Glabridin protects against paraquat-induced acute lung injury by targeting ME1 to mitigate oxidative stress,...

Acute lung injury (ALI) resulting from paraquat (PQ) poisoning constitutes a significant mortality risk, predominantly due to oxidative stress and mitochondrial dysfunction. Despite this, effective treatment options are currently limited.

This study examines the protective effects of Glabridin (Glab), a flavonoid with noted antioxidant properties, against PQ-induced ALI, with a focus on its mitochondrial function and modulation of oxidative stress.

The research utilized human normal lung epithelial line BEAS-2B cells (B2B) and PQ-exposed C57BL/6J mice to evaluate the role of Glab. Assessments included lung inflammation, oxidative stress markers, and mitochondrial dysfunction, as well as the involvement of the cGAS-STING and caspase-3 pathways. Molecular docking and western blot analyses were used to investigate the interaction between Glab and malic enzyme 1 (ME1).

The findings indicate that Glab significantly enhances survival rates, reduces inflammation, and mitigates oxidative stress in PQ-exposed mice. In vitro experiments demonstrated that Glab inhibited the cGAS-STING and caspase-3 pathways, release of mitochondrial contents (cytochrome C and mtDNA), decreased mitochondrial ROS production, and stabilized ME1, resulting in increased NADPH levels.

Glab confers protection against PQ-induced ALI by modulating oxidative stress, preserving mitochondrial function, and inhibiting both inflammatory and apoptotic pathways. Notably, the stabilization of malic enzyme 1 (ME1) and the consequent increase in NADPH levels play a critical role in this protective mechanism. These results underscore the potential of Glab as a therapeutic agent for addressing PQ poisoning, with particular emphasis on the pivotal role of ME1 in mediating its effects.