Promising effects on ameliorating mitochondrial function and enhancing Akt signaling in SH-SY5Y cells by (M)-bicelaphanol A, a novel dimeric podocarpane type trinorditerpene isolated from Celastrus orbiculatus

Abstract Oxidative stress plays an important role in the pathological processes of various neurodegenerative diseases. In this study, we investigated the neuroprotective effects of ( M )-bicelaphanol A, which has been the first dimeric podocarpane type trinorditerpene isolated from Celastrus orbiculatus , against hydrogen peroxide (H 2 O 2 )-induced injury in human SH-SY5Y neuroblastoma cells. Our study showed that cells pretreated with ( M )-bicelaphanol A significantly attenuated H 2 O 2 -induced cell viability reduction and cell apoptosis. These neuroprotective effects of ( M )-bicelaphanol A were associated with a reduction of reactive oxygen species and an increase in the level of adenosine triphosphate. In addition, ( M )-bicelaphanol A pretreatment markedly increased the phosphorylation level of Akt in SH-SY5Y cells. In conclusion, our results for the first time demonstrate that the protection of ( M )-bicelaphanol A on SH-SY5Y cells against H 2 O 2 -induced oxidative stress may attribute, at least partially, to its attenuation of mitochondrial dysfunction and activation of Akt signaling pathway. Above results shed more light on the molecular mechanisms involved in the neuroprotective effects of ( M )-bicelaphanol A, which could be a potential drug candidate for the treatment of oxidative stress-associated neurodegenerative diseases.