Glucosamine activates intestinal P-glycoprotein inhibiting drug absorption
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 w...
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| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-61437-2 |
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| Summary: | 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. |
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| ISSN: | 2041-1723 |