Debasis De, 1 Kausik Chatterjee, 1 Kazi Monjur Ali, 1 Tushar Kanti Bera, 1, 2 and Debidas Ghosh Introduction

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1 Hindwi Pulishing Corportion Evidene-Bsed Complementry nd Alterntive Mediine Volume 211, Artile ID 89287, 11 pges doi:1.1155/211/89287 Reserh Artile Antidieti Potentility of the Aqueous-Methnoli Extrt of Seed of Swieteni mhgoni (L.) Jq. in Streptozotoin-Indued Dieti Mle Alino Rt: A Correltive nd Evidene-Bsed Approh with Antioxidtive nd Antihyperlipidemi Ativities Desis De, 1 Kusik Chtterjee, 1 Kzi Monjur Ali, 1 Tushr Knti Ber, 1, 2 nd Deids Ghosh 1 1 Deprtment of Bio-Medil Lortory Siene nd Mngement, (U.G.C Innovtive Deprtment), Vidysgr University, Midnpore , West Bengl, Indi 2 Phrmeutil Division, Southern Helth Improvement Smity (SHIS), South 24 Prgns, Bhngr , West Bengl, Indi Correspondene should e ddressed to Deids Ghosh, deids ghosh@yhoo.o.in Reeived 3 My 29; Revised 6 Otoer 29; Aepted 31 August 21 Copyright 211 Desis De et l. This is n open ess rtile distriuted under the Cretive Commons Attriution Liense, whih permits unrestrited use, distriution, nd reprodution in ny medium, provided the originl work is properly ited. Antidieti, ntioxidtive, nd ntihyperlipidemi tivities of queous-methnoli (2 : 3) extrt of Swieteni mhgoni (L.) Jq. (fmily Meliee) seed studied in streptozotoin-indued dieti rts. Feeding with seed extrt (25 mg.25 ml distilled wter 1 1 gm.w. 1 rt 1 dy 1 ) for 21 dys to dieti rt lowered the lood gluose level s well s the glyogen level in liver. Moreover, tivities of ntioxidnt enzymes like tlse, peroxidse, nd levels of the produts of free rdils like onjugted diene nd thiorituri id retive sustnes in liver, kidney, nd skeletl musles were orreted towrds the ontrol fter this extrt tretment in this model. Furthermore, the seed extrt orreted the levels of serum ure, uri id, retinine, holesterol, triglyeride, nd lipoproteins towrds the ontrol level in this experimentl dieti model. The results indited the potentility of the extrt of S. mhgoni seed for the orretion of dietes nd its relted omplitions like oxidtive stress nd hyperlipidemi. Theextrt my e good ndidte for developing sfety, tolerle, nd promising neutreutil tretment for the mngement of dietes. 1. Introdution Dietes mellitus is multifrious group of symptoms hrterized y hyperglyemi, norml lipid nd protein metolism, long with speifi long-term omplitions ffeting the retin, the kidney, nd the nervous system minly [1]. Consumption of lorie-rih diet, oesity, nd sedentry life style hve led to tremendous inrese in the numer of dietis worldwide espeilly in Asi [2]. Mny orl hypoglyemi gents, suh s sulfonylure nd igunides, re ville long with insulin for the tretment of dietes mellitus, ut these gents hve signifint side effets [3], nd some re ineffetive in hroni dieti ptients [4]. Thus, there is n inresing demnd of new ntidieti nturl produts espeilly neutreutils with lesser side effets nd high ntidieti potentil. In this ontext, worldwide efforts hve een tken to improve plnt-sed therpies [5]. WHO [6] reommended for the ssessment of trditionl mediinl plnt in onnetion with the mngement of dietes mellitus [7 9]. Currently, severl hundred plnts hve een reported to hve enefiil effets for the tretment of dietes mellitus, nd we hve severl reports in this line [1 12] swells of others [13 15]. Reserh on phytomoleules s dieti remedies is uprising grdully s these re with miniml or no side effets [16 18]. Swieteni mhgoni (S. mhgoni), is under fmily Meliee, eutiful, lofty, evergreen, lrge ntive tree of tropil Ameri, Mexio, South Ameri, nd Indi. Usully, this plnt is 3 4 meters in height nd 3-4 meters in girth [19]. The seeds of S. mhgoni hve een reported for its nti-inflmmtory, ntimutgeneity, nd ntitumour tivities [2]. In Indonesi nd in Indi,

2 2 Evidene-Bsed Complementry nd Alterntive Mediine S. mhgoni seed used s folk mediine to ure dietes [21]. There is no systemti work out the ntidieti tivity of S. mhgoni though there re very few informtions of this plnt in this line [22, 23]. The present study ws therefore rried out to evlute the trditionl used of S. mhgoni s ntidieti sientifilly. Furthermore, the positive roles of nturl produts (neutreutils) for the orretion of oxidtive stress nd hyperlipidemi, whih re dietes-relted omplitions, were lso ssessed. 