|ISSN No. 1606-7754 Vol.17 No.1 April 2009|
Anti-hyperglycaemic activity of IND 01 and its interaction with glyburide and pioglitazone in alloxan induced diabetic mice
Prasad P Shitole,1 Sachin L Badole,1 Subhash L Bodhankar,1 Mohan V,2 Sunil Bhaskaran2
Department of Pharmacology, Poona College of Pharmacy, Bharati Vidyapeeth University1.Indus Biotech Private Ltd, Maharashtra2, India
The antihyperglycaemic activity of IND 01 and its interaction with glyburide and pioglitazone on serum glucose, body weight and oral glucose tolerance test (OGTT) was determined in alloxan-induced diabetic mice. IND 01 (100 mg/kg), glyburide (10 mg/kg), pioglitzone (10 mg/kg) and their concomitant administration were administered orally in alloxan (80 mg/kg, i.v.) induced diabetic mice. The study design consisted of estimation of serum glucose after acute, subacute and glucose load administration. Administration of IND 01 (100 mg/kg) alone significantly (p<0.001) reduced serum glucose level at 6 h after administration. The antihyperglycaemic effect of glyburide and their concomitant administration of IND 01 with glyburide were similar, that is, onset was 2 h; peak effect was 6 h but the effect waned at 24 h. The onset of concomitant administration of IND 01 with pioglitazone was 4 h; peak effect was at 6 h but the effect waned at 24 h. In the subacute study, reduction in serum glucose was observed on 28th day after withdrawal for 7 days. The effects of concomitant administration were more pronounced than single drug treatment. In mice treated with either IND 01 (100 mg/kg), glyburide, pioglitazone alone or their combination, the body weight was not reduced in contrast to that in the control group. In the oral glucose tolerance test (OGTT), increased glucose utilization was observed in animals after concomitant administration of IND 01 (100 mg/kg) and glyburide (10 mg/kg) as well as IND 01 (100 mg/kg) and pioglitazone (10 mg/kg). The concomitant administration of IND 01 with glyburide as well as pioglitzone produced synergistic antihyperglycaemic effect than either drug alone.
Keywords: Antihyperglycaemic, OGTT, IND 01, glyburide, pioglitazone
Diabetes mellitus is a metabolic disorder treated by oral hypoglycemic agents such as sulphonylureas, biguanides, thiazolidinediones, meglitinide derivatives, and alpha glucosidase inhibitors.1 IND 01 contains 40% 4-hydroxyisoleucine, 30% trigonelline and 30% galactomannan isolated from seeds of Fenugreek (Trigonella foenum-graecum L. Family: Leguminasae).
Fenugreek (Trigonella foenum-graecum) locally called as Methi; is one of the oldest medicinal plants, originating in India.2 Fenugreek seed contain trigonelline, 4-hydroxyisoluecine, flavonoids, carotinoids, coumarins, proteins, saponins, lipids, galactomanan.2,3 Galactomanan are polysaccharides consisting of mannose backbone with galactose side groups. The galactomannan in Trigonella foenum-graecum seed contain galactose and mannose in the ratio 48:52.
The antidiabetic effect of 4-hydroxyisoluecine4-7 trigonelline8,9 have been reported. In view of the antidiabetic effect of fenugreek seeds a formulation containing three pure compounds isolated from seeds of fenugreek was prepared for first time. Therefore the present study was to study the antihyperglycaemic activity of this compound in diabetic mice, in order to access the suitability of this formulation. A study of the interaction of this compound with glyburide and pioglitazone was also undertaken. No study has yet been undertaken to evaluate the herb-drug interaction in terms of onset, rate and extent of effect, duration and effect on the dose of glyburide and pioglitazone with IND 01. The objective of the present investigation was to study the antihyperglycaemic activity of IND 01 2) and its interaction with glyburide and pioglitazone on serum glucose, body weight and oral glucose tolerance test (OGTT) in alloxan-induced diabetes in mice.