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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.
- Source :
- Evidence-based Complementary & Alternative Medicine (eCAM); 2013, Vol. 2013, p1-14, 14p, 8 Graphs
- Publication Year :
- 2013
-
Abstract
- Decursin (D), purified from Angelica gigas Nakai, has been proven to exert neuroprotective property. Previous study revealed that D reduced Aβ<subscript>25-35</subscript>-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 Aβ<subscript>25-35</subscript>. Western blot revealed that D significantly increased the expression and activity of HO-1, which was correlated with its protection against Aβ<subscript>25-35</subscript>-induced injury. Addition of ZnPP, an HO-1 competitive inhibitor, significantly attenuated its protective effect in Aβ<subscript>25-35</subscript>-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 Aβ<subscript>25-35</subscript>-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 Aβ<subscript>25-35</subscript>-induced oxidative cytotoxicity. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 1741427X
- Volume :
- 2013
- Database :
- Complementary Index
- Journal :
- Evidence-based Complementary & Alternative Medicine (eCAM)
- Publication Type :
- Academic Journal
- Accession number :
- 95495803
- Full Text :
- https://doi.org/10.1155/2013/467245