Decursin Isolated from Angelica gigas Nakai Rescues PC12 Cells from Amyloid β-Protein-Induced Neurotoxicity through Nrf2-Mediated Upregulation of Heme Oxygenase-1 : Potential Roles of MAPK

Abstract EN

Decursin (D), purified from Angelica gigas Nakai, has been proven to exert neuroprotective property.

Previous study revealed that D reduced Aβ25‒35-induced cytotoxicity in PC12 cells.

Our study explored the underlying mechanisms by which D mediates its therapeutic effects in vitro.

Pretreatment of cells with D diminished intracellular generation of ROS in response to Aβ25‒35.

Western blot revealed that D significantly increased the expression and activity of HO-1, which was correlated with its protection against Aβ25‒35-induced injury.

Addition of ZnPP, an HO-1 competitive inhibitor, significantly attenuated its protective effect in Aβ25‒35-treated cells, indicating the vital role of HO-1 resistance to oxidative injury.

Moreover, D induced Nrf2 nuclear translocation, the upstream of HO-1 expression.

While investigating the signaling pathways responsible for HO-1 induction, D activated ERK and dephosphorylated p38 in PC12 cells.

Addition of U0126, a selective inhibitor of ERK, blocked D-induced Nrf2 activation and HO-1 induction and meanwhile reversed the protection of D against Aβ25‒35-induced cell death.

These findings suggest D augments cellular antioxidant defense capacity through both intrinsic free radical scavenging activity and activation of MAPK signal pathways that leads to Nrf2 activation, and subsequently HO-1 induction, thereby protecting the PC12 cells from Aβ25‒35-induced oxidative cytotoxicity.