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