Mechanistic insights into monomer level prevention of amyloid aggregation of lysozyme by glycyrrhizic acid

As the primary bioactive compound of glycyrrhiza rhizome, the triterpene glycoside conjugate Glycyrrhizic acid (GA) has demonstrated neuroprotective effects in vivo. This study evaluates the effectiveness of GA as an in-hibitor of GuHCl-induced amyloid aggregation of hen egg white lysozyme (HEWL). Fibril formation as measured by Thioflavin-T fluorescence, 90 degrees light scattering, and 8-Anilinonaphthalene-1-sulfonic acid (ANS) fluorescence illustrated similar to 90 % prevention of fibrils at [GA]/[HEWL] >= 2:1. Images of Transmission electron microscopy evidence for the absence of any fibril or amorphous aggregation products. The spectral characteristics of soluble HEWL were in close resemblance to unfolded monomer. Computational and fluorescence investigations per-formed to analyse GA-HEWL interactions demonstrated slightly higher affinity of GA to unfolded HEWL and aggregation-prone regions. The likely mechanism of monomer level aggregation prevention by GA as dermined by computational, stability, and ANS experiments illustrated that GA modulated the compactness, solvent-accessible surface, and solvent-exposed hydrophobic surfaces of aggregation-prone state of HEWL. Our find-ings corroborate GA as an effective inhibitor of HEWL amyloid formation. To our knowledge, GA interaction-induced inhibition of aggregation-prone states has not been previously discussed. GA's modulation of aggregation-prone states of disease-related proteins will successfully develop GA as an amyloid inhibitor for clinical trials of amyloidosis and neurodegenerative illnesses.

Automated summary

This study evaluates the effectiveness of Glycyrrhizic acid (GA) as an inhibitor of amyloid aggregation of lysozyme. The results show that GA can prevent fibril formation and modulate the aggregation-prone state of lysozyme. This research highlights the potential of GA as a treatment for amyloidosis and neurodegenerative diseases.