Guaiane sesquiterpenoid—Glucozaluzanin C from Ainsliaea fragrans Champ. targets TLR4/p65 to regulate NF-κB/MAPK pathway, alleviating sepsis-induced acute liver injury

Abstract

Six guaiane sesquiterpenoids were isolated from the Ainsliaea fragrans Champ., including four new compounds and two known compounds. Their structures were elucidated through comprehensive nuclear magnetic resonance (NMR), high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), and electronic circular dichroism (ECD) analyses. Compared to other compounds, Compound 1, glucozaluzanin C (GC), which has an intact α, β-unsaturated ketone structure, demonstrated superior anti-inflammatory activity. In vitro and in vivo experimental studies had shown that GC had a significant effect in alleviating LPS-induced macrophage inflammation and acute liver injury. GC could target TLR4 and p65 proteins and significantly inhibit the activation and expression of NF-κB/MAPK pathways.