Procyanidin B2 alleviates triphenyl phosphate-induced colon injury through Tmigd1/NF-κB/NLRP3 signal axis

Procyanidin B2 (PCB2), a natural dietary polyphenol with anti-inflammatory and antioxidant properties, demonstrates potential in mitigating chemical-induced toxicity. This study aimed to investigate the mechanism of triphenyl phosphate (TPHP)-induced colon injury and the protective role of PCB2. In a mouse model, TPHP exposure caused colon shortening, barrier damage, inflammation, and oxidative stress, all of which were dose-dependently reversed by PCB2. RNA-seq analysis identified the NF-κB signaling pathway as a key pathway and highlighted Tmigd1 as a core differential gene. TPHP downregulated the expression of Tmigd1 in the colon, while PCB2 directly bound to and increased Tmigd1 expression. Further investigation confirmed that PCB2, by upregulating Tmigd1, suppressed the phosphorylation of the NF-κB pathway and the activation of the NLRP3 inflammasome, thereby reducing the production of pro-inflammatory cytokines. Silencing Tmigd1 abolished the protective effects of PCB2. In Vitro studies using Caco-2 and NCM460 cells validated these findings concerning apoptosis, oxidative stress, and barrier function. Overall, TPHP induces colon injury by downregulating Tmigd1 and activating the NF-κB/NLRP3 axis, whereas PCB2 exerts a protective effect by targeting Tmigd1 to inhibit this inflammatory signaling. This study reveals a novel mechanism of TPHP toxicity and supports PCB2 as a promising intervention for environmental chemical-associated intestinal damage.