Hepatoprotective effect of flavonoid-enriched fraction from Cyclocarya paliurus leaves on LPS/D-GalN-induced acute liver failure

[Display omitted] •The chemical composition of flavonoids from Cyclocarya paliurus (CPF) was identified.•CPF treatment effectively protected against LPS/D-GalN-induced acute liver failure (ALF).•CPF treatment inhibited oxidative stress, inflammation, and apoptosis in liver of ALF mice.•CPF treatment suppressed the NF-κB pathway, whereas activated the Nrf2/HO-1 pathway. This study aimed to investigate the chemical composition and hepatoprotective effect of flavonoid fraction from Cyclocarya paliurus leaves (CPF) on the lipopolysaccharide/D-galactosamine (LPS/D-GalN)-induced acute liver failure (ALF). UPLC-MS analysis revealed that CPF mainly contained quercetin-3-O-glycoside, quercetin-3-O-rhamnoside, kaempferol-3-O-rhamnoside, quercetin and kaempferol. CPF treatment (100, 200, and 400 mg/kg) effectively prevented LPS/D-GalN-induced ALF by lessening the mortality; improving hepatic morphological structures and oxidative stress; decreasing the ALT and AST levels and inflammatory cytokines. Additionally, CPF alleviated hepatocyte apoptosis and mitochondrial dysfunction, which could be attributed to the activation of nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase (HO)-1 pathway and the regulation of caspse-3, reactive oxygen species modulator 1 (Romo1) and B-cell lymphoma-extra large (Bcl-XL) expressions. Moreover, CPF dose-dependently inhibited the activation of NF-κB pathway and downregulated the expression of CD14 and TNF-R1. These results indicate that CPF could be developed as a promising functional food for the prevention of ALF.