The cinnmon extrcts were prepred t the Industril Technology Institute (ITI), Colomo, Sri Lnk. A cinnmon smple ws otined from the collection center of S.D.S. Spices (Pvt) Ltd, Kosgod, Sri Lnk. The voucher specimen is deposited t the Herl Technology Section of Industril Technology Institute under voucher specimen numer HTS-CIN-01 (Hm), nd ws identified y Dr Siriml Premkumr. The cinnmon ws extrcted to distilled wter from the stem rks of C. zeylnicum using Soxhlet pprtus nd the resulting hot wter extrct ws freeze-dried to otin crude wter extrct (yield 8.3% w/w dry weight sis). This solid freeze-dried extrct in dosge form in distilled wter ws dministered to experimentl rts. The dosge for rts ws clculted ccording to the ody surfce re s shown elow, using the humn dosge (6 g) otined from previous studies. [9] The dily cinnmon dose given for 200 g rt ws 120 mg (600 mg/kg) in 1 ml of distilled wter dministered vi metl oro-gstric tue. Dose (mg/kg) = Humn dose (mg/kg) [Humn Km fctor/rt Km fctor] [14] Phse I The im of Phse I ws to determine the short-term effects of C. zeylnicum on lood glucose in the unfed nd postprndil stte. Helthy Sprgue-Dwley rts hving men ody weight of 190 ± 25 g nd ged 3 4 months (n = 32, mle:femle = 1:1) were used s the niml model. They were divided into four equl groups of eight nimls ech. In Groups 1 nd 2 lood glucose levels in the unfed stte were mesured, while in Groups 3 nd 4 lood glucose levels following stndrd orl glucose lod (1.25 g/kg) ws mesured. In ll four groups, the nimls were kept fsting for 12 h overnight. In Groups 1 nd 2 the fsting lood glucose (FBG) vlue ws determined t 0 h nd the cinnmon extrct nd distilled wter, respectively, were dministered immeditely. Susequently the lood glucose levels in the unfed stte were mesured t 0.5, 1, 2, 4, 8, 12, nd 24 h. Similrly in Groups 3 nd 4 the FBG vlues were determined t 0 h nd n orl glucose lod ws dministered. The cinnmon nd distilled wter were dministered fter 0.5 h following the glucose lod with mesuring of lood glucose vlues t tht time. Susequently lood glucose levels were mesured t 1, 2, 4, 8, 12 nd 24 h. In ll four groups, the nimls were fed t 24 h nd kept fsting for 12 h for repetition of this cycle the next dy. This protocol ws crried out for three consecutive cycles nd men lood glucose vlues were nlysed. The percentge reductions of the lood glucose vlues of ech hour from the respective FBG of Groups 1 nd 2 were compred. The percentge reductions were clculted s follows: Percentge reduction = (FBG - Blood glucose vlue) FBG 100 Phse II The im of Phse II ws to determine the medium-term effects of C. zeylnicum on food consumption, ody weight, lood glucose nd glycemic control, nd lipids. Group A (n = 8) nd Group B (n = 8) were helthy Sprgue-Dwley rts, while Group C (n = 5) nd Group D (n = 5) were 74 Phrmcognosy Reserch April-June 2012 Vol 4 Issue 2

Rnsinghe, et l.: Effects of C. zeylnicum on lood glucose nd lipids dietes-induced Sprgue-Dwley rts. In groups A nd B distilled wter nd cinnmon were dministered, respectively, on dily sis for period of 1 month. Similrly, in Groups C nd D distilled wter nd cinnmon were dministered, respectively, for 1 month. In ll four groups, the nimls were kept fsting overnight for period of 12 h, nd cinnmon or distilled wter were dministered, followed y 30 min intervl prior to commencing of the stndrd dily pellet feed. In ll four groups lood for estimtion of serum totl cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, nd HA1c were drwn on dy 0 nd dy 30 from the til vein of the rts. FBG nd 2 h post-prndil lood glucose were mesured from dy 0 every fifth dy till dy 30. Induction of dietes In