1,2,3,4,6-Pentagalloyl glucose efficiently chelate excess iron to treat iron overload disorders and to prevent ferroptosis.

The accumulation of iron potentially results in organ damage and various diseases. Polyphenols can chelate iron in solution; however, there is a paucity of direct evidence supporting their efficacy in treating iron overload- mediated damage. This study sought to assess the chelating efficacy of galloyl glucoses with iron, as well as the potential of 1,2,3,4,6-Pentagalloyl glucose (PGG) to mitigate ferroptosis and liver injury induced by iron overload. RSL3 was employed to establish a cell model, while mice were treated with dextrose iron. PGG markedly mitigated cell death and the accumulation of lipid peroxides in RSL3 treated cells by chelating iron and inhibiting the RSL3-mediated autophagic degradation of ferroportin. Additionally, oral administration of PGG significantly reduced iron accumulation, inhibited oxidative stress, and ameliorated liver injury induced by iron overload. PGG has the potential to serve as an intervention for cell death and liver damage resulting from iron overload. The findings aim to contribute to the development of strategies for the intervention of iron overload-related injuries.