Novel Caffeic Acid - Zinc Acetate Complex: Studies on Promising Antidiabetic and Antioxidative Synergism Through
Godfrey R Matowane1,2, Limpho M Ramorobi1,2, Samson S Mashele1,2
1Department of Health Sciences, Faculty of Health and Environmental Sciences, Central University of Technology, Bloemfontein, 9301, Free State, South Africa.
Background:
The role of Zn(II) in storage, insulin secretion and function has been documented, while plant phenolics have antioxidant and other pharmacological credence.
Objective:
The study aimed at synthesizing a novel medicinal Zn(II) complex. The medicinal properties of zinc(II) and caffeic acid were considered in synthesizing a novel complex with promising and improved antioxidant and anti-hyperglycaemic attributes.
Methods:
Complex synthesis was done using a 1:2 molar ratio of zinc acetate and caffeic acid and structurally characterized using NMR, FT-IR, high resolution-mass spectroscopy and HPLC. Its cellular toxicity was assessed in Chang liver cells and L-myotubes. In vitro, cellular, and isolated tissue models were used to evaluate the antioxidant and anti-hyperglycaemic properties of the complex relative to its precursors. Molecular docking was used to investigate the interaction with insulin signalling target proteins: GLUT-4 and protein kinase B (Akt/PKB).
Results:
Zinc(II) and caffeic acid interacted via Zn:O4 coordination, with the complex having one moiety of Zn(II) and 2 moieties of caffeic acid. The complex showed in vitro radical scavenging, α- glucosidase and α-amylase inhibitory activity up to 2.6 folds stronger than caffeic acid. The ability to inhibit lipid peroxidation (IC50 = 26.4 μM) and GSH depletion (IC50 = 16.8 μM) in hepatocytes was comparable to that of ascorbic acid (IC50 = 24.5 and 29.2 μM) and about 2 folds stronger than caffeic acid. Complexation improved glucose uptake activity of caffeic acid in L-6 myotubes (EC50 = 23.4 versus 169 μM) and isolated rat muscle tissues (EC50 = 339 versus 603 μM). Molecular docking showed better interaction with insulin signalling target proteins (GLUT-4 and Akt/PKB) than caffeic acid. The complex was not hepatotoxic or myotoxic.
Conclusion:
Data suggest a synergistic antioxidant and anti-hyperglycaemic potential between zinc and caffeic acid, which could be attributed to the Zn:O4 coordination. Thus, it may be of medicinal relevance.
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