Poly (gallic acid) (PGAL) mitigates monosodium urate crystal-induced inflammatory damage in a cell-based gout model

Abstract

Introduction. Gout is an inflammatory disease caused by the deposition of monosodium urate crystals (MSU) in the joints, leading to a pro-oxidant microenvironment characterized by increased production of reactive oxygen species (ROS), nitric oxide (NO⁻), and the release of proinflammatory cytokines such as IL-1β. In cellular models, MSU crystals induce phagocytosis and cell death, exacerbating inflammation. In this context, poly(gallic acid) (PGAL), a polyphenolic antioxidant, has demonstrated cytoprotective and anti-inflammatory properties. Objective. This study evaluated the effect of PGAL on inflammation and oxidative stress markers induced by MSU crystals in an in vitro gout model. Methodology. THP-1 monocytes were activated with phorbol 12-myristate 13-acetate (100 ng/mL) and stimulated with 150 µg/mL of MSU crystals. Cells were subsequently treated with PGAL at two concentrations (100 µg/mL and 200 µg/mL). Mitochondrial viability was assessed using the MTT assay; apoptosis and necrosis with Annexin V/EthD-1 staining; O₂⁻, H₂O₂ and NO⁻ production via flow cytometry; crystal phagocytosis using polarized light microscopy; IL-1β levels in supernatants by ELISA; and PGAL–MSU interactions were analyzed by molecular docking. Results. MSU exposure significantly reduced cell viability (26.68%) and increased apoptosis (37.24%), as well as the production of O₂⁻ (52.6 ± 16%) and NO⁻ (22.6 ± 1.5%) compared to the control. Treatment with PGAL100 significantly improved mitochondrial viability (78.83 ± 1.53 vs. 61.35 ± 9.84 with MSU) and reduced apoptosis (as low as 7.16%) and NO⁻ levels (down to 11.3%). PGAL also decreased crystal phagocytosis (down to 63.5 ± 4.9%) and IL-1β levels (2906 ± 1189 pg/mL), compared to MSU without PGAL (5486 ± 900 pg/mL). In silico analyses revealed that PGAL–MSU interaction is mediated by electrostatic forces, mainly involving sodium ions. Conclusions. PGAL attenuates MSU-induced cellular damage and inflammation by reducing ROS and NO⁻ production, IL-1β levels, and modulating crystal phagocytosis through specific physicochemical interactions. These findings support the potential use of PGAL as a therapeutic adjuvant in strategies aimed at controlling joint inflammation in diseases such as gout, with relevant applications in musculoskeletal rehabilitation.