Blueberry anthocyanins and their metabolites synergistically alleviated ferroptosis induced by acrylamide in HepG2 cells.

Acrylamide (ACR), which is formed in foods during high-temperature cooking, triggers ferroptosis in the liver. Blueberry anthocyanins (BAs) are effective in protecting the liver against ACR-induced injury; however, this effect is also associated with metabolites generated in vivo. To determine their functional interaction with ACR defense, the dominating anthocyanin monomer-cyanidin-3-O-glucoside (C3G) and metabolites gallic acid (GA), 4-hydroxybenzoic acid (HA), and vanillic acid (VA) according to our previous study were combined to explore their influence on ferroptosis in HepG2 cells. The results showed that C3G and its metabolites (GA, HA, and VA) synergistically inhibited ferroptosis by suppressing oxidative stress, via compounds and antioxidant enzymes related to the Nrf2-Keap1 pathway, iron, lipid reactive oxygen species, and targeted genes and proteins, such as Nrf2, GPX4, SLC7A11, ACSL4, and others. Overall, this study provides a novel perspective on the health benefits of BAs following their digestion and metabolism.