Work

Quercetin attenuates polystyrene nanoplastic-induced intestinal barrier injury through modulation of macrophage inflammatory responses

Year: 2026

Type: article

Abstract: Introduction: Polystyrene nanoplastics (PS-NPs) are emerging environmental contaminants that may impair intestinal barrier integrity, but the involvement of macrophage inflammatory responses remains incompletely understood. Quercetin is a natural flavonoid with well-established anti-inflammatory and immunomodulatory properties. This study investigated the role of macrophage inflammatory responses in PS-NP-induced intestinal injury and evaluated the protective effects of quercetin. Methods: . An indirect Transwell co-culture system of RAW 264.7 macrophages and MODE-K intestinal epithelial cells was established to assess macrophage-mediated epithelial barrier alterations. NF-κB and STAT1 signaling activation was also examined. Results: PS-NP exposure induced dose-dependent colonic histopathological injury, increased the expression of the pro-inflammatory cytokines IL-1β, TNF-α, and IL-6, and reduced the expression of the tight junction proteins ZO-1 and occludin. PS-NPs were also associated with a shift toward a pro-inflammatory macrophage phenotype, characterized by increased CD86 and decreased CD206 expression. Consistently, PS-NPs promoted inflammatory responses in RAW 264.7 macrophages and increased NF-κB p65 and STAT1 phosphorylation. In the Transwell co-culture system, MODE-K cells co-cultured with PS-NP-stimulated macrophages exhibited reduced tight junction-associated protein expression and disrupted junctional integrity. Quercetin treatment attenuated PS-NP-induced colonic injury and inflammatory responses, partially restored ZO-1 and occludin expression, modulated macrophage polarization-associated markers, and reduced NF-κB and STAT1 activation. Discussion: These findings indicate that 50 nm PS-NP exposure induces intestinal inflammatory responses and barrier-associated injury accompanied by pro-inflammatory macrophage activation and altered NF-κB/STAT1 signaling. The co-culture findings further support the involvement of macrophage-derived inflammatory responses in epithelial barrier impairment. Quercetin attenuates PS-NP-induced intestinal injury, potentially in part through modulation of macrophage inflammatory responses accompanied by reduced NF-κB and STAT1 activation.

Source: Frontiers in Pharmacology

DOI: 10.3389/fphar.2026.1973458