机构：[1]School of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.[2]Institute of Traditional Chinese Medicine of Sichuan Academy of Chinese Medicine Sciences, Chengdu 610031, China.[3]Wenjiang District Traditional Chinese Medicine Hospital, Wenjiang 611130, China.[4]College of public health, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.[5]Academic Department, Chengdu hemoyunyin medical laboratory Co., Ltd., Wenjiang 611135, China.
Irinotecan (CPT-11) is a chemotherapy agent commonly used for the treatment of gastrointestinal tumors, with diarrhea being a frequent adverse effect. Hesperidin is a flavonoid abundant in citrus fruits and has shown potential in managing CPT-11-induced diarrhea (CID). However, the mechanisms underlying its effects remain unclear. This study established a mouse model of CID using CPT-11 administration to evaluate the effects of hesperidin on diarrhea severity, intestinal pathology, gut microbiota composition, and metabolite profiles by conducting biochemical analysis, histopathology, immunohistochemistry, 16S rRNA sequencing, and untargeted metabolomics. In addition, transcriptomic analysis, molecular docking, and molecular dynamics simulations were conducted to investigate potential mechanisms of action. Hesperidin supplementation was found to significantly alleviate CID in mice. Analysis of gut microbiota using 16S rRNA sequencing revealed that hesperidin improved microbial composition, with key taxa such as Alistipes, Limosilactobacillus, Rikenella, and Mucispirillum playing a central role in ameliorating CID. Furthermore, hesperidin enhanced intestinal barrier function by upregulating tight junction proteins, mitigating epithelial damage, and reducing the expression of IL-17A, TARF6, p38, phosphorylated-p38 (P-p38), and AP-1 proteins in the colon. These findings suggest that hesperidin supplementation mitigates CID by modulating gut microbiota and inhibiting the IL-17 signaling pathway, thereby improving intestinal barrier integrity.
基金：
We thank Home for Researchers editorial team (www.home-forresearchers.
com) for language editing service. This work was
supported by the “Xinglin Scholars” Discipline Talent Research
Promotion Plan of Chengdu University of Traditional Chinese
Medicine (No. BSH2021016).
语种：
外文
PubmedID：
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出版当年[2025]版：
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最新[2023]版：
大类|1 区农林科学
小类|1 区农业综合2 区应用化学2 区食品科技
第一作者：
第一作者机构：[1]School of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
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推荐引用方式(GB/T 7714)：
Zhang Xiaobo,Yang Yang,Wen Mingchao,et al.Supplementary Hesperidin Alleviated CPT-11-Induced Diarrhea by Modulating Gut Microbiota and Inhibiting the IL-17 Signaling Pathway[J].Journal Of Agricultural And Food Chemistry.2025,doi:10.1021/acs.jafc.4c09602.
APA：
Zhang Xiaobo,Yang Yang,Wen Mingchao,Zhong Fanghui,Shu Xinyao...&Shen Tao.(2025).Supplementary Hesperidin Alleviated CPT-11-Induced Diarrhea by Modulating Gut Microbiota and Inhibiting the IL-17 Signaling Pathway.Journal Of Agricultural And Food Chemistry,,
MLA：
Zhang Xiaobo,et al."Supplementary Hesperidin Alleviated CPT-11-Induced Diarrhea by Modulating Gut Microbiota and Inhibiting the IL-17 Signaling Pathway".Journal Of Agricultural And Food Chemistry .(2025)
农林科学