文献类型：期刊文献

英文题名：Protective effect of HPS against irinotecan-induced intestinal injury in drosophila and mice via modulation of inflammation, oxidation, and gut microbiota

作者：Li, Shuang[1,2,3];Chen, Qiqi[1,5];Du, Xianqin[1,2,3];Gao, Rongni[1,5];Li, Liangliang[1,2,3];Li, Botong[1,2,3];Han, Shuzhen[1,2,3];Zhang, Li[1,2,3];Xiu, Minghui[1,4];He, Jianzheng[1,2,3];Lin, Xingyao[1,2,3]

第一作者：李爽;Li, Shuang

通信作者：He, JZ[1];Lin, XY[1]

机构：[1]Minist Educ, Key Lab Dunhuang Med, Lanzhou 730000, Peoples R China;[2]Gansu Univ Chinese Med, Coll Basic Med, Lanzhou 730000, Peoples R China;[3]Gansu Univ Chinese Med, Res & Expt Ctr, Lanzhou 730000, Peoples R China;[4]Gansu Univ Chinese Med, Coll Publ Hlth, Lanzhou 730000, Peoples R China;[5]Gansu Univ Chinese Med, Coll Clin Chinese Med, Lanzhou 730000, Peoples R China

第一机构：Minist Educ, Key Lab Dunhuang Med, Lanzhou 730000, Peoples R China

通信机构：[1]corresponding author), Gansu Univ Chinese Med, Lanzhou 730000, Peoples R China.|[10735]甘肃中医药大学;

年份：2025

卷号：321

外文期刊名：INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES

收录：;EI(收录号：20253118902415);Scopus(收录号：2-s2.0-105011949237);WOS:【SCI-EXPANDED(收录号:WOS:001544967900001)】；

基金：This work was supported by the Gansu Higher Education Industry Support Plan Project (No. 2025cYzc-47) , the 2021 Talent Development Special Fund of Gansu Province (No. 40160401) , and the Gansu Natural Science Foundation (No. 23JRRA1202) .

语种：英文

外文关键词：Radix Hedysari polysaccharides; Irinotecan; Intestinal mucositis; Keap1/Nrf2 signaling pathway; JAK1/STAT6 signaling pathway; Intestinal flora

摘要：Intestinal mucositis is a common and debilitating complication of the chemotherapeutic agent irinotecan (CPT11), characterized by intestinal barrier disruption, oxidative stress, inflammation, and gut microbiota dysbiosis. Radix Hedysari polysaccharides (HPS) possess anti-inflammatory, antioxidant, and microbiota-regulating properties, but their protective effects against CPT-11-induced intestinal injury remain unclear. In this study, we investigated the protective effect and mechanism of HPS in CPT-11-induced intestinal mucositis using Drosophila melanogaster and BALB/c mouse models. HPS supplementation significantly improved survival and locomotor activity in CPT-11-induced flies, and ameliorated intestinal phenotypes including excessive feeding, increased excretion, crop enlargement, shortened gut length, impaired acid-base balance, and elevated intestinal cell death. HPS also suppressed reactive oxygen species (ROS) levels and modulated antioxidant-related genes (gstD1, cat, sod1, sod2) and the JAK pathway (STAT92E, UPD3, UPD3-1) in fly guts. In mice, administration of HPS reversed the CPT-11-induced gut microbial dysbiosis, restored microbial diversity, and suppressed serum proinflammatory cytokines (TNF-alpha and IL-6). Mechanistic studies revealed that HPS alleviated colonic injury by up-regulating the Keap1/Nrf2 antioxidant response and down-regulating the JAK1/STAT6 inflammatory signaling. These findings suggest that HPS has a protective role in CPT-11-induced intestinal mucositis via antioxidant, anti-inflammatory, and microbiota-modulatory activities, supporting its potential as a therapeutic agent for chemotherapy-induced intestinal injury.