DOI 10.1007/s00221-007-1100-3RESEARCH ARTICLE Protection against hydrogen peroxide-induced injury by Z-ligustilide in PC12 cells

Abstract Z-ligustilide (Z-LIG) is the primary lipophilic compound of the Chinese medicine Danggui (Radix Angel-ica sinensis). Previous studies demonstrated that Z-LIG had signiWcant neuroprotective potential in both transient and permanent cerebral ischemia, possibly through antioxidant and anti-apoptotic mechanisms. The present study exam-ined the mechanisms of Z-LIG on hydrogen peroxide (H2O2)-induced injury in PC12 cells. Following exposure of the cells to H2O2 (500 M), a signiWcant reduction in cell survival and total antioxidant capacity (TAC), as well as increased intracellular reactive oxygen species (ROS), were observed. In addition, H2O2 treatment signiWcantly upregu-lated Bax expression, cleaved-caspase 3, and cytosolic cytochrome-c, and decreased Bcl-2 protein levels. Pretreat-ment of the cells with Z-LIG (0.1, 1.0, 2.5, or 5.0 g/ml) signiWcantly attenuated H2O2-induced cell death, attenuated increased intracellular ROS levels, and decreased Bax expression, cleaved-caspase 3, and cytochrome-c. Further, Z-LIG improved cellular TAC and concentration-depen-dently upregulated Bcl-2 expression. These results demon-strate that Z-LIG has a pronounced protective eVect against H2O2-induced cytotoxicity, at least partly through improv-ing cellular antioxidant defense and inhibiting the mito-chondrial apoptotic pathway. These Wndings suggest that Z-LIG may be useful in the treatment of neurodegenerative disorders in which oxidative stress and apoptosis are mainly implicated