Tuning the Aggregation Behavior of Human Insulin in the Presence of Luteolin: An in Vitro and in Silico Approach
Human Insulin, Aggregation, Misfolding, Alzheimer's Disease, Simulation, Conformational Diseases
Digital Object Identifier (DOI)
Protein misfolding and related formation of amyloid fibrils are associated with several conformational diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), prion diseases, and Diabetes mellitus, Type 2 (DM-II). Several molecules including antibiotics, polyphenols, flavonoids, anthraquinones, and other small molecules are implicated to modulate amyloid assembly. The stabilization of the native forms of the polypeptides and prevention of their misfolding and aggregation are of clinical and biotechnological importance. Among the natural flavonoids, luteolin is of great importance because of its therapeutic role against neuroinflammation. Herein, we have explored the inhibitory effect of luteolin (LUT) on aggregation of a model protein, human insulin (HI). To understand the molecular mechanism of the inhibition of aggregation of HI by LUT, we employed molecular simulation, UV–Vis, fluorescence, and circular dichroism (CD) spectroscopies along with the dynamic light scattering (DLS). The analysis of the tuning of the HI aggregation process by luteolin revealed that interaction of HI with LUT resulted in the decrease in binding of the various fluorescent dyes, such as thioflavin T (ThT) and 8-anilinonaphthalene-1-sulfonic acid (ANS) to this protein. Retention of the native-like CD spectra and resistance to the aggregation in the presence of LUT has confirmed the aggregation inhibitory potential of LUT. The maximum inhibitory effect was found at the protein-to-drug ratio of 1:12, and no significant change was observed beyond this concentration.
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Citation / Publisher Attribution
International Journal of Biological Macromolecules, v. 237, art. 124219
Scholar Commons Citation
Ali, Syed Moasfar; Nabi, Faisal; Furkan, Mohammad; Hisamuddin, Malik; Malik, Sadia; Zakariya, Syed Mohammad; Rizvi, Irum; Uversky, Vladimir N.; and Khan, Rizwan Hasan, "Tuning the Aggregation Behavior of Human Insulin in the Presence of Luteolin: An in Vitro and in Silico Approach" (2023). Molecular Medicine Faculty Publications. 1055.