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Objective: Due to the multifactorial and multisystemic nature of diabetes mellitus (DM), it is often treated with a combination of therapeutic agents. Earlier, we have synthesized and characterized several organozinc complexes and evaluated their safety and antidiabetic properties in experimental DM. In the present study, a new zinc mixed ligand (metformin-3-hydroxyflavone) was synthesized and characterized by various spectral studies and its antidiabetic properties were evaluated in high-fat diet (HFD) fed -low-dose streptozotocin (STZ)-induced Type 2 D (T2D) in rats. Methods:The zinc mixed ligand complex was characterized by spectral studies. The toxicity and dosage fixation studies were carried out as per OECD guidelines 423. HFD fed low-dose STZ-induced T2DM in rats was used as the experimental model. The hypoglycemic efficacy of the complex was evaluated through oral glucose tolerance test, homeostasis model assessment of insulin resistance (IR), QUICK I and by determining the status of important biochemical parameters. The activities of marker enzymes such as aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase were assayed. Metformin was used as a standard drug. Results:The spectral data evidenced the synthesis of a new zinc mixed ligand complex. The biochemical studies evidenced that the oral administration of the complex at a concentration of 10 mg/kg b.w/rat/day for 30 days to diabetic rats significantly improved the glucose homeostasis which was comparable to metformin treatment (50 mg/kg b.w). Conclusion:The zinc mixed complex possesses significant antidiabetic properties in ameliorating IR and stimulatory properties.

Due to the multifactorial and multisystemic nature of diabetes mellitus, it is often treated with a combination of therapeutic agents having different mode of action. Earlier, we have synthesized several organozinc complexes and evaluated their safety and antidiabetic properties in experimental type 2 diabetes mellitus (T2DM). More recently, we have synthesized a metformin-3-hydroxyflavone complex and studied its antidiabetic efficacy in experimental rats. In the present study, a new zinc-mixed ligand (metformin-3-hydroxyflavone) was synthesized, characterized by spectral studies and its antidiabetic properties was evaluated in HFD fed—low dose streptozotocin induced T2DM in rats. The hypoglycemic efficacy of the complex was evaluated through oral glucose tolerance test, homeostasis model assessment of insulin resistance, quantitative insulin sensitivity check index and by determining the status of important biochemical parameters. Oral administration of the complex at a concentration of 10 mg/kg body weight/rat/day for 30 days significantly improved the glucose homeostasis. The complex possesses significant antidiabetic properties relatively at a less concentration than metformin-3-hydroxyflavone complex in ameliorating hyperglycemia.

Diabetic retinopathy (DR) is one of the earliest complications of chronic hyperglycemia and is a major cause of vision loss. Nearly all patients with type 1 diabetes mellitus and more than 60 % with chronic type 2 diabetes develop some degree of retinopathy after 10 years. Aldose reductase, the first enzyme in polyol pathway chiefly contributes to the development of diabetic retinopathy and other secondary complications. None of the currently available drugs used to inhibit the activity of aldose reductase is found to be ideal due to their adverse effects. Hence, the screening and identification of more effective and safer aldose reductase inhibitors from natural products have been critical requirement in the management and treatment of T2DM. Recently, we have reported the antidiabetic properties of phytochemicals such as Gymnemic acid, Trigonelline and Ferulic acid in high fat diet fed- low dose STZ induced experimental type 2 diabetes in rats. In the present study, the structure based computational method was employed to identify the in silico inhibitory effect of the above phytoingredients on aldose reductase activity. Auto Dock 4.2 is used to study the molecular interactions between the ligands and the receptor. The data obtained evidenced that the docking efficacy of the antidiabetic ligands which are comparable with fidarestat, the standard used in the present study. Thus, the antidiabetic properties of the above lead molecules may attribute to its aldose reductase inhibitory effect.