2. Mterils nd Methods 2.1. Preprtion of Seed Extrt. Swieteni mhgoni seeds were olleted from Midnpore, Distrit Pshim Midnpore, West Bengl, Indi, in the month of Deemer nd were identified y txonomist of Botny Deprtment, Vidysgr University, Midnpore. A vouher speimen ws sumitted in the Deprtment of Botny, Vidysgr University nd numered s Swieteni mhgoni (L.) Jq./VU/1/9. Seeds were dried in n inutor for 2 dys t 4 C, rushed in n eletri grinder, nd then pulverized. Out of this powder, 5 g ws suspended in the mixture solvent onsisting of 8 ml of wter nd 12 ml methnol nd the mixture ws kept in n inutor t 37 C for 36 hours. The mixture ws stirred intermittently for 4-hours intervl. The mixture ws then filtered nd filtrte ws dried under low pressure nd low temperture using rotry evportor fitted with vuum pump. Finlly, 3.2 gm of powder ws olleted. This ws disovered in distilled wter in fixed dose nd used for the tretment Chemils. Streptozotoin (STZ) ws otined from Sigm (USA). All other hemils used here were of nlytil grde otined from E. Merk, Mumi, nd HIMEDIA, Mumi, Indi or purhsed from Sigm-Aldrih Dignosti Ltd. USA. Kits for different enzyme ssy were purhsed from Crest Biosystems, Go, Indi Seletion of Animl nd Animl Cre. Twenty four mtured normoglyemi (hving fsting lood gluose level 8 9 mg/dl) Wistr strin mle lino rts, 3 months of ge, weighing out 12 ± 1 g were seleted for this experiment. Animls were limted for period of 15 dys in our lortory ondition prior to the experiment. Rts were housed t n mient temperture of 25 ± 2 Cwith 12 hours light : 12 hours drk yle. Rts were fed pellet diet nd wter d liitum. The priniple of Lortory Animl Cre nd instrutions given y our Institutionl Ethil Committee were followed throughout the experiment Indution of Dietes in Rts. Twenty-four hours fsted eighteen rts out of twenty four were sujeted to single intrmusulr injetion of STZ (4 mg 1 1.w) in.1 ml of itrte uffer (ph = 4.5) 1 g 1,.w. 1 rt 1.After7dys of STZ injetion, dieti rts (fsting lood gluose level >25 mg/dl <35 mg/dl) were seleted for the study Animl Tretment. Twelve dieti rts hving sid riteri were seleted. Six rts were tegorized into dieti ontrol nd the rest of rts were pled in extrt dministered dieti group. Other six normoglyemi rts were onsidered under ontrol group. Extrt tretment of S. mhgoni seed ws strted from the 7th dy of postinjetion period of STZ nd ws onsidered s 1st dy of experiment. Thetretmentwsontinuedfornext21dys. Group I (ontrol group). Rts of this group reeived single intrmusulr injetion of itrte uffer (.1 ml 1 g 1.w. 1 ) t the time of STZ injetion to the other nimls for dieti indution. Group II (dieti ontrol group). Dieti rts of this group were forefully fed with wter t dose of.25 ml of distilled wter 1 g.w 1 dy 1 for 21 dys y gvge. Group III (extrt dministered dieti group). Dieti rts of this group were forefully fed with queousmethnoli (2 : 3) extrt of S. mhgoni seed t dose of 25 mg.25 ml wter 1 1 g.w. 1 dy 1 for 21 dys t fsting stte y gvge. Extrt dministrtion to the rts of group III ws performed erly in the morning nd t fsting stte y gvge. Animls of the ontrol group (Group I) were sujeted to gvge of distilled wter like group II for 21 dys t the time of extrt tretment to the nimls of group III to keep ll the nimls under the sme experimentl ondition nd stress imposition if ny due to tretment of extrt nd niml hndling. Strting from first dy of extrt tretment to dieti rts, fsting lood gluose levels (12 hours fter feed delivery) in ll the groups were mesured y single touh gluometer on every 7-dy intervl. On the 21st dy of experiment, lood ws olleted from the til vein, nd fsting gluose level ws monitored y single touh gluometer. All the nimls were srified t fsting stte y light ether nesthesi followed y depittion fter reording the finl ody weight. Blood ws olleted from the dorsl ort y syringe nd the serum ws seprted y entrifugtion t 5 rpm for 5 minutes for the estimtion of serum toxiity study. The liver, kidney, nd skeletl musles were disseted out nd stored t 2 C for the quntifition of glyogen, for the ssessment of the tivities of the ntoxidnt enzymes tlse (CAT) nd peroxidse (Px), nd for the quntifition of the levels of the produts of free rdils like onjugted diene (CD) nd thiorituri id (TBARS). Assessment of protein metoli nd lipid metoli disorders ws lso performed y the mesurement of the levels of serum ure, uri id, retinine, totl holesterol, triglyeride, high density, nd low-density nd very low-density lipoprotein holesterol Estimtion of Glyogen Level. Hepti glyogen level ws mesured ording to the stndrd protool [24]. In rief, hepti tissues ws homogenized in hot ethnol (8%) t tissue onentrtion of 1 mg ml 1 nd then entrifuged t 95 rpm for 2 minutes. The residue ws olleted, dried over wter th, nd then extrted t Cfor2 minutes y dding mixture of 5 ml wter nd 6 ml of 52% perhlori id. The olleted mteril ws entrifuged

3 Evidene-Bsed Complementry nd Alterntive Mediine 3 t 95 rpm for 15 minutes for reovery of the superntnt. From the reovered prt,.2 ml superntnt ws trnsferred in grduted test tue nd mde to 1 ml volume y the ddition of distilled wter. Grded stndrds were prepred using.1,.2,.4,.6,.8, nd 1. ml of working stndrd solution, nd volume of ll eh stndrd solution ws mde to 1 ml using distilled wter. Anthrone regent (4 ml) ws dded to ll the test tues nd the tues, were then heted in oiling wter th for 8 minutes, llowed to ool t room temperture, nd the intensity of the green to drk green olor of the solution ws reorded t 63 nm. Glyogen ontent of the smple ws determined from stndrd urve prepred with stndrd gluose solution Biohemil Assy of Antioxidnt Enzymes. The tivities of tlse of the liver, kidney, nd skeletl musles were mesured iohemilly [25]. For the evlution of tlsetivity, trget orgn of eh