Xuebijing Protects Against Septic Acute Liver Injury Based on Regulation of GSK-3β Pathway.

Xuebijing (XBJ), the only drug approved for the sepsis and multiple organ dysfunction, and its protective effects against acute liver injury (ALI) and its mechanism. The aim of this study was to evaluate the protective effect of XBJ on cecal ligation and perforation (CLP)-induced mouse ALI model and LPS-induced RAW264.7 cell ALI model. Mice were pretreated with XBJ before the CLP model was established, and serum and liver tissues were collected at the end of the experiment to assess the levels of inflammatory factors and liver injury. Results showed that XBJ pretreatment reduced liver/body weight, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities in serum, and inhibited levels of pro-inflammatory factors in serum. Cells were treatment with XBJ and modeled by LPS modeling increased cell viability in the XBJ-treated group compared to the model group and XBJ also decreased serum pro-inflammatory factors in a dose-dependent manner. Western blot detected that XBJ also up-regulated the phosphorylated levels of glycogen synthase kinase-3β (p-GSK-3β) and cAMP-response element-binding protein (p-CREB) and down-regulated the phosphorylated level of nuclear factor kappa-B (p-NF-κB) in liver and cell. After overexpression of GSK-3β in cells, the mechanism was further investigated using CO-IP analysis. The binding of p-NF-κB and p-CREB to CREB-binding protein (CBP) was increased and decreased, respectively, indicating that GSK-3β regulated inflammation by regulating the binding of p-NF-κB and p-CREB to CBP. The present studies suggested that the hepatoprotective effect of XBJ may be through up-regulation of GSK-3β (Ser9) and increasing the binding of p-CREB to CBP, thereby alleviating the inflammatory response.

Cao L ，Li Z ，Ren Y ，Wang M ，Yang Z ，Zhang W ，Han X ，Yao M ，Sun Z ，Nie S ... -  《Frontiers in Pharmacology》

Ferulic acid positively modulates the inflammatory response to septic liver injury through the GSK-3β/NF-κB/CREB pathway.

Ferulic acid (FA) is a component found in plants that has free radical scavenging and liver-protective properties. Acute liver injury (ALI) is a serious complication of sepsis and is closely associated with changes in the levels of inflammatory factors. This study was taken to examine the role of FA in cecal ligation and perforation (CLP)-induced murine ALI and lipopolysaccharide (LPS)-induced cellular ALI models. An in vivo ALI model was established by performing CLP surgery on C57BL/6 mice. After the ALI model was established, mice were examined for liver injury, including HE staining to observe tissue sections, the percentage of liver/body weight and inflammatory factor levels. Myeloperoxidase (MPO), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were measured in liver or serum using commercial kits. An in vitro ALI model was established using LPS-stimulated RAW264.7 cells. Cell viability was measured by MTT method and the intracellular levels of IL-10, IL-1β, IL-6, IL-12 and TNF-α inflammatory factors were measured using kits. The expression of GSK-3β, NF-κB and CREB was measured by western blot or immunofluorescence. FA pretreatment significantly reduced liver/body weight ratio, decreased MPO, AST and ALT activity, alleviated the inflammatory responses and improved CLP-induced histopathological changes in liver. In addition, in vitro results showed that FA could dose-dependently increase the viability of RAW264.7 cells and decrease the levels of pro-inflammatory factors. In conclusion, our data suggest that FA can ameliorate ALI-induced inflammation via the GSK-3β/NF-κB/CREB pathway, suggesting that FA can be used to protect the liver against ALI.

Cao L ，Li Z ，Yang Z ，Wang M ，Zhang W ，Ren Y ，Li L ，Hu J ，Sun Z ，Nie S ... -  《-》

Protective effect of Xuebijing injection on D-galactosamine- and lipopolysaccharide-induced acute liver injury in rats through the regulation of p38 MAPK, MMP-9 and HO-1 expression by increasing TIPE2 expression.

Liu MW ，Liu R ，Wu HY ，Zhang W ，Xia J ，Dong MN ，Yu W ，Wang Q ，Xie FM ，Wang R ，Huang YQ ，Qian CY ... -  《-》

GSK-3β inhibition attenuates CLP-induced liver injury by reducing inflammation and hepatic cell apoptosis.

Zhang H ，Wang W ，Fang H ，Yang Y ，Li X ，He J ，Jiang X ，Wang W ，Liu S ，Hu J ，Liu A ，Dahmen U ，Dirsch O ... -  《-》

[To explore the preventive and therapeutic effects of Xuebijing injection on acute lung injury induced by cardiopulmonary bypass in rats by regulating the expression of microRNA-17-5p and its mechanism].

Xu Z ，Liu D ，Li K ，Li X ，Song L ... -  《-》