Hypoglycemic Activity of Polygala erioptera (Whole Plant) in Normal and Alloxan Induced Diabetic Rats

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1 Asin Journl of Chemistry Vol. 20, No. 1 (2008), Hypoglycemic Activity of Polygl eriopter (Whole Plnt) in Norml nd Alloxn Induced Dibetic Rts G. SAMMAIAH* nd R.S. SRIVASTAVA Deprtment of Phrmceutics, Institute of Technology Bnrs Hindu University, Vrnsi , Indi E-mil: g_smmih@rediffmil.com Investigtions were crried out to find out the hypoglycemic ctivity of lcoholic extrct of Polygl eriopter Linn, in norml nd dibetic lbino rts nd to evlute its probble mechnism of hypoglycemic ctivity if ny. Orl nd intrperitonel dministrtion of the plnt produced significnt hypoglycemic effect in norml s well s hyperglycemic rts. It is suggested tht the hypoglycemic ctivity of this plnt my be medited through enhncement of peripherl metbolism of glucose nd increse in insulin relese. Key Words: Polygl eriopter, Dibetes mellitus. INTRODUCTION Dibetes mellitus is n endocrine disorder chrcterized by hyperglycemi effecting nerly 10 % of the popultion ll over the world. Insulin nd orl hypoglycemeic gents like sulphonylures nd bigunides re still the mjor plyers in the mngement of the disese. However, complete cure of the disese hs been eluding physicins for centuries nd the quest for the development of more effective ntidibetic gents is pursued relentlessly. Mny herbl products, including severl metls nd minerls hve been described for the cure of dibetes mellitus in ncient literture. Herbl preprtions lone or in combintion with orl hypoglycemic gents sometimes produce good therpeutic response in some resistnt cses where modern medicines lone fil. There is incresing demnd by ptients to use nturl products with ntidibetic ctivity due to side effects ssocited with the use of insulin nd orl hypoglycemic gents. The World Helth Orgniztion hs lso recommended the evlution of the effectiveness of plnts in condition where there is lck of sfe mde drugs. Currently vilble tretment for this disorder is fr from stisfctory nd expensive. Polygl eriopter Linn. (Fmily: Polyglcee) is smll tree vriety found throughout Indi including the Telngn region. It is commonly clled Nel Jnumu in Telugu nd Surjvrt in Snskrit 1,2. It is

2 108 Smmih et l. Asin J. Chem. widely used for heling of wounds, effecive ginst chronic white dischrge (leucori), ntibcteril nd ntifungl 3,4. It is found to be muscrinic effect. The preliminry phytochemicl studies revel the presence of flvnoid glycosides nd flvones, flvnoids, lignns, ftty cids. The focus of the present study is to evlute lcoholic extrct of Polygl eriopter whole plnt mteril t vrious doses in norml nd lloxn induced dibetic rts. However, no scientific dt re vilble regrding the effect of Polygl eriopter on blood glucose levels. The present study is undertken to explore the effect of Polygl eriopter whole plnt extrct on the blood glucose level of experimentl nimls nd to determine the probble mechnism of ction. The effect of the lcoholic extrct of Polygl eriopter on fsting blood sugr level hs been evluted s compred to the stndrd drug glibenclmide, both in norml nd dibetic lbino rts. The effects of Polygl eriopter extrct on glucose uptke by rt hemi-diphrgm nd the glycogen content of the liver, skeletl muscle nd crdic muscle re evluted to study its probble mechnism of ction s hypoglycemic gent. EXPERIMENTAL Polygl eriopter Linn. whole plnt mteril ws collected during riny seson in the month of August freshly in nd round The Kktiy University, Wrngl, South Indi. The botnist Dr. V.S. Rju, Deprtment of Botny, Kktiy University, Wrngl, identified the plnt. Alcoholic extrction: Alcoholic extrct ws prepred from powder of the whole plnt mteril of Polygl eriopter prepred in electric grinder. The 500 g powder ws extrcted with lcohol (95 % v/v) in soxhlte pprtus. The extrct ws evported to dryness under vcuum nd dried in vcuum desicctor (15.5 % w/w). Animls nd experimentl set-up: Colony bred, helthy mle Wistr lbino rts (NIN strin) of either sex weighing g were tken for the study. The nimls were fed on stndrd lbortory diet with wter d libitum nd housed t room temperture. The rts were kept fsting overnight with free ccess to wter during the experiment in the sme mbience. The nimls were divided into three groups of six nimls ech. 1 ml of blood ws tken from the orbitl sinus of ech rt with the help of cpillry tube for the estimtion of blood sugr. The Institutionl Ethics Committee pproved ll experimentl protocols. Hypoglycemic effect in norml rts: Groups of eight rts ech (fsted for 18 h) received 10 ml/kg of the infusion, intrgstriclly (p.o.) or intrperitonelly (i.p.). Blood smples were drwn by puncture from the til immeditely before dministrtion nd fter dministrtion in the time intervls of 20, 60, 120, 240 nd 360 min lter. Control group received n

