Glucosamine activates intestinal P-glycoprotein inhibiting drug absorption

Qinghua Wu, Qing Wang, Xiaohong Luo, Peng Jin, Ming Jin, Sajid Hussain, Yiming Qi, Junfeng Mo, Yinglan Yu, Hao Shao and Lei Luo ()
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Qinghua Wu: Southwest University
Qing Wang: Children’s Hospital of Chongqing Medical University
Xiaohong Luo: The Fourth People’s Hospital of Liaocheng
Peng Jin: Southwest University
Ming Jin: Southwest University
Sajid Hussain: Southwest University
Yiming Qi: Southwest University
Junfeng Mo: Southwest University
Yinglan Yu: Southwest University
Hao Shao: Southwest University
Lei Luo: Southwest University

Nature Communications, 2025, vol. 16, issue 1, 1-14

Abstract: Abstract 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.

Date: 2025
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DOI: 10.1038/s41467-025-61437-2

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