Protection against hydrogen peroxide-induced injury by Z-ligustilide in PC12 cells

Z-ligustilide (Z-LIG) is the primary lipophilic compound of the Chinese medicine Danggui (Radix Angelica sinensis). Previous studies demonstrated that Z-LIG had significant neuroprotective potential in both transient and permanent cerebral ischemia, possibly through antioxidant and anti-apoptotic mechanisms. The present study examined the mechanisms of Z-LIG on hydrogen peroxide (H(2)O(2))-induced injury in PC12 cells. Following exposure of the cells to H(2)O(2 )(500 microM), a significant reduction in cell survival and total antioxidant capacity (TAC), as well as increased intracellular reactive oxygen species (ROS), were observed. In addition, H(2)O(2 )treatment significantly upregulated Bax expression, cleaved-caspase 3, and cytosolic cytochrome-c, and decreased Bcl-2 protein levels. Pretreatment of the cells with Z-LIG (0.1, 1.0, 2.5, or 5.0 microg/ml) significantly attenuated H(2)O(2)-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-dependently upregulated Bcl-2 expression. These results demonstrate that Z-LIG has a pronounced protective effect against H(2)O(2)-induced cytotoxicity, at least partly through improving cellular antioxidant defense and inhibiting the mitochondrial apoptotic pathway. These findings suggest that Z-LIG may be useful in the treatment of neurodegenerative disorders in which oxidative stress and apoptosis are mainly implicated.