niml ws homogenized seprtely in.5 M Tris-HCl uffer solution (ph-7.) t the tissue onentrtion of 5 mg ml 1. These homogenized smples were entrifuged t 1, rpm t 4 C for 1 minutes. In spetrophotometri uvette,.5 ml of.35 M H 2 O 2 nd 2.5 ml of distilled wter were mixed nd reding of sorne ws noted t 24 nm. Superntnt of smple ws dded t volume of 4 μl nd the susequent six redings were noted t 3-seond intervl. The peroxidse tivity ws mesured in the ove-sid tissues, ording to the stndrd method [26]. The smples were homogenized in ie-old of.1 M phosphte uffer sline (ph-7.) t the tissue onentrtion of 5 mg ml 1. Next, 2 mm guiol ws mixed with.1 ml superntnt olleted from the homogente. In presene of.3 ml of 12.3 mm H 2 O 2, the time ws reorded for n inrese in the sorne y.1 t 436 nm Mesurement of Protein Metoli Disorders Serum Ure, Uri id, nd Cretinine. Levels of serum ure, uri id, nd retinine were mesured using kits from Merk Dignosti Ltd, Indi [27 29], following spetrometri methods. The vlues were expressed in mg dl 1 in ll the ses Mesurement of Lipid Metoli Disorders Serum Totl Cholesterol (TC), Lipoprotein Cholesterol, nd Triglyeride (TG). Serum TC ws quntified spetrophotometrilly [3] y the ddition of enzyme present in the regent kit (Spn Dignosti Ltd, Surt, Indi). The sorne of red quinoneimine omplex ws determined t 55 nm. The vlue of TC present in serum ws expressed in mg dl 1. Levels of serum low-density lipoprotein holesterol (LDL) nd very low-density lipoprotein holesterol (VLDL) were mesured ording to stndrd protool [31]. High-density lipoprotein holesterol (HDL) level ws mesured iohemilly [32]. Serum TG level ws mesured y using kit from Spn Dignostis Pvt. Ltd, Borod, Indi. The sorne ws mesured t 52 nm. The vlue ws expressed in mg dl 1 [33] Quntifition of Lipid Peroxidtion from Conentrtion of Thiorituri Aid Retive Sustne (TBARS) nd Conjugted Diene (CD) in Liver, Kidney, nd Skeletl Musles. The ove mentioned tissues were homogenized seprtely t the onentrtion of 5 mg ml 1 in.1 M of ieold phosphte uffer (ph-7.4) nd the homogentes were entrifuged t 1, rpm t 4 C for 5 min individully. Eh superntnt ws used for the estimtion of TBARS nd CD levels. For the quntifition of TBARS, the homogenized mixture of.5 ml ws mixed with.5 ml of norml sline (.9 g % NCl) nd 2 ml of TBA-TCA mixture (.392 g thiorituri id in 75mL of.25n HCl with 15g trihloroeti id). The volume of the mixture ws mde up to 1 ml y 95% ethnol nd oiled t 1 Cfor1 minutes. This mixture ws then ooled t room temperture nd entrifuged t 4 rpm for 1 minutes. The whole superntnt ws tken in spetrophotometer uvette, nd sorne ws red t 535 nm [34]. Quntifition of the CD ws performed y stndrd method [35]. In rief, the lipids from the homogente were extrted with hloroformmethnol (2 : 1) mixture followed y entrifugtion t 1 rpm for 5 min. The hloroform lyer ws evported to dryness under strem of nitrogen. The lipid residue ws dissolved in 1.5 ml of ylohexne nd the sorne ws noted t 233 nm to mesure the mount of hydroperoxide formed Sttistil Anlysis. Anlysis of vrine (ANOVA) followed y multiple omprison two-til t test ws used for sttistil nlysis of olleted dt [36]. Differenes were onsidered signifint t P<.5. All the vlues were indited in the figures s Men ± S.E.M (Stndrd Error of Men). 3. Results 3.1. Blood Gluose Level. Dietes indued y STZ resulted in signifint elevtion in lood gluose level in omprison to the ontrol group. After dministrtion of queousmethnoli (2 : 3) extrt of S. mhgoni seed to the dieti nimls for 21 dys, signifint redution in lood gluose level ws noted whih ws lose to the ontrol level (Tle 1) Hepti Glyogen Level. Hepti glyogen ontent ws deresed in the dieti ontrol group in omprison with the ontrol group. After tretment of this herl extrt to the dieti nimls, there ws signifint reovery in the glyogen ontent towrds the ontrol level (Figure 1) Ativities of CAT nd Px. Ativities of CAT nd Px in liver, kidney, nd skeletl musles were deresed signifintly in dieti ontrol group with respet to the ontrol group. After the tretment of queous-methnoli (2 : 3)

4 4 Evidene-Bsed Complementry nd Alterntive Mediine Tle 1: Effet of queous-methnol extrt of S. mhgoni seed on fsting lood gluose level in streptozotoin-indued dieti mle lino rt. Group Fsting lood gluose level (mg/dl) dy 1st dy 8th dy 15th dy 22nd dy 29th dy (2nd dy of (21st dy of (Dy of STZ extrt extrt dministrtion) tretment) tretment) ± ± ± ± ± ± 4.7 Dieti group ± ± ± ± ± ± ± ± ± ± ± ± 4.9 Dt re expressed s Men ± S.E.M; n = 6. ANOVA followed y multiple omprison two til t test. Vlues with supersripts (,,) in eh vertil olumn differ from eh other signifintly, P< towrds the ontrol level fter dministrtion of queousmethnoli extrt of the seeds of S. mhgoni to the dieti rt (Figure 4). μg of gluose/mg of tissue Dieti group Hepti glyogen 3.5. Serum Lipid Profile. Serum totl holesterol (TC) nd triglyeride (TG) levels were signifintly elevted in the dieti ontrol group in omprison with the ontrol group. After tretment with the ove-mentioned extrt to the dieti nimls, serum TC nd TG levels were