文献类型：期刊文献

英文题名：Dunhuang Gancao Fuling Xingren decoction and its components alleviate CPT-11 induced intestinal mucositis by regulating gut microbiota related innate immunity and inflammatory response in Drosophila and mice

作者：Wu, Jinhan[1];Xiu, Minghui[2,3];Wang, Xiaoqian[1];Zhang, Peihao[1];Qin, Yujie[2];Li, Jiangnan[1];Jiang, Xiaolin[1];Duan, Yaoxing[4];Liu, Yongqi[1,3];He, Jianzheng[1,4,5]

第一作者：Wu, Jinhan

通信作者：Liu, YQ[1];He, JZ[1];Liu, YQ[2];He, JZ[3];He, JZ[4]

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

第一机构：甘肃中医药大学

通信机构：[1]corresponding author), Gansu Univ Chinese Med, Gansu Prov Res Ctr Basic Disciplines Dunhuang Med, Lanzhou 730000, Peoples R China;[2]corresponding author), Minist Educ, Key Lab Dunhuang Med, Lanzhou 730000, Peoples R China;[3]corresponding author), Gansu Prov Hosp, Lanzhou 730000, Peoples R China;[4]corresponding author), Gansu Univ Chinese Med, Res & Expt Ctr, Lanzhou 730000, Peoples R China.|[10735]甘肃中医药大学;

年份：2026

卷号：21

期号：1

外文期刊名：CHINESE MEDICINE

收录：;Scopus(收录号：2-s2.0-105026491967);WOS:【SCI-EXPANDED(收录号:WOS:001652994700001)】；

基金：This work was supported by Gansu Natural Science Foundation (Nos. 25JRRA1177, and 25JRRA303), Foundation from Key Laboratory of Dunhuang Medicine (Nos. DHYX24-15), and Lanzhou Youth Science and Technology Talent Innovation Project (No. 2024-QN-35).

语种：英文

外文关键词：Chemotherapy-induced intestinal mucositis; Dunhuang Gancao Fuling Xingren decoction; Molecular mechanism; Gut microbiota dysbiosis

摘要：BackgroundDunhuang Gancao Fuling Xingren decoction (GFXD) is a traditional formulation derived from the Dunhuang Ancient Medical Prescriptions, has been historically utilized for its immunomodulatory and anti-inflammatory properties. However, the protective effect against irinotecan (CPT-11)-induced intestinal mucositis (CIM) remains poorly elucidated.PurposeTo investigate the therapeutic efficacy of GFXD in alleviating CIM and elucidate its underlying mechanism and components using Drosophila melanogaster and C57BL/6 J mouse models.MethodsThe therapeutic efficacy of GFXD was assessed in both Drosophila and mouse models by phenotype assay, hematoxylin and eosin (H&E) staining, and Alcian blue-periodic acid schiff (AB-PAS) staining. Transcriptomic profiling combined with 16S rRNA sequencing were employed to identify potential mechanisms of GFXD regulating CPT-11-induced mucositis. Cytokine levels were measured using ELISA, while the expression levels of key signaling pathways, including Toll-Imd and JAK-STAT pathways were analyzed via qRT-PCR, immunofluorescence, fecal microbiota transplantation (FMT) experiment, and antibiotic treatment. Furthermore, functional components of GFXD were characterized via liquid chromatography-mass spectrometry (LC-MS), and their efficacy was validated in CPT-11-treated Drosophila.ResultsGFXD significantly mitigated CPT-11-induced systemic and intestinal damage in Drosophila, evidenced by improved survival rate, restored digestive function, elongated intestinal length, reduced acid-base imbalance, and enhanced epithelial and stem cell proliferation. In mice, GFXD alleviated mucositis symptoms, attenuated histopathological damage, and normalized inflammatory cytokine levels. Mechanistically, GFXD suppressed gut microbiota dysbiosis by enriching probiotics (Lactobacillus, Prevotella) and reducing pathogens (Bacteroides, Enterobacter, Enterococcus and Helicobacter). Transcriptomic and molecular analyses revealed that GFXD inhibited hyperactivation of Toll-Imd pathways and JAK-STAT signaling. Finally, three compounds of GFXD, formononetin, kaempferol, and ergosterol were found to alleviate CPT-11 induced intestinal injury.ConclusionsGFXD alleviates CPT-11-induced intestinal mucositis by modulating gut microbiota composition, suppressing JAK-STAT and Toll-Imd pathways. Thus, this study demonstrates GFXD and its bioactive constituents as novel therapeutic agents to mitigate CIM.