Abstract: To explore the protective effects and its molecular mechanism of action of gypenoside (GPS) on the improvement of peripheral nerve toxicity induced by oxaliplatin in rats.Male SD rats were randomly divided into normal control group,model control group,the low-,medium-and high-dose of GPS groups.Except of the normal control group,peripheral nerve toxicity rat models were established by intraperitomeal injection with oxaliplatin (4 mg/kg),meanwhile,different doses of GPS were given by gavage,the behavior changes of rats under mechanical stimulation and temperature were observed at different point time.At the end of the experiment,rats were sacrificed,the levels of serum NGF were determined by ELISA,and the relative expression levels of Nrf2 and its downstream molecular NQO-1,HO-1 in L4-5 dorsal root ganglion were detected by Western blot.Results:When compared with the normal control group,the mechanical withdrawal threshold and the cold stimulus response threshold were significantly reduced in the model control group.In addition,the levels of serum NGF and the protein expression levels of Nrf2,NQO-1 and HO-1 in L4-5 dorsal root ganglion were significantly reduced.Conversely,GPS significantly elevated threshold of mechanical withdrawal and cold stimulus response,significantly increased the levels of NGF in serum and the relative expression levels of Nrf2,NQO-1 and HO-1 protein in L4-5 dorsal root ganglion.In conclusion,GPS improves oxaliplatin-induced peripheral nerve toxicity by increasing the levels of serum NGF and upregulating the Nrf2 signal.

Key words: oxaliplatin, gypenoside, nerve toxicity, dorsal root ganglion, Nrf2 signal