3 Vol. 20, No. 1 (2008) Hypoglycemic Activity of Polygl eriopter 109 equl volume (10 ml/kg) of norml sline, glibenclmide (0.13 mg/kg) nd metformin (11.3 mg/kg), clculted on the bsis of the dily doses (5 nd 850 mg, respectively) for mn weighing 75 kg were used s refer ence drugs 5. Hypoglycemic effect on lloxn-dibetic rts: Chroniclly hyperglycemic rts were obtined by i.p. injection of 150 mg/kg of lloxn dissolved in distilled wter 6. After 8 h dministrtion, the hyperglycemic rts were selected (plsm glucose level g/l) nd used in the experiments. The sme experimentl protocol described bove ws then dopted. Glucose tolernce test (GTT) in rts: A polyethylene cnnul ws injected into the jugulr vein under ethyl crbmte nesthesi. Another ctheter ws injected into right crotid. All rts received orlly 10 ml/kg of 25 % glucose solution. One group of nimls received the plnt infusion (10 ml/kg) through the venous ctheter, while the control group received norml sline. Blood smples (0.2 ml) were tken from the crotid ctheter t time intervls of 5, 10, 20, 30, 40, 50 nd 60 min fter injection. The coefficient of glucose ssimiltion (K G ) ws determined with the formul. K G = (log C log C/2) T ½ = 0.639/T ½ where: C = glycemi (g/l); T ½ : Time for the blood glucose concentrtion C/2. Sttisticl nlysis: Results re reported s men ± SEM sttisticl nlysis ws crried out using nlysis of vrince (Anov). The difference of the mens ws clculted using Newmn-Keuls test. P vlues of 0.05 or less were tken s significnt. RESULTS AND DISCUSSION The infusion of Polygl eriopter exhibited remrkble hypoglycemic ction 20 min fter orl nd i.p. dministrtion to norml rts (Tble- 1). Blood glucose level reched men vlue of 0.59 nd 0.68 g/l, respectively compred to 1.02 g/l obtined in the control group. The lowest hypoglycemic effect ws observed 2 h fter tretment. After 4 h dministrtion, the blood glucose level rose to rech the initil glycemi vlues for orlly treted nimls, while i.p. dministrtion still showed hypoglycemic effect even fter 6 h. Polygl eriopter hypoglycemic effect ws comprble nd sometimes higher thn tht obtined with 0.13 mg/kg of glibenclmide or 11.3 mg/kg of metformin. After i.p. dministrtion, the vrition in insulin plsm levels showed n opposite trend to tht of glucose (Tble-2). The increse becme significnt fter 1 h of dministrtion nd persisted for t lest 6 h. Plsm insulin reched mximum level ( µiu/ml) 4 h fter i.p. dministrtion.

4 110 Smmih et l. Asin J. Chem. TABLE-1 EFFECT OF P. eriopter ON PLASMA GLUCOSE LEVELS AFTER INTRAGASTRIC (p.o.) AND INTRAPERITONEAL (i.p.) ADMINISTRATION TO NORMOGLYCAEMIC RATS Plsm glucose (g/l) t time (min) fter tretment Tretment Route Control p.o ± ± ± ± ± ± 0.07 (sline. 10 ml/kg) i.p ± ± ± ± ± ± 0.08 Glibenelmide p.o ± ± 0.11* 0.46 ± ± ± ± 0.05 (o.13 mg/kg) i.p ± ± 0.1* 0.48 ± ± ± 0.06* 0.93 ± 0.13 Metformin P.o ± ± 0.06* 0.65 ± 0.1* 0.54 ± ± 0.06* 0.93 ± 0.13 (11.3 mg/kg) i.p ± ± 0.05* 0.57 ± ± 0.05* 0.74 ± ± 0.05 P.eriopter p.o ± ± ± ± ± ± 0.06 (0.7 g/kg) i.p ± ± ± ± ± ± 0.08 Vlues re men ± SEM, n = 8. *p < 0.05; p < 0.01; p < vs. control; Anov nd Newmn Keuls (test). TABLE-2 PLASMA INSULIN IN NORMOGLYCAEMIC RATS AFTER INTRAGASTRIC (p.o.) AND INTRAPERITONEAL (i.p.) ADMINISTRATION OF P. eriopter Insulinemi (uiu/ml) t time (min) fter tretment Tretment Route Control P.o ± ± ± ± ± ± 6.16 (sline. 10 ml/kg) i.p ± ± ± ± ± ± 7.91 P. eriopter p.o ± ± ± ± ± ± (0.7 g/kg) i.p ± ± ± 7.16* ± ± ± Vlues re men ± SEM, n = 8; *p < 0.01; p < vs. Control; Anov nd Newmn Keuls test.