Groups C nd D (n = 16), dietes ws induced y single intrvenous injection of streptozotocin (Sigm Chemicls Co, St. Louis, MO, USA) to the til vein t dose of 75 mg/kg ody weight. Confirmtory FBG tests were performed fter 14 dys of injection nd nimls with FBG of >200 mg/dl (six femles nd four mles) fter induction were rndomly llocted to Groups C (n = 5) nd D (n = 5) with n equl gender distriution. Mesurements: Biochemicl nd physiologicl The lood glucose vlues were determined using n Optium Xceed glucometer nd strips (Aott Dietes Cre Ltd, Oxon, UK). A cross-vlidtion to estlish the ccurcy of the glucometer ws done y compring with 10 lortory plsm glucose tests. Blood for estimtion of lipid prmeters were collected to plin tues while for estimtion of HA1c lood ws collected to K3 EDTA tues. HA1c ws determined y the HPLC Bio-Rd vrint method (Bio-Rd, USA), cholesterol y the CHOD- PAP method (Bio System S.A., Brcelon, Spin), HDL cholesterol y n enzymtic colorimetric direct HDL ssy (Anlyticon Biotechnologies AG, Lichtenfels, Germny), LDL cholesterol y homogeneous enzymtic direct LDL ssy (Anlyticon Biotechnologies AG, Lichtenfels, Germny) nd triglycerides y the GPO-PAP method (Bio System S.A., Brcelon, Spin). During the study period, the nimls were fed with stndrd pellet diet nd wter dily with dded vitmins s required. The nimls were housed in seprte cges in rrier procedure room t mient temperture with reltive humidity of 40 60% nd 12 h light/drk cycle. The dily food nd wter consumption ws mesured, while ody weight ws mesured on every fifth dy. Determintion of the effects on orgns On completion of Phse II, histo-pthologicl study ws conducted on 3 nimls from ech group. The selected nimls were dissected under ether nesthesi y trined resercher nd the liver (10% formlin preservtive), oth kidneys (modified Bouin s solution) nd pncres (10% formlin preservtive) were hrvested to determine the effects of cinnmon on these orgns. The liver ws exmined for spotty/zonl liver cell necrosis, heptocyte swelling, ftty chnges, nd inflmmtion. In the kidenys, tuulr epithelil cell dmdge, presence of csts/crystls, glomulr chnges, nd inflmmtion were exmined. The pncres ws exmined for cell necrosis, inflmmtion, islet cell hyperplsi, nd/or trophy. Sttisticl nlysis Dt from the experiments re presented s men ± stndrd devition. Sttisticl nlysis ws performed using the Sttisticl Pckge for Socil Science (SPSS) softwre for windows version 14 (SPSS Inc., Chicgo, Illinois, USA). In ll sttisticl nlysis P vlues of <0.05 were considered significnt. RESULTS Phse I The men ody weight of nimls in Groups 1 4 were 185 ± 12 g, 192 ± 8 g, 180 ± 14 g nd 188 ± 10 g, respectively. There ws no sttisticlly significnt difference in the men ody weights of the respective groups. There were no sttisticlly significnt differences oserved etween the men lood glucose vlues t ech hour of Groups 1 nd 2 [Tle 1]. When compring the percentge reductions of the lood glucose vlues of ech hour from the respective FBG of Groups 1 nd 2 only the cinnmon dministered group demonstrted greter men percentge reduction t 0.5, 1 nd 2 h. However, this difference ws not sttisticlly significnt [Figure 1]. When stndrd loding dose of glucose ws dministered to Groups 3 nd 4, in oth groups the pek plsm glucose Tle 1: Effect of Cinnmomum zeylnicum on fsting lood glucose nd post-orl glucose lod Time (h) Group 1 (Distilled wter) Men lood glucose (±SD) mg/d1 Fsting Group 2 (Cinnmon) Post-orl glucose lod Group 3 (Distilled wter) Group 4 (Cinnmon) 0 92 (±9) 96 (±11) 96 (±11) 93 (±10) 0.5 101 (±18) 90 (±19) 149 (±27)* 190 (±39)* 1 96 (±24) 86 (±14) 137 (±14) 137 (±48) 2 91 (±11) 90 (±14) 99 (±21) 109 (±37) 4 81 (±12) 86 (±10) 88 (±8) 80 (±11) 8 85 (±11) 78 (±11) 79 (±5)* 69 (±7)* 12 65 (±8) 72 (±4) 74 (±4)* 65 (±8)* 24 65 (±11) 76 (±10) 71 (±8) 67 (±10) *P < 0.05, Comprison etween Groups 3 nd 4 Phrmcognosy Reserch April-June 2012 Vol 4 Issue 2 75

