Yohimbine as a multifunctional therapeutic agent: inhibition of lysozyme aggregation, glycation and antioxidant properties.

Protein misfolding and glycation are central to the pathogenesis of several chronic diseases, including neurodegenerative disorders and diabetes. Lysozyme (Lyz), a model protein, serves as an excellent system to study these pathological processes due to its propensity to form amyloid fibrils and undergo glycation. This study investigates the multifunctional therapeutic potential of yohimbine (Yoh) as an inhibitor of Lyz aggregation and glycation and its role as an antioxidant. The ability of Yoh to suppress amyloid fibrillation was evaluated using thioflavin T fluorescence, Congo red absorbance, and Nile red assays, which confirmed its efficacy in reducing fibrillar and surface hydrophobic changes in Lyz. Glycation inhibition was assessed through fluorescence spectroscopy, showing a significant reduction in the formation of advanced glycation end products (AGEs) in the presence of Yoh. Antioxidant assays demonstrated Yoh's capability to scavenge free radicals, contributing to its protective role against oxidative stress. Molecular modelling revealed stable binding of Yoh to lysozyme, driven by hydrogen bonds, hydrophobic contacts, and van der Waals interactions. These findings position Yoh as a promising therapeutic agent with dual activity in mitigating protein misfolding and glycation-associated diseases.