Potential impact of Novel Polyherbal Formulations on Streptozotocin-Nicotinamide Induced Diabetic wistar rats

Abstract

Diabetes is a chronic and group of metabolic disease which might lead to severe associated complications. Many synthetic anti-diabetic drugs used in first line treatment does not significantly control nor protect other organs from diabetes associated damage, but it increases the risk of developing complications due to their adverse effects. Hence, present research was designed to develop and evaluate polyherbal anti-diabetic formulations for the management of diabetes and its complications associated with liver, kidney and hematological parameters. Ethanolic extracts (50%) of four plants including calyx of Hibiscus sabdariffa (H), leaves of Annona squamosa (A), stem bark of Ficus religiosa (F) and leaves of Aegle marmelos (A), i.e., HAFA, were used for development of formulations by using geometrical dilution methods, which were named HAFA 1 to HAFA 24. To identify the most effective formulations, they were evaluated using oral glucose tolerance test (OGTT) in normal rats. Four most effective HAFA formulations selected were subjected to hypoglycemic study in normal rats, acute and sub-acute anti-hyperglycemic activity in streptozotocin-nicotinamide induced diabetic rats. HAFA formulations were further evaluated for the parameters like body weight change, food and water intake and biochemical parameters like lipid profile, cardiovascular risk and complete blood count using standard parameters. From the hypoglycemic studies of four most effective HAFA formulation, it was revealed that a single dose of HAFA 2, 4, 8 and 10 did not reduced the blood glucose below the normal level, whereas glibenclamide did and caused hypoglycemia. Streptozotocin-nicotinamide induced anti-hyperglycemic studies revealed that HAFA potentially reduced and maintained blood glucose level to near normal. Out of four formulations, HAFA 4 not only showed significant result in hypoglycemic study, but it also showed significant activities in both acute and sub acute anti-hyperglycemic study. In acute study HAFA 4 reduced fasting blood glucose by 48.96%, in sub-acute study reduction was observed 75.34% followed by HAFA 10, 2 and 8. Apart from that HAFA 4 significantly reversed and improved body weight change by 23% and water and food intake by 45 and 58%. HAFA 4 formulation significantly acted on biochemical parameters and increased plasma insulin by approx 117%, decreased HOMA-IR by 42%, HbA1c by 58% and significantly reversed the alteration of complete blood count, thus prevented from anemia. HAFA 4 significantly reverted the altered lipid profile to near normal. Thus, by research study it was concluded that, HAFA 4 formulations significantly improved glucose tolerance and effectively controlled blood glucose, without causing hypoglycemia. It significantly improved mean body weight, normalized food and water intake, corrected diabetes induced anemia, and reversed the altered lipid profile to near normal after 28 days of continuous treatment. Thus HAFA 4 was considered to be safer and effective antidiabetic with potential to prevent development of other associated complications.