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Ecotoxicology and Environmental Safety

Ecotoxicology and Environmental Safety

IF: 6.2
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Natural compound library screening identifies triptolide for the treatment of okadaic acid-induced intestinal dysfunction

Published:17 September 2025 DOI: 10.1016/j.ecoenv.2025.119042 PMID: 40966952
Ji-qian-zhu Zhang , Xiao-yu Dai , Jing-jing Mao , Lang Yan , Li-jun Ren , Jin-feng Li , Yi-jun Tian , Wen-lin Li , Jiang-bo Zhu , Ji-kuai Chen

Abstract

Okadaic acid (OA), a diarrhetic shellfish toxin, causes significant intestinal and systemic toxicity. Currently, there are no approved therapeutics specifically targeting OA-induced diarrhea. Using high-throughput screening of 2131 natural compounds, we identified triptolide as a compound conferring protection against OA-induced apoptosis. In mice exposed to OA, triptolide administration reduced intestinal permeability and ameliorated mucosal injury. In HUVECs, triptolide (0.1–3?μM) dose-dependently increased cell viability and suppressed apoptotic activity. Biotin-based labeling identified the hydroxyl group as the essential active site of triptolide. RNA sequencing analysis showed that triptolide inhibited the OA-induced upregulation of endoplasmic reticulum (ER) protein synthesis-related genes. Furthermore, triptolide prevented the OA-induced decrease in the p-eIF-2α/eIF-2α ratio, thereby attenuating ER stress. These results demonstrate that triptolide mitigates OA-induced toxicity by inhibiting ER stress-mediated endothelial cell apoptosis and maintaining intestinal barrier integrity, highlighting its potential as a therapeutic agent against OA-related poisoning.

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