Investigating binding mechanism of thymoquinone to human transferrin, targeting Alzheimer's disease therapy

Abstract

Iron deposition in the central nervous system (CNS) is one of the causes of neurodegenerative diseases. Human transferrin (hTf) acts as an iron carrier present in the blood plasma, preventing it from contributing to redox reactions. Plant compounds and their derivatives are frequently being used in preventing or delaying Alzheimer's disease (AD). Thymoquinone (TQ), a natural product has gained popularity because of its broad therapeutic applications. TQ is one of the significant phytoconstituent of Nigella sativa. The binding of TQ to hTf was determined by spectroscopic methods and isothermal titration calorimetry. We have observed that TQ strongly binds to hTf with a binding constant (K) of 0.22 × 106 M−1 and forming a stable complex. In addition, isothermal titration calorimetry revealed the spontaneous binding of TQ with hTf. Molecular docking analysis showed key residues of the hTf that were involved in the binding to TQ. We further performed a 250 ns molecular dynamics simulation which deciphered the dynamics and stability of the hTf‐TQ complex. Structure analysis suggested that the binding of TQ doesn't cause any significant alterations in the hTf structure during the course of simulation and a stable complex is formed. Altogether, we have elucidated the mechanism of binding of TQ with hTf, which can be further implicated in the development of a novel strategy for AD therapy.

Design and investigation of targeting agent orientation and density on nanoparticles for enhancing cellular uptake efficiency

“…Transferrin (Tf) is a widely used targeting ligand and can selectively bind with the transferrin receptor (TfR) on the cancer cell membrane, suggesting that Tf is a good choice in the application of cell targeted delivery and disease treatment. [45][46][47] Human Tf (hTf, 79 kDa) is a kind of monomeric glycoprotein and the carbohydrate moieties approximately represent 6% of its mass. 48 Based on the cis-diols structure in the sugar chain of glycoproteins, Tf can be covalently conjugated on the benzoboroxole modified nanoparticles in a siteoriented manner by the formation of a five-membered cyclic ester.…”

From kitchen to clinic: Pharmacotherapeutic potential of common spices in Indian cooking in age-related neurological disorders

“…N. sativa effects on memory have been subject to only a few studies, but existing evidence point out that it would have a positive impact on memory and learning ( Alasmari et al, 2022 ; Kantar et al, 2022 ; Khan et al, 2022 ; Xue et al, 2022 ). In the radial arm maze test of rats, research has shown that both long- and short-term administration of N. sativa oil can improve working memory, especially short-term memory.…”

Therapeutic targeting of microtubule affinity‐regulating kinase 4 in cancer and neurodegenerative diseases

“…Naturally occurring compounds have been comprehensively investigated to develop safe and potent inhibitor(s) of MARK4 24,36‐38 . Natural products (NPs) have conventionally been the wealthiest resource of biologically active compounds utilized as therapeutic drugs 34,39‐44 .…”