reovered signifintly towrds the ontrol level (Figure 5). Other prmeters of this lipid profile like serum LDL nd VLDL levels were elevted nd serum HDL level ws deresed in the dieti ontrol group in respet to the ontrol. The levels of the ove-mentioned prmeters were reovered signifintly towrds the ontrol group fter tretment of the extrt of S. mhgoni seed when ompre with the dieti ontrol group (Figure 6) Levels of CD nd TBARS. Levels of CD nd TBARS in liver, kidney, nd skeletl musles were inresed signifintly in the dieti ontrol group when ompred to the ontrol group. Signifint reovery ws noted in the levels of the ove-mentioned prmeters in liver, kidney nd skeletl musles fter dministrtion of the seed extrt to the dieti niml (Figures 7 nd 8). Figure 1: Corretion of glyogen ontent in hepti tissue fter dministrtion of queous-methnoli extrt of S. mhgoni seed in STZ-indued dieti mle lino rt. Eh r represents Men ± S.E.M; n = 6. ANOVA followed y multiple omprison two til t test. Brs digrms with different supersripts (,,) differ from eh other signifintly, P<.5. extrt of S. mhgoni seed to STZ-indued dieti rt, the levels of ove enzyme tivities were resettled towrds the ontrol level (Figures 2 nd 3) Serum Ure, Uri id, nd Cretinine Levels. Serum ure, uri id, nd retinine levels were inresed signifintly in the dieti ontrol group with respet to the ontrol group. The levels of these prmeters were restored 4. Disussion The present study fouses the ntidieti, ntihyperlipidemi, nd ntioxidtive pities, s well s protein metoli disorders mngement effiy of the queousmethnoli extrt (2 : 3) of S. mhgoni seed in STZindued dieti mle lino rt. The pilot studies foused on the ft tht the queous-methnol (2 : 3) extrt ws the most effetive studied here out of the other extrts, for the orretion of ove sid disorders in STZ-indued dieti rt. Here, metoli disorders in STZ-indued dieti rt hve een estlished y the levels of lood gluose, hepti glyogen, serum ure, uri id, retinine, holesterol, triglyeride, nd lipoproteins. These results re in the sme line of our previous studies [1 12, 37] ndof others [38, 39]. Oxidtive stress developed in dieti stte is

5 Evidene-Bsed Complementry nd Alterntive Mediine mm of H2O2 onsumption/mg of tisssue (hr) μmofh2o2 onsumption/ mg of tissue Kidney Liver Skeletl musle Dieti group Dieti group () () Figure 2: Resettlement in the tivities of peroxidse in kidney, liver, nd skeletl musles fter dministrtion of queous-methnoli extrt of S. mhgoni seed in STZ-indued dieti mle lino rt. Br expressed s Men ± S.E.M; n = 6. ANOVA followed y multiple omprison two-til t -test. Brs with different supersripts (,,) differ from eh other signifintly, P<.5. Tissue (mg) Tissue (mg) Kidney Liver Skeletl musle Dieti group Dieti group () () Figure 3: Effet of queous-methnoli extrt of S. mhgoni seed on the tivities of tlse in kidney, liver, nd skeletl musles in STZindued dieti mle lino rt. Br represents Men ± S.E.M;n = 6. ANOVA followed y multiple omprison two-til t -test. Brs with different supersripts (,,) differ from eh other signifintly, P<.5. in prllel to our previous reports nd lso in greement with others [11, 12, 4 43]. Oxidtive stress in dieti model hs een foused here y the ssessment of CAT nd Px tivities in liver, kidney, nd skeletl musles, importnt iosensors for oxidtive stress ssessment [44, 45]. Dietesindued oxidtive stress hs een onfirmed here y the elevtion in the levels of end produts of free rdils, tht is, TBARS nd CD, inditors of oxidtive injury [46, 47]. Dietes-ssoited oxidtive stress is developed y mny iohemilpthwyssuhsgluoseutoxidtion,protein glytion, nd so forth [48]. In dietes, protein tolism is inresed due to defiieny of rohydrte-derived energy in onnetion with low-serum insulin [49]. This hs een indited here y high levels of serum ure, uri id, nd

6 6 Evidene-Bsed Complementry nd Alterntive Mediine (mg/dl) (mg/dl) Serum ure level.5 Serum uri id level Serum retinine level Dieti group Dieti group () () Figure 4: Corretion in the levels of ure, uri id, nd retinine in serum fter dministrtion of queous-methnoli extrt of S. mhgoni seed in STZ-indued dieti mle lino rt. Br represents Men ± S.E.M; n = 6. ANOVA followed y multiple omprison two-til t -test. Brs with different supersripts (,,) differ from eh other signifintly, P<.5. (mg/dl) (mg/dl) Serum HDL Serum LDL Serum VLDL Dieti group Serum holesterol Dieti group Serum triglyeride Figure 5: Corretion in the levels of totl holesterol nd triglyeride in serum fter tretment of queous-methnoli extrt of S. mhgoni seed in STZ-indued dieti mle lino rt. Br re expressed s Men ± S.E.M; n = 6. ANOVA followed y multiple omprison two-til t -test. Brs with different supersripts (,,) differ from eh other signifintly, P<.5. retinine. High-serum retinine level is lso the mrker of musle wstge [5]. All these metoli disorders in STZindued dieti rt were represented here y line digrm (Figure 9()). Glyemi ontrolling pity of the extrt in STZ indued dieti stte hs een supported here y the orretion of lood gluose, nd glyogen ontent in liver, importnt sensors in this