Chika I. Chukwuma*, Samson S. Mashele and Shasank S. Swain Pages 913 - 925 ( 13 )
Background: The role of zinc in diabetes has been a subject of considerable interest due to the insulin-mimetic properties associated with this mineral. On the other hand, phenolic acids are known as plant-derived polyphenols with antioxidative and antidiabetic pharmacological credence.Objective: This study was conducted in order to develop a novel therapeutic nutraceutical with an improved and multi-mode antidiabetic and antioxidative pharmacological property using cinnamic acid and Zn(II) mineral framework. Methods: A Zn(II) acetate complex of cinnamic acid was synthesized and characterized using FT-IR and 1HNMR spectroscopy. Cytotoxicity evaluation was done using Chang liver cells and differentiated L6 myotubes. DPPH and ABTS scavenging, as well as Fe3+ reducing effects, were used to evaluate the antioxidant capacity. The antiglycation, as well as α-glucosidase and α-amylase inhibitory properties, were evaluated. Insulin mimetic property was evaluated as glucose uptake in L6 myotubes, while the complex was docked against GLUT-4 and PKB. Results: FTIR and 1HMR suggested that Zn(II) complexed with cinnamic acid through a Zn(O4) coordination mode, thus affording the resulting complex 2 cinnamic acid molecules. Hence, complexation increased (p ˂ 0.05) the antiglycation effect of cinnamic acid (IC50 = 29.3 μM) by 2 folds (IC50 = 13.9 μM). Also, Zn(II) conferred a potent glucose uptake (EC50 = 31 μM) and α-glucosidase inhibitory (IC50 = 59.4 μM) property on cinnamic acid; hence the activity of the complex was 162 and 2.1 folds higher than (p ˂ 0.05) its precursor, respectively. Further molecular docking studies showed that the complex had a stronger interaction with insulin signaling proteins (GLUT-4 and PKB) than its precursor. Interestingly, the complex showed no severe cytotoxicity. Conclusion: Data suggested a structure-activity relationship. Complexation of Zn(II) to cinnamic acid resulted in a complex with improved and multi-facet pharmacological effects, which may be further studied as a safe glycemic control nutraceutical for T2D and glycation-induced complications.
Zinc(II) acetate, cinnamic acid, Zn(II) complex, diabetes, glucose uptake, glycation.
Centre on Quality of Health and Living (CQHL), Faculty of Health and Environmental Sciences, Central University of Technology, Bloemfontein, 9300, Free State, Department of Health Sciences, Faculty of Health and Environmental Sciences, Central University of Technology, Bloemfontein, 9300, Free State, Division of Microbiology and NCDs, ICMR-Regional Medical Research Centre, Bhubaneswar-751023, Odisha