Synthesis, Spectral Characterization, and Biochemical Evaluation of Antidiabetic Properties of a New Zinc-Diosmin Complex Studied in High Fat Diet Fed-Low Dose Streptozotocin Induced Experimental Type 2 Diabetes in Rats

Abstract

In view of the established antidiabetic properties of zinc, the present study was aimed at evaluating the hypoglycemic properties of a new zinc-diosmin complex in high fat diet fed-low dose streptozotocin induced experimental type 2 diabetes in rats. Zinc-diosmin complex was synthesized and characterized by various spectral studies. The complexation between zinc ions and diosmin was further evidenced by pH-potentiometric titrations and Job's plot. Diabetic rats were orally treated with zinc-diosmin complex at a concentration of 20 mg/kg b.w./rat/day for 30 days. At the end of the experimental period, the rats were subjected to oral glucose tolerance test. In addition, HOMA-IR and various biochemical parameters related to glucose homeostasis were analyzed. Treatment with zinc-diosmin complex significantly improved the glucose homeostasis in diabetic rats. Treatment with zinc-diosmin complex significantly improved insulin sensitivity, at least in part, through enhancing protein metabolism and alteration in the levels of muscle and liver glycogen. The assay of clinical marker enzymes revealed the nontoxic nature of the complex. Determination of renal tissue markers such as blood urea and serum creatinine indicates the renoprotective nature of the complex. These findings suggest that zinc-diosmin complex is nontoxic and has complimentary potential to develop as an antihyperglycemic agent for the treatment of diabetes mellitus.

Antihyperglycaemic action of diosmin, a citrus flavonoid, is induced through endogenous β‐endorphin in type I‐like diabetic rats

“…Previous research has demonstrated that chronic diosmin treatment significantly increased plasma insulin and improved diabetic symptoms in STZ‐NA‐induced diabetic rats . In HFD‐STZ induced type 2 diabetic rats, oral administration of zinc‐diosmin complex leads to improve insulin secretion . However, in the present study, the plasma insulin level was not influenced by diosmin, even at the highest dose in STZ‐diabetic rats.…”

“…6,11 In HFD-STZ induced type 2 diabetic rats, oral administration of zinc-diosmin complex leads to improve insulin secretion. 12 However, in the present study, the plasma insulin level was not influenced by diosmin, even at the highest dose in STZ-diabetic rats. Therefore, the hypoglycaemic action of diosmin in STZ-induced type 1 diabetes rats seems not to be associated with the endogenous insulin.…”

“…Diosmin has also been demonstrated to affect the rate‐limiting enzymes of carbohydrate metabolism and was found to reverse the abnormalities in glycoprotein components in type‐2 DM rats . A new complex of Zn‐diosmin has recently been developed to improve another model of type‐2 DM rats . However, the potential mechanisms of diosmin action have yet to be elucidated.…”

“…6 A new complex of Zn-diosmin has recently been developed to improve another model of type-2 DM rats. 12 However, the potential mechanisms of diosmin action have yet to be elucidated.…”

Synthesis and Evaluation of Antidiabetic Properties of a Zinc Mixed Ligand Complex in High-Fat Diet - Low-Dose Streptozotocin-Induced Diabetic Rats

“…Ever since in 1980, Coulston and Dandona reported the insulin mimetic activity of zinc ions, several research groups developed insulin mimetic zinc complexes with various coordination modes around zinc (II) ion and evaluated its glucose normalizing effect [14]. In the recent past, we have synthesized several new zinc complexes such as zinc-flavonol [15], zinc-morin [16], zinc-silibinin [17], zinc-diosmin [18] and evaluated for its toxicity as well as pharmacological properties in high-fat diet (HFD) fed -low-dose streptozotocin (STZ)-induced experimental T2D in rats. In the light of knowledge and expertise gained, in the present study an attempt has been made to synthesize a new metformin-zinc-flavonol complex and biochemically evaluated its toxicity as well as antidiabetic properties.…”