The oral administration of AEPP and AESP did not show any toxicity signs and mortality up to 14 days during acute toxicity study. Both the powders were found to be safe at a dose level of 2000 mg/kg body weight. Therefore, to study the antidiabetic potential of AEPP and AESP, the dose of 100 and 200 mg/kg was selected. In animals, diabetes was induced after the administration of STZ due to its cytotoxicity on pancreatic islet β-cells.[25
] The selective toxicity on β-cell, by alkylation of DNA after the STZ injection, produces reduction in insulin level, which leads to alteration of glucose metabolism and utilization thereby causing hyperglycemia.[26
] Moreover, intracellular metabolism of STZ produces nitric oxide (NO) free radical and it further initiates the alkylation of β-cells DNA strands and its breaks.[27
] In our study, administration of AEPP (100 and 200 mg/kg) and AESP (100 and 200 mg/kg) decreased elevated blood glucose levels significantly (P
< 0.001) from first to fourth week compared to diabetic control rats. The AEPP and AESP at a dose 200 mg/kg showed significantly (P
< 0.001) more blood glucose reduction than its 100 mg/kg dose. Also, treatment of both the doses of AESP significantly (P
< 0.001) produced greater blood glucose reduction when compared to AEPP 100 and 200 mg/kg dose . There are many reports available to support the multiple mechanisms of antidiabetic plants to exert their blood glucose lowering effect, such as inhibition of carbohydrate metabolizing enzymes, enhancement of insulin sensitivity, regeneration of damaged pancreatic islet β-cells, and enhancement of insulin secretion and release.[28
] The AEPP and AESP may exert blood glucose lowering activity possibly above mechanism(s) and the antidiabetic activity of both powders was comparable to that of glibenclamide. A significant (P
< 0.001) body weight loss was observed after the administration of STZ and it may be due to the degradation of structural proteins.[29
] In our study, AEPP and ASEP treated animals showed significant (P
< 0.05, P
< 0.01, P
< 0.001) increase in body weight compared to diabetic control . This action may be due to the preventive effect of AEPP and AESP on structural protein degradation.
Effect of AEPP and AESP on blood glucose level in STZ-induced diabetic rats
Figure 1 Effect of AEPP and AESP on body weight in STZ-induced diabetic rats.(All data are expressed as mean ± SEM (n=6). aP < 0.001 All groups compared with normal control. bP < 0.001 Diabetic control compared to normal control. cP < (more ...)
Glycosylated hemoglobin is formed through the nonenzymatic binding of circulating glucose to hemoglobin. Higher levels of glucose in the blood contribute to more binding and consequent increased levels of glycosylated hemoglobin.[30
] In diabetic condition, decrease in protein synthesis in all tissues and thus the synthesis of hemoglobin is also reduced due to relative deficiency of insulin.[31
] HbA1c concentration is associated with diabetic micro, macrovascular complications and risk of death.[30
] In the present study, increased level of HbA1c and decreased level of Hb and total protein was observed in diabetic control rats than normal control rats. Total protein level was significantly (P
< 0.001) increased after the administration of both doses of AEPP and AESP compared with diabetic control rats. Also, administration of AEPP and AESP significantly (P
< 0.001) reduced elevated HbA1c levels and increased the Hb level in diabetic rats . The above actions indicate that AEPP and AESP have potential to prevent the diabetic associated complications.
Effect of AEPP and AESP on Hb, HbA1c, total protein, and SGPT in STZ-induced diabetic rats
The liver damage produced by administration of STZ leads to leakage of SGPT from liver cytosol into the blood stream which in turn increases its level in serum.[29
] In the present study, the significant (P
< 0.001) increase in serum SGPT was observed in STZ-induced diabetic rats compared to control rats . It represents that liver damage occurred in diabetic rats and oral administration of AEPP and AESP significantly (P
< 0.001) reduced the elevated level of SGPT, which supports its protective potential on liver tissue.
Hyperlipidemia was reported as common in adults with diabetes and it is characterized most often by increased triglyceride and reduced HDL cholesterol levels. This is generally observed in both type 1 and type 2 diabetes, representing the defect of insulin action in each, either due to inadequate secretion or resistance. It is well known that hyperlipidemia is accepted as an independent risk factor for cardiovascular disorders (CVD) in diabetic patients.[34
] Diabetes induced by STZ in rats significantly (P
< 0.001) elevated the TC, TG, LDL, VLDL levels and decreased the HDL levels compared with normal control rats. In the present study, administration of AEPP and AESP at 100 and 200 mg/kg doses to the diabetic rats showed significant (P
< 0.001, P
< 0.05) reduction in TC, TG, LDL, and VLDL levels than diabetic control rats. The HDL level was increased significantly (P
< 0.001) after the treatment of both the dose of AEPP and AESP in diabetic rats compared with diabetic control rats . These actions of AEPP and AESP directly support its ability to reduce hyperlipidemia in diabetes and hence, it may prevent CVD related to diabetes.
Effect of AEPP and AESP on lipid profiles in STZ-induced diabetic rats