Hydrogen-rich water (HRW) has been shown to prevent cognitive impairment caused by ionizing radiation. This study aimed to investigate the pharmacological effects and mechanisms of HRW on ionizing radiation by coupling the brain metabolomics and biological target network methods. HRW significantly improves cognitive impairment in rats exposed to ionizing radiation. Based on metabolomics and biological network results identified that, 54 differential metabolites and 93 target genes. The KEGG pathway indicates that glutathione metabolism, ascorbic acid, and aldehyde acid metabolism, pentose and glucuronic acid interconversion, and glycerophospholipid metabolism play important roles in ionizing radiation therapy. This study has systematically elucidated the molecular mechanism of HRW against ionizing radiation, which can be mediated by modulating targets, pathways, and metabolite levels. This provides a new perspective for identifying the underlying pharmacological mechanism of HRW.
