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Chrysanthemum has a long history of being used to attenuate various oxidative stress-related discomforts and diseases; however, its mechanisms remain unclear. In this study, the antioxidant effect of chrysanthemum aqueous extract was investigated, and the potential mechanisms were explored via a metabolomics study. Chrysanthemum extract could significantly inhibit hydrogen peroxide (H 2 O 2 )-mediated cell death in L-O2 hepatocytes. Propidium iodide staining and annexin V-PI dual staining revealed that the antioxidant effect of chrysanthemum extract was related to the relief of cell cycle arrest and inhibition of non-apoptotic cell damage. The activities of antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) were also upregulated by chrysanthemum extract. Through metabolomics studies, it was found that chrysanthemum extract mainly targeted the arginine synthesis pathway and purine metabolism pathway, in which antioxidation-related endogenous substrates including L-arginosuccinate, citrulline and inositol monophosphate were significantly upregulated by chrysanthemum extract. These results indicated that chrysanthemum extract can antagonize oxidative stress through multiple pathways and have potential therapeutic applications.

Antioxidant Effect of Chrysanthemum morifolium (Chuju) Extract on H2O2-Treated L-O2 Cells as Revealed by LC/MS-Based Metabolic Profiling