Computational and spectroscopic insight into the binding of citral with human transferrin: Targeting neurodegenerative diseases.

The involvement of neuroinflammation in the pathogenesis of neurodegenerative disorders (NDs) is very significant. Currently, only symptomatic treatments exist, and there are no drugs that modify the progression of Alzheimer's disease (AD) or other NDs. Consequently, there is increasing attention on addressing AD-related neuroinflammation using anti-inflammatory compounds and antioxidants. Currently, there is a growing exploration of dietary phytochemicals as potential therapeutic agents for treating inflammation. Citral, a monoterpene, is under increasing investigation due to its neuroprotective effects. The dysregulation of iron homeostasis is a crucial factor in supporting neuroinflammation, underscoring the significance of proper iron balance. Human transferrin (htf) is a major player involved in iron homeostasis. In this study, we examined binding and dynamics of htf-citral complex through diverse experimental methods. Molecular docking studies revealed that citral binds to crucial residues of htf, forming a stable complex. UV-visible spectroscopy demonstrated binding of citral with htf with good affinity, evident from binding constant of 1.48 × 105 M-1. Further, fluorescence spectroscopy entrenched a stable htf-citral complex formation; citral demonstrates an excellent binding affinity to htf with a binding constant of 106 M-1. Moreover, fluorescence binding assay at various temperatures deciphered htf-citral complex to be driven by both static and dynamic quenching. The analysis of enthalpy change (ΔH) and entropy change (ΔS) demonstrated that htf-citral complex formation was driven mainly by hydrophobic interactions.The current work gives a platform to develop innovative therapeutic strategies targeting neuroinflammation through citral, particularly iron homeostasis.