onern [51]. The ovemntioned orretion my e due to insulin mimeti tion of the ove-mntioned extrt s insulin is one of the Figure 6: Effet of queous-methnoli extrt of S. mhgoni seed on serum high density lipoprotein holesterol (HDL), low density lipoprotein holesterol (LDL) nd very low density lipoprotein holesterol (VLDL) levels in STZ-indued dieti rt. Br represents Men ± S.E.M; n = 6. ANOVA followed y multiple omprison two-til t -test. Brs with different supersripts (,,) differ from eh other signifintly, P<.5. importnt regultors of glyogen synthesis [52]. Corretion of oxidtive injury whih is ssoited with dietes [53] is nother possiility of the reovery in glyemi disorders. The plnt extrt ws le to reover the protein metoli disorders possily y stimulting the existing βells nd or y regenerting βells like other plnt produts whih hve een limed y us [4]swellsyothers[15, 51]. Hyperlipidemi is ssoited with dieti stte [54] nd this my e due to uninhiited tion of lipse [55]. High levels of serum holesterol, triglyeride, LDL, nd VLDL long with low level of serum HDL in STZ-indued dieti stte foused the low level of serum insulin nd the results re onsistene to our previous findings [11] nd of others [56]. Sine insulin inhiits dipose tissue hormone sensitive lipse

7 Evidene-Bsed Complementry nd Alterntive Mediine 7 Tissue (nm/mg) Kidney Tissue (nm/mg) Liver Skeletl musle Dieti group () Dieti group () Figure 7: Effet of queous-methnoli extrt of S. mhgoni seed on the levels of onjugted diene (CD) in kidney, liver, nd skeletl musles in STZ-indued dieti mle lino rt. Br represents Men ± S.E.M; n = 6. ANOVA followed y multiple omprison two-til t -test. Brs with different supersripts (,,) differ from eh other signifintly, P<.5. Tissue (nm/mg) Tissue (nm/mg Kidney Liver Skeletl musle Dieti group Dieti group () () Figure 8: Corretion in the levels of thio-rituri id retive sustnes (TBARS) in kidney, liver, nd skeletl musles fter dministrtion of queous-methnoli seed extrt of S. mhgoni in STZ-indued dieti mle lino rt. Vlues expressed s Men ± S.E.M; n = 6. ANOVA followed y multiple omprison two-til t -test. Brs with different supersripts (,,) differ from eh other signifintly, P<.5. nd redues lipolysis, the queous-methnoli extrt of S. mhgoni seed my orret the ove mntioned disorders y mimiking insulin tion. The most exiting results nd the dditionl dvntge of this extrt over the existing drugs in this onern is the orretion of triglyeride nd elevtion in HDL level s the most of the drugs those deresed the lood level of triglyeride lso deresed the level of HDL [57]. High level of triglyeride nd low level of HDL re independently relted to moridity nd deths in dieti sujets y the indution of to oronry hert diseses [58, 59]. The extrt is le to orret the dietes-indued oxidtive injury whih hs een supported here y the elevtion in the tivities of ntioxidnt enzymes nd diminution in the quntity of the produts of the free rdils. This orretion my e due to the ntidieti effiy of this extrt tht prevents the retive oxygen speies genertion y preventing gluose utooxidtion nd y glytion. Another possiility is the presene of ntioxidtive types of neutreutil like flvonoids in the ove-mntioned extrt. From the ove results, the ntidieti potentility of queous-methnoli extrt of S. mhgoni seed my e

8 8 Evidene-Bsed Complementry nd Alterntive Mediine (+) High free rdil Oxidtive stress Low ntioxidnt enzyme tivity (+) STZ Islets of Lngerhns Islets of Lngerhns (ontrol) Islets of Lngerhns β ell degenertion Low serum insulin Norml liver glyogen () Low liver glyogen High lipid, ure, uri id nd retinine in serum Islets of Lngerhns Dieti islet Aqueous-methnoli extrt of S. mhgoni (neutreutils) Islets of Lngerhns β ell regenertion (+) (+) Minimiztion of oxidtive stress Mngement of lipid profile Reovery of protein metolism Reovery in serum insulin Low liver glyogen Liver with norml glyogen () Figure 9: Digrmmti representtion of dietes indution y STZ () nd the hypothetil wys the orretion of dietes-indued metoli disorders y queous-methnoli extrt of S. mhgoni (). explined y two wys. One wy my e the insulinotrophi effet of this extrt tht results orretion in lood gluose level, glyogen level in liver, the levels of serum lipid profile, nd io-sensors of protein metolism s ll of these re under the ontrol of serum insulin [6 62]. Another wy my e the oxidtive stress protetion whih is developed minly in metoli tissues in dietes. This hs een refleted here y the orretion of ntioxidnt enzyme tivities tht lowered the levels of end produts of free rdils. These ntioxidnt tivities lso protet the metoli enzymes in ells tht resettled the ellulr homeostsis towrds the norml level. The hypothetil view for the orretive effet of the plnt extrt on STZindued dieti hyperglyemi, hyperlipidemi, oxidtive injury, nd high-protein tolism my e expressed y the digrm (Figures 9() nd 9()). The speifi ioingredient(s) or neutreutils present in the extrt responsile for suh ntidieti tivity nnot e deteted ut this is under our oservtion nd would e foused from future work in this line.

