Mangiferin and oleocanthal in the modulation of oxidative stress in monocytes and macrophages

Oxidative stress and inflammation are tightly interconnected processes that contribute to the pathogenesis of numerous chronic diseases. In this study, we investigated the anti-inflammatory and antioxidant potential of two plant-derived bioactive compounds, mangiferin and oleocanthal, in human monocytic U-937 cells differentiated into macrophage-like cells. Cells were stimulated with phorbol 12-myristate 13-acetate (PMA), with or without lipopolysaccharide (LPS), to induce oxidative and inflammatory responses. The effects of mangiferin and oleocanthal (5 µM) were evaluated using cell viability assays, confocal microscopy, western blot analysis of tumor necrosis factor-α (TNF-α), 5-lipoxygenase (5-LOX) and electron paramagnetic resonance (EPR) spin-trapping spectroscopy for reactive oxygen species (ROS) detection. Both compounds were well tolerated and did not compromise membrane integrity or cell viability. Mangiferin and oleocanthal significantly reduced TNF-α expression and increased IL-4 expression in PMA and PMA/LPS-stimulated cells. While 5-LOX expression remained unchanged under PMA-induced differentiation alone, both compounds decreased 5-LOX levels under LPS-induced inflammatory conditions. EPR analysis confirmed suppression of ROS-derived radical formation following treatment with the bioactive compounds. Our results demonstrate that mangiferin and oleocanthal modulate oxidative stress and inflammatory signaling in macrophage-like cells by targeting TNF-α, 5-LOX, and ROS generation. These findings highlight their potential as natural therapeutic candidates for controlling inflammation-associated disorders.