Rnsinghe, et l.: Effects of C. zeylnicum on lood glucose nd lipids following the stndrd orl glucose lod ws recorded t 0.5 h. When the test sustnce (cinnmon or distilled wter) ws dministered to the respective groups t 0.5 h, Group 4 (cinnmon) demonstrted fster decline in lood glucose in comprison to Group 3 (distilled wter) [Figure 2]. The men percentge reduction in lood glucose from 0.5 to 1 h in Groups 3 nd 4 were 7.7% nd 27.7%, respectively, with the cinnmon dministered group demonstrting significntly higher percentge reduction (P < 0.001). In ddition, the cinnmon group lso demonstrted lower lood glucose vlue t 8 nd 12 h post-orl glucose lod (P < 0.05) [Tle 1]. Phse II In helthy nimls the men ody weight (±SD) of the cinnmon group nd control group on dy 0 ws 193.9 ± 9.2 g nd 191.6 ± 8.6 g, respectively. At the end of the study period (D-30), the men weight of the control group incresed significntly (P < 0.001) to 210.0 ± 16.8 g, while in the cinnmon group the weight gin ws not significnt (202.5 ± 15.7 g, P > 0.05). The men food consumption of helthy rts on dy 0 in the cinnmon nd control groups ws 10.9 ± 1.2 g nd 11.4 ± 1.9 g, respectively, wheres on dy 30 it ws 10.3 ± 1.5 g nd 11.4 ± 1.3 g, respectively, indicting no significnt difference in the men food consumption etween dy 0 nd dy 30 [Figure 3]. The dietes-induced nimls hd men ody weights of 176.5 ± 13.9 g in the cinnmon group nd 169.9 ± 6.5 g in the control group t the eginning of the study (dy 0). On dy 30, the men ody weight of the cinnmon group ws 168.8 ± 33.4 g nd in the control group it ws 163.1 ± 17.6 g. The weight reduction oserved in oth groups during the study period ws not sttisticlly significnt. The men food consumption per niml hd significntly reduced from dy 0 to dy 30 in the cinnmon group, ut not in the control group of dietes-induced nimls (P < 0.001) (cinnmon group D0: 15.7 ± 1.2 g, D30: 9.1 ± 0.5 g; control group D0: 13.2 ± 1.6 g, D30:12.3 ± 1.3 g) [Figure 3]. In helthy nimls, there ws no significnt difference in the FBG or 2-h post-prndil lood glucose etween the cinnmon nd control groups from dy 0 to dy 30. However, in the dietes-induced nimls the FBG ws significntly lower in the cinnmon group thn the control Figure 1: Percentge reduction of hourly lood glucose vlues from fsting lood glucose in Groups 1 (distilled wter) nd 2 (cinnmon extrct) Figure 2: Blood glucose vlues following post-orl glucose lod in Groups 3 (distilled wter) nd 4 (cinnmon extrct) Figure 3: Men food consumption of nimls during the study period, () in helthy nimls nd () dietes-induced nimls 76 Phrmcognosy Reserch April-June 2012 Vol 4 Issue 2

Rnsinghe, et l.: Effects of C. zeylnicum on lood glucose nd lipids group on dy 20 nd dy 30, while the 2-h post-prndil glucose ws significntly lower on dy 30 in the cinnmon group [Tle 2]. In oth helthy nd dietes-induced nimls, the cinnmon group showed significntly lower totl nd LDL cholesterol level on dy 30 compred to dy 0. However, this difference ws not oserved in the control groups [Tle 2]. The HDL cholesterol nd triglycerides remined unchnged in ll four groups of nimls in Phse II. The men HA1C remined unchnged in helthy nimls in dy 0 nd dy 30, while in dietes-induced nimls the men HA1C in the control group incresed significntly from 2.2% (±0.1) in dy 0 to 4.5% (±0.9) on dy 30 (P < 0.001). In the cinnmon group of dietes-induced nimls, the men HA1C on dy 0 nd dy 30 