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

• Published in: Toxicology (Amsterdam) 2019-12, Vol.428, p.152307, Article 152307
• Main Authors: Huang, Zhenlin, Zhao, Qing, Chen, Minwei, Zhang, Jingnan, Ji, Lili
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphate - metabolism; Animals; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Chaperonin 60 - metabolism; Flavanones - pharmacology; Flavanones - therapeutic use; Glucosides - pharmacology; Glucosides - therapeutic use; Hepatic Veno-Occlusive Disease - chemically induced; Hepatic Veno-Occlusive Disease - drug therapy; Hepatic Veno-Occlusive Disease - metabolism; Hepatic Veno-Occlusive Disease - pathology; HSOS; HSP60; Liquiritigenin; Liquiritin; Liver - drug effects; Liver - metabolism; Liver - pathology; Lon; Male; Mice; Mitochondria - drug effects; Mitochondria - metabolism; Monocrotaline; NFκB; Rats, Sprague-Dawley; RAW 264.7 Cells; Reactive Oxygen Species - metabolism
• ISSN: 0300-483X; 1879-3185
• DOI: 10.1016/j.tox.2019.152307

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 κB (NFκB) 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 NFκB nuclear accumulation and decreased the elevated cellular mRNA expression of NFκB-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.