Baicalein attenuates acute liver injury by blocking NLRP3 inflammasome. - GreenMedInfo Summary
Baicalein attenuates acute liver injury by blocking NLRP3 inflammasome.
Biochem Biophys Res Commun. 2020 Nov 30. Epub 2020 Nov 30. PMID: 33272570
Infection and/or drug-mediated acute liver injury, the leading cause of lethal liver failure, is a critical health problem worldwide and lacks effective treatment. Here, we used Lipopolysaccharides (LPS)/D-galactosamine (D-gal)-treated primary hepatocytes to screen a natural library that contains 1130 chemicals. Baicalein in the library showed highest inhibitory effects against LPS/D-Gal-induced liver injury. In-vivo study similarly validated the protection of baicalein against dampened liver function and increased lethality after a challenge of LPS/D-Gal. Using a cytometric bead array, we found that IL-1α and IL-1β, the downstream of NLRP3, had highest reduction among the plasma inflammatory cytokines in LPS/D-Gal-challenged mice after a treatment of baicalein. To determine the target of baicalein and the underlying mechanism, Nlrp3, Gsdmdor WT mice were treated with or without baicalein, IL-1R antibody or recombinant mouse IL-1β (rmIL-1β) prior to a challenge of LPS/D-Gal. Deficiency of Nlrp3 or Gsdmd significantly restored LPS/D-Gal-induced acute liver injury and lethality, and further administration of baicalein did not have additive effects. In addition, the inhibition of the downstream by IL-1R antibody phenocopiedthe knockout of Nlrp3 or Gsdmd. Moreover, a challenge of rmIL-1β reversed the improvement in Nlrp3mice or the mice treated with baicalein. Taken together, NLRP3 functions as a pivotal promoter in acute liver injury and baicalein attenuates acute liver injury by inhibiting NLRP3 inflammasome.