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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| Format: | Article |
| Language: | English |
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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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| author | Qinghua Wu Qing Wang Xiaohong Luo Peng Jin Ming Jin Sajid Hussain Yiming Qi Junfeng Mo Yinglan Yu Hao Shao Lei Luo |
| author_facet | Qinghua Wu Qing Wang Xiaohong Luo Peng Jin Ming Jin Sajid Hussain Yiming Qi Junfeng Mo Yinglan Yu Hao Shao Lei Luo |
| author_sort | Qinghua Wu |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-9299e828efae44ffab33ac2b13887a39 |
| institution | DOAJ |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-9299e828efae44ffab33ac2b13887a392025-08-20T03:03:41ZengNature PortfolioNature Communications2041-17232025-07-0116111410.1038/s41467-025-61437-2Glucosamine activates intestinal P-glycoprotein inhibiting drug absorptionQinghua Wu0Qing Wang1Xiaohong Luo2Peng Jin3Ming Jin4Sajid Hussain5Yiming Qi6Junfeng Mo7Yinglan Yu8Hao Shao9Lei Luo10College of Pharmaceutical Sciences, Southwest UniversityChildren’s Hospital of Chongqing Medical UniversityDepartment of Clinical Laboratory, The Fourth People’s Hospital of LiaochengCollege of Pharmaceutical Sciences, Southwest UniversityCollege of Pharmaceutical Sciences, Southwest UniversityCollege of Pharmaceutical Sciences, Southwest UniversityCollege of Pharmaceutical Sciences, Southwest UniversityCollege of Pharmaceutical Sciences, Southwest UniversityCollege of Pharmaceutical Sciences, Southwest UniversityCollege of Pharmaceutical Sciences, Southwest UniversityCollege of Pharmaceutical Sciences, Southwest UniversityAbstract 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.https://doi.org/10.1038/s41467-025-61437-2 |
| spellingShingle | Qinghua Wu Qing Wang Xiaohong Luo Peng Jin Ming Jin Sajid Hussain Yiming Qi Junfeng Mo Yinglan Yu Hao Shao Lei Luo Glucosamine activates intestinal P-glycoprotein inhibiting drug absorption Nature Communications |
| title | Glucosamine activates intestinal P-glycoprotein inhibiting drug absorption |
| title_full | Glucosamine activates intestinal P-glycoprotein inhibiting drug absorption |
| title_fullStr | Glucosamine activates intestinal P-glycoprotein inhibiting drug absorption |
| title_full_unstemmed | Glucosamine activates intestinal P-glycoprotein inhibiting drug absorption |
| title_short | Glucosamine activates intestinal P-glycoprotein inhibiting drug absorption |
| title_sort | glucosamine activates intestinal p glycoprotein inhibiting drug absorption |
| url | https://doi.org/10.1038/s41467-025-61437-2 |
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