Protective Effect of Eupatilin Pretreatment Against Hepatic Ischemia-Reperfusion Injury in Mice

• Eupatilin from Artemisia spp is an antioxidant, antiinflammatory, and antiapoptotic compound.
• To our knowledge, this is the first study applying eupatilin for hepatic IRI.
• Eupatilin significantly decreased sALT and sAST, and malondialdehyde levels.
• Eupatilin lowered apoptotic, TLR2/4 and increased antiapoptotic factor levels.
• Eupatilin is a promising therapy for acute ischemia-induced hepatic damage.

BackgroundEupatilin, a pharmacologically active flavone derived from Artemisia species, is known to have antioxidant and antiinflammatory activities. Ischemia-reperfusion injury (IRI) is a major critical event that commonly occurs after liver transplantation and resection. Furthermore, inflammatory responses to IRI exacerbate the resultant hepatic injury. In this study, we investigated whether eupatilin protects against IR-induced acute liver injury in mice.Materials and MethodsPartial (70%) hepatic IRI was induced in male C57BL/6 mice by portal triad pedicle occlusion for 90 minutes followed by reperfusion for 6 hours. Eupatilin (10 mg/kg body weight, oral) was administered 4 days before the IRI.ResultsTreatment with eupatilin significantly decreased serum alanine aminotransferase and serum aspartate aminotransferase as well as liver histologic changes. Eupatilin also prevented hepatic glutathione depletion and increased malondialdehyde levels induced by IRI. Western blotting indicated that eupatilin significantly increased the levels of heat shock protein and B-cell lymphoma 2 protein, attenuated inducible nitric oxide synthase, and cleaved caspase-3 levels 6 hours after IRI. The expression of the Toll-like receptor 2/4, and phosphorylated nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor was significantly decreased in the eupatilin pretreatment group.ConclusionsEupatilin improved the acute hepatic IRI by reducing inflammation and apoptosis. These findings suggest that eupatilin is a promising therapeutic agent against acute IR-induced hepatic damage.