Ampelopsin attenuates 6-OHDA-induced neurotoxicity by regulating GSK-3β/NRF2/ARE signalling

• Ampelopsin has promising therapeutic potential for Parkinson's disease.
• Ampelopsin can execute neuroprotective role.
• Ampelopsin attenuates neurotoxicity through regulating GSK-3β/NRF2/ARE signalling pathway.

Increasing evidence has demonstrated that oxidative stress is involved in the pathogenesis of Parkinson's disease (PD), suggesting that pharmacological targeting of the antioxidant machinery may have therapeutic potential. Ampelopsin, a natural flavonoid compound, has been reported to possess various pharmacological functions, including anti-inflammatory, anti-oxidative and anti-cancer effects. However, its neuroprotective effect and neurotoxicity-attenuating role as well as underlying mechanisms are still unclear. In the present study, we investigated the potential role of ampelopsin in neuroprotective function and neurotoxicity attenuation, and explored its corresponding mechanisms against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in the cell model of PD. The pretreatment with ampelopsin for 1 h significantly improved cell viability, reduced the release of lactate dehydrogenase (LDH) and inhibited the accumulation of reactive oxygen species (ROS) in 6-OHDA-stimulated PC12 cells. In addition, ampelopsin treatment attenuated 6-OHDA-induced apoptosis of PC12 cells by inhibiting the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK). Moreover, ampelopsin treatment significantly increased the localization of nuclear factor-erythroid 2-related factor 2 (Nrf2) and subsequent activation of haem oxygenase-1 (HO-1) gene associated with antioxidant response element (ARE) pathway in a dose-dependent manner. Further study demonstrated that ampelopsin treatment suppressed the expression of glycogen synthase kinase-3β (GSK-3β). The present results suggest that the neuroprotective role of ampelopsin is due to the increased expression of Nrf2 through suppressing GSK-3β signalling, thereby correspondingly inhibiting ROS/p-p38/p-JNK MAPK signalling pathway. Therefore, ampelopsin has promising therapeutic potential for PD.