Electrostatic Interaction of Enzyme-Mediated Poly(gallic acid) with Monosodium Urate Crystals Attenuates Inflammasome Activation and Oxidative Stress

Background. Gout is an inflammatory disease caused by the deposition of monosodium urate (MSU) crystals, leading to reactive oxygen species (ROS) production and activation of the NLRP3 inflammasome with subsequent IL-1β release. Poly-gallic acid (PGAL), enzymatically synthesized polymer, has demonstrated antioxidant and anti-inflammatory properties; however, its effect on MSU-induced inflammasome activation remains unclear. Thus, this work aims to evaluate the effect of PGAL on oxidative stress and inflammatory responses induced by MSU crystals in THP-1-derived macrophages. Methods. Macrophages were pretreated with PGAL and stimulated with MSU crystals. Cell viability, apoptosis, phagocytosis, ROS and NO production, soluble urate levels, and NLRP3 and IL-1β expression were evaluated. Molecular docking and binding free energy calculations were performed to characterize PGAL–MSU interactions. Results. PGAL significantly reduced ROS and NO production, and apoptosis. PGAL treatment also decreased MSU crystal phagocytosis and significantly reduced NLRP3 and IL-1β. Computational analysis revealed that PGAL interacts with MSU crystals predominantly through electrostatic interactions, including Na+ coordination and hydrogen bonding. Conclusions. PGAL attenuates MSU-induced oxidative stress and NLRP3/IL-1β activation, possibly by interfering with crystal internalization. These findings suggest a mechanism based on modulation of crystal–cell interactions and downstream inflammation responses.