Protective Effects of Geniposide on Hepatic Ischemia/Reperfusion Injury

Abstract

BackgroundGeniposide (GEN) is the major ingredient of Gardenia jasminoides Ellis, which has anti-inflammatory and anti-apoptotic activities and is widely used to treat ischemia disease. Inflammation and apoptosis play an important role in hepatic ischemia/reperfusion (I/R) injury. The current study was conducted to explore the effects of geniposide on hepatic I/R injury and its potential molecular mechanism in mice. MethodsFifty Sprague-Dawley rats were randomly divided into 5 groups: the sham group (sham), the hepatic I/R injury group (IRI) and the GEN groups (low, middle, and high). In the GEN and IRI groups, hepatic IRI by was induced by means of clamping the left and median liver lobes for 30 minutes with noninvasive endoclips. The GEN groups were pretreated with GEN (5, 10, 20 mg/kg) at 30 minutes before ischemia by use of intraperitoneal injection. Rats in the IRI group and sham group were administrated with same dosage of saline at the same time. After reperfusion for 6 hours, the hepatic pathology and the expression of alanine aminotransferase (ALT), AST aspartate aminotransferase, LDH lactic acid dehydrogenase, PI3K, AKT, p-AKT, m-TOR, Bax, BCL-2, interleukin (IL)-6, MCP-1, and tumor necrosis factor (TNF)-α were examined. ResultsCompared with the sham group, the IRI group had higher expression of ALT, AST, LDH, Bax, IL-6, MCP-1, and TNF-α and lower expression of BCL-2, PI3K, p-AKT, and mammalian target of rapamycin (mTOR), with more inflammatory cell infiltration, cellular swelling, and vacuolar degeneration. Compared with the IRI group, the GEN group had lower expression of ALT, AST, LDH, Bax, IL-6, MCP-1, and TNF-α and higher expression of BCL-2, PI3K, p-AKT, and mTOR, with less inflammatory cell infiltration, cellular swelling, and vacuolar degeneration. There were no differences in the expression of AKT among several groups. ConclusionsGEN can protect rats against hepatic I/R injury and partly relies on suppressing inflammation and apoptosis by inducing the activation of the PI3K/Akt/mTOR signaling pathway.