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Methylated Metabolites of Chicoric Acid Ameliorate Hydrogen Peroxide (H2O2)-Induced Oxidative Stress in HepG2 Cells.

Chicoric acid (CA) can display health benefits as a dietary polyphenol. However, as CA is widely metabolized in vivo, the actual compounds responsible for its bioactivities are not entirely known. Herein, the major methylated metabolites of CA were isolated from an in vitro co-incubation system, and their structures were elucidated. The antioxidant activities of the monomethylated metabolites (M1) and dimethylated metabolites (M2) of CA were evaluated against H2O2-induced oxidative stress damage in HepG2 cells and compared to CA. The results indicated that both M1 and M2 had better antioxidant capacities than CA by increasing cell viability, improving mitochondrial function, and balancing cellular redox status. These compounds also prevented oxidative stress by mediating the Keap1/Nrf2 transcriptional pathway and downregulating enzyme activity. The current research indicates that the methylated metabolites of CA could potentially be the candidates that are responsible for the biological efficacies attributed to CA.