Celastrol mitigates inflammation in sepsis by inhibiting the PKM2-dependent Warburg effect.

ABSTRACT:

Background

Sepsis involves life-threatening organ dysfunction and is caused by a dysregulated host response to infection. No specific therapies against sepsis have been reported. Celastrol (Cel) is a natural anti-inflammatory compound that shows potential against systemic inflammatory diseases. This study aimed to investigate the pharmacological activity and molecular mechanism of Cel in models of endotoxemia and sepsis.

Methods

We evaluated the anti-inflammatory efficacy of Cel against endotoxemia and sepsis in mice and macrophage cultures treated with lipopolysaccharide (LPS). We screened for potential protein targets of Cel using activity-based protein profiling (ABPP). Potential targets were validated using biophysical methods such as cellular thermal shift assays (CETSA

SUBMITTER: Luo P 

PROVIDER: S-EPMC9121578 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature