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作者

Fengxian Jiang Pancen Ran Liyin Pan Jingjiang Lai Junlei Zhang Jing Zhao Wei Xu Jingliang Wang Yang Shu Yahui Wang Rui Zhao Weihao Wang Jian Wei Guobin Fu

作者单位

⁹Department of Cell Biology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong 250012, PR China ⁴The Second Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, 250002, PR China ¹⁰Department of Medical Oncology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250021, PR China ⁵Innovative Institute of Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, 250002, PR China ⁸Department of Medical Oncology, The Third Affiliated Hospital of Shandong First Medical University, Jinan, 250031, PR China ⁷The Clinical Medical College, Shandong First Medical University (Shandong Academy of Medicine), Jinan, 250117, PR China ⁶Department of Pathology, Shandong Provincial Hospital, Shandong University, Jinan, 250021, PR China ¹Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, PR China ³Fengxian Jiang and Pancen Ran contributed equally to this work. ²Department of Radiation Oncology, The 960th Hospital of the PLA Joint Logistics Support Force, Jinan, 250031, PR China

刊名

Journal of Traditional and Complementary Medicine

年份

2024

ISSN

2225-4110

关键词

Atractylenolide III Pyrotinib-induced diarrhea Chloride secretion Gut microbiota Metabolites

摘要

Atractylenolide III, a sesquiterpene extracted from the rhizome of Atractylodes macrocephala , exhibits pharmacological effects, including improvement of gastrointestinal function, regulation of immune function, anti-inflammatory and antibacterial properties. Pyrotinib, a representative TKI originally developed in China, is classified as a Class 1.1 novel drug, exhibits superior efficacy compared to similar drugs. Notably, the overall incidence of pyrotinib-induced diarrhea stands at 95 %, with ...更多

Atractylenolide III, a sesquiterpene extracted from the rhizome of Atractylodes macrocephala , exhibits pharmacological effects, including improvement of gastrointestinal function, regulation of immune function, anti-inflammatory and antibacterial properties. Pyrotinib, a representative TKI originally developed in China, is classified as a Class 1.1 novel drug, exhibits superior efficacy compared to similar drugs. Notably, the overall incidence of pyrotinib-induced diarrhea stands at 95 %, with 40 % of cases classified as grade ≥3 diarrhea. Currently, the effect of Atractylenolide III on pyrotinib-induced diarrhea and the underlying mechanisms remain unclear. Therefore, in this study, we established a pyrotinib Wistar rat diarrhea model to explore the effect of Atractylenolide III on pyrotinib-induced diarrhea. We exploded the potential mechanism of Atractylenolide III via MQAE chloride fluorescent probe, RT-qPCR, Western blot, 16S rRNA sequencing, metabolomics, etc. We found that Atractylenolide III demonstrated the ability to alleviate pyrotinib-induced diarrhea without compromising its anti-tumor effects, inhibited pyrotinib-induced chloride secretion, and the potential mechanism of action involved enhancing AMPK phosphorylation while decreasing CFTR protein expression. Additionally, Atractylenolide III alleviated pyrotinib-induced diarrhea by modulating intestinal flora structure and increasing lithocholic acid content. This study could provide potential novel traditional Chinese medicine targets for treating diarrhea caused by tyrosine kinase inhibitor drugs, such as pyrotinib. The study emphasizes the role of TCM in minimizing adverse effects during tumor treatment.收起

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