9 Evidene-Bsed Complementry nd Alterntive Mediine 9 5. Conlusion In onlusion, it my e stted tht the queous-methnoli extrt of S. mhgoni seed my provide new therpeuti venue ginst dietes nd dietes-relted omplitions. Moreover, further work is neessry to serh out the tive ingredients present in this extrt hving ntidieti effiy. Extensive reserh is urrently tking ple in Indi, Chin, nd Kore nd in other ountries in order to develop potentil herl mediine to prevent metoli diseses inluding dietes nd its relted omplitions. Aknowledgment This study ws supported y grnt from Southern Helth Improvement Smity (SHIS), A Phrmeutil Industry to Professor Deids Ghosh. Referenes [1] S.M.Setter,R.K.Cmpell,ndC.J.Choon, Biohemil pthwys for mirovsulr omplitions of dietes mellitus, Annls of Phrmotherpy, vol. 37, no. 12, pp , 23. [2] G. Klein, J. Kim, K. Himmeldirk, Y. Co, nd X. Chen, Antidietes nd nti-oesity tivity of Lgerstroemi speios, Evidene-Bsed Complementry nd Alterntive Mediine, vol. 4, no. 4, pp , 27. [3] H. P. Rng, M. M. Dle, nd J. M. Ritter, Phrmology, Longmn Group Ltd, London, UK, [4] L. Pri nd R. Srvnn, Antidieti effet of disulin, herl drug, on lood gluose, plsm insulin nd hepti enzymes of gluose metolism hyperglyemi rts, Dietes, Oesity nd Metolism, vol. 6, no. 4, pp , 24. [5] P. Disy, R. Jsmine, S. Ignimuthu, nd E. Murugn, A novel Steroid from Elephntopus ser L. n Ethnomediinl plnt with ntidieti tivity, Phytomediine, vol.16,no.2-3, pp , 29. [6] World Helth Orgniztion, World Helth Orgniztion Expert Committee on Dietes Mellitus: Seond Report, Tehnil Report Series, no. 646, WHO, Genev, Switzerlnd, 198. [7] S. L. Bdole, N. M. Ptel, P. A. Thkurdesi, nd S. L. Bodhnkr, Intertion of queous extrt of Pleurotus pulmonrius (Fr.) Quel-Chmp. with Glyuride in lloxn indued dieti mie, Evidene-Bsed Complementry nd Alterntive Mediine, vol. 5, no. 2, pp , 28. [8] J. H. Hsu, Y. C. Wu, S. S. Liou, nd I. M. Liu, Medition of endogenous β-endorphin y tetrndrine to lower plsm gluose in streptozotoin-indued dieti rts, Evidene- Bsed Complementry nd Alterntive Mediine, vol. 1, pp , 24. [9] K. E. Innes nd H. K. Vinent, The influene of yogsed progrms on risk profiles in dults with type 2 dietes mellitus: systemti review, Evidene-Bsed Complementry nd Alterntive Mediine, vol. 4, no. 4, pp , 27. [1] R. Miti, U. K. Ds, nd D. Ghosh, Attenution of hyperglyemi nd hyperlipidemi in streptozotoin-indued dieti rts y queous extrt of seed of Tmrindus indi, Biologil nd Phrmeutil Bulletin, vol. 28, no. 7, pp , 25. [11] C. Mllik, R. Miti, nd D. Ghosh, Comprtive study on ntihyperglyemi nd ntihyperlipidemi effets of seprte nd omposite extrt of seed of Eugeni jmoln nd root of Mus prdisi in streptozotoin-indued dieti mle lino rt, Irnin Journl of Phrmology nd Therpeutis, vol. 5, no. 1, pp , 26. [12] C. Mllik, R. Miti, nd D. Ghosh, Antidietogeni effets of seprte nd omposite extrt of seed of Jmun (Eugeni jmoln) nd root of Kdli (Mus prdisi) in streptozotoin-indued dieti mle lino rt: omprtive study, Interntionl Journl of Phrmology, vol. 2, no. 5, pp , 26. [13] P. Ljuuni, H. Azizeh, U. Cogn, nd A. Bomzon, The effets of deotion prepred from the leves nd unripe fruits of Crtegus roni in streptozotoin-indued dieti rts, Journl of Complementry nd Integrtive Mediine, vol. 3, no. 1, rtile 6, 26. [14] A. Shrm, M. Vijykumr, C. V. Ro, M. K. Unnikrishnn, nd G. D. Reddy, Ation of Portul olere ginst streptozotoin-indued oxidtive stress in experimentl dieti rts, Journl of Complementry nd Integrtive Mediine, vol. 6, no. 1, rtile 1, 29. [15] M. Bht, S. K. Kothiwle, A. R. Tirmle, S. Y. Bhrgv, nd B. N. Joshi, Antidieti properties of Azrdirt indi nd Bouginville spetilis: in vivo studies in murine dietes model, Evidene-Bsed Complementry nd Alterntive Mediine, vol. 6, pp. 1 8, 29. [16] O. Sid, S. Fulder, K. Khlil, H. Azizeh, E. Kssis, nd B. Sd, Mintining physiologil lood gluose level with gluolevel, omintion of four nti-dietes plnts used in the trditionl Ar herl mediine, Evidene-Bsed Complementry nd Alterntive Mediine, vol.5,no.4,pp , 28. [17] B. Qin, M. Ngski, M. Ren, G. Bjotto, Y. Oshid, nd Y. Sto, Gosh-jinki-gn ( Herl Complex) orrets norml insulin signling, Evidene-Bsed Complementry nd Alterntive Mediine, vol. 1, pp , 24. [18] B. K. Ro, P. R. Sudrshn, M. D. Rjsekhr, N. Ngrju, nd C. A. Ro, Antidieti tivity of Terminli pllid fruit in lloxn indued dieti rts, Journl of Ethnophrmology, vol. 85, no. 1, pp , 