Paeoniflorin Attenuates Fumonisin B1-Induced Cytotoxicity by Inhibiting the p38 MAPK Pathway in 3D4/21 Cells

Fumonisin B1 (FB1), a water-soluble mycotoxin produced by Fusarium moniliforme, poses significant health risks to both humans and animals through widespread contamination of agricultural commodities. Paeoniflorin (PF), a bioactive monoterpene glycoside extracted from Paeonia lactiflora, exhibits potent anti-inflammatory and antioxidant properties. This study investigated the protective effects of PF against FB1-induced cytotoxicity in porcine alveolar macrophages (3D4/21) and explored the underlying molecular mechanisms. Cells were treated with FB1 (50 μg/mL) in combination with PF (100 μg/mL) for 24 h. Results demonstrated that PF significantly attenuated FB1-induced cytotoxicity by improving cell viability, restoring cytoskeletal and tight junction protein expression (α-Tubulin and ZO-1), and reducing apoptosis and oxidative stress. PF treatment successfully restored the balance of inflammatory cytokines (including IL-6, IL-8, IL-1β, IFN-α, and INF-γ) that had been dysregulated in 3D4/21 cells upon FB1 exposure. Transcriptomic analysis revealed that PF reversed FB1-induced gene expression alterations, particularly within clusters associated with cellular stress responses. Further investigation identified the p38 MAPK pathway as a critical mechanism through which PF exerts its protective effects, with significant downregulation of key pathway components including MAPK14, MAP2K3, ATF2, and MAPKAPK2 in cells co-treated with PF and FB1. These findings provide mechanistic insights into the protective effects of PF against environmental mycotoxins and suggest its potential application in mitigating FB1-induced agricultural and ecological toxicity.