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作者

Pancen Ran Fengxian Jiang Liying Pan Yang Shu Fangyan Hu Yahui Wang Rui Zhao Weihao Wang Huaiqian Mu Juqiong Wang Jian Wei Guobin Fu

作者单位

¹Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China ²The Second Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250013, China ⁶Department of Medical Oncology, The Third Affiliated Hospital of Shandong First Medical University, Jinan, Shandong 250031, China ⁴Department of Radiation Oncology, The 960th Hospital of the PLA Joint Logistics Support Force, Jinan 250031, China ³These authors contributed equally to this work. ⁵School of Basic Medical Sciences, Shandong University, Jinan, Shandong 250012, China

刊名

International Journal of Biological Macromolecules

年份

2025

卷号

Vol.308 Part 3

页码

142512

ISSN

0141-8130

摘要

Polysaccharide from Atractylodes macrocephala Koidz. , a bioactive component of Atractylodes macrocephala Koidz. , demonstrates a wide range of pharmacological activities, including the enhancement of gastrointestinal function and regulation of internal homeostasis. This study explores the potential of PAMK in alleviating pyrotinib-induced diarrhea and modulating gut microbiota and its metabolites. Pyrotinib is a tyrosine kinase inhibitor used in cancer treatment, is known for its side effect of...更多

Polysaccharide from Atractylodes macrocephala Koidz. , a bioactive component of Atractylodes macrocephala Koidz. , demonstrates a wide range of pharmacological activities, including the enhancement of gastrointestinal function and regulation of internal homeostasis. This study explores the potential of PAMK in alleviating pyrotinib-induced diarrhea and modulating gut microbiota and its metabolites. Pyrotinib is a tyrosine kinase inhibitor used in cancer treatment, is known for its side effect of diarrhea, which significantly diminishes patients' quality of life. Our prior research suggests that pyrotinib-induced diarrhea may be linked to CFTR-mediated dysregulation of chloride secretion. The present findings indicate that PAMK alleviates pyrotinib-induced diarrhea by reducing cAMP levels, activating the LKB1/AMPK pathway, and inhibiting CFTR activity, as confirmed by enzyme-linked immunosorbent assay , qRT-PCR, and western blot analyses. PAMK effectively decreased CFTR-mediated chloride ion secretion in pyrotinib-treated cells, as shown by the MQAE assay. At specific doses, PAMK alleviated pyrotinib-induced diarrhea in rats and significantly restored intestinal barrier integrity. Furthermore, PAMK treatment rebalanced the gut microbiota, reversing the pyrotinib-induced increase in Clostridium and Erysipelotrichi species. Metabolomic profiling further highlighted the involvement of the AMPK signaling pathway. These findings provide a basis for future research aimed at developing cancer treatments with reduced side effects.收起

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