2. Academic Validation
  3. Polysaccharide from Atractylodes macrocephala Koidz. alleviates pyrotinib-induced diarrhea through regulating cAMP/LKB1/AMPK/CFTR pathway and restoring gut microbiota and metabolites

Polysaccharide from Atractylodes macrocephala Koidz. alleviates pyrotinib-induced diarrhea through regulating cAMP/LKB1/AMPK/CFTR pathway and restoring gut microbiota and metabolites

  • Int J Biol Macromol. 2025 May;308(Pt 3):142512. doi: 10.1016/j.ijbiomac.2025.142512.
Pancen Ran 1,  Fengxian Jiang 2,  Liying Pan 3,  Yang Shu 3,  Fangyan Hu 4,  Yahui Wang 3,  Rui Zhao 5,  Weihao Wang 5,  Huaiqian Mu 5,  Juqiong Wang 4,  Jian Wei 6,  Guobin Fu 7
Affiliations

Affiliations

  • 1 Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China; The Second Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250013, China.
  • 2 Department of Radiation Oncology, The 960th Hospital of the PLA Joint Logistics Support Force, Jinan 250031, China.
  • 3 The Second Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250013, China.
  • 4 School of Basic Medical Sciences, Shandong University, Jinan, Shandong 250012, China.
  • 5 Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China.
  • 6 School of Basic Medical Sciences, Shandong University, Jinan, Shandong 250012, China. Electronic address: jianwei@sdu.edu.cn.
  • 7 Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China; The Second Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250013, China; Department of Medical Oncology, The Third Affiliated Hospital of Shandong First Medical University, Jinan, Shandong 250031, China. Electronic address: fgbs@email.sdu.edu.cn.
PMID: 40157659 DOI: 10.1016/j.ijbiomac.2025.142512
Abstract

Polysaccharide from Atractylodes macrocephala Koidz. (PAMK), a bioactive component of Atractylodes macrocephala Koidz. (AMK), 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 (ELISA), 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.

Keywords

CFTR; Gut microbiota; Metabolites; Polysaccharide from Atractylodes macrocephala Koidz.; Pyrotinib-induced diarrhea.

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  • HY-D0090
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