Employing spectroscopic, calorimetric and structural bioinformatics approaches to decipher the binding mechanism of mangiferin with human transferrin

In recent times, neurodegenerative diseases (NDs), such as Alzheimer's disease (AD), Parkinson's disease (PD) and others, represent a major global health challenge with increasing prevalence and significant socio-economic impact. These diseases, characterized by progressive neuronal loss, currently lack effective therapies. Phytochemicals offer promising therapeutic potential due to their diverse bioactive properties. Mangiferin, a glucosylxanthone found in mangoes and other plants, has shown significant therapeutic potential in NDs. Human transferrin (Tf), an iron-binding protein crucial for iron homeostasis, is implicated in ND pathogenesis. This study delineates the interaction between Mangiferin and Tf. Molecular docking revealed Mangiferin predominantly interacts with Tf's binding site, engaging critical residues. Molecular dynamics simulations over 200 ns demonstrated the stability of the Tf-Mangiferin complex without major deviations. Fluorescence binding assays confirmed the strong binding affinity of Mangiferin to Tf. Additionally, Isothermal titration calorimetry (ITC) validated the spontaneous binding of Mangiferin with Tf, providing detailed thermodynamic parameters. The findings highlight the therapeutic potential of Mangiferin in NDs treatment through its interaction with Tf, offering insights into novel mechanisms of action and pathways for disease modification.