23. [19] R. P. Rstogi nd B. N. Mehrotr, Compendium of Indin Mediinl Plnts, PID, New Delhi, Indi, 199. [2] A. P. Guevr, A. Apildo, H. Skuri, M. Kozuk, nd H. Tokud, Anti-inflmmtory, ntimutgeni nd ntitumor promoting tivities of Mhogny seeds, Swieteni mrophyll (Meliee), Philippine Journl of Siene, vol. 125, pp , [21] S. Joshi, Mediinl Plnts, Oxford nd IBH Pulishing Co. Pvt. Ltd., New Delhi, Indi, 2. [22] K. Shigetoshi, M. Lmik, K. Tohru, nd E. Hiso, Constituents of the seeds of Swieteni mhgny Jq, isoltion, struture nd 1 Hnd 13 C NMR signl ssignments of new tetrnor triterpenoids relted to swietenin nd swietenolide, Chemil & Phrmeutil Bulletin, vol. 38, pp , 199. [23] D.-D. Li, J.-H. Chen, Q. Chen et l., Swieteni mhgony extrt shows gonisti tivity to PPARγ nd gives meliortive effets on dieti d/d mie, At Phrmologi Sini, vol. 26, no. 2, pp , 25. [24] V. Bu, T. Gngdevi, nd A. Surmonim, Antidieti tivity of ethnol extrt of Cssi kleinii lef in streptozotoin-indued dieti rts nd isoltion of n tive

10 1 Evidene-Bsed Complementry nd Alterntive Mediine frtion nd toxiity evlution of the extrt, Indin Journl of Phrmology,, vol. 35, no. 5, pp , 23. [25] R.F.BeersJr.ndI.W.Sizer, Aspetrophotometrimethod for mesuring the rekdown of hydrogen peroxide y tlse, The Journl of Biologil Chemistry, vol. 195, no. 1, pp , [26] S. Sdsivm nd A. Mnikm, Biohemil Methods, New Age Interntionl, New Delhi, Indi, 28. [27] R. G. Mrtinek, Review of methods for determining ure nitrogen in iologi fluid, The Amerin Journl of Medil Tehnology, vol. 31, pp , [28] P. Fossti, L. Prenipe, nd G. Berti, Use of 3,5-dihloro- 2-hydroxyenzenesulfoni id/4-minophenzone hromogeni system in diret enzymi ssy of uri id in serum nd urine, Clinil Chemistry, vol.26,no.2,pp , 198. [29] K. Kpln nd L. L. Szo, Clinil Interprettion nd Tehniques, Lee nd Feiger, Phildelphi, P, USA, [3] C. C. Allin, L. S. Poon, nd C. S. G. Chn, Enzymti determintion of totl serum holesterol, Clinil Chemistry, vol. 2, no. 4, pp , [31] W. T. Friedewld, R. I. Levy, nd D. S. Fredrikson, Estimtion of the onentrtion of low-density lipoprotein holesterol in plsm, without use of the preprtive ultrentrifuge, Clinil Chemistry, vol. 18, no. 6, pp , [32] R. G. Weni nd J. J. Alert, A omprehensive evlution of the heprin mngnese preipittion proedure for estimtion high density lipoprotein holesterol, Journl of Lipid Reserh, vol. 19, pp , [33] M. W. MGown, J. D. Artiss, D. R. Strndergh, nd B. Zk, A peroxidse-oupled method for the olorimetri determintion of serum triglyerides, Clinil Chemistry, vol. 29, no. 3, pp , [34] H. Ohkw, N. Ohishi, nd K. Ygi, Assy for lipid peroxides in niml tissues y thiorituri id retion, Anlytil Biohemistry, vol. 95, no. 2, pp , [35] T. F. Slter, Overview of methods used for deteting lipid peroxidtion, Methods in Enzymology, vol. 15, pp , [36] R. R. Sokl nd F. J. Rohle, Biometry,WHFreemn,NewYork, NY, USA, [37] C. Mllik, K. Chtterjee, U. Mndl, nd D. Ghosh, Antihyperglyemi, ntilipidperoxidtive nd ntioxidtive effets of extrts of Mus prdisi nd Coini indi in streptozotoin indued dieti rt, Ethiopin Phrmeutil Journl, vol. 25, pp. 9 22, 27. [38] S. K. Singh, P. K. Ri, D. Jiswl, nd G. Wtl, Evidenesed ritil evlution of glyemi potentil of Cynodon dtylon, Evidene-Bsed Complementry nd Alterntive Mediine, vol. 5, no. 4, pp , 28. [39] E. M. Hlim nd H. Ali, Reversl of dieti retinopthy in STZ indued dieti rts using trditionl Indin ntidieti plnt, Azdirht indi (L.), Indin Journl of Clinil Biohemistry, vol. 17, pp , 22. [4] C. Mllik, S. Mndl, B. Brik, A. Bhtthry, nd D. Ghosh, Protetion of testiulr dysfuntions y MTEC, formulted herl drug, in streptozotoin indued dieti rt, Biologil nd Phrmeutil Bulletin, vol. 3, no. 1, pp. 84 9, 27. [41] H. A. H. Kty nd A. A. Hmz, Red ge (Brssi olere) meliortes dieti nephropthy in rts, Evidene- Bsed Complementry nd Alterntive Mediine, vol. 5, no. 3, pp , 28. [42] D. Tle-Senoui, H. Ghomri, D. Krouf et l., Antioxidnt effet of Ajug iv queous extrt in streptozotoin-indued dieti rts, Phytomediine, vol. 16, no. 6-7, pp , 29. [43] A. Eidi, M. Eidi, nd E. Esmeili, Antidieti effet of grli (Allium stivum L.) in norml nd streptozotoin-indued dieti rts, Phytomediine, vol. 13, no. 9-1, pp , 26. [44] M. Benderitter, L. Vinent-Genod, J. P. Pouget, nd P. Voisin, The ell memrne s iosensor of oxidtive stress indued y rdition exposure: multiprmeter investigtion, Rdition Reserh, vol. 159, no. 4, pp , 23. [45] I. S. R. Punith, K. Rjendrn, A. Shirwikr, nd A. Shirwikr, Aloholi stem extrt of Cosinium fenestrtum regultes rohydrte metolism nd improves ntioxidnt sttus in streptozotoin-niotinmide indued dieti rts, Evidene-Bsed Complementry nd Alterntive Mediine, vol. 2, no. 3, pp , 25. [46] J. Ji, X. Zhng, Y.