5 Vol. 20, No. 1 (2008) Hypoglycemic Activity of Polygl eriopter 111 TABLE-3 EFFECT OF P. eriopter ON PLASMA GLUCOSE LEVELS AFTER INTRAGASTRIC (p.o.) AND INTRAPERITONEAL (i.p.) ADMINISTRATION TO ALLOXAN-DIABETIC RATS Plsm glucose (g/l) t time (min) fter tretment Tretment Route Control P.o ± ± ± ± ± ± 0.48 (sline. 10mL/kg) i.p ± ± ± ± ± ± 0.51 Glibenclmide p.o ± ± ± ± ± ± 0.34 (0.13 mg/kg) i.p ± ± ± 0.47* 0.88 ± 0.11* 1.44 ± 0.22* 1.70 ± 0.34 Metformin p.o ± ± ± ± ± ± 0.47 (11.3 mg/kg) i.p ± ± ± 0.41* 1.63 ± 0.25* 1.50 ± 0.35* 1.80 ± 0.30* P.eriopter p.o ± ± 0.53* 1.05 ± ± ± ± 0.20.y.x (0.7 g/kg) i.p ± ± ± ± ± ± 0.19.b.x Vlues re men ± SEM, n = 8. *p < 0.05; p < 0.01; p < vs. control; b p < 0.05 vs. glibenclmide; x p < 0.05; y p < 0.01 vs. metformin; Anov nd Newmn Keuls test. TABLE-4 BLOOD GLUCOSE IN GLUCOSE LOADED (0.25 g/kg) RATS BEFORE AND AFTER THE INTRAVENOUS ADMINISTRATION OF P. eriopter Blood glucose (g/l) t time (min) fter lod Tretment Control (o.25 g/kg glucose) P. eriopter (0.7 g/kg) 0.99 ± ± ± ± ± ± ± ± ± ± ± ± ± 0.08* 1.31 ± ± ± 0.13 Vlues re men ± SEM, n = 5. *p < 0.05; p < 0.01; p < vs. control; Anov nd Newmn Keuls test.

6 112 Smmih et l. Asin J. Chem. On the other hnd, no vrition in blood insulin level ws found in norml rts orlly treted with the PA extrct. When compred with the control, P. eriopter (Tble-3) significntly reduced the blood glucose levels in dibetic rts. The mximum decrese observed 2 h fter the dministrtion in plsm glucose level recorded s [1.01 g/l ( %) nd 0.79 g/l ( %), respectively fter orl nd i.p. tretment. In glucose tolernce test, intrvenous tretment with P. eriopter significntly reduced t time intervls of 30, 40, 50 nd 60 min nd the increse in plsm glucose level induced by glucose lod dministrtion (Tble-4). Glycemic vlues returned to bsl levels more rpidly thn in control group. The coefficient of glucose ssimiltion (KG) showed significnt increse in treted rts compred to control ( vs ). In conclusion, P. eriopter showed hypoglycemic effect in normoglycemic nd hyperglycemic rts fter both orl nd intrperitonel dministrtion. The effect could be comprble to tht of well known hypoglycemic compounds like metformin nd glibenclmide used t 11.3 nd 0.13 mg/kg, respectively. As fr s the mechnism of ction is concerned, in the light of the obtined results it cn be speculted tht P. eriopter ctivity could be due to n enhncement of peripherl metbolism of glucose. An increse of insulin relese cnnot be excluded. Further studies to identify the ctive constituents of P. eriopter nd their mechnism of ction re in progress. ACKNOWLEDGEMENT The uthors express their grtitude to the University Grnts Commission, Government of Indi, for finncil ssistnce to crry out this study. REFERENCES 1. A.B. Rendle, The Clssifiction of Flowering Plnts, The Syndics of the Cmbridge University Press, London, Vol. 2, p. 304 (1952). 2. R.D. Gibbs, Chemotxonomy of Flowering Plnts, McGill Queen's University Press, London, Vol. 2, p. 839 (1974). 3. S. Ghosl, G. Kumrswmy, R.B.S. Chuhn nd R.S. Srivstv, Phytochemistry, 12, 2550 (1973) 4. S. Ghosl, R.P.S. Chuhn nd R.S. Srivstv, Phytochemistry, 13, 2281 (1974). 5. I. Adde-Menzh nd R.W. Munenger, Fitoterpi, 60, 359 (1989) 6. A. Trovto, R.I. Forestie, L. luk, R. Brber, M.T. Monforter nd E.M. Glti, Plnt Med. Phytother., 26, 300 (1993). (Received: 19 August 2006; Accepted: 13 August 2007) AJC-5793