Therapeutic Antidiabetic and Antioxidative Synergism of Zn(II)-Syringic Acid Complexation

Zinc(II) and syringic acid are natural supplements with medicinal attributes. The antidiabetic and antioxidative synergism between zinc(II) and syringic acid in diabetic rats by complexing both was investigated. Diabetes was induced in male Sprague Dawley rats using 10% fructose and 40 mg/kg bw streptozotocin and, thereafter, subjected to a 4-week treatment with the complex and its precursors (syringic acid and zinc sulfate) at predetermined doses. Then, the effect of the treatments on diabetes and oxidative stress–related parameters was measured. Diabetic polyphagia and polydipsia were reduced, and weight loss was appreciably recovered by the complex. Complexing zinc(II) and syringic acid improved their anti-hyperglycemic action by ∼28 to 36% and ∼37 to 40%, respectively, suggesting a complexation-mediated synergism. This is attributed to the modulatory action of the complex on insulin secretion and sensitivity, tissue glycogen production, muscle hexokinase activity, and Akt phosphorylation, thus improving glucose tolerance in diabetic rats, relative to its precursors. Concomitantly, the complex reduced systemic and tissue lipid peroxidation and increased the activity of antioxidant enzymes in the diabetic rats. The complex outperformed its precursors. In some cases, the antidiabetic action of the complex was comparable to metformin. Complexing Zn(II) and syringic acid may be an under-explored therapeutic approach to improving the effectiveness for diabetes and oxidative stress management. Graphical Abstract