Urolithin A (UA) attenuates ferroptosis in LPS-induced acute lung injury in mice by upregulating Keap1-Nrf2/HO-1 signaling pathway
Lejing Lou, Min Wang, Jingjing He, Song Yang, Fanxi Meng, Shijia Wang +3 more
Frontiers in Pharmacology
Abstract
Acute lung injury (ALI) is a life-threatening disease with high incidence and mortality rates. Urolithin A (UA) is a pomegranate intestinal flora metabolite with anti-inflammatory, antioxidant, and anti-aging properties. Ferroptosis is a critical factor in lipopolysaccharide (LPS)-induced acute lung injury (ALI). However, the link between UA and ferroptosis is unknown. The purpose of this research was to look into the role of UA in regulating LPS-induced ferroptosis in ALI. The current study used LPS to injure two models, one BEAS-2B cell injury model and one ALI mouse model. UA effectively alleviated LPS-induced ALI compared to the LPS group by lowering <i>in vivo</i> lung wet/dry weight ratio, reactive oxygen species, and malondialdehyde production, as well as superoxide dismutase, catalase, and glutathione depletion. Furthermore, by increasing GPX4 and SLC7A11 expression and decreasing Fe<sup>2+</sup> levels, lung histopathological damage, inflammatory cytokine secretion, and ferroptosis levels can be significantly reduced. The Keap1-Nrf2/HO-1 pathway was upregulated by UA, which inhibited LPS-induced ALI and ferroptosis. ML385 inhibited UA's protective effect against LPS-induced ALI. These findings suggested that UA could be a novel potential therapeutic target for ALI.
Extracted Claims
4 claims extracted from this paper into the knowledge graph
UA reduces LPS-induced ALI
“UA effectively alleviated LPS-induced ALI compared to the LPS group by lowering in vivo lung wet/dry weight ratio, reactive oxygen species, and malondialdehyde production, as well as superoxide dismut...”
Urolithin A (UA) attenuates ferroptosis in LPS-induced acute lung injury (ALI)
“Urolithin A (UA) is a pomegranate intestinal flora metabolite with anti-inflammatory, antioxidant, and anti-aging properties. Ferroptosis is a critical factor in lipopolysaccharide (LPS)-induced acute...”
UA decreases Fe2+ levels
“Furthermore, by increasing GPX4 and SLC7A11 expression and decreasing Fe2+ levels, lung histopathological damage, inflammatory cytokine secretion, and ferroptosis levels can be significantly reduced.”