Abstract

Gynostemma pentaphyllum is a traditional Chinese medicine that has previously been used for the treatment of chronic inflammation, hyperlipidemia and liver disease. Gypenoside (GP), the predominant component of Gynostemma pentaphyllum, exhibits a therapeutic effect on chronic hepatic injury, fibrosis and fatty liver disease via its anti-inflammatory and anti-oxidant activity. However, the effect of GP on ischemia/reperfusion (I/R)-induced hepatic injury has, to the best of our knowledge, not previously been investigated. In the present study, a hepatic I/R-injury model was successfully established using C57BL/6 mice. In the treatment group, 50 mg/kg GP was administered orally 1 h prior to ischemia. Following hepatic I/R, the levels of hepatic lipid peroxidation and serum alanine aminotransferase increased, while the ratio of hepatic glutathione (GSH):oxidized GSH was reduced, which was effectively attenuated by pretreatment with GP. Furthermore, an increased protein expression of heme oxygenase-1 in the liver tissues of the I/R mice was attenuated by the administration of GP. In addition, the present study indicated that treatment with GP suppressed the I/R-induced increase in the pro-apoptotic protein levels of Bax and cytochrome c and the activity of caspase-3/8, as well as the I/R-induced decrease in the levels of anti-apoptotic protein Bcl-2. In conclusion, the present study indicated that GP effectively protected against I/R-induced hepatic injury via its anti-oxidative and anti-apoptotic bioactivity.

Highlights

  • Ischemia/reperfusion (I/R) is a predominant cause of hepatic injury, which is of clinical significance following liver surgery, hemorrhagic shock and liver transplantation [1]

  • It has been demonstrated that I/R-induced hepatic injury is initially triggered by reactive oxygen species (ROS), which induce oxidative damage and apoptosis, an important mechanism for cell death following hepatic I/R injury [2]

  • GP exhibits a therapeutic effect on chronic hepatic injury, fibrosis, as well as fatty liver disease, which were induced by a high fat, high cholesterol diet and alcohol in mice [5,8]

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Summary

Introduction

Ischemia/reperfusion (I/R) is a predominant cause of hepatic injury, which is of clinical significance following liver surgery, hemorrhagic shock and liver transplantation [1]. Developing effective preventive and therapeutic strategies for I/R-induced hepatic injury is required. Certain pro-inflammatory chemokines and cytokines are key during the initial period of reperfusion, whereas the late period of hepatic injury is neutrophil-mediated [3]. Gynostemma pentaphyllum is a traditional Chinese medicine, which has previously been used for the treatment of chronic inflammation, hyperlipidemia and liver diseases [4]. GP exhibits a therapeutic effect on chronic hepatic injury, fibrosis, as well as fatty liver disease, which were induced by a high fat, high cholesterol diet and alcohol in mice [5,8]. To the best of our knowledge, the role of GP in hepatic I/R injury and the underlying molecular mechanism, have not yet been investigated

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