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Objectives Our aim was to synthesize, characterize and evaluate the antihyperglycaemic and anti-oxidative properties of a new Zn(II) complex of vanillic acid. Methods The complex was synthesized using ZnSO4.7H2O and vanillic acid as precursors. NMR and FTIR techniques were used to characterize the synthesized complex. The cytotoxicity of the complex was measured. The antihyperglycemic and anti-oxidative properties of the complex were evaluated using in vitro, cell-based and ex vivo models and compared with those of its precursors. Key findings Zn(II) coordinated with vanillic acid via a Zn(O6) coordination, with the complex having three moieties of vanillic acid. The radical scavenging, Fe3+ reducing and hepatic antilipid peroxidative activity of the complex were, respectively, 2.3-, 1.8- and 9.7-folds more potent than vanillic acid. Complexation increased the α-glucosidase and glycation inhibitory activity of vanillic acid by 3- and 2.6-folds, respectively. Zn(II) conferred potent L-6 myotube (EC50 = 20.4 μm) and muscle tissue (EC50 = 612 μm) glucose uptake effects on vanillic acid. Cytotoxicity evaluation showed that the complex did not reduce the viability of L-6 myotubes and Chang liver cells. Conclusions The data suggest that Zn(II)–vanillic acid complex had improved bioactivity relative to vanillic acid. Thus, Zn(II) may be further studied as an antihyperglycaemic and anti-oxidative adjuvant for bioactive phenolic acids.

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Aim: This study was done to investigate the anti-diabetic and anti-oxidative synergism between zinc(II) and ferulic acid through complexation.Methods: Zinc sulphate was complexed with ferulic acid in a 1:2 molar ratio.The complex was characterized using Fourier-transform infrared spectroscopy, proton NMR and high-resolution mass spectroscopy techniques and evaluated for cellular toxicity. In silico, in vitro, cell-based and tissue experimental models were used to test the anti-diabetic and anti-oxidant activities of the complex relative to its precursors. Results:A zinc(II)-biferulate.2H 2 O complex was formed. The in vitro radical scavenging, anti-lipid peroxidative and αglucosidase and αamylase inhibitory activity of the complex was 1.7-2.1 folds more potent than ferulic acid. Zn(II) complexation increased the anti-glycation activity of ferulic acid by 1.5 folds. The complex suppressed lipid peroxidation (IC 50 = 48.6 and 331 μM) and GHS depletion (IC 50 = 33.9 and 33.5 μM) in both Chang liver cells and isolated rat liver tissue. Its activity was 2.3-3.3 folds more potent than ferulic acid and statistically comparable to ascorbic acid. Zn(II) complexation afforded ferulic acid improved glucose uptake activity in L-6 myotube (EC 50 = 11.7 vs. 45.7 μM) and isolated rat muscle tissue (EC 50 = 501 and 1510 μM). Complexation increased muscle tissue zinc(II) uptake and hexokinase activity. Docking scores of the complex (−7.24 to −8.25 kcal/mol) and ferulic acid (−5.75 to 6.43 kcal/mol) suggest the complex had stronger interaction with protein targets related to diabetes, which may be attributed to the 2 ferulic acid moieties and Zn(II) in the complex. Moreover, muscle tissue showed increased phospho-Akt/pan-Akt ratio upon treatment with complex. The complex was not hepatotoxic and myotoxic at in vitro cellular level. Conclusion:Zn(II) complexation may be promising therapeutic approach for improving the glycaemic control and anti-oxidative potential of natural phenolic acids.

Natural supplements are important in diabetes and oxidative stress management.A complexation-mediated antihyperglycemic and antioxidant synergism between zinc(II) and p-coumaric acid was investigated. p-Coumaric acid was complexed with ZnSO 4 and characterized by FT-IR, 1 H NMR, and mass spectroscopy. The antioxidant and antihyperglycemic potential of the complex and precursors were evaluated with different experimental models. Molecular docking with target proteins linked to diabetes was performed. A Zn(II)-bicoumarate.2H 2 O complex was formed. The in vitro radical scavenging, α-glucosidase inhibitory, antiglycation, and anti-lipid peroxidative activities of the complex were several folds stronger than p-coumaric acid. In Chang liver cells and rat liver tissues, the complex inhibited lipid peroxidation (IC 50 = 56.2 and 398 μM) and GSH depletion (IC 50 = 33.9 and 38.7 μM), which was significantly stronger (2.3-5.4-folds) than p-coumaric acid and comparable to ascorbic acid. Zn(II) and p-coumaric synergistically modulated (1.7-and 2.8-folds than p-coumaric acid) glucose uptake in L-6 myotubes (EC 50 = 10.7 μM) and rat muscle tissue (EC 50 = 428 μM), which may be linked to the observed complexation-mediated increase in tissue zinc uptake. Glucose uptake activity was accompanied by increased hexokinase activity, suggesting increased glucose utilization. Docking scores α-glucosidase, GLUT-4, and PKB/Akt showed stronger interaction with the complex (−6.31 to −6.41 kcal/ mol) compared to p-coumaric acid (−7.18 to −7.74 kcal/mol), which was influenced by the Zn(II) and bicoumarate moieties of the complex. In vitro, the complex was not hepatotoxic or myotoxic. Zn(II) complexation may be a therapeutic approach for improving the antioxidative and glycemic control potentials of p-coumaric acid.