ws not significntly different [Tle 2]. The histologicl nlysis of the liver, kidney, nd pncres were within norml histologicl limits with no evidence indictive of toxicity. The liver histology demonstrted no evidence of spotty/zonl liver cell necrosis, heptocyte swelling, ftty chnges, nd inflmmtion. In the kidneys, tuulr epithelil cell dmge, presence of csts/crystls, glomerulr chnges, nd inflmmtion were not seen. The pncres demonstrted no evidence of cell necrosis, inflmmtion, islet cell hyperplsi, nd/or trophy. DISCUSSION To our knowledge, this is the first report on the effects of uthentic Ceylon cinnmon collected from ntive cultivtors on lood glucose, lthough there re studies on C. zeylnicum. [10] Our results demonstrte tht C. zeylnicum improves the ody s ility to hndle glucose lod s demonstrted y the rpid metolism shown in the cinnmon group of helthy nimls following stndrd orl glucose lod. This proly occurs s result of the ility of cinnmon to potentite insulin-regulted glucose utiliztion vi enhncing insulin signling. [5,8,15] In the study y Qin et l., [8] enhnced cellulr glucose uptke due to the stimultion of the insulin receptor ctivity y the incresing concentrtions of the phosphorylted intrcellulr protein IRS-1 nd the incresing of PI 3-kinse hs een shown with cinnmon. Studies hve shown tht this potentiting effect of cinnmon on insulin cuses dose-dependent reduction in the serum insulin concentrtion. [16] This rpid reduction in lood glucose concentrtion nd the reduced insulin requirement could help prevent β-cell destruction Tle 2: Effect of Cinnmomum zeylnicum on lood glucose, lipids, nd HA1C in helthy nd dietes-induced rts Biochemicl test Fsting lood glucose Dy 0 Dy 10 Dy 20 Dy 30 Post-prndil lood glucose Dy 0 Dy 10 Dy 20 Dy 30 Totl cholesterol Dy 0 Dy 30 LDL cholesterol Dy 0 Dy 30 HDL cholesterol Dy 0 Dy 30 Triglycerides Dy 0 Dy 30 HA1C Dy 0 Dy 30 Group 1 (Distilled wter) 72 (±6) 81 (±8) 75 (±7) 77 (±8) 106 (±15) 101 (±13) 99 (±11) 94 (±14) 68.4 (±12.3) 67.3 (±10.3) 12.3 (±8.6) 8.8 (±3.8) 40.2 (±8.0) 51.6 (±8.1) 78.9 (±21.3) 72.8 (±33.1) 1.9 (±0.1) 3.0 (±0.3) Helthy rts * P < 0.05, Comprison etween dys 0 nd 30, Comprison etween groups 3 nd 4 Group 2 (Cinnmon) 70 (±8) 83 (±9) 76 (±13) 77 (±10) 102 (±19) 103 (±8) 96 (±9) 90 (±9) 74.5 (±9.5)* 59.2 (±13.2)* 13.6 (±6.2)* 3.0 (±1.3)* 45.4 (±10.7) 46.5 (±11.5) 77.6 (±16.2) 59.7 (±20.5) 2.3 (±0.5) 3.2 (±0.3) Men (±SD) mg/dl Group 3 (Distilled wter) 296 (±20) 322 (±36) 372 (±74)* 320 (±53)* 395 (±63) 403 (±108) 419 (±52) 493 (±21)* 69.7 (±11.8) 72.0 (±15.2) (±4.6) 12.9 (±18.8) 25.4 (±11.8) 19.5 (±5.3) 197.0 (±87.5) 198.2 (±80.1) 2.2 (±0.1)* 4.5 (±0.9)* Dietes-induced rts Group 4 (Cinnmon) 271 (±42) 290 (±66) 254 (±28)* 247 (±63)* 378 (±72) 346 (±110) 384 (±115) 369 (±111)* 64.3 (±9.8)* 50.8 (±14.7)* 15.9 (±3.0)* 3.1 (±0.9)* 32.0 (±9.5) 26.9 (±4.6) 121.4 (±54.9) 131.0 (±76.9) 4.2 (±2.2) 4.9 (±1.4) Phrmcognosy Reserch April-June 2012 Vol 4 Issue 2 77

Rnsinghe, et l.: Effects of C. zeylnicum on lood glucose nd lipids occurring s result of β-cell exhustion from chronic hyperglycemi in dietes. [17] The cinnmon group of dietes-induced nimls demonstrted significnt reduction in men food consumption implying tht cinnmon lso tends to promote stiety. In ddition with long-term usge in dietesinduced nimls the cinnmon group demonstrted lower FBG (on dy 20 nd 30) nd 2-h post-prndil lood glucose (on dy 30). These results re comptile with results from previous studies. [9,18] However, the sme result ws not oserved in helthy nimls where norml glucose homeosttic mechnisms re intct indicting tht the effects of cinnmon re under the regultion of norml physiologicl feedck