文献类型：期刊文献

英文题名：Astragalus licorice prescription and its active components alleviate chemotherapy-induced intestinal mucositis by apoptosis and fatty acid β-oxidation: Integrative multi-omics approaches

作者：Wang, Xiaoqian[1,3,4];Zhang, Yuemei[5];Wu, Jinhan[1,3,4];Chen, Dandan[2,3];Xiu, Minghui[2,3];Chang, Linghui[1,3,4];Wang, Yan[2,3];Li, Jiangnan[1,3,4];He, Jianzheng[1,3,4];Liu, Yongqi[1,3,4]

第一作者：Wang, Xiaoqian

通信作者：He, JZ[1];Liu, YQ[1]

机构：[1]Gansu Univ Chinese Med, Prov Level Key Lab Mol Med Major Dis & Prevent & T, 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]Dunhuang Med Basic Res Ctr Gansu Prov, Lanzhou 730000, Peoples R China;[5]Lanzhou Univ, Affiliated Hosp 1, 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, Prov Level Key Lab Mol Med Major Dis & Prevent & T, Lanzhou 730000, Peoples R China.|[10735]甘肃中医药大学;

年份：2026

卷号：150

外文期刊名：PHYTOMEDICINE

收录：;Scopus(收录号：2-s2.0-105025696991);WOS:【SCI-EXPANDED(收录号:WOS:001653240600004)】；

基金：Funding This work was supported by Foundation from Key Laboratory of Dunhuang Medicine (No. DHYX22-01) , Gansu Natural Science Foun-dation (No. 23JRRA1202) , Gansu Province Joint Scientific Research Foundation (No. 24JRRA875) , Gansu Province Outstanding Doctoral Student Program (No. 23JRRA1224) .

语种：英文

外文关键词：Chemotherapy-induced intestinal mucositis; Astragalus licorice prescription; Multi-omics approaches; Fatty acid beta-oxidation; Apoptosis

摘要：Background: Chemotherapy-induced intestinal mucositis (CIM) is one of the most common side effects of chemotherapy agents. Astragalus licorice prescription (ALP), a traditional Chinese formula, commonly used to treat gastrointestinal disorders, has an unclear mechanism and potential active components in alleviating CIM. Purpose: This study aims to comprehensively explore the mechanism and bioactive components of ALP in alleviating CIM. Methods: ALP's efficacy on CIM was evaluated in Drosophila melanogaster (flies) and C57BL/6 mice using phenotype assays, hematoxylin-eosin (H&E) staining, and immunohistochemistry. ALP's synergistic effect with 5-FU (5-fluorouracil) on tumors was assessed in 615 tumor-bearing mice by measuring tumor volume/weight and performing HE/immunohistochemical staining. Ki67 staining assessed tumor proliferation. Multi-omics integration (transcriptomics, lipidomics, microbiome analysis, network pharmacology) analyzed ALP's mechanism against CIM. Functional pathways were validated via RT-qPCR, biochemical kits, and immunofluorescence, as well as transgenetic flies targeted with GFP. ALP's functional components were characterized by liquid chromatography-mass spectrometry (LC-MS) and validated in CIM flies. Results: ALP significantly mitigated chemotherapy-induced systemic and intestinal damage in flies, evidenced by improved survival rate, elongated intestinal length, reduced acid-base imbalance, and enhanced epithelial and stem cell proliferation. Similarly, ALP alleviated intestinal mucositis symptoms and pathological damage in 5-FUtreated mice, such as reducing diarrhea levels, increasing intestinal length and villus height. Mechanistically, ALP inhibited the expressions of the JAK/STAT pathway related genes (upd3, stat92E, hop, dome, and Dronc) and proteins (UPD3, STAT92E, cleaved caspase-3), and reduced intstinal cells apoptosis. Concurrently, ALP elevated lipid metabolism levels by activating the fatty acid beta-oxidation (FAO) pathway related genes expressions (Wdh, Mtp-alpha, Mtp-beta, and Scully) and decreased intestinal free fatty acids. Integrated microbiome, lipidomic, and transcriptomic analyses revealed that ALP corrected multiple gut microbial and lipid metabolic disorders associated with the JAK/STAT apoptotic pathway and FAO lipid metabolism pathway. Furthermore, ALP combined with 5FU enhanced the anti-tumor effect of 5-FU, as shown by reduced tumor volume and weight, and decreased the proliferation of tumor cells. Finally, four bioactive compounds in ALP, including berberine, dihydrotanshinone I, licochalcone A, and resveratrol, were identified as alleviating CIM. Conclusion: ALP mitigated CIM by inhibiting the JAK/STAT pathway to reduce cellular apoptosis and activating the FAO pathway to improve lipid metabolism, thereby positioning it as a promising novel therapeutic option. Meanwhile, four bioactive compounds of ALP demonstrated protective effects against CIM.