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Gossypetin Attenuates Concanavalin A-Induced Inflammatory Responses in Macrophages in vitro by Suppressing Oxidative Stress and p38 MAPK/NF-κB Signaling

Year: 2026

Type: article

Abstract: Introduction: Excessive macrophage activation and oxidative stress contribute to inflammatory disease by sustaining pro-inflammatory signaling. Gossypetin, a naturally occurring hexahydroxyflavone with antioxidant and kinase-modulatory activities, may be particularly relevant to macrophage-mediated inflammation because oxidative stress and MAPK/NF-κB signaling are central regulators of macrophage activation. However, its mechanisms in macrophage-mediated inflammation remain incompletely understood. This study investigated the anti-inflammatory effects and underlying mechanisms of gossypetin in concanavalin A (ConA)-stimulated macrophages. Methods: RAW264.7 macrophages were stimulated with ConA with or without gossypetin pretreatment. Oxidative stress, mitochondrial membrane potential, MAPK and NF-κB signaling, inflammatory mediator expression, cytokine production, and autophagy-associated changes were evaluated. Pharmacological inhibitors were used to examine the involvement of p38 MAPK, NF-κB, and autophagy-related processes. Key findings were validated in primary bone marrow-derived macrophages (BMDMs). Results: ConA increased intracellular and mitochondrial reactive oxygen species production, activated MAPK and NF-κB signaling, enhanced COX-2 and iNOS expression, and increased TNF-α and IL-6 production. Gossypetin attenuated oxidative stress, restored mitochondrial membrane potential, suppressed p38 MAPK/NF-κB signaling, and reduced inflammatory mediator expression and cytokine production. Pharmacological inhibition of p38 or NF-κB produced effects consistent with those of gossypetin. Autophagy-associated modulation also appeared to contribute partially to the anti-inflammatory response. These effects were reproduced in primary BMDMs. Discussion: Gossypetin attenuates ConA-induced macrophage inflammatory responses in vitro, primarily through suppression of oxidative stress and p38 MAPK/NF-κB signaling. Autophagy-associated regulation may additionally contribute to these effects.

Source: Journal of Inflammation Research

DOI: 10.2147/jir.s646279