mechnisms. The fct tht cinnmon lowers lood glucose usully within physiologicl levels without hypoglycemi nd increses stiety leds to the hypothesis tht it my ct y potentiting the effects of incretin hormones. [19] The cinnmon extrcts lso promoted etter glycemic control in dietes-induced nimls s demonstrted y the stle HA1c in the cinnmon group s opposed to the dietic control group. According to the United Kingdom Prospective Dietes Study (UKPDS), drop of HA1C from 7.9% to 7% lowers the risk of mcro- nd microvsculr disese significntly; [20] thus, etter control of HA1c levels in ptients with cinnmon supplementtion might e expected to yield similr eneficil effects on the long-term complictions of dietes. In ddition, oth in helthy nd dietes-induced nimls, cinnmon cused very significnt reduction in the totl nd LDL cholesterol levels. This cholesterol lowering effect of cinnmon together with its ntioxidnt properties [21] hs the potentil to reduce the long-term crdiovsculr complictions ssocited with dietes, [22] while lso eing effective s supplement in ptients with hyperlipdiemi nd crdiovsculr diseses without dietes. The usge of cinnmon s regulr supplement with mels ws not dvocted or the dily dosge ws restricted in mny countries due to the toxic effects of C. romticum on the liver nd cogultion. [23] In contrst, C. zeylnicum hs shown to contin lesser content of coumrin [11,24] nd thus it my e possile tht Ceylon cinnmon could e used in higher doses without toxic effects for longer durtions. In ddition our pthologicl nlysis lso reveled no evidence indictive of toxicity of C. zeylnicum. Our study hs severl limittions, the study ws conducted with single dose of cinnmon the dose-dependent effect of cinnmon extrcts on the serum insulin level ws not evluted. The serum insulin levels tht were mesured in Phse II were <2 miu/l in ll nimls (the sensitivity limit of the ssy). The study involved oth helthy nd dietes-induced mle nd femle rts, the difference in the ody composition nd lipid profile etween genders were not considered during nlysis, however since ll comprtive groups hd equivlent numers of mles nd femles this effect is likely to e miniml. CONCLUSION In conclusion, C. zeylnicum lowered lood glucose, reduced food intke, nd reduced therogenic LDL cholesterol. Its effect on humns nd the possiility of incretin mimetic effects need further study. REFERENCES 1. Wild S, Roglic G, Green A, Sicree R, King H. Glol prevlence of dietes: Estimtes for the yer 2000 nd projections for 2030. Dietes Cre 2004;27:1047-53. 2. Mther HM, Keen H. The Southll Dietes Survey: Prevlence of known dietes in Asins nd Europens. Br Med J (Clin Res Ed) 1985;291:1081-4. 3. Americn Dietes Assocition. Nutrition Recommendtions nd Interventions for Dietes: A position sttement of the Americn Dietes Assocition. Dietes Cre 2007;30:S48-65. 4. Biley CJ, Dy C. Trditionl plnt medicines s tretments for dietes. Dietes Cre 1989;12:553-64. 5. Imprl-Rdosevich J, Des S, Polnsky MM, Bedke DA, Ingeritsen TS, Anderson RA, et l. Regultion of PTP-1 nd insulin receptor kinse y frctions from cinnmon: Implictions for cinnmon regultion of insulin signling. Horm Res 1998;50:177-82. 6. Jrvill Tylor KJ, Anderson RA, Grves DJ. A hydroxychlcone derivtive from cinnmon functions s mimetic for insulin in 3T3 L1 dipocytes. J Am Coll Nutr 2001;20:327-36. 7. Co H, Polnsky MM, Anderson RA. Cinnmon extrct nd polyphenols ffect the expression of tristetrprolin, insulin receptor, nd glucose trnsporter 4 in mouse 3T3 L1 dipolytes. Arch Biochem Biophys 2007;459:214-22. 8. Qin B, Ngski M, Ren M, Bjotto G, Oshid Y, Sto Y. Cinnmon extrct (trditionl her) potentites in vivo insulin regulted glucose utiliztion vi enhnced insulin signling in rts. Dietes Res Clin Prct 2003;62:139-48. 