Nymphoides peltata Alleviates Patulin-Induced Glutamine Metabolic Stress and Epithelial Toxicity in Small Intestinal Epithelial Cells
2025
Chae Hyun Lee | Sangsu Shin | Tae Hyun Kim | Sang In Lee
Patulin (PAT) is a mycotoxin commonly found in fruits and contaminated feedstuffs, known for its gastrointestinal and systemic toxicity. However, the mechanisms underlying PAT-induced damage to intestinal epithelial cells remain poorly understood. In this study, we demonstrated that 6.5 µ:M PAT exposure for 24 h reduced glutamine (GLN) uptake and altered the expression of GLN transporters and related metabolic enzymes in IPEC-J2 cells. This concentration was selected based on previous in vitro studies that reported PAT-induced cytotoxicity in porcine intestinal epithelial cells. Moreover, PAT also upregulated ER stress markers (DDIT3, EIF2AK3, ERN1, and HSPA5) and inflammatory cytokines (IL-8, IL-1&beta:, and TNF-&alpha:), while decreasing ZO-1 localization, indicating disrupted epithelial barrier integrity. Although 6 mM GLN supplementation only partially mediated ER stress and inflammatory responses, it more effectively restored ZO-1 localization. A high-throughput screening of 324 natural products was conducted to identify potential protective agents, identifying Nymphoides peltata extract as a promising candidate. Co-treatment with 80 ng/&mu:L N. peltata extract improved GLN uptake, partially alleviated ER stress and inflammation, and significantly restored tight junction structure in PAT-exposed cells. Collectively, these findings suggest that N. peltata could serve as a novel natural therapeutic for enhancing intestinal resilience against PAT-induced toxicity. Specifically, this study highlights the potential use of N. peltata extract as a natural feed additive to protect intestinal health in livestock under mycotoxin stress.
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