-S. Hu et l., Evlution of in vivo ntioxidnt tivities of Gnoderm luidum polyshrides in STZ-dieti rts, Food Chemistry, vol. 115, no. 1, pp , 29. [47] P. Chturvedi, Inhiitory response of Rphnus stivus on lipid peroxidtion in lino rts, Evidene-Bsed Complementry nd Alterntive Mediine, vol. 5, no. 1, pp , 28. [48] A. Amin, M. Lotfy, M. Shfiullh, nd E. Adeghte, The protetive effet oftriulus terrestris indietes, Annls of the New York Ademy of Sienes, vol. 184, pp , 26. [49] K. S. Nir, D. Hllidy, D. E. Mtthews, nd S. L. Welle, Hyperglugonemi during insulin defiieny elertes protein tolism, Amerin Journl of Physiology, vol. 253, no. 2, pp , [5] J. Z. Luo nd L. Luo, Ginseng on hyperglyemi: effets nd mehnisms, Evidene-Bsed Complementry nd Alterntive Mediine, vol. 6, pp , 29. [51] E. Kokuun, S. M. Hirr, J. Fimonini, R. Curi, nd H. Heish, Chnges of glyogen ontent in liver, skeletl musle, nd hert from fsted rts, Cell Biohemistry nd Funtion, vol. 27, no. 7, pp , 29. [52] G. W. Cline, K. Johnson, W. Regittnig et l., Effets of novel glyogen synthse kinse-3 inhiitor on insulin-stimulted gluose metolism in Zuker dieti ftty (f/f) rts, Dietes, vol. 51, no. 1, pp , 22. [53] J.-H. Lee, J.-W. Prk, J.-S. Kim, B.-H. Prk, nd H.-W. Rho, Protetive effet of momi semen extrt on lloxn-indued pnreti β-ell dmge, Phytotherpy Reserh, vol. 22, no. 1, pp. 86 9, 28. [54] C. T. Kumrppn, T. N. Ro, nd S. C. Mndl, Polyphenoli extrt of Ihnorpus frutesens modifies hyperlipidemi sttus in dieti rts, Journl of Cell nd Moleulr Biology, vol. 6, no. 2, pp , 27. [55] O. Bngr, E. Jrld, S. Asghr, nd S. Ahmd, Antidieti tivity of polyherl formultion (Krnim Plus), Interntionl Journl of Green Phrmy, vol. 3, no. 3, pp , 29. [56]A.-S.A.Newiry,H.A.Mnsour,M.I.Yousef,ndS.A. Sheweit, Altertions of lipid profile in plsm nd liver of dieti rts: effet of hypoglyemi hers, Journl of Environmentl Siene nd Helth, Prt B, vol.37,no.5,pp , 22. [57] P. J. Rndle, P. B. Grlnd, C. N. Hles, nd E. A. Newsholme, The gluose ftty-id yle. Its role in insulin sensitivity nd the metoli disturnes of dietes mellitus, The Lnet, vol. 281, no. 7285, pp , 1963.

11 Evidene-Bsed Complementry nd Alterntive Mediine 11 [58] P. W. F. Wilson, High density lipoprotein, low density lipoprotein nd oronry hert disese, Amerin Journl of Crdiology, vol. 66, pp. 7 1, 199. [59]E.H.M.Temme,P.G.A.VnHoydonk,E.G.Shouten, nd H. Kesteloot, Effets of plnt sterol-enrihed spred on serum lipids nd lipoproteins in mildly hyperholesterolemi sujets, At Crdiologi, vol. 57, no. 2, pp , 22. [6] G. Vn Den Berghe, How does lood gluose ontrol with insulin sve lives in intensive re? Journl of Clinil Investigtion, vol. 114, no. 9, pp , 24. [61] N. Tzim, C. Pitsvos, D. B. Pngiotkos et l., Mediterrnen diet nd insulin sensitivity, lipid profile nd lood pressure levels, in overweight nd oese people; The Atti study, Lipids in Helth nd Disese, vol. 6, rtile 22, 27. [62] V. C. Kieh nd J. M. Luk, The effet of insulin on protein metolism, The Journl of Biologil Chemistry, vol. 328, pp , 1928.

12 MEDIATORS of INFLAMMATION The Sientifi World Journl Hindwi Pulishing Corportion Gstroenterology Reserh nd Prtie Hindwi Pulishing Corportion Journl of Hindwi Pulishing Corportion Dietes Reserh Hindwi Pulishing Corportion Hindwi Pulishing Corportion Interntionl Journl of Journl of Endorinology Immunology Reserh Hindwi Pulishing Corportion Disese Mrkers Hindwi Pulishing Corportion Sumit your mnusripts t BioMed Reserh Interntionl PPAR Reserh Hindwi Pulishing Corportion Hindwi Pulishing Corportion Journl of Oesity Journl of Ophthlmology Hindwi Pulishing Corportion Evidene-Bsed Complementry nd Alterntive Mediine Stem Cells Interntionl Hindwi Pulishing Corportion Hindwi Pulishing Corportion Journl of Onology Hindwi Pulishing Corportion Hindwi Pulishing Corportion Prkinson s Disese Computtionl nd Mthemtil Methods in Mediine Hindwi Pulishing Corportion AIDS Behviourl Neurology Hindwi Pulishing Corportion Reserh nd Tretment Hindwi Pulishing Corportion Hindwi Pulishing Corportion Oxidtive Mediine nd Cellulr Longevity Hindwi Pulishing Corportion

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