Hypoglycaemic and antidiabetic effect of aqueous extract of leaves of Annona squamosa (L.) in experimental animal

Natural remedies from medicinal plants are considered to be effective and safe alternative treatment for diabetes mellitus. Our aim was to demonstrate the hypoglycaemic and antidiabetic activity of the water extract of Annona squamosa (custard apple) in diabetic animals with a view to explore its use for the treatment of diabetes mellitus in humans. Hot-water extract of the leaves of A. squamosa was prepared by boiling fresh and airdried leaves (25°C for 5 days) with water (20 ml/g) for 2 h and was tried by oral route in alloxan (80 mg/kg bw)-induced diabetic rabbits and streptozotocin (STZ) (50 mg/kg bw)-induced diabetic rats. The hot-water extract of leaves of A. squamosa at a dose 350 mg/kg bw reduced the fasting blood glucose (FBG) level slightly by 6.5% within 1 h and the peak blood glucose at 1 h during glucose tolerance test (GTT) was reduced by 15% in normal healthy rats. The same dose of water extract showed antidiabetic activity in two species of animals, namely rabbits and rats with induced diabetes. In the case of alloxan-induced diabetes in rabbits, a significant (P < 0.001) reduction in FBG by 24.4% and improvement in glucose tolerance as indicated by 36.8 and 40.5% fall in blood glucose at 1 h and 2 h during GTT was observed. In STZ diabetic rats also, there was 16.5% decrease in FBG, 24 and 67% reduction in blood glucose at 1 h and 2 h during GTT. After ten days of treatment of a group of STZ diabetic rats with 350 mg/kg bw of the water extract, there was 75.5% fall in FBG level and no sugar in fasting urine was observed. Treatment of alloxan-induced severely diabetic rabbits for 15 days with a dose of 350 mg/kg bw of extract reduced FBG by 48.7% and sugar in urine was reduced by 75%. It brought about fall in the levels of total cholesterol by 41.3% with increase of 29.14% in high density lipoprotein (HDL) cholesterol and 70% fall in low density lipoprotein (LDL) cholesterol, including 25% decrease in triglyceride (TG) levels. After 15 days of treatment, glycosylated haemoglobin level (HbA1c) was reduced by 30%, with a 10.8% increase of total haemoglobin. Extract enhanced the serum insulin level by 27.6% in diabetic animals during GTT and insulin release by 38.1% from isolated pancreatic islets. Water extract increases uptake of glucose in psoas muscles by 57% in the presence of insulin and inhibits glucose absorption by 18.1% through the isolated intestinal segments. Water extract inhibits the activity of glucose-6-phosphatase in isolated rat microsomes. No mortality was found up to 15 times the effective dose. The present study reveals that A. squamosa has both hypoglycaemic and antidiabetic activity. It seems to act by enhancing insulin level from pancreatic islets, increased utilization of glucose in muscle and inhibited the glucose output from liver. It reverses the abnormal lipid profile seen in diabetic animals. Its margin of safety is high. Extract obtained from leaves of A. squamosa is useful in maintaining healthy blood sugar and cholesterol levels.