# Inhibition of Peroxidation Potential and Protein Oxidative Damage by Metal Mangifera Complexes
###### Abstract  
Background: Metal coordination complexes of polyphenolic compounds have been claimed to have better antioxidant and protection against protein oxidative damage effects than the isolated ligands. Whereas flavonoids have been extensively studied, xanthones such as mangiferin are lacking extensive research. Methods: Cu (II), Zn (II), and Se (IV) mangiferin complexes were synthesized with different stoichiometric ratios. Products were isolated by preparative chromatography and subjected to spectral analysis by FT-IR, HPLC-DAD, and HPLC-ESI-MS. The inhibition effects on peroxidation potential and protein oxidative damage were determined for all the metal-MF complexes. Results: Eight metal-MF complexes were isolated. Cu (II)-MF complexes did not improve MF antioxidant/protective effects; Zn (II) complexes (stoichiometric ratio 1:2) antioxidant/protective effects had no significant differences to MF; Zn (II)- and Se (IV)-MF complexes (stoichiometric ratio 1:3) showed the best inhibition effects on peroxidation potential (49.06% and 32.08%, respectively), and on the protection against protein oxidative damage (14.49% and 20.81%, respectively). Conclusions: The antioxidant/protective effects of Se (IV)- and Zn (II)-MF coordination complexes were significantly improved as compared to isolated MF, when the reaction between the metal salt and MF was performed with a stoichiometric ratio 1:3.  
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a low stability [10]. However, xanthones like mangiferin (2-\(\beta\)-D-glucopyranosyl-1,3,6,7-tetrahydrooxy-9H-xanthen-9-one) have not been studied extensively. Mangiferin (MF) has been shown to be not only a potent antioxidant but also a potential candidate for the treatment of neurodegenerative diseases [11]. Its cardiovascular, liver, and brain protecting activities have been related to its capacity to protect cells from oxidative damage [12]. We reported previously that MF had a protective effect against protein oxidative damage in serum, liver, and brain from mice [13]. However, its poor water solubility has always brought the question of how to improve MF bioavailability, and several procedures have been attempted for this goal, including its integration to polymer systems for controlled release formulations [14; 15; 16]. However, there is the risk to reduce MF antioxidant properties, i.e., when it has been nano-encapsulated with \(\beta\)-lactoglobulin to increase its oral bioavailability [17]. The formation of MF metal complexes in plant aqueous extracts seems to be a possibility to explain that sometimes the biological activity of the MF-containing extract is higher than the isolated MF [11]. We investigated the presence of copper (II), zinc (II), and selenium (IV) in several varieties of mango trees and found that Se concentration was consistent among the varieties while Cu and Zn concentrations varied according to the mango variety [18]. Therefore, we hypothesized that the combination of MF with those micronutrients (Cu, Zn, and/or Se), probably through MF metal complexes, was a possible explanation for such behavior. The alternative to enhance MF antioxidant mechanism through the formation of metal complexes appears to be a possible route to increase not only its bioavailability but bioactivity. We report the synthesis, spectral characterization, and evaluation of the peroxidation potential and protection against protein oxidative damage of MF metal complexes with Cu (II), Zn (II), and Se (IV) for the first time to demonstrate the possibility to develop new compounds with the capability to increase the antioxidant effect and protection against protein oxidative damage as compared to the isolated ligand (MF). New metal-MF complexes might be useful in antioxidant adjuvant therapies for neurodegenerative diseases treatment such as cancer, diabetes, and cardiovascular disorders among others.