Gypenoside attenuates renal ischemia/reperfusion injury in mice by inhibition of ERK signaling

Abstract

Gynostemma pentaphyllum is a traditional Chinese medicine reported to possess a wide range of health benefits. As the major component of G. pentaphyllum, gypenoside (GP) displays various anti-inflammatory and anti-oxidant properties. However, it is unclear whether GP can protect against ischemia/reperfusion (I/R)-induced renal injury, and the underlying molecular mechanisms associated with this process remain unknown. In the present study, a renal I/R injury model in C57BL/6 mice was established. It was observed that, following I/R, serum concentrations of creati- nine (Cr) and blood urea nitrogen (BUN) were significantly increased (P<0.01), indicating renal injury. Pretreatment with GP (50 mg/kg) significantly inhibited I/R-induced upregula- tion of serum Cr and BUN (P<0.01). Furthermore, renal malondialdehyde levels were significantly reduced in the I/R+GP group, compared with the I/R group (P<0.01), whereas renal tissue superoxide dismutase activity was significantly higher in the I/R+GP group compared with the I/R group (P<0.01). Further investigation demonstrated that pretreat- ment with GP produced inhibitory effects on the I/R-induced production of pro-inflammatory cytokines, including inter- leukin (IL)-1β, IL-6, tumor necrosis factor-α and interferon-γ (P<0.01). In addition, heme oxygenase 1 (HO-1) expression levels were significantly increased in the I/R group compared with the control (P<0.01), indicating the presence of oxidative damage. However, the I/R-induced upregulation of HO-1 was significantly attenuated by pretreatment with GP (P<0.01), which also suppressed I/R-induced apoptosis by inhibiting pro-apoptotic Bax and upregulating anti-apoptotic Bcl-2 in renal cells (P<0.01). Finally, the activity of ERK signaling was significantly increased in the I/R+GP group compared with the I/R group (P<0.05), which may be associated with the protective effect of GP against I/R-induced renal cell apoptosis. To conclude, the present results suggest that GP produces a protective effect against I/R-induced renal injury as a result of its anti-inflammatory and anti-apoptotic properties.