Liquiritigenin and liquiritin alleviated monocrotaline-induced hepatic sinusoidal obstruction syndrome via inhibiting HSP60-induced inflammatory injury

Hepatic sinusoidal obstruction syndrome (HSOS) is a life-threatening liver disease caused by the damage to liver sinusoidal endothelial cells (LSECs). Liquiritigenin and liquiritin are two main compounds in Glycyrrhizae Radix et Rhizoma (Gan-cao). Our previous study has shown that both liquiritigenin and liquiritin alleviated monocrotaline (MCT)-induced HSOS in rats via inducing the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant signaling pathway. This study aims to further investigate whether inhibiting liver inflammatory injury also contributed to the liquiritigenin and liquiritin-provided alleviation on MCT-induced HSOS. The results of serum alanine/aspartate aminotransferases (ALT/AST) activities and total bilirubin (TBil) amount, liver histological evaluation, scanning electron microscope observation and hepatic metalloproteinase-9 (MMP9) expression showed that liquiritigenin and liquiritin both alleviated MCT-induced HSOS in rats. Liquiritigenin and liquiritin reduced the increased liver myeloperoxidase (MPO) activity, mRNA expression of pro-inflammatory factors, hepatic infiltration of immune cells, hepatic toll-like receptor 4 (TLR4) expression and nuclear factor kappa B (NF kappa B) nuclear accumulation induced by MCT in rats. Furthermore, liquiritigenin and liquiritin attenuated MCT-induced liver mitochondrial injury, increased the decreased Lon protein expression and reduced the release of heat shock protein 60 (HSP60). Moreover, liquiritigenin and liquiritin also reduced NF kappa B nuclear accumulation and decreased the elevated cellular mRNA expression of NE kappa B-downstream pro-inflammatory cytokines induced by HSP60 in macrophage RAW264.7 cells. In conclusion, our study revealed that both liquiritigenin and liquiritin alleviated MCT-induced HSOS by inhibiting hepatic inflammatory responses triggered by HSP60.