Upregulation of HBXIP contributed to the anti-DND by ginsenoside Rg1 after global cerebral ischemia-reperfusion

Abstract

AbstractObjectivesGinsenoside Rg1 (Rg1) has been well-documented to be effective against ischemic/reperfusion (I/R) injury. However, whether it has therapeutic effect on delayed neuronal death is still unclear. The aim of this study is to investigate the effect of Rg1 on delayed neuronal death and elucidate its underlying mechanism.MethodsDelayed neuronal death model was prepared by global cerebral ischemia-reperfusion in rats, Rg1 was intravenously administered once a day. Nissl and Fluoro Jade B staining were carried out to evaluate the effect of Rg1 on delayed neuronal death. Western blot and qPCR were used to investigate the levels of HBXIP and Survivin. HBXIP/Survivin complex was observed by co-immunoprecipitation. AAV-CMV-shRNA (HBXIP) was used to observe the role of HBXIP on delayed neuronal death improved by Rg1.Key findingsRg1 attenuated delayed neuronal death at the dose of 20 mg/kg, which also improved the mRNA and protein levels of HBXIP, as well as Survivin. Moreover, administration of Rg1 promoted the formation of HBXIP/Survivin complex, which contributed to the reduction of caspases signaling pathway. Knockdown of HBXIP abolished the alleviation of DND and inhibition of caspase cascade induced by Rg1.ConclusionsRg1 alleviated delayed neuronal death by promoting anti-apoptosis effect by HBXIP/Survivin complex.