Citral protects against LPS-induced endometritis by inhibiting ferroptosis through activating Nrf2 signaling pathway.

Abstract

Endometritis is the inflammatory condition of the uterus. Citral, a component of lemongrass oil, is known to exhibit anti-inflammatory activity. The effects of citral on LPS-induced endometritis were tested and the mechanisms were investigated. LPS-induced endometritis mice model was established and the effects of citral were detected using this model. Inflammatory cytokines were tested by ELISA. Ferroptosis was assessed by detecting GSH, ATP, MDA, and Fe2+ levels. Signaling pathway was tested by western blot analysis. Citral prevented LPS-induced endometritis through attenuating uterine pathological changes and inflammatory cytokine release. Meanwhile, citral prevents LPS-induced ferroptosis through attenuating MDA and Fe2+ levels, as well as increasing ATP and GSH levels. Furthermore, citral up-regulated Nrf2 and HO-1 expression and attenuated NF-κB activation. In addition, in Nrf2 knockdown mice, the inhibitory roles of citral on ferroptosis and endometritis were largely reversed. Taken together, citral inhibited LPS-induced endometritisthrough preventing ferroptosis, which were regulated by Nrf2 signaling pathway.