Andrographolide ameliorates sepsis-induced acute liver injury by attenuating endoplasmic reticulum stress through the FKBP1A-mediated NOTCH1/AK2 pathway.

ABSTRACT: Andrographolide (AP) has been shown to possess anti-inflammatory activities. In this study, the impact of AP in sepsis-induced acute liver injury (ALI) and the molecules involved were dissected. FKBP1A was predicted to be the sole target protein of AP that was also differentially expressed in the GSE166868 dataset. AP induced the protein expression of FKBP1A and suppressed that of NOTCH1 in a dose-dependent manner. AP ameliorated ALI in mice induced by D-galactosamine and LPS and inhibited LPS-induced liver parenchymal cell injury in vitro. By contrast, the protective effect of AP was significantly lost after the knockdown of FKBP1A. As a positive control, the therapeutic effect of dexamethasone on ALI may be related to NOTCH1, which was not related to FKBP1A. NOTCH1 promoted AK2 transcrip

SUBMITTER: He J 

PROVIDER: S-EPMC11889056 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature