Wu Qinghua, Wang Qing, Luo Xiaohong, Jin Peng, Jin Ming, Hussain Sajid, Qi Yiming, Mo Junfeng, Yu Yinglan, Shao Hao, Luo Lei
College of Pharmaceutical Sciences, Southwest University, Chongqing, 400715, China.
Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.
Nat Commun. 2025 Jul 2;16(1):6100. doi: 10.1038/s41467-025-61437-2.
P-glycoprotein (P-gp) is a crucial drug efflux transporter in the gastrointestinal tract, reducing drug uptake and expelling harmful xenobiotics to prevent pathological changes. Current P-gp enhancers primarily increase P-gp expression, requiring 1-3 days, thus missing the critical rescue window for acute poisoning. This study identifies glucosamine (GlcN) as a potent P-gp activator that swiftly enhances drug efflux, significantly reducing drug absorption without altering P-gp expression levels. GlcN directly binds to P-gp, boosting its transport efficiency. Only GlcN with a polymerization degree below 5 can activate P-gp, whereas higher polymerized chitooligosaccharides enhance drug absorption. Additionally, GlcN activation of P-gp has significant implications for cellular metabolism by expelling xenobiotics and metabolic by-products, maintaining cellular homeostasis. Our findings suggest GlcN's potential as an effective antidote for paraquat poisoning and offer a detoxification strategy. This research provides a foundational understanding for developing improved detoxification agents and metabolic modulators.
P-糖蛋白（P-gp）是胃肠道中一种关键的药物外排转运蛋白，可减少药物摄取并排出有害的外源性物质以预防病理变化。目前的P-gp增强剂主要是增加P-gp的表达，这需要1至3天，因此错过了急性中毒的关键抢救窗口。本研究确定氨基葡萄糖（GlcN）是一种有效的P-gp激活剂，可迅速增强药物外排，显著减少药物吸收，而不改变P-gp的表达水平。GlcN直接与P-gp结合，提高其转运效率。只有聚合度低于5的GlcN才能激活P-gp，而聚合度更高的壳寡糖则会增强药物吸收。此外，GlcN对P-gp的激活通过排出外源性物质和代谢副产物，维持细胞内稳态，对细胞代谢具有重要意义。我们的研究结果表明GlcN作为百草枯中毒有效解毒剂的潜力，并提供了一种解毒策略。这项研究为开发改进的解毒剂和代谢调节剂提供了基础认识。