9. Khn A, Sfdr M, Ali Khn MM, Khttk KN, Anderson RA. Cinnmon improves glucose nd lipids in people with type 2 dietes. Dietes Cre 2003;26:3215-8. 10. Shen Y, Fukushim M, Ito Y, Murki E, Hosono T, Seki T, et l. Verifiction of the ntidietic effects of cinnmon (Cinnmomum zeylnicum) using insulin-uncontrolled type 1 dietic rts nd cultured dipocytes. Biosci Biotechnol Biochem 2010;74: 2418-25. 11. Outtr B, Simrd RE, Holley RA, Piette GJ, Bégin A. Anticteril ctivity of selected ftty cids nd essentil oils ginst six met spoilge orgnisms. Int J Food Microiol 1997;37:155-62. 12. Archer AW. Determintion of cinnmldehyde, coumrin nd cinnmyl lcohol in cinnmon nd cssi y high-performnce liquid chromtogrphy. J Chromtogr 1988;447:272-6. 13. Ghosh P, Mrkin RS, Sorrell MF. Coumrin-induced heptic necrosis. Am J Gstroenterol 1997;92:348-9. 78 Phrmcognosy Reserch April-June 2012 Vol 4 Issue 2

Rnsinghe, et l.: Effects of C. zeylnicum on lood glucose nd lipids 14. Regn-Shw S, Nihl M, Ahmd N. Dose trnsltion from niml to humn studies revisited. FASEB J 2008;22:659-61. 15. Khn A, Bryden NA, Polnsky MM, Anderson RA. Insulin potentiting fctor nd chromium content of selected foods nd spices. Biol Trce Elem Res 1990;24:183-8. 16. Plexopthy DL. Cinnmon dose-dependently reduces insulin concentrtion. Am J Clin Nutr 2009;89:815-21. 17. Donth MY, Ehses JA, Medler K, Schumnn DM, Ellingsgrd H, Eppler E, et l. Mechnisms of β-cell Deth in Type 2 Dietes. Dietes 2005;54:S108-13. 18. Vnderweele DA. Insulin nd stiety from feeding in pncreticnorml nd dietic rts. Physiol Behv 1993;54:477-85. 19. Perfetti R, Brown TA, Velikin R, Busselen S. Control of glucose homeostsis y incretin hormones. Dietes Technol Ther 1999;1:297-305. 20. UK Prospective Dietes Study (UKPDS) Group. Intensive lood-glucose control with sulphonylures or insulin compred with conventionl tretment nd risk of complictions in ptients with type 2 dietes (UKPDS 33). Lncet 1998;352:837-53. 21. Mncini-Filho J, Vn-Koiij A, Mncini DA, Cozzolino FF, Torres RP. Antioxidnt ctivity of cinnmon (Cinnmomum zeylnicum, Breyne) extrcts. Boll Chim Frm 1998;137:443-7. 22. Roussel A, Hininger I, Benr R, Ziegenfuss TN, Anderson RA. Antioxidnt effects of cinnmon extrct in people with impired fsting glucose tht re overweight or oese. J Am Coll Nutr 2009;28:16-21. 23. Lungrini S, Aureli F, Coni E. Coumrin nd cinnmldehyde in cinnmon mrketed in Itly: A nturl chemicl hzrd? Food Addit Contm Prt A Chem Anl Control Expo Risk Assess 2008;25:1297-305. 24. Rychlik M. Quntifiction of free coumrin nd its liertion from glucosylted precursors y stle isotope dilution ssys sed on liquid chromtogrphy-tndem mss spectrometric detection. J Agric Food Chem 2008;56:796-801. Cite this rticle s: Rnsinghe P, Perer S, Guntilke M, Aeywrdene E, Gunpl N, Premkumr S, Perer K, Lokuhetty D, Ktulnd P. Effects of Cinnmomum zeylnicum (Ceylon cinnmon) on lood glucose nd lipids in dietic nd helthy rt model. Phcog Res 2012;4:73-9. Source of Support: Nil, Conflict of Interest: None declred. Announcement Android App A free ppliction to rowse nd serch the journl s content is now ville for Android sed moiles nd devices. The ppliction provides Tle of Contents of the ltest issues, which re stored on the device for future offline rowsing. Internet connection is required to ccess the ck issues nd serch fcility. The ppliction is comptile with ll the versions of Android. The ppliction cn e downloded from https://mrket.ndroid.com/detils?id=comm.pp.medknow. For suggestions nd comments do write ck to us. Phrmcognosy Reserch April-June 2012 Vol 4 Issue 2 79