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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. [ABSTRACT FROM AUTHOR]

Acute lung injury (ALI) is an inflammatory disease with high mortality, but therapeutics against it is unavailable. Recently, we elaborated a formula, named Chung-pae (CP), that comprises four ethnic herbs commonly prescribed against various respiratory diseases in Asian traditional medicine. CP is being administered in aerosol to relieve various respiratory symptoms of patients in our clinic. Here, we sought to examine whether CP has a therapeutic effect on ALI and to uncover the mechanism behind it. Reporter assays show that CP suppressed the transcriptional activity of proinflammatory NF-kB and activated that of anti-inflammatory Nrf2. Similarly, CP suppressed the expression of NF-kB dependent, proinflammatory cytokines and induced that of Nrf2 dependent genes in RAW 264.7. An aerosol intratracheal administration of CP effectively reduced neutrophilic infiltration and the expression of pro- inflammatory cytokines, hallmarks of ALI, in the lungs of mice that received a prior intraperitoneal injection of lipopolysaccharide. The intratracheal CP administration concomitanfly enhanced the expression of Nrf2 dependent genes in the lung. Therefore, our results evidenced a therapeutic effect of CP on ALI, in which differential regulation of the two key inflammatory factors, NF-kB and Nrf2, was involved. We propose that CP can be a new therapeutic formula against ALI. [ABSTRACT FROM AUTHOR]