A dual-function host-guest antioxidant system for synergistic treatment of diquat poisoning

Diquat (DQ), a widely used herbicide, is highly toxic to humans. DQ ingestion can lead to severe multi-organ dysfunction and high mortality, primarily due to the lack of effective antidotes and detoxification strategies. To address this, we developed a host-guest formulation for the combinatorial treatment of DQ poisoning. This formulation encapsulates ergothioneine (EGT), a potent reactive oxygen species (ROS) scavenger, within the host molecule pillar[6]MaxQ (P6AS). The strong complexation between P6AS and both EGT and DQ was confirmed by NMR and fluorescence titration studies. In vitro and in vivo evaluations demonstrated the excellent detoxification efficacy of this formulation. The EGT/P6AS complex effectively ameliorated DQ-induced organ damage and promoted the normalization of key hematological and biochemical parameters. Notably, treatment with EGT/P6AS resulted in a 50-percentage-point increase in survival rate, underscoring its remarkable therapeutic potential. These favorable outcomes are attributed to a combinatorial mechanism: DQ triggers the release of EGT to counteract peroxidation damage, while free DQ is simultaneously sequestered within the cavity of P6AS.