Mechanistic insights into the interaction of Abamectin and Ivermectin with bovine serum albumin and the protective role of ganoderic acid A: An integrated spectroscopic and in silico study.

Abstract

Abamectin and Ivermectin are widely used macrocyclic lactones whose exposure may induce oxidative stress and protein structural alterations. Since serum albumin plays a key role in xenobiotic transport, understanding ligand-albumin interactions is important for evaluating their molecular effects. Ganoderic acid A (GAA), a bioactive triterpenoid from Ganoderma lucidum, has reported antioxidant properties and may reduce ligand-induced protein damage. The interactions of Abamectin and Ivermectin with bovine serum albumin (BSA) were investigated in the absence and presence of GAA using UV-Vis, fluorescence, ANS fluorescence, ATR-FTIR spectroscopy, urea-induced unfolding, DTT-induced aggregation assays, molecular docking, and complementary in silico toxicity prediction. Both ligands caused concentration-dependent hypochromic effects, fluorescence quenching, increased surface hydrophobicity, and enhanced protein aggregation, indicating structural perturbation of BSA. GAA attenuated these changes by reducing ligand binding, preserving protein stability during chemical denaturation, and suppressing aggregation. Molecular docking supported the spectroscopic findings, and statistical analysis confirmed significant differences among the docking groups (p < 0.001). Overall, these findings suggest that ganoderic acid A modulates the interaction of Abamectin and Ivermectin with serum albumin and contributes to preserving protein structural stability under the experimental conditions employed, supporting its potential as a modulator of protein-ligand interactions. Although the present study provides comprehensive spectroscopic and computational evidence for the protective role of GAA, additional mechanistic investigations using time-resolved fluorescence and cellular validation are required to further elucidate the molecular basis and biological relevance of these interactions.