Skimmianine attenuates liver ischemia/reperfusion injury by regulating PI3K-AKT signaling pathway-mediated inflammation, apoptosis and oxidative stress

Abstract Liver ischemia/reperfusion (I/R) injury is a common injury after liver transplantation and hepatectomy. Skimmianine (Ski) has antibacterial, antiviral pharmacological effects. However, it is not clear whether Ski has a protective effect against liver I/R injury. In the present study, we established mouse liver I/R model and AML12 cell hypoxia-reoxygenation (H/R) model pretreated with different concentrations of Ski. Serum transaminase levels, necrotic liver area, cell viability, inflammatory factors, oxidative stress and apoptosis-related levels were measured to assess the protective effect of Ski against liver I/R injury. Western blotting was used to detect apoptosis-related proteins and PI3K-AKT pathway-related proteins. Mice and cells were also treated with PI3K inhibitor LY294002 to assess changes in indicators of liver injury. The results showed that Ski significantly reduced transaminase levels, liver necrosis area, oxidative stress and apoptosis levels in mice with I/R. Ski also inhibited cell injury and apoptosis after H/R. Ski also activated phosphorylation of PI3K-AKT pathway-related proteins after liver I/R and cell H/R. PI3K inhibitor LY294002 could well reverse the alleviation of I/R injury caused by Ski. These results confirm that Ski exerts a protective effect against liver I/R injury through activation of the PI3K-AKT pathway.