Protective effects of chicoric acid on LPS-induced endometritis in mice via inhibiting ferroptosis by Nrf2/HO-1 signal axis

Int Immunopharmacol. 2022 Dec;113(Pt B):109435. doi: 10.1016/j.intimp.2022.109435. Epub 2022 Nov 17.

Abstract

Chicoric acid (CA), a natural phenolic acid extracted from Mediterranean vegetable chicory, has anti-oxidative effect. We aimed to investigate the effects of CA on endometritis and clarify the underlying mechanism. C57BL/6 mice were divided into five groups: control group, LPS group, and LPS + CA groups. All mice except control group were infused of LPS into the uterus. The mice of LPS + CA groups were intraperitoneally injected CA 1 h before LPS challenge. CA significantly alleviatedLPS-induced pathological damage, MPO activity, and inflammatory cytokine production. CA significantly suppressed ferroptosis in LPS-induced endometritis. CA also attenuated LPS-induced NF-κB activation. Furthermore, Nrf2 and HO-1 expression were increased by CA. Moreover, the inhibition of CA on LPS-induced endometritis and ferroptosis were markedly prevented in Nrf2 knockdown mice. In conclusion, the results suggested CA protected mice against LPS-induced endometritisthrough inhibiting ferroptosis via Nrf2/HO-1 signaling pathway.

Keywords: Chicoric acid; Endometritis; Ferroptosis; LPS; Nrf2.

MeSH terms

  • Animals
  • Endometritis* / chemically induced
  • Endometritis* / drug therapy
  • Female
  • Ferroptosis*
  • Lipopolysaccharides
  • Mice
  • Mice, Inbred C57BL
  • NF-E2-Related Factor 2

Substances

  • chicoric acid
  • Hmox1 protein, mouse
  • Lipopolysaccharides
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, mouse