Antidiabetic effects of ethanolic extract of pheria. macrocarpa (scheff) boer.l fruits on streptozotocin-induced rats

Abstract

Traditionally P. macrocarpa fruits have been used as an herbal anti diabetic remedy for a long time in South-East Asia. The purpose of this study was to evaluate the cytotoxicity, acute oral toxicity and antidiabetic effects of Phaleria macrocarpa (EEPM) fruits in streptozotocin-induced Sprague-Dawley rat model. The plant fruits were extracted using 70% ethanol followed by cold maceration. Brine shrimp lethality bioassay, using sea water was prepared by dissolving 38 g sea salt in 1 liter distilled water for two days, this is allowed to hatch the shrimp to nauplii and potassium dichromate was used as a positive control. In an acute oral toxicity study, twelve male adult Sprague-Dawley rats (10 weeks) weighing 180-200 g were divided into Group-I (Control- 10% normal saline) and Group-II (extract), n=6. The fruit extract (5000 mg/kg/b.w) was given orally to each rat and observation carefully at 4 and 6 hr intervals for any physical changes. In antidiabetic study, a total of thirty-six healthy adult male rats were divided into six groups (n=6). Diabetes was induced under light ether anesthesia by a single dose (65 mg/kg/b.w) of intraperitoneally injected streptozotocin. Their glycemic status (Oral glucose Tolerance Test) was re-evaluated intermittently at 0, 30, 60, 90 and 120 min, respectively. Blood sugar level (mg/dl) and body weight of each rat in the respective groups were repeatedly measured on day 0, 7, 14, 21, 28 and 35 of the experiment. The findings of the present toxicity study suggest that the ethanol extract of EEPM fruits is non-toxic. It was found that the EEPM at 50, 100 and 200 mg/kg and glibenclamide (0.5 mg/kg) reduced the blood glucose level (hyperglycemia due to glucose load 2 g/kg p.o.) significantly after 2 hr of oral administration, when compared to the diabetic control group. The repeated oral administration of EEPM daily up to 35 days exhibited significant (p˂0.01) blood glucose activity in STZ-induced diabetic rats compared with diabetic control. At the end of 35 days of treatment, the blood glucose level of normal control, drug control and diabetic control was 132.16±5.79, 134.33±7.18 (p˂0.01) and 514.83±7.96 respectively. In the treatment groups, the dose of EEPM 200 mg/kg (392.66±3.2 to 174.33±4.3 mg/dl, p˂0.01) was shown to be more effective than EEPM 100 mg/kg (392.5±3.9 to 240.5±9.2, p?0.05) and EEPM 50 mg/kg 395.66±4.4 to 284.66±4.8 (p˂0.05). However, all selected doses showed antidiabetic activity gradually in STZ-induced diabetic rats. In histopathological examination results showed the pancreas of diabetic control were degranulated and dilated islet cells, whereas the drug control group showed granulated, nonappearance of dilation and hyperplasticity of islets. In treatment groups (EEPM at 100 and 200 mg/kg) also showed granulated pancreatic islets and prominent hyper plasticity islets. Light micrographs of rat kidney tissue in treatment groups showed various regions of the kidneys of treated animals with absence of matrix expansion and glomerular basement membrane thickening suggesting normal histoarchitecture of pancreas and renal. Biochemical aspects of the treated animal group were almost similar to the drug control group except the EEPM 50mg/kg group. In conclusion, EEPM may also serve as a good alternative in the present armamentarium of antidiabetic drugs. Keywords: P. macrocarpa, Toxicity, Antidiabetic, Histopathology, Kidney, Pancreas, Streptozotocin.