Alpinetin protects against hepatic ischemia/reperfusion injury in mice by inhibiting the NF-κB/MAPK signaling pathways.

• Alpinetin pretreatment improves liver function and reduces the degree of necrosis. • Alpinetin suppresses inflammatory response and apoptosis during hepatic I/R injury. • Alpinetin inhibits hepatocyte inflammation and apoptosis after H/R stimulation. • Alpinetin suppresses the NF-κB signaling pathway during hepatic I/R injury. • Alpinetin inhibits MAPK signaling pathways during hepatic I/R injury. Liver damage induced by ischemia/reperfusion (I/R) remains a primary issue in liver transplantation and resection. Alpinetin, a novel plant flavonoid derived from Alpinia katsumadai Hayata, is widely used to treat various inflammatory diseases. However, the effects of alpinetin on hepatic I/R injury remain unclear. The present study investigated the protective effects of alpinetin pretreatment on hepatic I/R injury in mice. C57BL/6 mice were subjected to 1 h of partial hepatic ischemia followed by 6 h of reperfusion. Alpinetin (50 mg/kg) was given by intraperitoneal injection 1 h before liver ischemia. The blood and liver tissues were collected to assess biochemical indicators, hepatocyte damage, and levels of proteins related to signaling pathways. Furthermore, a hepatocytes hypoxia/reoxygenation (H/R) model was established for in vitro experiments. In vivo , we observed that alpinetin significantly attenuated the increases in alanine aminotransferase, aspartate transaminase, proinflammatory cytokines, hepatocyte damage, and apoptosis caused by hepatic I/R. Moreover, the hepatic I/R-induced nuclear factor kappa-B (NF-κB)/mitogen-activated protein kinase (MAPK) pathways were suppressed by alpinetin. In vitro , we also observed that alpinetin inhibited the inflammatory response, apoptosis, and activation of the NF-κB/MAPK pathways in hepatocytes after H/R treatment. Our data indicate that alpinetin ameliorated the inflammatory response and apoptosis induced by hepatic I/R injury in mice. The protective effects of alpinetin on hepatic I/R injury may be due to its ability to inhibit the NF-κB/MAPK signaling pathways. These results suggest that alpinetin is a promising potential therapeutic reagent for hepatic I/R injury. [ABSTRACT FROM AUTHOR]